Peripheral neuropathy



Anti- Emetics 5-HT3 antagonistsDopamine antagonists?H1-receptor antagonist Serotonin receptor antagonists (5-hydroxytryptamine) ?Blocks 5-HT3 receptors GIT and CNS) specifically chemoreceptor trigger zone (CTZ) act in the chemoreceptor trigger zone area of the medulla oblongata.Mainly TTT?chemotherapy-related?nausea.ExamplesOndansetronGranisetronAdverse effectsconstipation is common↑↑ QT interval Polymorphic VTExamplesMetoclopramide Acts directly on GIT nausea and vomiting associated with gastroduodenal, hepatic and biliary disease. W caution in young women (acute dystonic reaction "oculogyric crises) Domperidone Does not cross BBB NO extra-pyramidal S/EHaloperidol & LevomepromazineS/E Parkinson like symptoms Movement disorders (young females)Histamine (H1 ) Receptor Antagonist Central?Anticholinergic (Antimuscarinic)?Direct action ?"HYPERLINK "" \o "Vestibular system"vestibular system"?and on the?chemoreceptor trigger zone. Action Indications ?Motion sickness,?Vertigo?post-operatively following general anesthesia?Opioid induced nausea ExamplesPiperazines CyclizineS/EConstipationurinary retention.TachyarrhythmiasContraindicationProstatic hypertrophyUrinary retentionAngle-closure?glaucoma.Motor Neuron Diseases Motor Neuron D. (mixed UMNL & LMNL)Motor neuron disease is a neurological condition of unknown cause. Rarely < 40 years. Various patterns amyotrophic lateral sclerosis the most common type Degeneration of neurones in the motor cortex and in the ventral spinal cord ( mixed UMN and LMN signs).progressive muscular atrophy Bulbar palsy.There are a number of clues:FasciculationsAbsence of sensory signs/symptoms (vague sensory symptoms may be early ( limb pain) but 'never' sensory signs)the?mixture LMN + UMNWasting of the small hand muscles/tibialis anterior is commonOther featuresDoesn't affect external ocular musclesNo cerebellar signsAbdominal reflexes are usually preserved and sphincter dysfunction if present is a late featureDiagnosis Is clinical nerve conduction studies will show?normal motor conduction?and can help exclude a neuropathy. Electromyography (↓↓ NO action potentials + ↑↑amplitude. MRI is usually performed to exclude cervical cord compression and myelopathyTypesAmyotrophic lateral sclerosis1ry lateral sclerosisProgressive Muscular trophyProgressive bulbar palsy(50% of patients)LMN " arms" and UMN " legs"in familial (chromosome 21) codes for superoxide dismutaseUMN signs onlyBest PrognosisLMN signs onlyaffects distal muscles before proximalWorst prognosisLoss of brainstem motor nuclei functionPalsy (Tongue, Muscles of chewing/swallowing and facial muscles ManagementRiluzoleprevents stimulation of glutamate receptorsused mainly in amyotrophic lateral sclerosisprolongs life by about 3 monthsRespiratory careNon-invasive ventilation (usually BIPAP) is used at nightSurvival benefit of around 7 monthsPrognosisPoor: 50% of patients die within 3 yearsDD. Absent ankle jerks, extensor plantars (Mixed UMNL &LMNL), CausesSubacute combined degeneration of the cordMotor neuron diseaseFriedreich's ataxiaSyringomyeliaTaboparesis (syphilis)Conus Medullaris lesionCervical Myelopathy LMN signs onlyDiabetic neuropathy myasthenia gravis Guillain Barre syndrome Multifocal motor neuropathy with conduction block, Myopathy Lambert Eton Autoimmune disorder involving the neuromuscular junctionUpper motor neuroneCervical artery dissection is a cause of stroke. (pain is not such a prominent component).Parkinsonion signs Progressive supranuclear palsy (Parkinsonism + Falls + Downgaze vertical gaze palsy)?Drugs causing a peripheral neuropathyAmiodaroneIsoniazidvincristineNitrofurantoinMetronidazoleCauses of transverse myelitisViral infections VZV, HSV, CMV, EBV, Echovirus, HIVbacterial infections Syphilis, Lyme diseasePost-infectious (immune mediated)First symptom of Multiple Sclerosis (MS) or Neuromyelitis optica (NMO)Radiographical features Hyperintense T2 signal extending across the spinal cord, between the levels of T9 and T12.Neuropathic painPain following damage or disruption of the nervous system. It is often difficult to treat and responds poorly to standard analgesia.Examples includeDiabetic neuropathyPost-herpetic neuralgiaTrigeminal neuralgiaProlapsed intervertebral discManagementfirst-line treatment: Amitriptyline, Duloxetine, Gabapentin or PregabalinCarbamazepine is used first-line for trigeminal neuralgiaif the first-line drug treatment does not work try one of the other 3 drugsTramadol may be used as 'Rescue therapy' for exacerbations of neuropathic painTopical capsaicin may be used for localised neuropathic pain (Post-herpetic neuralgia)pain management clinics may be useful in patients with resistant problemsTrigeminal neuralgiaSevere unilateral pain the majority are idiopathic but compression of the trigeminal roots by tumours or vascular problems. Define as:a unilateral disorder electric shock-like pains.Abrupt in onset and termination limited to one or more divisions of the trigeminal nerve↑↑↑ (light touch Washing, Shaving, smoking, talking, and brushing the teeth and spontaneouslyTrigger areas small areas in the Nasolabial fold or chin precipitation of pain the pains usually remit for variable periodsRed flag symptoms and signs suggesting a serious underlying cause:A family history of M.SAge of > 40 yearsSensory changesHistory of skin or oral lesions that could spread perineurall.Ear problems Deafness or otherPain only in the ophthalmic division of the trigeminal nerve (eye socket, forehead, and nose), or bilaterallyOptic neuritisManagementCarbamazepine is first-linefailure to respond to treatment or atypical features (< 50 years old) should prompt referral to plex regional pain syndrome (CRPS) Conditions such as reflex sympathetic dystrophy and causalgia. occur following surgery or a minor injury. 3 times ↑↑Women.Type I (most common): there is No lesion to a major nerveType II: there is a lesion to a major nerveFeaturesprogressive, disproportionate symptoms to the original injury/surgeryallodyniaTemperature and skin colour changesOedema and sweatingMotor dysfunctionthe Budapest Diagnostic Criteria are commonly used in the UKManagementEarly physiotherapy is importantneuropathic analgesia in-line with NICE guidelinesspecialist management (Pain team) is requiredAutonomic neuropathyImpotenceInability to sweatCVSPostural Hypotension ↓↓ 30/15 mmHgLoss ↓↓ HR following deep breathingPupils: Dilates following adrenaline instillation (Eager to sympathetic ++)CausesD.M Guillain-Barre syndromeMultisystem atrophy (MSA)Shy-Drager syndromeParkinson'sInfections HIVChagas' DiseaseNeurosyphilisDrugsAntihypertensiveTCACraniopharyngiomaPeripheral neuropathyPredominately motor lossPredominately sensory lossGuillain-Barre syndromePorphyrialead poisoningHereditary Sensorimotor Neuropathies (HSMN) - Charcot-Marie-ToothChronic inflammatory demyelinating polyneuropathy (CIDP)DiphtheriaD.MUremiaLeprosyAlcoholism2ry Direct toxic effects and ↓↓ absorption of B vitaminsSensory symptoms typically present prior to motor symptomsVit B12 deficiencySCD of spinal cordDorsal column 1st (joint position, vibration) Distal paraesthesiaAmyloidosisPeripheral neuropathy: demyelinating vs. axonalDemyelinating pathologyAxonal pathologyGuillain-Barre syndromeAmiodaroneParaprotein neuropathyHereditary sensorimotor neuropathies (HSMN) Type IChronic inflammatory demyelinating polyneuropathy (CIDP)alcoholdiabetes mellitus*Vit B12 deficiency may also cause a demyelinating picturevasculiticHereditary sensorimotor neuropathies (HSMN) Type IITransient global amnesiaClinical syndrome of uncertain aetiology thought to be due to transient ischaemia to the thalamus (aAmygdala and Hippocampus).Diagnostic criteria Discrete episode lasting for a few hours (< 24 hours)Reliable witness to episode (Absence of head trauma or loss of consciousness at the onset)Absence of other cognitive or neurological impairments preserved personal identity and absence of epileptic featuresAnterograde amnesia & Retrograde amnesia presents with transient loss of memory function patients have no recall of events after the attackAnxious and repeatedly ask the same questionMultiple sclerosisChronic cell-mediated autoimmune disorder characterised by demyelination CNS.?Epidemiology3 times ↑↑women (20-40 Ys)↑↑↑↑ higher latitudes (5 times tropics)GeneticsMonozygotic twin concordance = 30%Dizygotic twin concordance = 2%FeaturesNon - specific features 75% of patients have significant lethargy.VisualOptic neuritis: common presenting featureoptic atrophyUhthoff's phenomenon: worsening of vision following rise in body temperatureInternuclear ophthalmoplegiaSensoryPins/needlesNumbnessTrigeminal neuralgiaLhermitte's syndrome paraesthesiae in limbs on neck flexionMotor Spastic weakness: most commonly seen in the legsCerebellarAtaxia: More often seen during an acute relapse than as a presenting symptomTremorDepression is obviously very common and may indeed be one of the subtle manifestations of multiple sclerosis.Othersurinary incontinencesexual dysfunctionintellectual deteriorationDiagnosis ≥ 2 Relapses ≥ 2 lesions (Demyelinating lesions separated in space and time) OR (Objective clinical evidence of one lesion + Evidence of a previous relapse).4 disease patterns in MS (Clinically isolated syndrome, relapsing-remitting MS, 1ry progressive MS, and 2ndary progressive MS).Relapsing-remitting disease2ndary progressive disease1ry progressive diseaseCommonest form (85% )Acute attacks (1-2 months) remissionRelapsing-remitting + Deteriorated and neurological between relapses(65%) of relapsing-remitting form develop secondary progressive disease within 15 years of diagnosisGait and bladder disorders are generally seen10% of patientsProgressive deterioration from onset↑↑↑older peopleGood prognosis featuresFemale sexyoung age of onset (i.e. 20s or 30s)Relapsing - Remitting diseaseSensory symptoms onlylong interval between first two relapsescomplete recovery between relapsesInvestigationDiagnosis requires demonstration of lesions disseminated in time and spaceMRIHigh signal T2 lesions Periventricular plaquesDawson fingers "FLAIR Images" hyperintense lesions penpendicular to the corpus callosumFat and water both appear bright on T1- and T2-weighted MRI. (Better differentiate soft tissue pathology).Detecting periventricular and cortical/juxtacortical lesions in the diagnosis of multiple sclerosis.N.B (Short Time Inversion Recovery "STIR" MRI) (- -) signal from fat bright signal in an acute inflammatory process ( oedema) tissue. Used Flare of thyroid eye disease. Most frequently affected (Medial and Inferior recti.CSFOigoclonal bands (and not in serum)↑↑ intrathecal synthesis of IgG.Visual evoked potentialsDelayed, but well preserved waveformManagement↓↓ frequency and duration of relapses. There is no cure.?In case of only detection of 1 lesion in MRI brain and optic neuritis symptoms MRI spine (Other lesions separated in space and time + Steroids current optic neuritisAcute relapseHigh dose steroids (oral or IV methylprednisolone)? 5 days to shorten the length of an acute relapse. ↓↓ duration of a relapse and do not alter the degree of recovery (Returning to baseline function)Disease modifying drugsBeta-interferon ↓↓ relapse rate by up to 30%. ↓↓ number of relapses and MRI changes, doesn't reduce overall disabilityIndication:Relapsing - Remitting disease + 2 relapses in past 2 years + able to walk 100m unaided2ry progressive disease + 2 relapses in past 2 years + able to walk 10m (aided or unaided)Other drugsGlatiramer Acetate immunomodulating drug - acts as an 'immune decoy'Natalizumab a recombinant monoclonal antibody antagonises Alpha-4 Beta-1-integrin (on the surface of leucocytes)(- -) migration of leucocytes across the endothelium across the blood-brain barrierFingolimod Sphingosine 1-phosphate receptor modulator, (- -) lymphocytes from leaving lymph nodes. An oral formulation is availableSome specific problemsFatigueExclude (Anaemia/ Thyroid/ Depression) Trial of AmantadineMindfulness training and CBT SpasticityBaclofen and gabapentin are first-line. Other options include Diazepam, Dantrolene and Tizanidinephysiotherapy is importantcannabis and botox are undergoing evalulationBladder dysfunctionmay take the form of urgency, incontinence, overflow etcU/S first to assess bladder emptying Anticholinergics may worsen symptoms in some patientsif significant residual volume → intermittent self-catheterisationif no significant residual volume → anticholinergics may improve urinary frequencyOscillopsia (visual fields apper to oscillate) Gabapentin is first-lineGuillain-Barre syndromeimmune mediated demyelination of the peripheral nervous system often triggered by an infection (classically?Campylobacter?jejuni)Pathogenesiscross reaction of antibodies with gangliosides in the peripheral nervous systemcorrelation between anti-ganglioside antibody (e.g. anti-GM1) and clinical features has been demonstratedanti-GM1 antibodies in 25% of patientsFeatures Progressive weakness flaccid paralysis. ascending (lower extremities are first) (proximal muscles earlier than the distal)Sensory symptoms mild (distal paraesthesia). Some patients experience back pain in the initial stages of the illnessAbsent or depressed deep tendon reflexes are classical findings in Guillain-Barre Syndrome (GBS). Hyperreflexia is seen in a GBS variant known as Bickerstaff's encephalitis.Other featuresthere may be a history of gastroenteritisareflexiacranial nerve involvement e.g. diplopiaAutonomic involvement: e.g. urinary retention, tachycardia diarrhea// hypertension, hypotension, bradycardia, or ileus, are not common.Less common papilloedema: thought to be secondary to reduced CSF resorptionInvestigationslumbar puncture↑↑ protein with a normal white blood cell count?(albuminocytologic dissociation) - found in 66%nerve condution studies may be performedManagementplasma exchangeIV immunoglobulins (IVIG): as effective as plasma exchange. No benefit in combining both treatments. IVIG may be easier to administer and tends to have fewer side-effectsSteroids and immunosuppressants have not been shown to be beneficialFVC regularly to monitor respiratory functionPrognosissevere motor problems persist in about 15%around 5% diePoor prognostic featuresage > 40 yearspoor upper extremity muscle strengthprevious history of a diarrhoeal illness (specifically?Campylobacter?jejuni)high anti-GM1 antibody titreneed for ventilatory supportThere is currently contradictory evidence as to whether a gradual or rapid onset of GBS is associated with a poor outcomeMiller Fisher syndromeVariant of Guillain-Barre syndromeAssociated with Ophthalmoplegia The eye muscles are typically affected first Areflexia Ataxia. Usually presents as a descending paralysis rather than ascending as seen in other forms of Guillain-Barre syndromeAnti-GQ1b antibodies are present in 90% of casesPostural hypotension due to is not a feature of Miller Fisher syndromeChronic inflammatory demyelinating polyneuropathy (CIDP)Chronic form of Guillain-barre syndrome (acute inflammatory demyelinating polyneuropathy). Guillain-barre syndrome reaches its nadir within three to four weeks, whereas CIDP is defined by progression for longer than 8 weeks.Normal pressure hydrocephalusA reversible cause of dementia seen in elderly patients 2ry to ↓↓ CSF absorption at the arachnoid villi. These changes may be secondary to head injury, subarachnoid haemorrhage or meningitis. Classical triad urinary incontinencedementia and bradyphreniagait abnormality (may be similar to Parkinson's disease)Around 60% of patients will have all 3 features at the time of diagnosis. Symptoms typically develop over a few months.Imaginghydrocephalus with an enlarged fourth ventricleAbsence of substantial sulcal atrophy.Managementventriculoperitoneal shuntingaround 10% of patients who have shunts experience significant complications such as seizures, infection and intracerebral haemorrhagesMultiple system atrophyThere are 2 predominant types of multiple system atrophy1) MSA-P - Predominant Parkinsonian features2) MSA-C - Predominant Cerebellar featuresShy-Drager syndrome is a type of multiple system atrophy.Featuresparkinsonismautonomic disturbanceerectile dysfunction: often an early featurepostural hypotensionatonic bladdercerebellar signs DDIdiopathic Parkinson's diseaseParkinsonism (rigidity, resting tremor and bradykinesia "slowness of movement"). Other features shuffling gait, mask-like face, micrographia (small handwriting) and dementia.Normal pressure hydrocephalusProgressive mental impairment and dementia, difficulty walking can resemble a parkinsonian and impaired bladder control. no rigidity or tremorProgressive supranuclear palsy Starts with impaired balance prone to many falls. vertical gaze palsy. ↓↓ responsive to levodopa, unlike Parkinson's disease.Corticobasal syndrome Movement disorder + unilateral absence of movements + muscle rigidity with a tremor. It is a progressive neurological disorder ↓↓ cognition.Facial nerve palsyThe facial nerve is the main nerve supplying the structures of the second embryonic branchial arch. It is predominantly an efferent nerve to the muscles of facial expression, digastric muscle and also glandular structures. It contains a few afferent fibres which originate in the cells of its genicular ganglion and are concerned with taste.Supply - 'face, ear, taste, tear'face: muscles of facial expressionear: nerve to stapediustaste: supplies anterior two-thirds of tonguetear: parasympathetic fibres to lacrimal glands, also salivary glandsLMN vs. UMNupper motor neuron lesion 'spares' upper face i.e. foreheadlower motor neuron lesion affects all facial musclesCauses of bilateral facial nerve palsysarcoidosisGuillain-Barre syndromeLyme diseasebilateral acoustic neuromas (as in neurofibromatosis type 2)as Bell's palsy is relatively common it accounts for up to 25% of cases f bilateral palsy, but this represents only 1% of total Bell's palsy Causes of unilateral facial nerve palsy - as above plusLower motor neuron?Bell's palsyRamsay-Hunt syndrome (due to herpes zoster)acoustic neuromaparotid tumoursHIVmultiple sclerosis may also cause an UMN palsydiabetes mellitusUpper motor neuron Stroke PathwaySubarachnoid pathOrigin motor- pons, sensory- nervus intermediusPass through the petrous temporal bone internal auditory meatus with the vestibulocochlear nerve combine to become the facial nerve.Facial canal pathThe canal passes superior to the vestibule of the inner earAt the medial aspect of the middle ear, it becomes wider and contains the geniculate ganglion. 3 branches:1. greater petrosal nerve2. nerve to stapedius Hyperacusis results from paralysis of the stapedius muscle. Overflow of tears may occur but hyperlacrimation does not3. chorda tympaniStylomastoid foramenPasses through the stylomastoid foramen (tympanic cavity anterior and mastoid antrum posteriorly)Posterior auricular nerve and branch to posterior belly of digastric and stylohyoid muscleBell's palsyacute, unilateral, idiopathic, facial nerve paralysis. The aetiology is unknown although the role of the herpes simplex virus has been investigated previously.The peak incidence is 20-40 years and ↑↑ pregnant women.Featureslower motor neuron facial nerve palsy - forehead affected*post-auricular pain (may precede paralysis), altered taste dry eyes Hyperacusis 1/3 of patients.No sensory loss.DD. Ramsey Hunt syndrome ? Vesicular rash around the ear would suggest a diagnosis of Investigationsclinical diagnosis of isolated lower motor neurone facial nerve weakness, with typical features of Bell's Palsy and in the absence of symptoms/signs that are atypical neuroimaging is not indicated.?upper motor neuron (UMN) facial nerve weakness (with forehead sparing) raises concern about the possibility of a stroke and would demand neuroimaging to exclude this. However, in the context of an ManagementPreviously no treatment, prednisolone only and a combination of aciclovir and prednisoloneUpdated Recommendation Prednisolone 1mg/kg for 10 days 72 hours of onset ↑↑ likelihood of complete recovery Adding in aciclovir gives no additional benefitEye care is important artificial tears and eye lubricants should be consideredPrognosisif untreated around 15% of patients have permanent moderate to severe weaknessFacioscapulohumeral muscular dystrophyis an autosomal dominant form of muscular dystrophy. As the name suggests it stypically affects the face, scapula and upper arms firstweakness and wasting of the right facial muscles, right trapezius, deltoid and biceps muscles.upper back pain, shoulder and arm weaknessSymptoms typically presents by the age of 20 years.Brachial neuritisAcute onset of unilateral (occasionally bilateral) severe pain shoulder and scapular weakness several days later. Sensory changes are usually minimal. There may be subsequent rapid wasting of the arm muscles in accordance to which nerve is involved. Precipitating factors Recent traumaInfectionSurgery or vaccination.Rarely may it be hereditary. Prognosis is usually good except when the phrenic nerve is involved significant breathlessness.Brachial plexus injuriesErb-Duchenne paralysisdamage to C5,6 rootswinged scapula, loss of sensation in the arm and paralysis of the Deltoid, Biceps, and Brachialis musclesmay be caused by a Breech presentationKlumpke's paralysisdamage to C8-T1 nerve root loss of intrinsic hand musclesdue to tractionDD. Median nerve damage weakness of the Thenar muscles.Carpal tunnel syndrome median nerve pathology and does not affect the other intrinsic hand muscles.Acute disseminated encephalomyelitis (ADEM) is an autoimmune demylinating disease of CNS (post infectious encephalomyelitis) Aetiology not fully understood OR infection bacterial or viral (Measles, Mumps, Rubella, Varicella and Small Pox, not exhaustive.?After a lag time of between a few days to 2 months there is an acute onset of multifocal neurological symptoms with rapid deterioration. Non-specific signs Encephalopathy, Seizures and coma headache, Fever, nausea and vomiting may also accompany the onset of illness.Motor and sensory deficits are frequent may also be brainstem involvement (Occulomotor defects)?Investigation There are no specific biomarkers for the diagnosis of ADEM.T2-weighted MRI poorly-defined hyperintensities in the subcortical white matterAreas of supra and infra-tentorial demylination. These lesions can develop throughout the course of the illness and hence serial MRIs may be required.Management IV Glucocorticoids and the consideration of IVIG where this fails.DD. Multiple sclerosis but is not necessarily definitively linked with a preceding illness.Alzheimer's disease and herpes encephalitis would not present with these MRI findings. Meningitis The absence of prominent meningism features makes less likely.Arnold-Chiari malformation (Chiari 1 malformation)Downward displacement, or?herniation, of the cerebellar tonsils?through the foramen magnum. Malformations may be congenital or acquired through trauma.FeaturesHeadacheDisturbed CSF flow compressing the brainstem, cerebellum Hydrocephalus (uncommon) or Syringomyelia (common;~50%) Syringomyelia is a dilatation of a CSF space within the spinal cord. It occurs within the cervical and thoracic segments and causes compression of the spinothalamic tracts decussating in the anterior white commissure. This results in dissociative loss of sensation of pain, temperature and non-discriminative touch. There is classically a 'cape-like' distribution of this sensory loss.Non-communicating hydrocephalus? due to obstruction of cerebrospinal fluid (CSF) outflow.Pituitary apoplexySudden enlargement of pituitary tumour secondary to haemorrhage or infarction. Featuressudden onset headache similar to that seen in subarachnoid haemorrhagevomitingneck stiffnessvisual field defects: classically bitemporal superior quadrantic defectextraocular nerve palsiesfeatures of pituitary insufficiency e.g. Hypotension secondary to hypoadrenalism, electrolytes and low free T4 pointRestless legs syndromespontaneous, continuous lower limb movements that may be associated with paraesthesia. It is extremely common, affecting between 2-10% of the general population. Males and females are equally affected and a family history may be present. Clinical featuresuncontrollable urge to move legs (akathisia). Symptoms initially at night but as condition progresses may occur during the day. Symptoms are worse at restparaesthesias e.g. 'crawling' or 'throbbing' sensationsmovements during sleep may be noted by the partner - periodic limb movements of sleeps (PLMS)Causes and associationsthere is a positive family history in 50% of patients with idiopathic RLSiron deficiency anaemia is the single most important blood testuraemiadiabetes mellituspregnancyDiagnosis Clinical although bloods such as?ferritin?to exclude iron deficiency anaemia may be appropriateManagementsimple measures: walking, stretching, massaging affected limbstreat any iron deficiencydopamine agonists are first-line treatment (e.g. Pramipexole,?ropinirole)benzodiazepinesGabapentinSpastic paraparesisUpper motor neuron pattern of weakness in the lower limbs. Causesdemyelination e.g.?multiple sclerosiscord compression: trauma, tumourparasagittal meningiomatropical spastic paraparesistransverse myelitis?e.g. HIV, varicellasyringomyeliahereditary spastic paraplegiaosteoarthritis of the cervical spineAmyloidosis is the least likely of the above options to result in a spastic paraparesisDD. Central pontine myelinolysis is a disease of the brainstem and therefore typically causes quadraparesis (in this case the arms are mostly spared). The weakness would be expected to come on more rapidlyNeuromyelitis optica ?"Devic's disease"Monophasic or relapsing-remitting demyelinating CNS disorder Abs NMO-IgG attack the optic nerves and spinal cord (DD. M.S, triggered T cells)↑↑ Asian populations. Diagnosis Obsolete criteria bilateral optic neuritis, Myelitis (Spinal Cord)2 of the follow 3 criteria:Spinal cord MRI with contiguous T2-weighted signal abnormality (Spinal cord lesion) involving 3 or more spinal levelsInitially normal MRI brain Brain MRI not meeting criteria for MS at disease onsetNMO-IgG seropositive status Aquaporin 4 positive serum antibody Vomiting is also a common presenting complaint.?Nerve conduction studies (NCS) are useful in determining between axonal and demyelinating pathologyAxonalnormal conduction velocityreduced amplitudeDemyelinatingreduced conduction velocity Guillain-Barre syndromenormal amplitudeNeurofibromatosisNF1 "von. Recklinghausen's syndrome"NF2AD chromosome 17?1 in 4,000SkinCafé-au-lait spots?(>= 6, 15 mm in diameter)Axillary/groin frecklesPeripheral neurofibromasPheochromocytomasIris hamatomas (Lisch nodules)in > 90% (1 = Ant)ScoliosisAD Chromosome 22?1 in 100,000CNSBilateral schwannomas (NF2)Mengiomas Ependymoma of the brain or spine.peripheral nerve tumoursEye Retinal hamartomas (2 = POST)CataractsCafe Au Lait markings Patients with neurofibromatosis may develop hypertension for three main reasons:coexistant essential hypertensionphaechromocytoma (24h collection of urine catecholamines)renal vascular stenosis secondary to fibromuscular dysplasiaThe normal renal function in this patient points away from a diagnosis of renal vascular diseaseTuberous sclerosis chromosome 16 (as is polycystic kidney disease type 1) of either the TSC1 or TSC2 genes. Features ( multiple CNS hamartomas (tubers), subependymal giant cell astrocytomas of the brain, kidneys angiomyolipomas, cardiac rhabdomyomas, facial angiofibromas, Shagreen patches and retinal astrocytic hamartomas) Von-Hippel Lindau chromosome 3 and visceral cysts and benign tumours in any system, including the brain. NO bilateral vestibular schwannomasTuberous sclerosisis a genetic condition of autosomal dominant inheritance. Like neurofibromatosis, the majority of features seen in TS are neurocutaneous.Cutaneous features'Ash-leaf' spots? depigmented which fluoresce under UV light DD. Lisch nodules are seen in neurofibromatosisShagreen patches roughened patches of skin over lumbar spine Adenoma sebaceum?(angiofibromas) butterfly distribution over nose.subungual fibromata fibromata beneath nails café-au-lait spots may be seen (more common in neurofibromatoma)Neurological featuresDevelopmental delayEpilepsy?(infantile spasms or partial)intellectual impairmentOthersDevelopment of multisystemic hamartomas Retinadense white areas on retina (phakomata)Angiofibromas Heart rhabdomyomasKidney angiomyolipomas. The majority of patients with TS will develop some form of kidney diseaseRenal Angiomyolipomata Benign tumour made of malformed tissues Interactions between polycystin 1 and tuberin implicated in the development of these growthsAround 1 in 10 diagnosed with a renal angiomyolipoma have TS. Most patients with TS will have several renal angiomyolipomata in both kidneys.polycystic kidneys↑↑↑ risk of developing certain Malignancies Renal cell carcinoma.Oncocytomas benign tumours which have a higher likelihood of developing in patients with TS.?Brain gliomatous changes can occur in the lesionsLung lymphangioleiomyomatosis (multiple cysts)Neuroleptic malignant syndromerare but dangerous condition seen in patients taking?antipsychotic medication. It carries a mortality of up to 10% and can also occur with atypical antipsychotics is typically seen in patients who have just commenced treatment.. It may also occur with?dopaminergic drugs (such as levodopa) for Parkinson's disease, usually when the drug is suddenly stopped?or the dose reduced.The pathophysiology is unknown but one theory is that the dopamine blockade induced by antipsychotics triggers massive glutamate release and subsequent neurotoxicity and muscle damage. It might be caused by an autosomal dominant mutation in ryanodine receptor type 1 which encodes the calcium-release channel of the sarcoplasmic reticulum, and CACNA1S, which encodes the alpha subunit of the L-type calcium channel isoform of the sarcolemma (dihydropyridine receptor).It occurs within hours to days of starting an antipsychotic (antipsychotics are also known as neuroleptics, hence the name) and the?typical pyrexiamuscle rigidityautonomic lability: typical features include hypertension, tachycardia and tachypnoeaagitated delirium with confusionA?raised creatine kinase is present in most cases.?A?leukocytosis?may also be seenAcute kidney injury?(secondary to rhabdomyolysis) may develop in severe cases. Myoclonus is the distinguishing feature of serotonin syndrome (found only in serotonin syndrome)Management. stop antipsychoticpatients should be transferred to a medical ward if they are on a psychiatric ward and often they are nursed in intensive care unitsIV fluids to prevent renal failuredantrolene?may be useful in selected casesthought to work by decreasing excitation-contraction coupling in skeletal muscle by binding to the ryanodine receptor, and decreasing the release of calcium from the sarcoplasmic reticulumbromocriptine, dopamine agonist, may also be usedPropranolol does not have any role as an antidote in serotonin syndrome. Beta blockers can mask tachycardia which is used to monitor the effectiveness of treatment.Para Neuoplastic SyndromesAnti-NMDA (N-methyl D-aspartate) receptor Encephalitisa paraneoplastic syndrome, presenting as prominent psychiatric features?including agitation, hallucinations, delusions and disordered thinking; seizures, insomnia, dyskinesias and autonomic instability.?Ovarian teratomas are detected in up to half of all female adult patients, particularly prevalent in Afro-Caribbean patients. InvestigationsMRI head can be normal but abnormalities can be visualised on FLAIR sequences in the deep subcortical limbic structures. CSF pleocytosis but can be normal initially.+Ve Anti-N-methyl D-aspartate receptor antibody.Anti-MuSK specific to muscle kinase in myasthenia gravis with no evidence of a thymoma and without antibodies to acetylcholine receptors. Anti-GM1 specific to acute inflammatory demyelinating polyneuropathy (AIDP) variant of Guillain-Barre syndrome.Treatment I.V steroids, immunoglobulins, rituximab, cyclophosphamide or plasma exchange, alone or in combination.Resection of teratoma is also therapeutic.Paraneoplastic syndromes affecting nervous systemLambert-Eaton myasthenic syndromeassociated with small cell lung cancer (also breast and ovarian) Anti- VGCC antibody directed against pre-synaptic voltage gated calcium channel in the peripheral nervous systemcan also occur independently as autoimmune disorderAnti-Huassociated with small cell lung carcinoma and neuroblastomassensory neuropathy - may be painfulcerebellar syndromeencephalomyelitisAnti-Yoassociated with ovarian and breast cancercerebellar syndrome ?nystagmus, 'unsteadinessAnti-GAD antibodyassociated with breast, colorectal and small cell lung carcinomastiff person's syndrome or diffuse hypertoniaAnti-Riassociated with breast and small cell lung carcinomaocular opsoclonus-myoclonusPurkinje cell antibodyPeripheral neuropathy in breast cancerLambert-Eaton syndromeassociation with?small cell lung cancerand to a lesser extent breast and ovarian cancer. It may also occur independently as an autoimmune disorder. Lambert-Eaton myasthenic syndrome is caused by an?antibody directed against presynaptic voltage-gated calcium channel?in the peripheral nervous system. presents in later life, unlike MG which has peaks in the 3rd and 6th decadesmoking history gives another clue in favour of this diagnosisFeaturesrepeated muscle contractions lead to increased muscle strength (in contrast to myasthenia gravis)in reality, this is seen in only 50% of patients and following prolonged muscle use muscle strength will eventually decreaselimb-girdle weakness (affects lower limbs first) ifficulty in standing from a seated position and climbing stairshyporeflexiaautonomic symptoms: dry mouth, impotence, difficulty micturatingophthalmoplegia and ptosis not commonly a feature (unlike in myasthenia gravis)InvestigationsThe voltage-gated calcium channel antibody is present in 85-95% of patients.?EMG incremental response to repetitive electrical stimulationManagementtreatment of underlying cancerimmunosuppression, for example with prednisolone and/or azathioprine3,4-diaminopyridine is currently being trialledworks by blocking potassium channel efflux in the nerve terminal so that the action potential duration is increased. Calcium channels can then be open for a longer time and allow greater acetylcholine release to the stimulate muscle at the end plateIV immunoglobulin therapy and plasma exchange may be benefiDDACh receptor antibodies are associated with Myasthenia Gravis (MG). MG can present with isolated proximal muscle weakness, however, more commonly presents with ocular symptoms i.e. ptosis. MG is characterized by increased fatigability with exercise, unlike this patient whose weakness initially improves with exercise.Anti-Musk is associated with myasthenia gravis patientsanti-Jo1 and anti-Mi2 with inflammatory myositis, and anti-mitochondrial antibody with primary biliary cirrhosisAnti-Mi-2 antibodies are associated with dermatomyositis. Another differential for proximal muscle weakness, but usually also presents with systemic upset and rash.Antinuclear antibody is used in the diagnosis of various autoimmune conditions, in particular, systemic lupus erythema which would present differently.Rheumatoid factor (RF) is used as a marker of inflammatory and autoimmune activity. RF is commonly used alongside other tests to aid the diagnosis of rheumatoid arthritis. Rheumatoid factor has no role in the diagnosis of Lambert-Eaton Myasthenic Syndrome (LEMS). This patient has no joint symptoms, which makes the diagnosis of rheumatoid disease less likely.Anti-NMDA receptor encephalitisParaneoplastic syndrome prominent psychiatric features?(agitation, hallucinations, delusions and disordered thinking; seizures, insomnia, dyskinesias and autonomic instability.?Ovarian Teratoma 50 % of all female (Afro-Caribbean) MRI head can be normal but abnormalities can be visualised on FLAIR sequences in the deep subcortical limbic structures. CSF pleocytosis but can be normal initially. Anti-MuSK is an autoantibody specific to muscle kinase in myasthenia gravis with no evidence of a thymoma and without antibodies to acetylcholine receptors. Anti-GM1 is an autoantibody specific to acute inflammatory demyelinating polyneuropathy (AIDP) variant of Guillain-Barre syndrome.Treatment IV steroidsImmunoglobulinsRituximabCyclophosphamide Plasma exchange, alone or in combination. Resection of teratoma is also therapeutic.Myasthenia gravisAutoimmune disorder resulting in insufficient functioning acetylcholine receptors.?Antibodies to acetylcholine receptors?are seen in 85-90% of cases*. Myasthenia is more common in women (2:1)The following drugs may exacerbate myasthenia:penicillaminequinidine, procainamidebeta-blockerslithiumphenytoinantibiotics: gentamicin, macrolides, quinolones, tetracyclinesAlthough macrolides, tetracyclines, and metronidazole are occasionally associated with exacerbation in myasthenic patients, they are usually well tolerated in this population.Aminoglycosides, including gentamicin, are relatively contra-indicated in myasthenia as they are more commonly associated with exacerbations. The mechanism is thought to be competitive inhibition of the release of acetylcholine at the presynaptic membrane of the neuromuscular junction.Amoxicillin is generally considered to be safe in myasthenia gravisThe key feature is muscle?fatigability?- muscles become progressively weaker during periods of activity and slowly improve after periods of rest:extraocular muscle weakness: diplopiaproximal muscle weakness: face, neck, limb girdleptosisdysphagiaAssociationsthymomas in 15%autoimmune disorders: pernicious anaemia, autoimmune thyroid disorders, rheumatoid, SLEthymic hyperplasia in 50-70%GBS is often accompanied by sensory disturbances (both motor and sensory nerves of the peripheral nervous system are attacked by the immune system)Investigationssingle fibre electromyography: high sensitivity (92-100%)CT thorax to exclude thymomaCK normalautoantibodies: around 85-90% of patients have antibodies to acetylcholine receptors. In the remaining patients, about about 40% are positive for anti-muscle-specific tyrosine kinase antibodiesTensilon test: IV edrophonium reduces muscle weakness temporarily - not commonly used anymore due to the risk of cardiac arrhythmiaManagementlong-acting anticholinesterase inhibitors?e.g.?pyridostigmineimmunosuppression: prednisolone initiallythymectomyManagement of myasthenic crisisplasmapheresisintravenous immunoglobulinsImmunosuppressive agents for MG include azathioprine (purine analogue), ciclosporin (calcineurin inhibitor), cyclophosphamide (alkylating agent) and methotrexate (dihydrofolate reductase inhibitor).Muscarinic agonists stimulate cholinergic receptors. Drugs of this class include cevimeline and pilocarpine.*antibodies are less commonly seen in disease limited to the ocular musclesMyotonic dystrophyMyotonic dystrophy (also called dystrophia myotonica) is an inherited myopathy with features developing at around 20-30 years old. It affects skeletal, cardiac and smooth muscle. There are two main types of myotonic dystrophy, DM1 and DM2.?Geneticsautosomal dominanta trinucleotide repeat disorderDM1 is caused by a CTG repeat at the end of the DMPK (Dystrophia Myotonica-Protein Kinase) gene on chromosome 19DM2 is caused by a repeat expansion of the ZNF9 gene on chromosome 3DM1DM2- DMPK gene on chromosome 19- Distal weakness more prominent- ZNF9 gene on chromosome 3- Proximal weakness more prominent- Severe congenital form not seenGeneral featuresDystrophia myotonica -?DM1distal weakness initiallyautosomal?dominantdiabetesdysarthriamyotonic facies (long, 'haggard' appearance)frontal baldingbilateral ptosiscataractsdysarthriaOther featuresmyotonia (tonic spasm of muscle)weakness of arms and legs (distal initially)mild mental impairmentdiabetes mellitustesticular atrophycardiac involvement: heart block (P20-40% of patients), cardiomyopathydysphagiaAphasia Broca's dysphasia: speech non-fluent, comprehension normal, repetition goodType of dysphasiaLesion locationSpeechComprehensionRepetitionWernicke’s (receptive) dysphasiaSuperior temporal gyrusFluentAbnormalGoodConduction (associative) dysphasiaArcuate fasiculusFluentAbnormalPoorBroca’s (expressive) dysphasiaInferior frontal gyrusNon-fluentNormalGoodThe middle cerebral artery medial part of cerebrum (frontal lobe and medial temporal lobe and therefore supplies Broca’s area (inferior frontal gyrus.?Aphasia (Remember that dysarthria is different and refers to a motor speech disorder.)Type of aphasiaNotesWernicke's (receptive) aphasiaDue to a lesion of the?superior temporal gyrus. It is typically supplied by the inferior division of the?left MCA?This area 'forms' the speech before 'sending it' to Broca's area. Lesions result in sentences that make no sense, word substitution and neologisms but speech remains fluentComprehension is impairedBroca's (expressive) aphasiaDue to a?lesion of the inferior frontal gyrus. It is typically supplied by the superior division of the?left MCA?Speech is non-fluent, laboured, and haltingComprehension is normalConduction aphasiaClassically due to a stroke affecting the arcuate fasiculus - the connection between Wernicke's and Broca's areaSpeech is fluent but repetition is poor. Aware of the errors they are makingComprehension is normalGlobal aphasiaLarge lesion affecting all 3 of the above areas resulting in severe expressive and receptive aphasiaHereditary sensorimotor neuropathy (HSMN) Relatively new term which encompasses Charcot-Marie-Tooth disease (also known as peroneal muscular atrophy). Over 7 types have been characterized - however only 2 are common to clinical practiceHSMN type I: primarily due to demyelinating pathologyHSMN type II: primarily due to axonal pathologyHSMN type IARdue to defect in PMP-22 gene (which codes for myelin)features often start at pubertymotor symptoms predominatedistal muscle wasting, pes cavus, clawed toesfoot drop, leg weakness often first featuresHuntington's diseaseInherited neurodegenerative condition. It is a progressive and incurable condition that typically results in death 20 years after the initial symptoms develop.GeneticsAD Trinucleotide repeat disorder CAGThe phenomenon of anticipation may be seen, the disease presents at an earlier age in successive generations.results in degeneration of cholinergic and GABAergic neurons in the striatum of the basal gangliadue to defect in huntingtin gene on chromosome 4Features typical develop after 35 years of agechoreapersonality changes (e.g. irritability, apathy, depression) and intellectual impairmentdystoniasaccadic eye movementsOther important commonly tested trinucleotide repeats:GAA: Friedrich AtaxiaCTG: Myotonic dystrophyCGG: Fragile X syndromeAtaxia telangiectasiaAR disorder defect in the ATM gene which encodes for?DNA repair enzymes. It is one of the inherited?combined immunodeficiency disorders. It typically presents in early childhood with abnormal movements.FeaturesCerebellar ataxiaTelangiectasia (spider angiomas)IgA deficiency resulting in recurrent chest infections DD. Friedreich's ataxia and Infantile-onset spinocerebellar ataxia do not present with immunodeficiency.10% risk malignancy, lymphoma or leukaemia, but also non-lymphoid tumoursrighttopFriedreich's ataxiaThe most common of the early-onset hereditary ataxias. It is an autosomal recessive, trinucleotide repeat disorder characterised by a?GAA repeat in the X25 gene on chromosome 9 (frataxin). Friedreich's ataxia is unusual amongst trinucleotide repeat disorders in not demonstrating the phenomenon of anticipation.The typical age of onset is 10-15 years old. Gait ataxia and kyphoscoliosis are the most common presenting features.Global spinal cord and cerebellar degeneration give a mixed patten of degeneration. Retinal degeneration is commonNeurological features absent ankle jerks/extensor plantarscerebellar ataxiaoptic atrophyspinocerebellar tract degenerationOther featuresHOCM (90%, most common cause of death)diabetes mellitus (10-20%)high-arched palateDD. Charcot-Marie-Tooth (also known as hereditary motor and sensory neuropathy), presents with pes cavus and peripheral motor/sensory neuropathy, No cerebellar or visual symptoms.Duchenne muscular dystrophy progressive degeneration and weakness of specific muscle groups. Typically affects males, rarely femaleMost patients lose the ability to walk by 12 Ys Require ventilatory support by the age of 25. Sensation is intact in these patients.Motor neuron disease presents with mixed UMNL and LMNL weakness (absent tendon reflexes and extensor plantars)However, no cerebellar signs or affect the retina.Bardet-Biedl syndrome is a rare AR condition that gives retinitis pigmentosa, obesity, polydactyly and frequently mental retardation.Subacute combined degeneration of the cord (SCDC) Ataxic gait (due to degeneration of the dorsal columns) and mixed UMN and LMN signs (due to degeneration of lateral motor tracts and peripheral nerves). The history will typically be subacute, occurring over months rather than decades. Often sensory symptoms before weakness.Charcot-Marie-Tooth diseaseThe?most common hereditary sensory and motor peripheral neuropathy with predominantly motor loss .UMN signs are not present in these patients. Patients can present with lower motor neurone signs in all limbs and reduced sensation (more pronounced distally. FeaturesThere may be a history of frequently sprained anklesFoot dropHigh-arched feet (pes cavus)Hammer toesDistal muscle weaknessDistal muscle atrophy ankles are becoming much thinnerHyporeflexiaStork leg deformityManagement There is no cure, and management is focused on physical and occupational therapy.Benign paroxysmal positional vertigoOne of the?most common causes?of vertigo sudden onset of dizziness and vertigo triggered by changes in head position. The average age of onset is 55 years and it is less common in younger patients. Featuresvertigo triggered by change in head position (e.g. rolling over in bed or gazing upwards)may be associated with nauseaeach episode typically lasts 10-20 secondspositive Dix-Hallpike manoeuvre (Diagnosis)The recurrent otitis media and family history of otosclerosis IN THE Q might given as distracters DD. Meniere disease hearing loss and tinnitus, typically lasts much longer. feeling of aural fullnessLabyrinthitis nystagmus in addition to vertigo and nauseaManagementEpley manoeuvre?(successful in around 80% of cases)Teaching the patient exercises they can do themselves at home (vestibular rehabilitation) EX:?Brandt-Daroff exercisesMedication is often prescribed (e.g. Betahistine) but it tends to be of limited value.PrognosisGood prognosis and usually resolves spontaneously after a few weeks to months. Symptomatic relief may be gained by:Around half of people with BPPV will have a?recurrence?of symptoms 3–5 years after their diagnosisBrain abscessCausesextension of sepsis from middle ear or sinuses trauma or surgery to the scalp penetrating head injuries.?embolic events from endocarditisFeaturesSinusitis + focal neurology and fever brain abscess Symptoms will depend upon the site of the abscess (those in critical areas e.g.motor cortex) will present earlier. Cerebellar abscesses are most commonly (Otogenic diseases like mastoiditis and sinusitis infections) slurring dysarthria and mild coarse nystagmusConsiderable mass effect in the brain ↑↑ ICPis common.Absence of any symptoms does not exclude the diagnosis fever may be absent or usually not the swinging pyrexia seen with abscesses. Assessment with CT scanning.DD. Cavernous sinus thrombosispresents unilateral facial oedema, photophobia, proptosis and palsies of the cranial nerves (III, IV, V, VI).Meningitis fever and chills, neck stiffness, photophobia associated with mental changes.Treatment Surgical craniotomy and the abscess cavity debrided may reform because the head is closed following abscess drainage.Herpes simplex encephalitisThe virus characteristically affects the temporal lobes questions may give the result of imaging or describe temporal lobe signs e.g. aphasiFeaturesFever, headache, psychiatric symptoms, seizures, vomiting along the course of viral illness.focal features e.g. aphasiaShort term memory problems might be there.peripheral lesions (e.g. cold sores) have no relation to presence of HSV encephalitis?Lymphocytosis and a moderate ↑of CRP, following a flu like illnessHSV-1 responsible for 95% of cases in adultsTypically affects temporal and inferior frontal lobesInvestigationCSF: lymphocytosis, elevated protein, glucose is either normal or slightly decreasedPCR for HSVCT: medial temporal and inferior frontal changes (e.g. petechial haemorrhages) - normal in one-third of patients No mass effect. Brain parenchyma otherwise normalMRI is better the investigation of choice initially, which should demonstrate temporal lobe changesEEG pattern: lateralised periodic discharges at 2 HzDD.Meningococcal meningitis No peripheral blood lymphocytosis, features of meningococcal bacteraemia (skin rash).Measles encephalitis sub acute presentation of gradual memory lossTuberculosis meningitis history of respiratory symptoms, or possible TB exposure. Severe influenza with encephalitis possible differential, although a predilection for memory loss would be unusual.TreatmentIV acyclovirPrognosis Dependent on whether aciclovir is commenced early. If treatment is started promptly the mortality is 10-20%. Left untreated the mortality approaches 80%MeningitisMost common adult cause (mortality)meningococcus (10%)pneumococcus (25%)Diagnosisif partially treated with antibiotics, negative CSF culture, but glucose, protein and white cells unchangedNeurological sequalaesensorineural hearing loss (most common)other neurological: epilepsy, paralysisinfective: sepsis, intracerebral abscesspressure: brain herniation, hydrocephalusIdiopathic intracranial hypertensionalso known as (pseudotumour cerebri / benign intracranial hypertension) classically seen in young, Obese females.Obese, young female with headaches / blurred vision + No neurological deficit think idiopathic intracranial hypertensionRisk Factorsobesityfemale sexpregnancydrugs*: oral contraceptive pill,?steroids, tetracycline > vitamin A (Retinoid), lithiumFeaturesheadacheblurred visionpapilloedema (usually present)enlarged blind spotsixth nerve palsy may be presentManagementweight lossDiuretics e.g. acetazolamideTopiramate is also used, and has the added benefit of causing weight loss in most patientsRepeated lumbar punctureSurgeryOptic nerve sheath decompression and fenestration prevent damage to the optic nerve.A lumbo-peritoneal or ventriculo-peritoneal shunt may also be performed ↓↓ intracranial pressure.Intracranial haemorrhagea collection of blood or active process of bleeding within the skull. Divided by the anatomical compartment in which they are found:Extradural haematomaBetween the skull and the dura caused by low-impact trauma presents with a loss of consciousness lucid interval and then a rapid decline in consciousness. Mass effect uncal herniation and 3rd cranial nerve compression (fixed, dilated pupil). CT imaging hyperdense (bright), biconvex (or lentiform) collection around the surface of the brain. Definitive management craniotomy and evacuation of the haematoma.Acute subdural haematomaA fresh collection of blood under the dura caused by trauma but can be caused by vascular lesions (arteriovenous malformations). It is ?most commonly caused by high-impact trauma (associated with high-impact injuries ) commonly associated with other brain injuries. Avarage severity of presentations asymptomatic to severely comatose. CT imaging hyperdense (bright), crescenteric collection surrounding the brain not limited by suture lines. Large acute subdural haematomas will push on the brain (‘mass effect’) and cause midline shift or herniation.Definitive treatment Decompressive craniectomy.Small or incidental acute subdurals can be observed conservatively.Chronic subdural haematomaOld collection of blood under the layer of the dura more common in elderly patients, alcoholics, people on anticoagulation or in infants due to the fragility and/or predisposition of the bridging veins to bleed. Patients present weeks after a mild head injury progressive confusion, loss of consciousness, weakness or higher cortical function. CT imaging hypodense (dark), crescenteric collection around the surface of the brain not limited by suture lines.(compress the brain (‘mass effect’)In symptomatic patients definitive treatment is burr hole drainage.Intracerebral haematomaCollection of blood within the substance of the brain risk factors include: hypertension, vascular lesion (aneurysm or A-V malformation), cerebral amyloid angiopathy, brain tumour or infarct (particularly in stroke patients undergoing thrombolysis). Symptoms hemorrhagic stroke similar to an ischaemic stroke (Must obtain a CT in head in all stroke patients prior to thrombolysis) or with a decrease in consciousness. CT imaging will show a hyperdensity (bright lesion) within the substance of the brain. Treatment often conservative, but large clots in patients with ↓↓ consciousness warrant surgical evacuation.Subarachnoid haemorrhageBleed into the subarachnoid space which is deep to the subarachnoid layer of the meninges The most common cause is trauma. In non-traumatic (‘spontaneous) Causes of spontaneous SAH include:?Intracranial aneurysm (saccular ‘berry’ aneurysms) Around 85% of non- traumatic cases, The Circle of Willis is the most common location 2ry to either autonomic neural stimulation from the hypothalamus or ↑↑ catecholaminesAssociated with (adult polycystic kidney disease,?Ehlers-Danlos syndrome?and coarctation of the aorta).A-V malformationPituitary apoplexyArterial dissectionMycotic (infective) aneurysmsPerimesencephalic (an idiopathic venous bleed)The classical presentation:?Headache: typically sudden-onset (‘thunderclap’ or ‘baseball bat’), severe (‘worst of my life’) and occipitalNausea and vomitingMeningism?(photophobia, neck stiffness)ComaSeizuresSudden deathECG changes including?ST elevation?may be seen.DiagnosisComputed tomography (CT) headAcute blood (hyperdense/bright on CT) is typically distributed in the basal cisterns, sulci and in severe cases the ventricular system.CT is negative for SAH (no blood seen) in 7% of cases.Lumbar puncture (LP)Used to confirm SAH if CT is negative.LP is performed at least?12 hours?following the onset of symptoms to allow the development of?xanthochromia (the result of red blood cell breakdown).Xanthochromia helps to distinguish true SAH from a ‘traumatic tap’ (blood introduced by the LP procedure).As well as xanthochromia, CSF findings consistent with subarachnoid haemorrhage include a normal or raised opening pressureManagementReferral to neurosurgery to be made as soon as SAH is confirmedAfter spontaneous SAH is confirmed, the aim of investigation is to identify a causative pathology that needs urgent treatment:CT intracranial angiogram?(to identify a vascular lesion e.g. aneurysm or AVM)+/- digital subtraction angiogram (catheter angiogram)TreatmentThe treatment in spontaneous SAH is in accordance with the causative pathologyRisk of rebleeding prompt intervention, preferably within 24 hoursMost treated with a coil by interventional neuroradiologists, but a minority require a craniotomy and clipping by a neurosurgeonUntil TTT prevent a re-bleed of the aneurysm Strict bed rest, well-controlled blood pressure and avoid straining .Preventing vasospasm (30% of patients) 21-day course of?nimodipine?(CCB targeting the brain vasculature) hypervolaemia, induced-hypertension and haemodilutionHydrocephalus external ventricular drain (CSF diverted into a bag at the bedside) or, if required, a long-term ventriculo-peritoneal shuntComplications of aneurysmal SAH:?Re-bleeding (in around 30%)Vasospasm?(also termed delayed cerebral ischaemia), typically 7-14 days after onsetHyponatraemia?(most typically due to syndrome inappropriate anti-diuretic hormone (SIADH))Cerebral salt-wasting syndrome is known to occur following subarachnoid haemorrhage but the sodium loss is accompanied by water loss as the kidneys are still functioning normally so urine output is high and there is a relative fluid depletion. In SIADH the kidneys hold on to too much water, diluting the serum sodium and resulting in concentrated urine as in this case.SeizuresHydrocephalusDeathImportant predictive factors in SAH:conscious level on admissionageamount of blood visible on CT headIntraventricular haemorrhageAn intraventricular haemorrahge is a collection of blood within the ventricular system of the brain. In children it can occur due to the prematurity of the periventricular vascular structures. In adults it may be caused by an extension of subarachnoid haemorrhage, vascular lesions (e,g. aneurysms or arteriovenous malformations) or tumours. On CT imaging it appears as hyperdensity within the dark CSF spaces within the ventricles. Patients with intraventricular haemorrhage at risk of obstructive hydrocephalus and this would required surgical CSF diversion.In neonatal practice the vast majority of IVH occur in the first 72 hours after birth, the aetiology is not well understood and it is suggested to occur as a result of birth trauma combined with cellular hypoxia, together the with the delicate neonatal CNS.Contusionsa common consequence of traumatic head injury. Over the two to three days following a head injury, contusions can expand and swell (caused by oedema). This effect is termed 'blossoming'. This is a slower process than the neurological deterioration seen in extradural haematoma, which is typically minutes to hoursDiffuse axonal injuryassociated with acceleration and deceleration forces (such as those imposed by a road traffic accident). Coma is of immediate onset and recovery typically takes weeks to monthsIntracranial venous thrombosiscan cause cerebral infarction, much lesson common than arterial causes50% of patients have isolated Sagittal sinus thromboses - the remainder have coexistent lateral sinus thromboses + cavernous sinus thrombosesFeaturesheadache (may be sudden onset) nausea & vomiting Sagittal sinus thrombosis Cavernous sinus thrombosis (3,4,5,6)Lateral sinus thrombosismay present with seizures and hemiplegiaParasagittal biparietal or bifrontal haemorrhagic infarctions are sometimes seenCT with contrast typical empty delta sign at the 'bottom' of the scan for the triangular shaped dural sinus. Dural Sinus should normally be white due to it being filled with contrast. Empty delta sign The thrombus fails to enhance within the dural sinus and is outlined by enhanced collateral channels in the falx.Only 25%-30% of cases but is highly diagnostic for sagittal sinus thrombosis Other causes of cavernous sinus syndrome: local infection (sinusitis) NeoplasiaTraumaPeriorbital oedemaOphthalmoplegia6th nerve damage typically occurs before 3rd & 4thTrigeminal 5th nerve involvement Hyperaesthesia of upper face and eye painCentral retinal vein thrombosis6th and 7th nerve palsiesMRI with Venogram 2nd line if ↑↑ suspension of cerebrovascular events or signs of ↑↑ intracranial tension of and best test to rule out other differentials.?CT angiography only be of use if you suspected a carotid or vertebral dissection?Brain lesionsFrontal lobes lesionsTemporal lobe lesionParietal lobe lesionsExpressive (Broca's) Aphasia: Located on the posterior aspect (lateral part) of the frontal lobe, inferior frontal Gyrus.Non-fluent, laboured, and difficulty in finding the right words DisinhibitionPerseverationAnosmiaInability to generate a listFoster-Kennedy syndrome. This syndrome reflects a frontal lobe tumour - usually a meningioma in this age group – ipsilateral optic atrophy (direct damage from the space occupying lesion) and papilloedema of the contralateral optic nerve. Other causes are AVMs and juvenile nasopharyngeal angiofibromaWernicke aphasiaArea 'forms' the speech before 'sending it' to Brocas area.?Lesions result in word substituion, neologisms but speech remains fluentSuperior Homonymous QuadrantanopiaAuditory AgnosiaProsopagnosia (difficulty recognising faces)Sensory inattentionApraxiasAstereognosis?(tactile agnosia)Inferior homonymous quadrantanopiaGerstmann's syndrome?Lesion of dominant parietal deficit in the angular and supramarginal gyri between the dominant parietal and temporal lobes.Space occupying lesions OR following strokeAlexia (inability to read)Acalculia.Finger Agnosia Right-left disorientationOppenheim's sign "sign of cerebral irritation" scratching of the inner side of leg leads to extension of the toes.Occipital lobe lesionshomonymous hemianopia (with macula sparing)cortical blindnessvisual agnosiaCerebellum lesionsmidline lesions: gait and truncal ataxiahemisphere lesions: intention tremor, past pointing, dysdiadokinesis, nystagmusMore specific areasAreaAssociated conditionsMedial thalamus and mammillary bodies of the hypothalamusWernicke and Korsakoff syndromeSubthalamic nucleus of the basal gangliaHemiballismRepetitive violent involuntary movements of LL and UL contralateral to the side of the lesion."clumsy with all movements and exaggerated 'flinging' actions"Caused by a stroke or other lesion of the subthalamic nucleus.Symptoms may decrease whilst the patient is asleep.Movement disorders in order of least speed to fastest (DACB)Dystonia - fixated positionAthetosis - Snake-like writhing (slow)Choreiform - Like a dance choreographer (distal muscles)Ballistic/Ballismus/Hemiballismus - Fast flinging movements, can injure themselves or others 'like a ballistic missile' (memorisation method), proximal limb musculatureAntidopaminergic agents (e.g. Haloperidol) are the mainstay of treatmentStriatum (caudate nucleus) of the basal gangliaHuntington chorea (Disease)Substantia nigra of the basal gangliaParkinson's diseaseAmygdaladamage both temporal lobes including amygdalaKluver-Bucy syndrome (hypersexuality, hyperorality, hyperphagia, visual agnosiaCerebral lesion Contra lateral (upper and lower limbs + facial weakness)Pons lesion above the level of decussation of the corticospinal tracts contralateral limb weakness + Ipsilaterl facial weakness.?Corpus callosum Lesionleft posterior cerebral artery perfuses the splenium of the corpus callosum and left visual (occipital) cortex.Infarction of the LPCA left visual cortex lesion (only right visual cortex process information) and Corpus Callosum (disconnect syndromes)If infarction in the corpus callosum information cannot be transmitted from the right hemisphere to the left hemisphere Therefore it is not able to reach the Wernicke's and Broca's areas in the left (dominant) hemisphere.?It presents with Alexia (inability to read), No agraphia (inability to write) Speech is unaffected as Broca's area remains intact and can transmit information to the primary motor cortex. There are many disconnect syndromes from lesions of the corpus callosum, the eponym for this one being 'Dejerine syndrome'.MidBrain LesionParinaud syndrome Rostral interstitial nucleus of medial longitudinal fasciculus lies at the dorsal midbrain and control vertical gaze. They project to the vestibular nuclei. It results in the following symptoms:Upward gaze palsy diplopiaPupillary light-near dissociation (Pseudo-Argyll Robertson pupils)Convergence-retraction nystagmus Aetiology include:Brain tumours in the midbrain or pineal gland (pinealoma)Multiple sclerosisMidbrain stroke ?Triangle of Mollaret lesion (Palatal myoclonus) (Triangle linking the ipsilateral (inferior olivary nucleus, red nucleus) + contralateral dentate nucleus)Hypertrophic olivary degenerationExamination of the oropharynx Palatal myoclonusHeadache seems to be worse on recumbency and coughing/sneezingupper and lower limbs are normal with intact cranial nerves?CT scan confirms a space occupying lesion Lateral medullary syndromeKnown as Wallenberg's syndrome, occurs following occlusion of the?posterior inferior cerebellar artery.Cerebellar + Ipsilateral facial + Contralateral limbs sensory loss (numbness)Cerebellar featuresataxianystagmusBrainstem features (like Pons lesion) Ipsilateral:?dysphagia,?facial numbness, cranial nerve palsy e.g. Horner'sContralateral: limb sensory lossCerebellar syndromeUnilateral cerebellar lesions cause ipsilateral signs DANISH:D - Dysdiadochokinesia, Dysmetria (past-pointing), patients may appear 'Drunk' Patients with cerebellar strokes can present like drunk and those with alcohol misuse this diagnosis can be missed.A - Ataxia (limb, truncal)N -?Nystamus (horizontal = ipsilateral hemisphere)I - Intention tremourS - Slurred staccato speech,?Scanning dysarthriaH -?HypotoniaCausesFriedreich's ataxia, ataxic telangiectasianeoplastic: cerebellar haemangiomastrokealcoholmultiple sclerosishypothyroidismdrugs:?phenytoin, lead poisoningparaneoplastic e.g. secondary to lung cancerStroke by anatomySite of the lesionAssociated effectsAnterior cerebral arteryContralateral hemiparesis and sensory loss, lower extremity > upperMiddle cerebral arteryContralateral hemiparesis and sensory loss, upper extremity > lowerContralateral homonymous hemianopia?AphasiaPosterior cerebral arteryContralateral homonymous hemianopia with macular sparing?Visual agnosiaWeber's syndrome (br. of posterior cerebral artery midbrain)Ipsilateral CN III palsyContralateral weakness of upper and lower extremityPosterior inferior cerebellar artery?(lateral medullary syndrome, Wallenberg syndrome) It is the most commonly survived stroke that affects the brainstemIpsilateral: facial pain and temperature lossContralateral: limb/torso pain and temperature lossAtaxia, nystagmusAnterior inferior cerebellar artery?(lateral pontine syndrome)Symptoms are similar to Wallenberg's (see above), but:Ipsilateral: facial paralysis and deafnessRetinal/ophthalmic arteryAmaurosis fugaxBasilar artery'Locked-in' syndrome the patient is unable to move or communicate but is fully conscious. Both of Ant Inf. Cerebellar Art. And Bassilar Art. more likely to affect the autonomic centres in the medulla and are associated with a higher mortality.Lacunar strokespresent with either isolated hemiparesis, hemisensory loss or hemiparesis with limb ataxiastrong association with hypertensioncommon sites include the basal ganglia, thalamus and internal capsuleStroke AssessmentThe FAST screening tool (Face/Arms/Speech/Time) is widely known by the general public. It has a positive predictive value of 78%.ROSIER score is useful for medical professionals (A variant of FAST) by the Royal College of Physicians.Exclude hypoglycaemia first, then assess the following:A stroke is likely if > 0.AssessmentScoringLoss of consciousness or syncope- 1 pointSeizure activity- 1 pointNew, acute onset of:? asymmetric facial weakness+ 1 point? asymmetric arm weakness+ 1 point? asymmetric leg weakness+ 1 point? speech disturbance+ 1 point? visual field defect+ 1 pointInvestigationsThe first line a non-contrast CT head scan to rule out a haemorrhagic event. An ischemic stroke is only seen on CT at the earliest after 6 hours following an ischemic episode.12 hours later the brain tissue swells ( hypo-attenuation visible on CT) scanCT with contrast not useful. more useful for detecting cerebral metastases and abscessesDiffusion-weighted MRI the early changes after a stroke and diagnose vascular strokes (early presence of hypoxic oedematous changes). T2-weighted imaging is more sensitive than T1-weighted imaging in detecting ischemic change(FLAIR) MRI estimating an onset of acute ischaemic stroke within six hours enabling more patients to receive thrombolytic therapy.(when the history of onset remains unclear. Managementblood glucose, hydration, oxygen saturation and temperature should be maintained within normal limits an aggressive approach with respect to this has been shown to improve outcomeblood pressure should not be lowered?in the acute phase unless there are complications e.g. Hypertensive encephalopathy (even ifthe reading is very high)aspirin 300mg orally or rectally as soon as possible if a haemorrhagic stroke has been excluded Neurosurgical referral if haemorrhagicDipyridamole should not be used in the acute phase.with regards to atrial fibrillation, the RCP state: 'anticoagulants should not be started until brain imaging has excluded haemorrhage, and usually not until 14 days have passed from the onset of an ischaemic stroke'if the cholesterol is > 3.5 mmol/l patients should be commenced on a statin. Many physicians will delay treatment until after at least 48 hours due to the risk of haemorrhagic transformationThrombolysis for acute ischaemic strokeAlteplase should only be given if:it is administered within?4.5 hours of onset?of stroke symptoms (unless as part of a clinical trial)haemorrhage has been definitively excluded?(i.e. Imaging has been performed)Contraindications to thrombolysis:AbsoluteRelative Previous intracranial haemorrhage Seizure at onset of stroke Intracranial neoplasm Suspected subarachnoid haemorrhage Stroke or traumatic brain injury in preceding 3 monthsLumbar puncture in preceding 7 daysGastrointestinal haemorrhage in preceding 3 weeksActive bleedingPregnancy Oesophageal varices Uncontrolled hypertension >200/120mmHgConcurrent anticoagulation (INR >1.7Haemorrhagic diathesis Active diabetic haemorrhagic retinopathySuspected intracardiac thrombus Major surgery / trauma in the preceding 2 weeksThrombectomy for acute ischaemic strokeAll decisions about thrombectomy take into account a patient's overall clinical status (Pre-stroke functional status)< 3 on the modified Rankin scale Score of > 5 on the National Institutes of Health Stroke Scale (NIHSS)Thrombectomy?6 hours of symptom onset + Thrombolysis (if within 4.5 hours), to people who have:acute ischaemic stroke and confirmed occlusion of the?proximal anterior circulation?demonstrated by computed tomographic angiography (CTA) or magnetic resonance angiography (MRA)Thrombectomy only as soon as possible to people known to be well between?6 hours and 24 hours previously(including wake-up strokes): CTA or MRA occlusion of the?proximal anterior circulation? CT perfusion or diffusion-weighted MRI there is the?potential to salvage brain tissue (sequences showing limited infarct core volume)Thrombectomy + Thrombolysis (if within 4.5 hours) for people last known to be well up to 24 hours previously (including wake-up strokes):CTA or MRA Confirmed occlusion of the?proximal posterior circulation (basilar or posterior cerebral artery)? CT perfusion or diffusion-weighted MRI there is the?potential to salvage brain tissue (sequences showing limited infarct core volume)2ry preventionlife long clopidogrel + of aspirin plus modified-release (MR) dipyridamole in people who have had an ischaemic strokeAspirin plus MR dipyridamole only if clopidogrel is contraindicated or not tolerated, but treatment is no longer limited to 2 years' MR dipyridamole?alone only if aspirin or clopidogrel are contraindicated or not tolerated, again with no limit on duration of treatmentCarotid artery endarterectomy:if patient has suffered stroke or TIA in the?carotid territory and are not severely disabledshould only be considered if carotid stenosis > 70% according ECST** criteria or > 50% according to NASCET*** criteriaManagement of fluids, glycaemic control, blood pressure, feeding assessment/management and disability scales.?Fluid managementNormovolaemic hydration of all patients with acute stroke on admission, with regular review during their stay> 80% of patients who cannot swallow post stroke will recover within 2-4 weeksimmediate post-event period hypovolaemia can worsen the ischaemic penumbra, ↑↑ risk infection, DVT constipation and deliriumOver-hydration cerebral oedema, cardiac failure and hyponatraemia regularly review fluid status in these patientsRecommendations for management:Oral hydration is preferable in all patients who are able to safely swallowIV hydration may be necessary (isotonic saline without dextrose as the agent of choice in most patients)Other factors to take into consideration when choosing fluid agent include electrolyte disturbances and/or cardiovascular status.Glycaemic controlcontrol blood sugar, particularly nil by mouth due to concerns regarding swallowing safety post stroke, and/or in diabeticsPost stroke, patients with hyperglycaemia ↑↑ mortality independent from their age and the severity of strokeDue to ↑↑ tissue acidosis from anaerobic metabolism, free radical generation, ↑↑ blood brain barrier permeability post injuryMaintaining a blood sugar level between 4 and 11 mmol/L in people with acute strokeDiabetic patientsintensive management for diabetics post acute stroke Optimising insulin IV insulin and glucose infusionsHypoglycaemia managed appropriately alone can cause neuronal injury as well as mimic stroke-related neurological deficitsBlood pressure managementUse of anti-hypertensive medications should only hypertensive emergency with one or more of the following serious concomitants Hypertensive encephalopathyHypertensive nephropathyHypertensive cardiac failure/myocardial infarctionAortic dissectionPre-eclampsia/eclampsia↓↓ Blood pressure too much ↓↓ collateral blood flow to the affected region hasten the time to complete and irreversible tissue infarction.If treatment is indicated ↓↓ blood pressure by approximately 15% in the first 24-hours after stroke onsetIV labetalol, nicardipine and clevidipine as first-line agents rapid and safe titration to control blood pressurePatients who are candidates for thrombolytic therapy for acute stroke, blood pressure ↓↓to 185/110mmHg or lowerElevated BP can affect thrombolytic eligibility and delay treatmentTimely management of elevated BP is crucial when patients are otherwise eligible for intravenous thrombolysisAfter thrombolytic blood pressure is maintained ≤ 180/105mmHg for at least 24 hours after treatmentFeeding assessment and managementAll patients with acute stroke?must?be screened for safe swallowing before oral intake ( food, fluids, and/or medications dysphagia is common after stroke↓↓ risk of aspiration and subsequent complicationsIf there are any concerns specialist assessment of swallowingWithin 24 hours of admission and not > 72 hours afterPrior to assessment is undertaken, a patient should remain nil by mouth to prevent complicationsUnsafe for oral intake:Nasogastric tube feeding ideally within 24 hours of admission, unless they have had thrombolytic therapyIf nasogastric tube feeding is not tolerated nasal bridle tube/gastrostomy insteadMedications are assessed if formulations are available for nasogastric feeding, or conversion to S.C or IV forms are requiredNutritional support patients at risk of malnutrition post stroke (Dysphagia, poor oral health or ↓↓ ability to self-feed due to weakness or paralysis)Disability scales?Disability in terms of functional status (basic activities of daily living), is often the leading cause of morbidity after strokeAfter stabilization after a stroke transfer to a rehabilitation team for ongoing treatment depending on their level of disabilityMeasured using the?Barthel index?(BI), an outcome measure for strokeDescribes 10 tasks, and scored according to amount of time or assistance required by the patient for each given task Tasks feeding /moving from wheelchair to bed/ personal toileting/ getting on/off toilet/ bathing/ walking on level surface, ascending/descending stairs/ dressing/ controlling bowels and controlling bladderThe total score is from 0 to 100 0 being completely dependent, and 100 being completely independentThis index assess the functional status post stroke, and monitor improvement with rehabilitation to regain independence after the event.The Rockwood frailty scale categorises patients into levels of frailty according to their function. It can help identify elderly patients at high risk for in-hospital mortality. It could be used in this scenario but is not as specific as the Barthel index for stroke.Stroke: typesOxford Stroke Classification?(also known as the Bamford Classification) based on the initial symptoms1. unilateral hemiparesis and/or hemisensory loss of the face, arm & leg2. homonymous hemianopia3. higher cognitive dysfunction e.g. dysphasiaTotal anterior circulation infarcts (TACI, c. 15%)involves middle and anterior cerebral arteriesall 3 of the above criteria are presentPartial anterior circulation infarcts (PACI, c. 25%)involves smaller arteries of anterior circulation (upper or lower division of middle cerebral artery).2 of the above criteria are presentLacunar infarcts (LACI, c. 25%)involves perforating arteries around internal capsule, thalamus and basal gangliapresents with 1 of the following:1. Unilateral weakness (and/or sensory deficit) of face and arm, arm and leg or all three.2. Pure sensory stroke.3. Ataxic hemiparesisPosterior circulation infarcts (POCI, c. 25%)involves?vertebrobasilar arteriespresents with 1 of the following:1. Cerebellar or brainstem syndromes2. Loss of consciousness3. Isolated homonymous hemianopiaLateral medullary syndrome (aka Wallenberg's syndrome)Posterior inferior cerebellar arteryIpsilateral: ataxia, nystagmus, dysphagia, facial numbness, cranial nerve palsy e.g. Horner'sC: limb sensory lossWeber's syndrome (Midbrain)Posterior br. Of posterior cerebral Art. Ipsilateral III palsyContralateral weaknessA central cause of vertigoInclude posterior circulation stroke the most urgent diagnosis to make, and the most likely in this patient with cardiovascular risk factors.?The brainstem, cerebellum, thalamus, midbrain, and parts of the temporal and occipital cortex. supplied by the (vertebral, basilar or posterior cerebral arteries). Posterior circulation strokes account for 20-25% of ischaemic strokes, but are more difficult to diagnose than anterior circulation strokes. Symptoms dizziness, vomiting, double vision, dysarthria, dysphagia, ataxia, limb weakness and visual field defects.Acoustic neuroma Benign and malignant brain tumoursMultiple sclerosis. Third nerve palsyFeatureseye is deviated 'down and out'ptosispupil may be dilated (sometimes called a 'surgical' third nerve palsy)Causesdiabetes mellitusvasculitis e.g. temporal arteritis, SLEfalse localizing sign* due to uncal herniation through tentorium if raised ICPposterior communicating artery aneurysmpupil dilatedoften associated?painGiven the combination of a headache and third nerve palsy it is important to exclude a posterior communicating artery aneurysmcavernous sinus thrombosisWeber's syndrome: ipsilateral third nerve palsy with contralateral hemiplegia -caused by midbrain strokesother possible causes: amyloid, multiple sclerosisTrans-tentorial or uncal herniation 3rd nerve palsy (fixed and dilated pupil with an eye deviated inferiorly and laterally ('down and out') + ↓↓conscious level and an intracranial mass (the haematoma).Cerebellar tonsillar herniation affects the medulla oblongata and is often a terminal event in an unconscious patient resulting in asystolic and arrest. Frontal eye field injury would cause a functional ocular paralysis and the eye would tend to the neutral position in a state of reduced consciousness. Optic nerve compression would not cause deviation of the eye.Fourth nerve palsysupplies superior oblique (depresses eye, moves inward)Featuresvertical diplopiaclassically noticed when?reading a book?or?going downstairssubjective tilting of objects (torsional diplopia)the patient may develop a head tilt, which they may or may not be aware ofwhen looking straight ahead, the affected eye appears to deviate upwards and is rotated outwardsSyringomyelia(‘syrinx’ for short) collection of cerebrospinal fluid within the spinal cord.?Syringobulbia fluid-filled cavity within the medulla of the brainstem. This is often an extension of the syringomyelia but in rare to be isolated finding.?Causes includeChiari malformation: strong associationtraumatumoursidiopathicThe classical presentation Syrinx is a patient who has a ‘cape-like’ (neck and arms) loss of sensation to temperature but preservation of light touch, proprioception and vibration. Classic examples are of patients who accidentally burn their hands without realising. This is due to the crossing spinothalamic tracts in the anterior commissure of the spinal cord being the first tracts to be affected. Other symptoms and signs include spastic weakness (predominantly of the upper limbs), paraesthesia, neuropathic pain, upgoing plantars and bowel and bladder dysfunction. Scoliosis will occur over a matter of years if the syrinx is not treated. It may cause a Horner’s syndrome due to compression of the sympathetic chain, but this is rare.InvestigationFull spine MRI with contrast exclude a tumour or tethered cord. A brain MRI is also needed exclude a Chiari malformation.Treatment Treating the cause of the syrinx. In patients with a persistent or symptomatic syrinx, a shunt into the syrinx can be placed.Spinal cord lesionsMotor lesionsAmyotrophic lateral sclerosis?(motor neuron disease)affects both upper (corticospinal tracts) and lower motor neuronsresults in a combination of upper and lower motor neuron signsPoliomyelitis affects anterior horns resulting in lower motor neuron signsCombined motor and sensory lesionsDisorderTracts affectedClinical notesBrown-Sequard syndrome(spinal cord hemisection)1. Lateral corticospinal tract2. Dorsal columns3. Lateral spinothalamic tract1. Ipsilateral spastic paresis below lesion2. Ipsilateral loss of proprioception and vibration sensation3. Contralateral loss of pain and temperature sensationSubacute combined degeneration of the spinal cord (vitamin B12 & E deficiency)1. Lateral corticospinal tracts2. Dorsal columns3. Spinocerebellar tracts1. Bilateral spastic paresis2. Bilateral loss of proprioception and vibration sensation3. Bilateral limb ataxiaFriedrich's ataxiaSame as?subacute combined degeneration of the spinal cordSame as subacute combined degeneration of the spinal In addition cerebellar ataxia → other features e.g. intention tremorAnterior spinal artery occlusion1. Lateral corticospinal tracts2. Lateral spinothalamic tracts1. Bilateral spastic paresis2. Bilateral loss of pain and temperature sensationSyringomyelia1. Ventral horns2. Lateral spinothalamic tract1. Flacid paresis (typically affecting the intrinsic hand muscles)2. Loss of pain and temperature sensationMultiple sclerosisAsymmetrical, varying spinal tracts involvedCombination of motor, sensory and ataxia symptomsSensory lesionsDisorderTracts affectedClinical notesNeurosyphilis?(tabes dorsalis)1. Dorsal columns1. Loss of proprioception and vibration sensationDegenerative cervical myelopathyRisk factorsSmoking due to its effects on the intervertebral discsGenetics Occupation - those exposing patients to high axial loading.DCM symptoms Features "variable" Early symptoms are often subtle and can vary in severity day to day, making the disease difficult to detect initially. The most common symptoms at presentation of DCM are unknown, but 50% of patients incorrectly diagnosed and treated for carpal tunnel syndromeCan include any combination of Pain (affecting the neck, upper or lower limbs)Loss of motor function (loss of digital dexterity, preventing simple tasks such as holding a fork or doing up their shirt buttons, arm or leg weakness/stiffness leading to impaired gait and imbalanceLoss of sensory function causing numbnessLoss of autonomic function (urinary or faecal incontinence and/or impotence) - these can occur and do not necessarily suggest cauda equina syndrome in the absence of other hallmarks of that conditionHoffman's sign sign of upper motor neuron dysfunction and points to a CNS disease It is performed by gently flicking distal phalanx one finger (usually of the middle finger) to cause momentary flexion on a patient's hand. A positive test results in exaggerated flexion (twitching) of the other fingers (thumb) on the same hand.InvestigationsMRI of the cervical spine is the gold standard test disc degeneration and ligament hypertrophy, cervical canal stenosis with cord signal change.CT imaging patients with contraindications to MRI. CT myelogram is the first line investigation in this case.X- Ray cannot visualise the soft tissue, such as the spinal cord.Other investigatons (nerve conduction studies, EMG) may be performed when the clinical picture is unclear help to exclude mononeuropathies and other LMND. However, where there is strong clinical suspicion and the diagnosis is suspected, an MRI of the cervical spine DD.In the context (History)of known lumbar degenerative spine DCM is the number one differential for this presentation.An MRI of the cervical spine is the gold standard test where cervical myelopathy is suspected.It is not uncommon for patients to suffer from tandem (cervical and lumbar) stenosis.?ManagementAll patients urgently referred for assessment by specialist spinal services (neurosurgery or orthopaedic spinal surgery). Early treatment Timing of surgery is important (existing spinal cord damage can be permanent). Early treatment (within 6 months of diagnosis) offers the best chance of a full recovery but at present, most patients are presenting too late.Patients averaged over 5 appointments before diagnosis, representing >2 years.?Decompressive surgery is the only effective treatment prevent disease progression. Close observation is an option for mild stable disease, but anything progressive or more severe requires surgery to prevent further deterioration. Physiotherapy only by specialist services manipulation can cause more spinal cord damage.?PrognosisPostoperatively ongoing follow-up as pathology can 'recur' at adjacent spinal levels, not treated by the initial decompressive surgery (adjacent segment disease)Surgery can change spinal dynamics ↑↑ likelihood of other levels being affected mal-alignment of the spine( kyphosis and spondylolisthesis)this can also affect the spinal cord. All patients with recurrent symptoms evaluated urgently by specialist spinal servicesSubacute combined degeneration of the cord The commonest cause of non-traumatic myelopathy in tropical countries Extremely rare in developed countriesCauseslong-standing vitamin B12 deficiency OR Replacing folate without vitamin B12 (hinted at in this case) SCDHistory of gastric or intestinal surgeryPernicious anaemiaMalabsorption (especially crohn's disease as it often affects the terminal ileum)Medications including proton-pump inhibitors and metformin can also reduce absorption of vitamin B12.Damage of :Posterior columns loss of proprioception, light touch and vibration sense (sensory ataxia and a positive Romberg's test) then parathesia.Lateral columns spastic weakness and upgoing plantars (UMN signs).Peripheral nerves absent ankle and knee jerks (LMN signs).Several neurological features myelopathy (classically the subacute combined degeneration of the cord), neuropathy and paraesthesias without neurological signs.if untreated stiffness and weakness persistDDAmyotrophic lateral sclerosis is a subtype of motor neurone disease. This may present with mixed UMN and LMN signs but no associated sensory deficits.?Guillain-Barre syndrome is an inflammatory?peripheral?neuropathy so will not present with UMN signs. There is nothing in the history to suggest a recent bacterial or viral infection.?Myasthenia gravis is an autoimmune disease affecting the?neuromuscular junction?so will not present with UMN signs or sensory loss.Charcot-Marie-Tooth disease is a hereditary sensory and motor?peripheral?neuropathy. UMN signs are not present in these patients. However, patients can present with LMN signs in all limbs and reduced sensation (more pronounced distally).Carpal Tunnel Syndrome disease of the peripheral nervous system, resulting from median nerve compression at the wrist inside the carpal tunnel. It therefore affects only the aspects of the hand innervated by the median nerve:Sensation; Thumb / Index / Middle Finger. This typically manifests as intermittent pain or parasthesiae.Motor; LOAF Muscles(lateral lumbricals, opponens pollicis, abductor pollicis brevis and flexor policis brevis). Motor signs are less commonly seen with presentations of CTS, but wasting of the thenar eminence may be present.Tinels test and Phalens test can be positive, but not always. Both tests aim to increase the pressure within the carpal tunnel, to try to exacerbate symptoms; Tinels test via tapping on it and Phalens test by sustained full flexion of the wrist.?Brown-Sequard syndromeCaused by lateral hemisection of the spinal cord. Featuresipsilateral weakness below lesionipsilateral loss of proprioception and vibration sensationcontralateral loss of pain and temperature sensation decussates at the level of the nerve rootCADASILCerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)AD due to a mutation in the NOCTH3 gene. It usually presents with the often migraines in middle age followed by recurrent TIAs and strokes, neuro-cognitive decline, psychiatric problems and dementia. rare cause of multi-infarct dementiaMRI often shows multiple widespread hyper-intense lesions in the white matter, basal ganglia, thalamus and ponsCreutzfeldt-Jakob diseaseis rapidly progressive neurological condition caused by prion proteins. These proteins induce the formation of amyloid folds resulting in tightly packed beta-pleated sheets resistant to proteases. Featuresrapidly progressive mental deterioration rapidly declining cognitive function dementia (rapid onset)myoclonus ?jerking movements in the armsExtrapyramidal and cerebellar features occur in two-thirds of cases. .rapid onset dementia and myoclonus CJD. Investigation?CSF is usually normalEEG: biphasic, high amplitude sharp waves (only in sporadic CJD)MRI: characteristic 'hockey stick sign' where the pulvinar region and dorsomedial thalamus are hyperintense on T2-weighted imaging (or pulvinar sign where the pulvinar region is hyperintense only) hyperintense signals in the basal ganglia and thalamusSporadic CJDaccounts for 85% of cases10-15% of cases are familial or a general family history of psychosis (OR 9.9) or Alzheimer's dementia has been shown to be associated with the disease.mean age of onset is 65 yearsCSF protein for 14-3-3 and periodic sharp wave complexes on the EEG are more commonly seen in sporadic CJD.New variant CJDyounger patients (average age of onset = 25 years)psychological symptoms such as anxiety, withdrawal and dysphonia are the most common presenting featuresin the later stages, mutism and vertical upgaze palsy (found in 50%)the 'prion protein' is encoded on chromosome 20 - it's role is not yet understoodmethionine homozygosity at codon 129 of the prion protein is a risk factor for developing CJD - all patients who have so far died have had thismedian survival = 13 monthsOther prion diseaseskurufatal familial insomniaGerstmann Straussler-Scheinker diseaseChoreainvoluntary, rapid, jerky movements which often move from one part of the body to another. Slower, sinuous movement of the limbs is termed athetosis.?Chorea is caused by damage to the basal ganglia, especially the caudate nucleus.Causes of choreaHuntington's disease,?Wilson's disease, ataxic telangiectasiaSLE, anti-phospholipid syndromerheumatic fever: Sydenham's chorea Infective Endocarditis (very rare manifestation following embolisation to the basal ganglia)drugs: oral contraceptive pill, L-dopa, antipsychoticsneuroacanthocytosispregnancy: chorea gravidarumthyrotoxicosispolycythaemia rubra veracarbon monoxide poisoningcerebrovascular diseaseCataplexysudden and transient loss of muscular tone?caused by?strong emotion?(e.g. laughter, being frightened) phasic muscle jerking around the mouth.?. Around two-thirds of patients with narcolepsy have cataplexy. cataplexy is highly specific for narcolepsyLaughter → fall/collapse ?cataplexy Features range from buckling knees to collapse.DDGelastic seizures are not caused by laughter but the outburst of laughter is the seizure itself- this can be caused by brain neoplasms.?Tourette's syndrome presents with verbal and physical 'tics'.Lennox Gastaut syndrome normally presents in childhood and can cause drop attacks but these are characterised by a single, generalized myoclonic jerk that precedes tonic contraction of axial muscles.Narcolepsyassociated with HLA-DR2it is associated with?low levels of orexin (hypocretin), a protein which is responsible for controlling appetite and sleep patterns early onset of REM sleep ? (hypocretin), which promotes wakefulness DD.Cryptochrome is also involved in sleep - mostly in how light influences the sleep cycle. Melatonin is a hormone released by the pineal gland that leads to the feeling of sleepiness. Leptin is a neuropeptide most associated with regulating the sensation of hunger.Featurestypical onset in teenage yearshypersomnolencecataplexy (sudden loss of muscle tone often triggered by emotion)sleep paralysisvivid hallucinations on going to sleep or waking upInvestigationmultiple sleep latency EEGManagementdaytime stimulants (e.g. modafinil) and nighttime sodium oxybateCerebrospinal fluid: raised lymphocytesNormal values of cerebrospinal fluid (CSF)raised lymphocytesraised protein levelsPressure = 60-150 mm (patient recumbent)Protein = 0.2-0.4 g/lGlucose = > 2/3 blood glucoseCellsRBCs = 0WBCs < 5/mm?Viral Meningitis / EncephalitisTB MeningitisPartially TTT bacterial meningitisLyme diseaseAutoimmune (Behcet's, SLE)Tumers (Lymphoma, Leukaemia)Guillain-Barre syndromeInfection T.BFungal Bacterial meningitisFroin's syndrome ↑↑CSF protein below a spinal canal blockage(Tumour, Disc, Infection)Viral EncephalitisCommon peroneal nerve lesionThe sciatic nerve divides into the tibial and common peroneal nerves (crosses laterally to curve over posterior rim of the fibula. It then divides into the superficial and deep branches. It supplies the tibialis anterior, extensor hallucis longus, extensor digitorum longus and peroneus tertius. Injury often occurs at the neck of the fibulaFeatureFoot Drop "The most characteristic" Other features include:weakness of foot dorsiflexionweakness of foot eversionweakness of extensor hallucis longussensory loss over the dorsum of the foot and the lower lateral part of the legwasting of the anterior tibial and peroneal muscles ?The degree of wasting would of course depend on how long the nerve palsy had been presentFoot DropFoot drop is a result of weakness of the foot dorsiflexors.Possible causes include:common peroneal nerve lesion - the most common causeL5 radiculopathysciatic nerve lesionsuperficial or deep peroneal nerve lesionother possible includes central nerve lesions (e.g. stroke) but other features are usually presentA?common peroneal nerve lesion is the most common cause?. This is often secondary to compression at the neck of the fibula. This may be caused by certain positions such as?leg crossing, squatting or kneeling. Prolonged confinement, recent weight loss, Baker's cysts and plaster casts to the lower leg are also known to be precipitating factors.Examinationif the patient has an isolated peroneal neuropathy there will be weakness of foot dorsiflexion and eversion. Reflexes will be normalweakness of hip abduction is suggestive of a L5 radiculopathyBilateral symptoms, fasiculations or other abnormal neurological findings (e.g. hyperreflexia) are indications for specialist referral.If the examination suggests a peroneal neuropathy then conservative management is appropriate. Leg crossing, squatting and kneeling should be avoided. Symptoms typically improve over 2-3 months.*DVLA: neurological disordersEpilepsy/seizures - all patient must not drive and must inform the DVLAfirst unprovoked/isolated seizure:?6 months?off if there are no relevant structural abnormalities on brain imaging and no definite epileptiform activity on EEG. If these conditions are not met then this is increased to 12 monthsEstablished epilepsy or those with multiple unprovoked seizures: may qualify for a driving licence if they have been free from any seizure for?12 months no seizures for 5 years (with medication if necessary) a ’til 70 licence is usually restoredwithdrawawl of epilepsy medication: should not drive whilst anti-epilepsy medication is being withdrawn and for 6 months after the last doseSyncopesimple faint:?no restrictionsingle episode, explained and treated: 4 weeks offsingle episode, unexplained: 6 months offtwo or more episodes: 12 months offStroke or TIA1 attack 1 month?off driving, may not need to inform DVLA if no residual neurological deficitmultiple TIAs over short period of times ?3 months?off driving and inform DVLACraniotomyFor meningioma: 1 year off driving if the tumour is a benign meningioma and there is no seizure history, licence can be reconsidered 6 months after surgery if remains seizure freepituitary tumour: craniotomy: 6 months; trans-sphenoidal surgery 'can drive when there is no debarring residual impairment likely to affect safe driving'Narcolepsy/cataplexyStop driving on diagnosis, can restart once 'satisfactory control of symptoms'Chronic neurological disorders multiple sclerosis, motor neuron disease: DVLA should be informedcomplete PK1 form (application for driving licence holders state of health)Epilepsy in children: syndromesInfantile spasms (West's syndrome)brief spasms beginning in first few (4-6) months of life; M>F1. Flexion of head, trunk, limbs → extension of arms (Salaam attack); last 1-2 secs, repeat up to 50 times2. Progressive mental handicap3.?EEG: hypsarrhythmiausually 2nd to serious neurological abnormality (e.g. TS, encephalitis, birth asphyxia) or may be cryptogenicpoor prognosisvigabatrin/steroidsLennox-Gastaut syndromemay be extension of infantile spasms (50% have hx)onset 1-5 yrsatypical absences, falls, jerks90% moderate-severe mental handicapEEG: slow spikeketogenic diet may helpBenign rolandic epilepsymost common in childhood, M>Fparaesthesia (e.g. unilateral face), usually on waking upTypical (petit mal) absence seizuresonset 4-8 yrsduration few-30 secs; no warning, quick recovery; often many per dayEEG: 3Hz generalized, symmetricalsodium valproate, ethosuximidegood prognosis: 90-95% become seizure free in adolescenceJuvenile myoclonic epilepsy (Janz syndrome)onset: teens; F:M = 2:11. Infrequent generalized seizures, often in morning2. Daytime absences3. Sudden, shock like myoclonic seizure?(these may develop before seizures)usually good response to sodium valproateNeonatal period - try vitamin B62nd: hypoglycaemia, meningitis, head traumapyridoxine dependency (AR, IV B6)benign familial neonatal seizures (AD)benign neonatal convulsions (5th day)Absence seizuresForm of generalised epilepsy, mostly in children (3-10Ys) old and girls are affected twice as commonly as boys. Featuresabsences last a few seconds and are associated with a quick recoveryseizures may be provoked by hyperventilation or stressthe child is usually unaware of the seizurethey may occur many times a dayEEG: bilateral, symmetrical?3Hz spike and wave patternManagementNa+ valproate and ethosuximide?are first-line treatmentgood prognosis - 90-95% become seizure free in adolescenceEpilepsy: classificationThe basic seizure classification is based on 3 key features:1. Where seizures begin in the brain2. Level of awareness during a seizure (important as can affect safety during seizure)3. Other features of seizuresFocal seizuresStarts in a specific area, on one side of the brainLevel of awareness?focal aware?(previously termed 'simple partial')focal impaired awareness?(previously termed 'complex partial') awareness unknown are used to further describe focal seizuresAssociated features Motor Jacksonian march Non-motor déjà vu, jamais vu Other features such as auraLocalizing features of focal seizuresLocationTypical seizure typeTemporal lobe (HEAD)Hallucinations (auditory/gustatory/olfactory), Epigastric rising/Emotional, Automatisms (lip smacking/grabbing/plucking),Déjà vuDysphasia post-ictal.Frontal lobe (motor)Head/leg movementsPosturingpost-ictal weaknessJacksonian marchParietal lobe (sensory)ParaesthesiaOccipital lobe (visual)Floaters/flashes Generalizedthese engage or involve networks on both sides of the brain at the onsetConsciousness lost immediately. The level of awareness in the above classification is therefore not needed, as all patients lose consciousnesssubdivided into motortonic-clonicnon-motor (absence)specific types include:tonic-clonic (grand mal)tonicclonictypical absence (petit mal)atonicthis termed is reserved for when the origin of the seizure is unknownFocal to bilateral seizurestarts on one side of the brain in a specific area before spreading to both lobespreviously termed secondary generalized seizuresDD Transient global amnesia syndrome of uncertain aetiology, characterised byDiscrete episode lasting for a few hours (always less than 24 hours) anterograde amnesia, retrograde amnesiaRepetitive questioning with an absence of other cognitive or neurological impairments.Diagnostic criteria (in addition to the above features) areReliable witness to episodeAbsence of head trauma or loss of consciousness at the onsetPreserved personal identity and absence of epileptic features.Epilepsy can present with discreet episodes of Amnesia (Transient epileptic amnesia)Onset on waking from sleep and accompanying epileptic features (motor automatism, stereotyped behaviours, limb shaking or rubbing).Shorter duration (< 1 hour) than Global amnesia multiple attacksPrevious stroke may be the underlying cause of his seizureTreatmentMost neurologists now start antiepileptics following a second epileptic seizure Antiepileptics after the first seizure if any of the following are present:The patient has a neurological deficitBrain imaging shows a structural abnormalityEEG shows unequivocal epileptic activityThe patient or their family or carers consider the risk of having a further seizure unacceptable.Sodium valproate first line treatment for patients with generalised seizuresCarbamazepine focal seizures.May exacerbate absence seizures ((along with phenytoin, vigabatrin and gabapentin).May exacerbate myoclonic seizuresGeneralized tonic-clonic seizuressodium valproatesecond line: Lamotrigine, carbamazepineAbsence seizures (Petit mal)Ethosuximide ?is the gold standard treatment sodium valproate, particularly effective if co-existent tonic-clonic seizures in primary generalised epilepsyMyoclonic seizuresSodium valproate2nd line Clonazepam, lamotrigineFocal seizuresCarbamazepine or lamotrigine2nd line levetiracetam, oxcarbazepine or sodium valproateNB. Monotherapy with another drug should be attempted before combination therapy is started. Caution should be when combining (sodium valproate and lamotrigine) serious skin rashes (Steven-Johnson's syndrome)Withdrawal of ttt if seizure free for > 2 years stopped over 2-3 m Benzodiazepines (over a longer period).Epilepsy: pregnancy and breast feedingThe risks of uncontrolled epilepsy during pregnancy generally outweigh the risks of medication to the fetus. All women thinking about becoming pregnant should be advised to take folic acid 5mg per day well before pregnancy to minimise the risk of neural tube defects.Around 1-2% of newborns born to non-epileptic mothers have congenital defects. This rises to 3-4% if the mother takes antiepileptic medication.Other pointsAim for monotherapyNo indication to monitor antiepileptic drug levelsNa valproate: associated with neural tube defects↑↑ risk of neurodevelopmental delay in children following maternal use of sodium valproate.Not be used during pregnancy and in women of childbearing age unless clearly necessary.Women of childbearing age should not start treatment without specialist neurological or psychiatric advice.Camazepine the least teratogenic of the older antiepilepticsPhenytoin with cleft palatePregnant women taking phenytoin are given vitamin K in the last month of pregnancy to prevent clotting disorders in the newbornlamotrigine: studies to date suggest the rate of congenital malformations may be low. The dose of may ↑↑in pregnancyBreast feeding generally safe for mothers taking antiepileptics with the possible exception of the barbituratesStatus epilepticusPriority is termination of seizure activity prolonged will lead to irreversible brain damage.1st line benzodiazepines such as diazepam or lorazepam. repeated once after 10 minutes If ineffective within 10 minutes phenytoin, sodium valproate, levetiracetam, or phenobarbital.If no response within 30 minutes from onset general anaesthesia.PhenytoinPhenytoin is used in the management of seizures binds to(block) Na channels ↑↑ refractory period protect against seizuresPhenytoin is also an inducer of the P450 systemAdverse effects.AcuteInitially (Cerebellar) dizziness,?diplopia,?nystagmus,?slurred speech,?ataxiaLater confusion, seizuresIV phenytoin hypotension and bradyarrhythmias (class IB antiarrhythmic drugs) blocks Na channels in the heart ↓↓repolarizationChronicCommonGingival hyperplasia?(↑↑ expression of platelet derived growth factor, PDGF)HirsutismCoarsening of facial features, drowsinessMegaloblastic anaemia?(secondary to altered folate metabolism)peripheral neuropathyenhanced vitamin D metabolism causing?osteomalacialymphadenopathydyskinesiaIdiosyncraticfeverRashes including severe reactions such as?(toxic epidermal necrolysis)HepatitisDupuytren's contracture contracture is a hand deformity (thickening issue that lies under the skin of your palm)Aplastic anaemiadrug-induced lupusTeratogenicassociated with?cleft palate and congenital heart diseasePhenytoin ↑↑ vitamin K metabolism relative vitamin K deficiency hemorrhagic disease of the newborn.The most common sites of bleeding Umbilicus, Mucous membranes, Gastrointestinal tract, and venepunctures.MonitoringPhenytoin levels do not need to be monitored routinely but?trough levels, immediately before dose?should be checked if:adjustment of phenytoin dosesuspected toxicitydetection of non-adherence to the prescribed medicationSodium valproatefirst-line therapy for generalised seizures ↑↑ GABA activity. Adverse effectsP450 inhibitorGITHepatotoxicity hyperammonemic encephalopathy?L-carnitine?may be used as treatment if this developspancreatitisgastrointestinal: nausea↑↑ appetite and?weight gainCNSAtaxiaTremorAlopecia: regrowth may be curlyTeratogenicBlood ↑↑↑ Thrombocytopaenia↓↓↓ Na+ Essential tremorAutosomal dominant condition which usually affects both upper limbs. Featurespostural tremor: worse if arms outstretchedimproved by alcohol and restmost common cause of titubation (head tremor /?worsening involuntary movements of the head)worse on movement and during stress and relieved by alcohol and sleepDD. Parkinson difficulty in initiating movement (bradykinesia), postural instability and unilateral symptoms (initially) ManagementPropranolol is first-linePrimidone is sometimes usedDeep brain StimulationBotulinum toxin Gingival hyperplasiaDrug causes of gingival hyperplasiaPhenytoinCiclosporincalcium channel blockers (especially nifedipine)Other causes Acute myeloid leukaemia (myelomonocytic and monocytic types)MacroglossiaCausesHypothyroidismAcromegalyAmyloidosisDuchenne muscular dystrophyMucopolysaccharidosis (e.g. Hurler syndrome)Patients with Down's syndrome are now thought to have apparent macroglossia due to a combination of mid-face hypoplasia and hypotoniaMiosisCauses of miosis (small pupil)Horner's syndromeArgyll-Robertson pupilsenile miosispontine haemorrhagecongenitalDrugs causesopiatesParasympathomimetics pilocarpineOrganophosphate toxicityParkinsonism Progressive neurodegenerative ?degeneration of dopaminergic neurons in the substantia nigra. Epidemiologytwice as common in menMean age of diagnosis is 65 yearsCausesParkinson's diseaseDrug-induced ?Antipsychotics,?Metoclopramide ().progressive supranuclear palsyMultiple system atrophyWilson's diseasePost-encephalitisDementia pugilistic 2ry to chronic head trauma e.g. boxingToxins: carbon monoxide, MPTPFeatures Classic triad Asymmetrical?symptoms. Bradykinesiapoverty of movement also seen, sometimes referred to as hypokinesiashort, shuffling steps with reduced arm swingingdifficulty in initiating movementTremor Most marked at rest, 3-5 Hzworse when stressed or tired,?improves with voluntary movementtypically 'pill-rolling', i.e. in the thumb and index fingerRigidity lead pipecogwheel: due to superimposed tremorOther characteristic featuresMask-like faciesflexed posturemicrographiaDrooling of salivaPsychiatric features:?depression is the most common feature (affects about 40%); dementia, psychosis and sleep disturbances.↓↓ olfactionREM sleep behaviour disorderFatigueAutonomic dysfunction postural hypotensionDrug-induced parkinsonismSlightly different features to Parkinson's disease:Motor symptoms rapid onset and bilateralRigidity and rest tremor uncommonDiagnosisClinically. If there is difficulty DD. between essential tremor and Parkinson's disease ?123IFPCIT Single Photon Emission Computed Tomography (SPECT).1st-line treatmentif the motor symptoms are affecting the patient's quality of life ?L- dopaMotor symptoms are not affecting quality of life Dopamine agonist (non-ergot derived), levodopa or monoamine oxidase B (MAOB) inhibitorLevodopaDopamine agonistsMAOB inhibitorsImproved Motor symptoms↑↑↑ ↑ ↑ Daily living Activities↑↑↑ ↑ ↑Motor complications↑↑↑ ↓↓ ↓↓ Adverse events↑↑sleepiness,?hallucinations? impulse control disorders↓↓↓↑↑↑↓↓Uncontrolled symptoms despite optimal levodopa treatment or developing Dyskinesia a dopamine agonist, MAOB inhibitor or COMT inhibitor Dopamine agonistsMAOB inhibitorsCOMT inhibitorsAmantadineMotor symptoms↑↑↑↑↑↑↑↑↑No evidence Activities of daily living↑↑↑↑↑↑No evidence Off time Reduction ↑↑↑↑↑No studies Adverse events↑↑↑↑↑↑No studies Hallucinations↑↑↑↑↑No studies Impulse control disorders (difficulty to control behaviors and emotions) with any dopaminergic therapy but are more common with:Dopamine agonist therapyHistory of previous impulsive behavioursHistory of alcohol consumption and/or smoking↑↑↑ daytime sleepiness patients should not drive. Medication should be adjusted to control symptoms. Modafinil can be considered if alternative strategies fail.Orthostatic hypotension Medication review looking at potential causes. If symptoms persist midodrine (acts on peripheral alpha-adrenergic receptors to ↑↑ arterial resistance).Drooling of saliva Glycopyrronium bromide. If this is not effective, not tolerated or contraindicated referral to a specialist service for botulinum toxin A.Sublingual atropine ophthalmic solution is preferred to inhalersFurther information regarding specific anti-Parkinson's medicationLevodopaCombined with a decarboxylase inhibitor (carbidopa or benserazide) to prevent peripheral metabolism of levodopa to dopamine.↓↓ Effectiveness with time (usually by 2 years) ONLY newly diagnosed Parkinson's + motor symptoms affecting quality of life.S/E(Involuntary writhing movements)'on-off' effect Motor fluctuations are alterations between periods of improved mobility known as “on” periods during which the patient responds to levodopa and periods of impaired motor function or “off” responses in which the patient responds poorly to levodopadry mouthAnorexia,?Cardiac Arrhythmia,?postural hypotension,?Psychosis, drowsinessReddish discolouration of urine upon standingNO use in neuroleptic induced parkinsonismNot to acutely stop Levodopa if a patient is admitted to hospital OR cannot take levodopa orally dopamine agonist patch as?rescue medication? prevent acute dystoniaDopamine receptor agonists?Bromocriptine,?Ropinirole,?Cabergoline,?Apomorphinefor motor symptoms that are not affecting a patient's quality of lifeS/EErgot-derived dopamine receptor agonists (Bromocriptine, Cabergoline) ?pulmonary, retroperitoneal and cardiac fibrosis. Echocardiogram, ESR, Creatinine and chest x-ray prior to treatment and patients should be closely monitored.Might cause impulse control disorders and excessive daytime somnolence↑↑↑ likely than levodopa to cause hallucinations in older patients. Nasal congestion and postural hypotension are also seen in some patientsMAO-B (Monoamine Oxidase-B) inhibitors Selegiline ↓↓ breakdown of dopamine secreted by the dopaminergic neuronsAmantadineMechanism is not fully understood, ↑↑ dopamine release and ↓↓ its uptake at dopaminergic synapsesS/E ?Ataxia,?Slurred speech,?Confusion,?Dizziness?and Livedo reticularisCOMT (Catechol-O-Methyl Transferase) inhibitorsEntacapone,?TolcaponeCOMT is an enzyme involved in the breakdown of dopamine as an adjunct to levodopa therapyused in conjunction with levodopa in patients with established PDAntimuscarinicsProcyclidine,?Benzotropine, Trihexyphenidyl (benzhexol)block cholinergic receptorsTreat drug-induced parkinsonism rather than idiopathic Parkinson's diseasehelp tremor and rigidityProgressive Supranuclear palsyaka Steele-Richardson-Olszewski syndrome'Parkinson Plus' syndrome. Features↓↓ of vertical gaze (down gaze > up gaze of difficultly reading or descending stairs)↓↓?Horizontal gaze sometimes seen later as the disease progresses, but would be atypical in a newly diagnosed patient.parkinsonismfallsslurring of speechcognitive impairmentManagementpoor response to L-dopaOtitis ExternaCommonly develops after swimming on holiday. Causes infectionBacterial (Staphylococcus?aureus,?Pseudomonas?aeruginosa)FungalSeborrhoeic DermatitisContact Dermatitis (allergic and irritant)Featuresear pain, itch, dischargeOtoscopy: red, swollen, or eczematous canalInitial management Topical antibiotic or a combined topical antibiotic with a steroidIf the Tympanic membrane is perforated aminoglycosides are traditionally not usedif there is canal debris then consider removalif the canal is extensively swollen ear wick is sometimes insertedSecond-line options includeConsider contact dermatitis secondary to neomycinOral antibiotics (flucloxacillin) infection is spreadingTaking a swab inside the ear canalEmpirical use of an antifungal agent.If a patient fails to respond to topical antibiotics then the patient should be referred to ENT.Malignant Otitis externa↑↑↑elderly diabetics extension of infection into the bony ear canal and the soft tissues deep to the bony canal IV antibiotics may be required.OtosclerosisReplacement of normal bone by vascular spongy bone. Progressive conductive deafness due to fixation of the stapes at the oval window. Autosomal dominant?and typically affects young adults (20-40 years)features?include:Conductive deafnessTinnitusNormal tympanic membrane 10% of patients may have a 'flamingo tinge', caused by hyperaemia+Ve family historyManagementHearing aidStapedectomyDD Stickler syndrome is a cause of Sensorineural hearing loss.Ramsay Hunt syndrome (herpes zoster oticus)Caused by the reactivation of the varicella zoster virus in the geniculate ganglion of the seventh cranial nerve. FeaturesAuricular pain is often the first featureFacial nerve palsyVesicular rash around the earother features include vertigo and tinnitusVesicular lesions are classically in the external auditory canal and pinna, but may be on the anterior 2/3rds of the tongue and the soft palate.ManagementOral aciclovir and corticosteroids?are usually givenRinne's and Weber's testPerforming both Rinne's and Weber's test allows differentiation of conductive and sensorineural deafness.Rinne's testtuning fork is placed over the mastoid process until the sound is no longer heard, repositioning just over external acoustic meatus'positive test': air conduction (AC) is normally better than bone conduction (BC)'negative test': if BC > AC then conductive deafnessWeber's testtuning fork is placed in the middle of the forehead equidistant from the patient's earsthe patient is then asked which side is loudestin unilateral sensorineural deafness sound is localised to the unaffected sidein unilateral conductive deafness sound is localised to the affected sideTinnitusMeniere's diseaseHearing lossVertigo tinnitus sensation of fullness or pressure in one or both earsOtosclerosis20-40 years Conductive deafnes, TinnitusNormal tympanic membrane 10% of patients 'flamingo tinge', caused by hyperaemiaPositive family historyAcoustic neuromaHearing loss, vertigo, tinnitusAbsent corneal reflex is important signAssociated with neurofibromatosis type 2Hearing lossCauses include excessive loud noise and presbycusisDrugsAspirin/NSAIDsAminoglycosidesLoop diureticsQuinineOther causes includeimpacted ear waxchronic suppurative otitis mediaVertigoFalse sensation that the body or environment is moving.DisorderNotesViral labyrinthitisRecent viral infectionSudden onsetNausea and vomitingHearing may be affectedVestibular neuronitisRecent viral infectionRecurrent vertigo attacks lasting hours or daysNo hearing lossBenign paroxysmal positional vertigoGradual onsetTriggered by change in head positionEach episode lasts 10-20 secondsMeniere's diseaseAssociated with hearing loss, sensation of fullness or pressure in one or both earsVertebrobasilar ischaemiaElderly patientDizziness on extension of neckAcoustic neuromaHearing loss, vertigo, tinnitusAbsent corneal reflex is important signAssociated with neurofibromatosis type 2Other causes of vertigo includePosterior circulation strokeTraumaMultiple sclerosisOtotoxicity e.g. gentamicineVestibular neuronitisVestibular neuronitis is a cause of vertigo that?often develops following a viral infection. Featuresrecurrent vertigo attacks lasting hours or daysnausea and vomiting may be presenthorizontal nystagmus is usually presentno hearing loss?or tinnitusDifferential diagnosisviral Labyrinthitis The absence of hearing loss suggests a diagnosis of vestibular neuronitis rather than viral labyrinthitis.posterior circulation stroke: the?HiNTs exam can be used to distinguish vestibular neuronitis from posterior circulation strokeManagementvestibular rehabilitation exercises are the preferred treatment?for patients who experience chronic symptomsBuccal or intramuscular?prochlorperazine?is often used to provide rapid relief for severe casesa short oral course of prochlorperazine, or an antihistamine (cinnarizine, cyclizine, or promethazine) may be used to alleviate less severe casesMeniere's diseaseA disorder of the inner ear of unknown cause excessive pressure and progressive dilation of the endolymphatic system. It is more common in middle-aged adults but may be seen at any age. Men = women.FeaturesRecurrent episodes of vertigo, tinnitus and hearing loss (sensorineural). Vertigo is usually the prominent symptoma sensation of aural fullness or pressure is now recognised as being commonother features include nystagmus and a positive Romberg testepisodes last minutes to hourstypically symptoms are unilateral but bilateral symptoms may develop after a number of yearsNatural historysymptoms resolve in the majority of patients after 5-10 yearsthe majority of patients will be left with a degree of hearing losspsychological distress is commonManagementENT assessment is required to confirm the diagnosispatients should inform the DVLA. The current advice is to cease driving until satisfactory control of symptoms is achievedacute attacks: buccal or intramuscular prochlorperazine. Admission is sometimes requiredprevention: betahistine and vestibular rehabilitation exercises may be of benefitVestibular schwannoma (acoustic neuroma)Vestibular schwannomas (sometimes referred to as acoustic neuromas) account for approximately 5% of intracranial tumours and 90% of cerebellopontine angle tumours.The classical history includes Combination (vertigo + hearing loss + tinnitus + absent corneal reflex). Features can be predicted by the?affected cranial nerves:VIII vertigo,?unilateral sensorineural hearing loss,?unilateral tinnitusV ?absent corneal reflexVII facial palsyBilateral vestibular schwannomas neurofibromatosis type 2.suspected vestibular schwannoma ?referred urgently to ENT. The tumors are often slow growing, benign and often observed initially.InvestigationMRI of the cerebellopontine angle?is the investigation of choice. Audiometry is also important as only 5% of patients will have a normal audiogram.Management Surgery OR radiotherapy OR observation.NystagmusUpbeat nystagmus Cerebellar vermis lesionsDownbeat nystagmus - foramen magnum lesions Arnold-Chiari MalformationVisual field defectsHomonymous hemianopiaIncongruous defects (incomplete or asymmetric) : lesion of optic tractCongruous defects (complete or symmetrical): lesion of optic radiation or occipital cortexMacula sparing: lesion of occipital cortexHomonymous quadrantanopias*superior: lesion of temporal lobeinferior: lesion of parietal lobeBitemporal hemianopialesion of optic chiasmUpper quadrant defect > Lower quadrant inferior chiasmal compression (Pituitary tumour)Lower quadrant defect > Upper quadrant superior chiasmal compression (Craniopharyngioma) (cranial = Upper)Craniopharyngioma is a common brain tumor in children and derived from the Rathke's pouch. often invades the pituitary and hypothalamus (ventromedial area of the hypothalamus controls the satiety center removed during surgery, the patient can have uninhibited hunger leading to significant weight gain). Supraoptic nucleus and Paraventricular nucleus of the hypothalamus synthesis of antidiuretic hormone and oxytocin transported to the posterior hypothalamus for storage and release.Posterior hypothalamus heat generation is responsible for to maintain core body temperature.Anterior hypothalamus heat dissipation to cool down the body to prevent a rise in temperature which would be detrimental to body's internal environment.Vigabatrin40% of patients develop visual field defects, which may be irreversiblevisual fields should be checked every 6 monthsVon Hippel-Lindau syndromeAutosomal dominant?condition predisposing to neoplasia, due to an abnormality in the VHL gene located on short arm of chromosome 3FeaturesRetinal + cerebellar haemangiomas + Family history of Cancer are key features of Von Hippel-Lindau syndrome.?Hemangiomas the most common tumors.cerebellar haemangiomas: might presented with neurological symptoms headache associated with vomiting, photophobia and stiff neck.due to compression by haemangiomas, or an acute headache due to intracerebral or subarachnoid haemorrhage?retinal haemangiomas: are bilateral in 25% of patients and lead to vitreous haemorrhage+Ve family history of cancerRenal cysts (premalignant) clear-cell renal cell carcinoma.Extra-renal cysts: epididymal, pancreatic, hepaticEndolymphatic sac tumoursPhaeochromocytomaDDPolycystic kidney disease subarachnoid haemorrhage due to berry aneurysms, but NO phaeochromocytoma and a family history of retinal bleeding and renal cell carcinoma do not fit with PKD.Tuberous sclerosis hamartomas of the brain, eye and kidneys but characteristic skin signs (angiofibroma, shagreen patches and adenoma sebaceum.Wernicke's encephalopathyNeuropsychiatric disorder thiamine deficiency which is most commonly seen in alcoholics. Rarer causes include: Persistent vomiting, Stomach cancer,Dietary deficiency (Vegetarians)A classic triad (ophthalmoplegia/nystagmus, ataxia and confusion). In Wernicke's encephalopathyPetechial haemorrhages occur in a variety of structures in the brain the mamillary bodies and ventricle wallsFeatures CAN OPENConfusion, altered GCS AtaxiaNystagmus (the most common ocular sign)OphthamoplegiaPEripheral?NeuropathyInvestigations↓↓ red cell transketolaseMRIEnhancement of the mamillary bodies due to petechial haemorrhages is specific for Wernicke's encephalopathy, although sensitivity is only 50%.?Treatment Urgent replacement of thiamine DDCerebellar Stroke ataxia and nystagmus but would be more likely to present with lateralizing signs and would not be associated with acute confusion.Relationship with Korsakoff syndromeIf not treated Korsakoff's syndrome may develop antero- and retrograde amnesia and confabulation in addition to the above symptoms.Baclofenis used to treat muscle spasticity in conditions such as multiple sclerosis, cerebral palsy and spinal cord injuries.Agonist of GABA receptors which acts in the central nervous system. It is used to treat muscle spasticityacts in the central nervous system (brain and spinal cord)Pilocarpine muscarinic receptor agonist, used in glaucoma.Ketamine NMDA receptor antagonist.Venlafaxine Serotonin–norepinephrine reuptake inhibitors (SNRIs), antidepressant medications .Dopamine antagonists antipsychotics (such as haloperidol) and antiemetics (such as metoclopramide and domperidone).Subacute combined degenerationLeftRightPower4/54/5Sensation to coarse touch, pain, temperature and pressurenormalnormalSensation to fine touch and vibrationreducedreducedProprioceptionreducedreducedAnkle reflexabsentabsentBabinski responseupgoingupgoingMedication overuse headacheOne of the most common causes of chronic daily headache. It may affect up to 1 in 50 people. Featurespresent for 15 days or more per monthdeveloped or worsened whilst taking regular symptomatic medicationpatients using opioids and triptans are at most riskmay be psychiatric co-morbidityManagement (from 2008 SIGN guidelines)simple analgesics and triptans should be withdrawn abruptly (may initially worsen headaches)opioid analgesics should be gradually withdrawnWithdrawal symptoms such as vomiting, hypotension, tachycardia, restlessness, sleep disturbances and anxiety may occur when medication is stoppedMigraine Common type of primary headache. It is characterised by:a severe, unilateral, throbbing headacheassociated with nausea, photophobia and phonophobiaattacks may last up to 72 hourspatients characteristically go to a darkened, quiet room during an attack'classic' migraine attacks are precipitated by an aura. These occur in around one-third of migraine patientstypical aura are visual, progressive, last 5-60 minutes and are characterised by transient hemianopic disturbance or a spreading scintillating scotomaformal diagnostic criteria are produced by the International Headache Society (see below)Epidemiology3 times > womenprevalence in men is around 6%, in women 18%Common triggers for a migraine attacktiredness, stressAlcoholcombined oral contraceptive pilllack of food or dehydrationcheese, chocolate, red wines, citrus fruitsmenstruationbright lightsMigraine diagnostic criteriaAAt least 5 attacks fulfilling criteria B-DBHeadache attacks lasting 4-72 hours* (untreated or unsuccessfully treated)CHeadache has at least two of the following characteristics:1. unilateral location*2. pulsating quality (i.e., varying with the heartbeat)3. moderate or severe pain intensity4. aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs)DDuring headache at least one of the following:1. nausea and/or vomiting*2. photophobia and phonophobiaENot attributed to another disorder (history and examination do not suggest a secondary headache disorder or, if they do, it is ruled out by appropriate investigations or headache attacks do not occur for the first time in close temporal relation to the other disorder)*In children, attacks may be shorter-lasting, headache is more commonly bilateral, and gastrointestinal disturbance is more prominent.ManagementIt should be noted that as a general rule 5-HT receptor agonists are used in the acute treatment of migraine whilst 5-HT receptor antagonists are used in prophylaxis. NICE produced guidelines in 2012 on the management of headache, including migraines.Acute treatmentfirst-line: offer combination therapy with an?oral triptan (sumatriptan 5-HT receptor agonists) and an NSAID, or an oral triptan and paracetamolfor young people aged 12-17 years consider a nasal triptan in preference to an oral triptanif the above measures are not effective or not tolerated offer a non-oral preparation of metoclopramide* Extrapyramidal side-effects (dystonic reactions) are particularly common in children and young adults or prochlorperazine and consider adding a non-oral NSAID or triptanEpilepsy is not a contraindication to the use of triptans. Opioids are not recommended in the management of migraineatients with migraine experience delayed gastric emptying during acute attacks. For this reason analgesics are often combined prokinetic agents such as metoclopramide. Paracetamol metabolism would not be significantly affected by changes in P450 enzyme activity (e.g. through smoking or drinking)Prophylaxisprophylaxis should be given if patients are experiencing?2 or more attacks per month. Modern treatment is effective in about 60% of patients.NICE advise either?topiramate or propranolol?'according to the person's preference, comorbidities and risk of adverse events'. Propranolol should be used in preference to topiramate in?women of child bearing age?as it may be teratogenic and it can reduce the effectiveness of hormonal contraceptivesif these measures fail NICE recommend 'a course of up to 10 sessions of acupuncture over 5-8 weeks'NICE recommend: 'Advise people with migraine that riboflavin (400 mg once a day) may be effective in reducing migraine frequency and intensity for some people'for women with predictable?menstrual migraine?treatment NICE recommend either frovatriptan (2.5 mg twice a day) or zolmitriptan (2.5 mg twice or three times a day) as a type of 'mini-prophylaxis'pizotifen is no longer recommend. Adverse effects such as weight gain & drowsiness are commonMigraine during pregnancyparacetamol 1g is first-lineNSAIDs can be used second-line in the first and second trimesteravoid aspirin and opioids such as codeine during pregnancyMigraine and the combined oral contraceptive (COC) pillif patients have migraine with aura then the COC is absolutely contraindicated due to an increased significant risk of stroke (relative risk 8.72)Migraine and menstruationmany women find that the frequency and severity of migraines increase around the time of menstruationSIGN recommends that women are treated with mefanamic acid or a combination of aspirin, paracetamol and caffeine. Triptans are also recommended in the acute situationMigraine and hormone replacement therapy (HRT)safe to prescribe HRT for patients with a history of migraine but it may make migraines worseTriptansTriptans are specific?5-HT1B?and 5-HT1D?agonists?used in the acute treatment of migraine. 1st-line in combination therapy with an NSAID or paracetamol.Prescribing pointsshould be taken as soon as possible?after the onset of headache, rather than at onset of auraoral, orodispersible, nasal spray and subcutaneous injections are availableAdverse effects'triptan sensations' - tingling, heat,?tightness (e.g. throat and chest), heaviness, pressureContraindicationspatients with a history of, or significant risk factors for,?ischaemic heart disease or cerebrovascular diseaseTopiramateTopiramate was developed as an antiepileptic and is used alone or as adjunctive treatment in generalised tonic-clonic seizures.s a first-line agent in the prophylaxis of migraine.There appear to be multiple mechanisms of action:blocks voltage-gated Na+ channelsincreases GABA actioncarbonic anhydrase inhibition: this results in a decrease in urinary citrate excretion and formation of alkaline urine that favours the creation of calcium phosphate stoneTopiramate is an inducer of the P450 enzyme CYP3A4. This may result in?hormonal contraception being less effective. As a result, the Faculty of Sexual and Reproductive Health (FSRH) suggests the following for patients taking topiramate:combined oral contraceptive pill and progestogen-only pill: UKMEC 3 (disadvantages outweigh advantages):implant: UKMEC 2 (advantages generally outweigh the disadvantages)The injection (Depo-Provera) and intrauterine system are not affected by topiramate.Adverse effects of topiramate include:reduced appetite and weight lossdizzinessparaesthesialethargy and poor concentrationrare but important: acute myopia and?secondary angle-closure glaucomaTopiramate is associated with a risk of foetal malformations.Cluster headacheone of the most painful conditions that patients can have the misfortune to suffer. The name relates to the pattern of the headaches - they typically occur in clusters lasting several weeks, with the clusters themselves typically once a year.Cluster headaches are more common in men (3:1) and smokers.?Alcohol may trigger an attack?and there also appears to be a relation to nocturnal sleep.Featurespain typical occurs once or twice a day, each episode lasting 15 mins - 2 hoursclusters typically last 4-12 weeksintense sharp, stabbing pain around one eye (recurrent attacks 'always' affect same side)patient is restless and agitated during an attackaccompanied by redness, lacrimation, lid swellingnasal stuffinessmiosis and ptosis in a minorityManagementacute: 100% oxygen (80% response rate within 15 minutes), subcutaneous or nasal triptan (75% response rate within 15 minutes)prophylaxis: verapamil is the drug of choice. There is also some evidence to support a tapering dose of prednisoloneIt is not recommended to offer paracetamol, NSAIDS, opioids, ergots or oral triptans for the acute treatment of a cluster headache rarely effectiveNICE recommend seeking specialist advice from a neurologist if a patient develops cluster headaches with respect to neuroimagingSome neurologists use the term trigeminal autonomic cephalgia to group a number of conditions including cluster headache, paroxysmal hemicrania and short-lived unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT). It is recommended such patients are referred for specialist assessment as specific treatment may be required, for example it is known paroxysmal hemicrania responds very well to indomethacinPost-lumbar puncture headacheApproximately one-third of patients. The pathophysiology of is unclear but may relate to a 'leak' of CSF following dural puncture. Post-LP headaches are more common in young females with a low body mass indexTypical featuresusually develops within 24-48 hours following LP but may occur up to one week latermay last several daysworsens with upright positionimproves with recumbent positionFactors which may contribute to headacheFactors which do not contribute to headacheIncreased needle sizeSharp needles associated with a greater frequency of post-lumbar puncture headaches when compared to atraumatic needles inserted using an introducer.?Direction of bevel Not replacing the styletIncreased number of LP attemptsIncreased volume of CSF removedBed rest following procedureIncreased fluid intake post procedureOpening pressure of CSFPosition of patientManagementsupportive initially (analgesia, rest)if pain continues for more than 72 hours then specific treatment is indicated, to prevent subdural haematomatreatment options include: blood patch, epidural saline and intravenous caffeineNeck lumpsConditionNotesReactive lymphadenopathyBy far the most common cause of neck swellings. There may be a history of local infection or a generalised viral illnessLymphomaRubbery, painless lymphadenopathyThe phenomenon of pain whilst drinking alcohol is very uncommonThere may be associated night sweats and splenomegalyUnicentric Castleman's diseaseis a lymphoproliferative disorder associated in a subset of cases with HIV and HHV-8. Patient's with unicentric Castleman's disease tend to be asymptomatic and lymphadenopathy is constrained to one lymph node group.The most common sites of the disease being the chest (24 percent), neck (20 percent), abdomen (18 percent), and retroperitoneum (14 percent). Biopsy of the lymph node commonly shows regressed germinal centres surrounded by prominent mantle zonesThyroid swellingMay be hypo-, eu- or hyperthyroid symptomaticallyMoves upwards on swallowingThyroglossal cystMore common in patients < 20 years oldUsually midline, between the isthmus of the thyroid and the hyoid boneMoves upwards with protrusion of the tongueMay be painful if infectedPharyngeal pouchMore common in older menRepresents a posteromedial herniation between thyropharyngeus and cricopharyngeus musclesUsually not seen but if large then a midline lump in the neck that gurgles on palpationTypical symptoms are dysphagia, regurgitation, aspiration and chronic coughCystic hygromaA congenital lymphatic lesion (lymphangioma) typically found in the neck, classically on the left sideMost are evident at birth, around 90% present before 2 years of ageBranchial cystAn oval, mobile cystic mass that develops between the sternocleidomastoid muscle and the pharynxDevelop due to failure of obliteration of the second branchial cleft in embryonic developmentUsually present in early adulthoodCervical ribMore common in adult femalesAround 10% develop thoracic outlet syndromeCarotid aneurysmPulsatile lateral neck mass which doesn't move on swallowingParinaud syndrome As a result of a lesion at the dorsal midbrain Rostral interstitial nucleus of medial longitudinal fasciculus lies at the dorsal midbrain and control vertical gaze. They project to the vestibular nuclei. Symptoms:Upward gaze palsy, often manifesting as diplopiaPupillary light-near "Accommodation" dissociation (Pseudo-Argyll Robertson pupils)Convergence-retraction nystagmusIt's aetiology include:Brain tumours in the midbrain or pineal gland (pinealoma)Multiple sclerosisMidbrain stroke ................
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