Bluedocs.duhs.duke.edu



Cases for CNS part 1504: Multiple sclerosis543: Parkinson disease515: Thiamine deficiency301: Encephalitis300: Meningitis503: Tay SachsReading:Tuesday:All labs: 255-60, 849-52, 857-60, 862-880Neurology assistance (cases 504 and 543)Neurology work through website cases for Parkinson disease and multiple sclerosis for about 30 minutes for each case. Once each case is presented (and the patient inevitably dies), pathology will discuss the gross and microscopic findings as well as pathogenesis. Then neurology will close the case with any additional comments and move on to the next caseID assistanceID work through website cases for encephalitis and meningitis for about 30 minutes for each case. Once each case is presented (and the patient inevitably dies), pathology will discuss the gross and microscopic findings as well as pathogenesis. Then ID will close the case with any additional comments and move on to the next caseWebsite cases:Tuesday:Labs 1, 2 and 3:. Neurology MS and Parkinson (about an hour); thiamine deficiency case.Labs 4, 5 and 6: ID encephalitis and meningitis cases (about an hour). Class will finish with the Tay-Sachs caseThursday:Labs 1, 2 and 3: ID encephalitis and meningitis cases (about an hour). Class will finish with the Tay-Sachs caseLabs 4, 5 and 6: Neurology MS and Parkinson (about an hour); thiamine deficiency case.Case 504: Multiple sclerosisA 25-year-old right handed woman with no prior medical history presents with one week of blurred vision in her left eye and pain worsened with eye movement. She noted no similar vision deficits in the past, but did have an episode of left arm and hand numbness/tingling for several weeks prior to her wedding a few years ago. Symptoms improved over a couple days so she did not present for medical attention. Not taking any medications and no known allergiesSocial: alcohol use only, never smoked, no illicit drug useNo family history of neurologic symptoms or autoimmune diseasePhysical ExamVital signs normalGeneral exam unremarkableOphthalmologic exam shows:Visual fields are grossly intact and extra-ocular movements are intact.Visual acuity in right eye: 20/20 with normal color saturationVisual acuity in left eye: 20/80 with reduced color saturationPupils: Both pupils briskly constrict when light is shown in the right eye, but neither constrict when light is shown in the left eye. Quickly moving the light from the right eye to the left allows for observed dilation of the left pupil, confirming a left afferent pupillary defect. Visual fields are grossly intact and extra-ocular movements are intact.Funduscopic exam shows mild disc edema in the left eyeThe rest of the neurologic exam is normal, except for hyperreflexia on left upper extremity reflexes but no pathologic responses and otherwise exam intact.CSF Analysis0 RBC (normal)7 WBC (mild elevation)58 protein (mild elevation)80 glucose (67% of serum, normal)CSF oligoclonal (immunoglobulin) bands: 5 that are not present in serum (elevated)Gross description: There were multiple well circumscribed somewhat depressed lesions in the white matter. A coronal section through the cerebrum has been stained with luxol fast blue/hematoxylin and eosin which stains the myelinated white matter blue and the cortex pink. There are multiple plaques of demyelination.Microscopic description: The section, stained with a myelin stain, shows an area of plaque with adjacent normal white matter. Areas with myelin are blue whereas the demyelinated areas are pale. In the lower left corner, you can see a vessel with prominent perivascular inflammation. The cells in MS are primarily CD8+ T cells, microglia and macrophages. Pathogenesis: CD4+ Th1 and Th17 cells that recognize myelin proteins activate macrophages, which destroy the myelin; etiology of autoimmunity not known; HLA class II allele HLA-DRB1*1501 increases risk of developing the disease 3-fold).MS: higher incidence in Caucasians of European descent, smokers, people at increasing latitude, women (2-3:1), 20-50 yo, early life EBV infection, UV light exposure/vitamin D; oligoclonal bands in CSF fluidCerebral spinal fluid studies can confirm demyelinating disease of the nervous system. They show an increase in immunoglobulin concentrations in more than 90% of patients with MS. IgG index (a comparison between IgG levels in the CSF and in the serum) is elevated in many MS patients. Oligoclonal Immunoglobulin Bands can be identified in the CSF of MS patients via electrophoresis. The overall protein level is also slightly elevated - up to 0.1 g/L. Protein level can be higher if the patient is going through a marked relapse (i.e.,. severe optic neuritis). Some patients also exhibit a slight elevation in cell count (up to 50 per cubic millimeter ). Most cells can be identified as T-lymphocytes.Case 543: Parkinson diseaseA previously healthy 62-year-old right-handed man noticed that his right hand trembles while relaxed. His wife has also noted that his handwriting has become smaller over the course of the past year. He has no memory deficits, and although hypertensive he never had a stroke. He does feel fatigued, but can still accomplish his activities of daily living. He has mild difficulty getting out of a taxi. His wife noticed reduced right arm swing with walking, but no falls. They have not noticed any cognitive decline. His wife mentioned he had been having “nightmares” for several years in which he would seem to act out dreams while asleep.Medications: Lisinopril (for blood pressure). No known allergiesSocial: denies use of alcohol, tobacco, or illicit drugsThere is no family history of neurologic problems.Physical examVital signs normalGeneral exam unremarkableMental status, cranial nerves, motor, reflexes, sensory, and cerebellar function was normal, with the following exceptions:Decreased facial expression and reduced blink frequency. Voice soft and monotone. Intermittent right-sided rest tremor of the arm without postural or kinetic components. Increased tone in both arms, worse on the right. Cogwheel rigidity was detected bilaterally, more pronounced on the right. Bilateral bradykinesia was found with finger tapping and pronation-supination of the hands, more prominent on the right. He walked with stooped posture, smaller shuffling steps, and reduced arm swing more notable on the right. He took 5 steps to turn around. Postural reflex testing was normal.TestsLabs: CBC, LFT’s, BMP, Thyroid function are normalImaging: brain MRI is normal The patient dies in a car accidentGross description: A coronal section through the midbrain illustrates pallor of the substantia nigra. The midbrain of the patient is displayed on the right. A normal midbrain is shown on the left. The locus ceruleus is also typically paleMicroscopic description: This is a phosphotungstic acid stain of the midbrain that shows loss of pigmented (catecholeminergic) Viable pigmented neurons contain eosinophilic cytoplasmic inclusions with a halo (Lewy bodies)Pathophysiology for discussion: protein accumulation and aggregation, mitochondrial abnormalities, and neuronal loss in the substantia nigra and elsewhere in the brain; abnormal protein and organelle clearance due to defects in autophagy and lysosomal degradation; Lewy body, a characteristic inclusion containing?α-synuclein, a protein involved in synaptic transmission; most cases are sporadic, point mutations and duplications of the gene encoding?α-synuclein and mutations affecting autophagic degradation cause familial PDCase 515 Thiamine deficiencyA 46-year-old man with a long history of alcohol abuse was brought to the emergency department by the police when he was found walking unsteadily and seemed confused. His speech was slurred and slow, though his blood alcohol was 0.01%. A mini mental status exam revealed that his short term memory was severely impaired. Physical exam revealed a right leg tremor and nystagmus. A cranial MRI was performed, but while the patient was still in radiology, when the patient tried get off of the gurney, he fell, hit his head on the floor and died.Summary of radiologic findings: MRI FLAIR imaging showed marked hyperintensity of the tectal region, periaqueductal area, mammillary bodies, and medial thalamic nuclei.Summary of gross findings: There are hemorrhages in the mammillary bodies which appear as petechiae515-1.?What is the differential diagnosis?Answer: Thiamine deficiency, hepatic encephalopathy, delirium tremens, diabetic ketoacidosis, uremic encephalopathy, depression515-2.?The constellation of symptoms shown by this patient is known as which of the following?KwashiorkorLeigh syndromeParkinsonismRickettsWernicke-Korsakoff syndrome515-3. Which of the following typically develops late in this disease?Amnesia (+)AtaxiaCognitive impairmentConfusionNystagmus515-4. Which of the following is true regarding this patient’s symptoms?Ataxia rarely improves with appropriate treatmentConfusion rarely improves with appropriate treatmentMemory loss typically improves with appropriate treatment Nystagmus typically improves with appropriate treatment (+)From syndrome (WKS)?is a combination of oculomotor abnormalities and mental symptoms seen in malnourished patients with?vitamin B1 (thiamine) deficiency. It is most common in alcoholics, but affects also demented people who neglect their nutrition, patients with gastric cancer, persons who have had bariatric surgery, gastrectomy (sometimes appearing many years after the procedure), hyperemesis gravidarum, anorexia nervosa, and other malnutrition settings. The WKS has also been reported following treatment with fedratinib, an inhibitor of thiamine uptake and transport, and other chemotherapeutic agents. The syndrome has 2 components:?Wernicke’s encephalopathy?(WE), and?Korsakoff’s amnesia?(KA). The classic clinical presentation of WE is a triad of?eye abnormalities?(nystagmus, oculomotor paralysis, paralysis of conjugate gaze),?ataxia?of stance and gait, and?mental symptoms, such as withdrawal and confusion. This may occur alone be accompanied by KA which is characterized by anterograde and retrograde?amnesia?and a distortion of memory such that patients recount imaginary stories that may have some basis in fact. An axonal?peripheral neuropathy?(a form of Beri-Beri disease) affecting the distal parts of the extremities is seen in 80% of patients. The syndrome may be partial, and a high index of suspicion is essential for diagnosis, especially in debilitated patients with unexplained confusion. The neurological symptoms may be accompanied by high output cardiac failure with peripheral edema. Administration of thiamine causes a rapid reversal of ophthalmoplegia within hours. Recovery from nystagmus and confusion is slower. Amnesia does not respond to treatment fully.The histopathology of WKS is incomplete loss of neurons, damage of axons and myelin which casuses loosening or vacuolization of the neuropil, and punctate hemorrhages.The lesions have a characteristic anatomical distribution which includes the mammillary bodies, the hypothalamus, thalamus,?periaqueductal gray matter, colliculi, and the floor of the fourth ventricle. The?mammillary bodies?are involved in all cases. This is the hallmark of WKS. Lesions of the colliculi and the?floor of the fourth ventricle(oculomotor nuclei, vestibular nuclei, dorsal motor nuclei of the vagus) cause the oculomotorand brain stem signs. Involvement of the?medial dorsal nuclei of the thalamus?was initially thought to be responsible for the memory defect, but more recent studies have found that this correlates with lesions of the?mammilothalamic tract and anterior thalamus. Anterograde amnesia has been reported in thalamic infarcts involving the mammillothalamic tracts (which project to the anterior thalamic nuclei). An identical memory defect (Korsakoff's amnesia) is caused by?bilateral hippocampal damage. The hippocampus projects to the mammillary bodies via the fornix but is not affected in the WKS. The MRI shows a hyperintense FLAIR signal in the affected areas. In full-blown WKS, all these structures are involved. In less severe cases, some may be spared. Each successive bout of WKS causes additional loss of neural tissue. Old cases show atrophy of the mammillary bodies and dilatation of the third ventricle. In 30% to 50% of cases, the cerebellum shows?degeneration (neuronal loss) of the superior vermis?(see below).The WKS is due to thiamine (B1)deficiency.?Thiamine pyrophosphate, the active form of thiamine, is required for oxidative metabolism of pyruvate for ATP production. The topography of the lesions in the WKS resembles the?Leigh syndrome, a metabolic disorder caused by defects of the pyruvate dehydrogenase complex and the respiratory chain. This suggests that damage of sensitive CNS structures in the WKS is due to energy failure. Thiamine is stored in several organs (heart, kidneys, liver, brain, muscles). These stores can be depleted in malnourished patients. Alcohol displaces more nutritious foods from the diet, adds carbohydrates that use up thiamine, and impairs the absorption of vitamins. Intravenous glucose administration to a patient with borderline thiamine deficiency may trigger the WKS. Therefore, vitamin B1 supplementation is mandatory for patients at risk.515-5.? In addition to alcoholism, in which of the following clinical settings is this disease process most likely to arise?Chronic blood lossGastric disorders (+)Inborn error metabolismObesityRenal diseaseCase 301: Acute viral meningo-encephalitis - ID case A 10 year-old boy travels with his family on a 4-week “eco-vacation” in Malaysia, backpacking in tropical and semi-tropical forests. They have no direct animal contact, but they are constantly exposed to mosquitos. One day prior to their return to the US, the patient begins to experience headaches, fevers, and chills. During the transcontinental flight, he becomes increasing disoriented and confused. Upon landing, the family rushes him to a local tertiary medical center. He was obtunded on admission. Physical exam: Obtunded. Temp 38.4, BP 102/66, P 96, R 20, O2 sats 99%No icterus, no skin lesions; no oral lesions, no papilledema; lungs and heart exams normal; Abd exam normalNeuro – obtunded, withdraws all extremities to painLaboratory values on admission: routine blood labs normal, but his CSF reveals the following: 110 WBCs (70% lymphocytes), 12 RBCs, normal glucose and protein. MRI of the brain reveals diffuse edema but no focal lesions. The child never regains consciousness. He develops intractable seizures and hemodynamic instability and dies.Gross image: The gross findings in viral encephalitis may be underwhelming. The intact brain may show hyperemia (as seen here) due to vascular congestion and edema. Fixed and cut specimens may show punctate hemorrhages in the white matter.Microscopic findings: Acute and subacute encephalitis are characterized by meningeal and perivascular inflammatory infiltrates that are predominantly T cells. In addition, “microglial nodules” composed of small, tight clusters of activated microglia may be seen around dying neurons. An immunohistochemical stain for West Nile Virus is positive. 300: Acute bacterial meningitis – ID case A 14-year-old girl is brought to the emergency department with a 1-day history of fevers and decreased consciousness. She had been well until the previous day when she awoke with left-sided headache, anorexia, fatigue, and subjective fevers. During the course of the day, her level of consciousness decreased. In the ED, her temperature is 38.8°C, and she is difficult to arouse. She resists neck flexion, but the remainder of her physical examination is unremarkable. Laboratory values: elevated white blood cell count of 29.3×109/L (93% neutrophils and 7% lymphocytes). Normal liver and kidney function. Lumbar puncture results included a nucleated cell count of 7200×106/L, (92% neutrophils, 7% lymphocytes and 1% monocytes), protein level 1.79 g/L (normal 0.2 g/L to 0.40 g/L) and glucose level 2.3 mmol/L (2.2 mmol/L to 3.8 mmol/L). The CSF Gram stain showed Gram-positive diplococci, subsequently growing S. pneumoniae. A peripheral blood culture revealed the same organism.CT scan of the head: opacification of the left mastoid with no obvious bony destruction.The patient is admitted to the pediatric intensive care unit, where she is treated with intravenous vancomycin, ampicillin, and ceftriaxone. Despite aggressive antibiotics and supportive care, the patient never regains consciousness. She develops intractable seizures and hemodynamic instability. The patient dies three days after hospital admission.Gross findings: There is thickening and opacification of the meninges. Pus can be seen filling the sulci.Microscopic findings: A neutrophilic exudate can be seen in the meninges. Neutrophils in the subarachnoid space can infiltrate and damage cranial nerves leading to focal deficits. Invasion into leptomeningeal blood vessels may lead to thrombosis and ischemic infarction. Blood vessels are dilated and congested. If the infection resolves, the fibrinopurulent exudate can organize into fibrous tissue that blocks the exits of the fourth ventricle and impairs CSF flow around the cerebral convexities, which may lead to hydrocephalus. Bacteria and neutrophils don’t usually gain access to the brain parenchyma due to the glia limitans, a thick mesh of astrocytic processes joined by dense junctions; therefore, brain abscesses are only a rare complication.Case 503 Tay-Sachs diseaseA mother brought her 3-month-old son to the pediatrician because he as been alternately crying inconsolably or lying down listlessly. He has also been vomiting for the last 3 days and has a mild fever. Physical exam reveals cherry red maculas. CSF analysis shows elevated protein levels. Gene sequencing reveals a mutation in the ?-subunit of hexosaminidase A. Summary of clinical findings: This ophthalmic exam shows a “cherry red” macula. Electron micrograph findings: These are cytoplasmic inclusions full of layered membranes.503-1.?What is the differential diagnosis?Answer: Tay Sachs disease, Sandhoff disease, Leigh syndromeGaucher disease, Metachromatic leukodystrophy503-2.?This disease is classified as which of the following?GlycogenosisMucopolylipidosisMucopolysaccharidosisSphingolipidosisSulfatidosis?503-3.?Which of the following is true regarding this disease?Boys are affected more commonly than girlsMost patients recover full neurological function in their teensThe “cherry red macula” is due to retinal hemangiomasThere is an increased incidence in Ashknazi JewsThese patients are at increased risk for colon cancer ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download