Neurology: Neuroimmunology & Neuroinflammation



Supplemental material for :Acute seroconversion to Sandfly Virus in Jerusalem, Israel, is associated with Neurological presentation including Myelitis and Basal-Ganglia involvementChen Makranz*1, Hiba Qutteineh*2, Hanna Bin3, Yaniv Lustig3, John Moshe Gomori4, Asaf Honig1, Abed El-Raouf Bayya5, Allon E. Moses6, Tamir Ben-Hur1, Diana Averbuch2, Roni Eichel1, Ran Nir-Paz6Departments of, 1Neurology, 2Pediatrics, 4Radiology, 5Medicine and 6Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical center.3Israel Central Virology Lab, Ministry of Health, Tel Hashomer, Israel.* Equal contributionTable e-1 detailed characteristics of patients:Patient numberAHEP3 - SA4 - DM5 - LA6 - HB7- OR8- AS9 -LHCommentsDate of admission26.10.111.11.1119.10.1123.10.112.7.109.4.1213.5.1125.1.1219.4.13?AGE (years)2885482612641.5151.5?Chief complaint/ reason for admissionAcute confusional state with feverAcute vertigo with unconscious episode and suspected convulsionAcute confusional state with feverConvulsions with feverAcute encephalopathy and feverHeadache confusional state and feverFever and suspected meningitisSudden onset of quadriparesisAcute facial myoclonus and feverMedical historyNo medical historyAF, CHF, Hyperlipidemia, BPH, TIACirrhosis, DM, HTNSchizophreniaRec UTIHTN, HyperlipidemiaNo medical historyNo medical historyPrematurity 36w, twin?Clinical features at presentation and during admissionTime from onset to presentation (days)311132111?HeadacheYesNoYesNoNoYesunavailableNounavailable?MeningitisYesNoYesNoYesNoYesNoNo?Behavioural change/Psychiatric presentaionYes (apathy, violence, confuisional state)NoYes (confusional state)Yes (suicide attempt)Yes (sleepiness, decreased consciousness)Yes (confusion)Yes sleepiness decreased consciousness NoApathy (apeared later)?EncephalitisYesNoYesYesYesYesYesNoYes (2w)?SeizuresNoYesYesYesYesNon-convulsive epileptogenic activity on EEGYesNoYes (focal right face)?Plegia/Paresisflaccid tetraparesisNoNoTriplegia followed by tetraplegiaTetraparesisNoNoTetraplegia– rapidly progressiveRt hemiparesis?Respiratory failureA few days after presentation (weakness of respiratory muscles)Yes (due to convulsions andYesYes (ARDS & Vocal cord paralysis)NoNo (RML nodule)NoYes (2th day of admission) - LLL pneumoniaNo?MyelitisYes: ascending myelitis after 7-14 daysNoNoYes – after 15 daysYes(clinically)NoNoYes – on presentation (transverse myelitis?)No?OpsitotonusYesNoNoNoNoNoNoNoNo?Admission and outcomeDuration of admission (days)3011303031811890 Resolution of illnessComplete after rehabilitationCompleteNACompleteRehab – has spastic gait Short term memoryComplete after rehabilitation had retinal vasculitisNAPermanent brain damage with rt hemiparesis and uncontrolable seziures Labs and ObjectivesFever (oC)Yes (38)No(36)NoYes(38.3)Yes (38.7)Yes (38.4)Yes (39.2)NoYes (38)?Blood pressure130/71150/70139/79116/68105\5996/60101/54200/100à144/77110\70?WBC (cell/mm3)1280075004900116006001600183001840017400?PMN (%)22.40%7.30%15.10%10.10%24.80%81.90%40%88.20%73%?LYM (%)60.20%84.70%76.20%80.80%67%12.10%51.70%5.20%20.10%?Lumbar punctureLP-PMN (cell/mm3)26NANA000004?LP-Lymphocytes(cell/mm3)103NANA348125102LP-Protein (g\l)1416NANA1441002793135279166?LP-glucose (mmol/l)2NANA334453.8?EEGDay 6 - NormalDay 1 – Intermittent slow wave activity (5-6Hz),frontotemporal bilateral (R>L)Day 3 – Periodic triphasic waves, compatible with metabolic encephalopathyArtifacts – not interpretativeNormal (day 1)Day2 – Spike and wave maily left sidedNANANormal--> encephalopathy--> delta and theta discharges , bilateral frontal discharges which may be compatible with epileptic activities??Day 7 - Delta wave encephlopathy?Day 5- Slow wave teta & delta activity (more pronounced on frontal areas)??After 1 month : Series of rhythmical activity more on the left side????Brain CTLeptomeningeal enhancementAtrophyNormalNormalNormalNormalNormalNormalNot done?Brain MRILeptomeningeal enhancement+splenium lesion with restricted diffusion (toxic/viral/unspecified).NANAMinimal restricted diffusion of BG (head of caudate and putamen, bilatrela and symmetrical) on T2 and DWI + Enhancement of anterior hypocampus on FLAIR (post seizure)Restricted diffusion of putamen n, caudate and upper brain stem (symetrical)+minimal pial enhancementBilateral nonenhancing hyperintense T2 and Flair foci involving the centrum, periventricular and subcortical regions (mosy likely represent sequela of previous microvascular pathology)Enhanced lesion with no gadolinium in the subcortical white matter, posterior capsula interna and capsula externaNABifrontal restricted diffusion, more on the left, without enhancement --> extension of signal changes to temporal and periinsular regions --> The non enhancing lesions have undergone atrophic changes??Follow-up MRI 10 days later – resolution of splenium lesion + new enhancement of BG and medial thalamus (bilateral and symmetrical)?????????Spinal MRIAanterior longitudinal enhancement of whole cervial spinal cord through the medula on T2 and T1 with gadulinum (white and gray matter)NANAT3-5 compressed fracture without spinal cord compression + upper cervical cord linear enhancement (white and gray matter without medulla involvementNANANAC2-C5 lesion on Flair, hyperintense on diffusion, hypointense in ADCNA?Serum 1 - Days from admission155111634112nd confirmational assay resultsToscana?√ IgM√ IgM√ IgG+IgM√ IgM√ IgM√ IgM√ IgG√ IgG?Naples?√ IgG√ IgM???√ IgM√ IgG√ IgG?Cyprus ?√ IgG√ IgM?√ IgM?√ IgM?√ IgG?sicily√ IgG√ IgG+IgM??√ IgM√ IgG+IgM√ IgM?√ IgG?Serum 1 IgM titer (dilution of 1:x)101010101010201010?Serum 1 IgG titer (dilution of 1:x)101010101010201010?Serum 2 - dayes from admission129271419141216142nd confirmational assay resultsToscana?√ IgG+IgM√ IgG+IgM√ IgM√ IgG+IgM√ IgG+IgM√ IgG+IgM√ IgG+IgM√ IgG+IgM?Naples√ IgG+IgM√ IgG√ IgG+IgM√ IgG+IgM√ IgG+IgM?√ IgG+IgM√ IgG√ IgG+IgM?Cyprus √ IgG+IgM√ IgG+IgM√ IgG+IgM√ IgM?√ IgG+IgM√ IgG+IgM√ IgM√ IgG+IgM?sicily√ IgG√ IgG√ IgG+IgM??√ IgG+IgM√ IgG+IgM√ IgM√ IgG+IgM?Serum 2 IgM titers (dilution of 1:x)1020404020106010100?Serum 2 IgG titers (dilution of 1:x)10320404020102010100?Figure e-1 Demonstrative Sandfly virus IFA assays:Control IFA assay-356870113665Negative controlPositive control IgMPositive control IgG00Negative controlPositive control IgMPositive control IgG885825295275IgGIgMSample ISample II00IgGIgMSample ISample IIPatient # AS IFA serology for Sandlfy fever Sicilian virus showing seroconversion for both IgM and IgGIFA for Sandlfy fever Sicilian virus demonstrates IgM and IgG antibodies seroconversion. Negative, IgM positive and IgG positive samples (A) as well as 2 serum samples taken from patient #AS (B) and 2 serum samples taken from patient #LH (C) were subjected to Indirect IFT (Euroimmun) to detect IgM and IgG antibodies against Sandlfy fever Sicilian virus. Type of antibodies (IgG and IgM) and sample numbers are indicated.As can be seen in panel B, specific staining in the cells cytoplasm is observed in sample II, but not in sample I for both IgM and IgG, indicating IgM and IgG seroconversion. Since only some of the cells on the slide are infected by Sandlfy fever Sicilian virus (according to the Euroimmune IFT protocol), not all of the cells are stained. Panel C shows specific staining in sample II only for IgM and not IgG, suggesting IgM seroconversion.842645297180IgGIgMSample ISample II00IgGIgMSample ISample IIPatient # LH IFA serology for Sandlfy fever Sicilian virus showing seroconversion in IgM ................
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