Clinical characteristics, treatment and long-term prognosis in patients with anti-NMDAR encephalitis.

OBJECTIVES: We aimed to (i) analyse the clinical characteristics, treatment outcome and long-term prognosis of anti-NMDAR encephalitis and (ii) study the differences between paediatric and adult patients. METHODS: This was a chart review of all patients with anti-NMDAR encephalitis. RESULTS: There were 28 patients with 18 patients belonging to the paediatric (<18 years) age group. There was female (94%) preponderance in the paediatric age group, while in adult patients, there was no gender predilection (p=0.006). There was no significant difference in clinical feature, outcome or number of relapses between paediatric and adult population groups. MRI brain was abnormal in 53% of patients. Among the 15 patients with MRI abnormalities at the onset, 53% had poor functional outcome at 1 year, while in 12 patients with normal initial MRI brain, only 8% had poor functional outcome at 1 year (p =0.01). Nearly 53% of patients with abnormal MRI at presentation had at least one clinical relapse within 2 years while in patients with normal MRI at presentation, 15% had a clinical relapse (p=0.037). EEG abnormalities were noticed in 71% of patients; among them, 40 and 15% had poor functional outcome at 1 and 2 years respectively. In comparison, those with normal first EEG at onset, 12% had poor functional outcome at 2 years (p=0.57). CONCLUSIONS: Both paediatric and adult patients presented with similar clinical features but the paediatric population had female preponderance. The functional outcome and number of relapse were comparable in both the paediatric and adult groups. Patients with parenchymal changes on MRI and abnormal EEG showed poorer response compared to those with normal MRI and/or EEG at the onset. Patients have lesser severity of symptoms at relapse than in the first episode. An early diagnosis and treatment are essential for better long-term functional outcome.

Neuronal Intranuclear Inclusion Disease: A Rare Etiology for Rapidly Progressive Dementia.

INTRODUCTION: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder pathologically characterized by localized neuronal loss, and presence of eosinophilic intranuclear inclusions in neurons and glial cells. CASE REPORT: A 50-year-old man presented with rapidly progressive dementia, behavioral changes, gait disturbances, and incontinence of 3 months duration. His brain magnetic resonance imaging showed diffuse T2/FLAIR hyperintensity of basal ganglia, thalami, cerebral peduncles, ventral pons, and supratentorial white matter with a frontal predominance. Hyperintensity was noted along the corticosubcortical junction on diffusion-weighted images. NIID was suspected and the patient underwent triple biopsy of the sural nerve with adjacent skin and biceps biopsy. Biopsy revealed ubiquitin-positive intranuclear inclusions surrounding the myofibers, and vascular smooth muscles suggestive of NIID. CONCLUSIONS: NIID is a rare neurodegenerative disorder usually diagnosed postmortem. The rectal and skin biopsy had proved helpful in antemortem diagnosis. We have increased the diagnostic armamentarium by showing the presence of intranuclear inclusions in smooth muscle cells of the muscle. Hence, a high degree of suspicion, magnetic resonance imaging features, with nerve/muscle/skin biopsy can help in diagnosis of NIID.

A Real-World Experience of Rituximab: A Panacea in Therapy of Multiple Sclerosis in Low- and Middle-Income Setting.

BACKGROUND: Anti-CD20 monoclonal antibodies have received increasing attention in the past few years in the treatment of multiple sclerosis (MS). OBJECTIVES: This study describes the (i) efficacy and safety of rituximab in people living with MS and (ii) assesses clinical and imaging outcomes following rituximab in MS. METHOD: This is a chart review from the MS registry maintained at the institute from a University Hospital in South India. RESULT: Eighty-three (M:F, 26:57) people living with MS received rituximab as immunomodulation between 2007 and 2022 with a median follow-up duration of 18 months. Fifty-nine (71%) were classified as relapsing-remitting MS, 16 (19%) were secondary progressive MS, and 8 (10%) were primary progressive MS. Seventy-two (87%) MS patients did not experience any relapse after receiving rituximab. In relapsing-remitting MS patients, the mean annualized recurrence rate dropped from 1.24 ± 1.19 to 0.16 ± 0.37. Infusion-related reaction occurred in 5 (6% of adverse events), urinary infections in 7 (8.4%), systemic infections in 3 (3%), Pneumocystis carinii pneumonia occurred in 1 (1%), and herpes zoster infection in 1 (1%) patient. Mortality was observed in 3 (3.5%) patients. While being on rituximab, 18 (22%) patients had mild COVID-19 illness and they all made complete recovery without any sequalae. CONCLUSIONS: Rituximab is a safe, well-tolerated, easily accessible, inexpensive, and effective therapeutic option for people with MS. Rituximab showed both clinical and radiological improvement after a median follow-up of 1.5 years. None of our patients showed any severe COVID infection nor side effects after receiving COVID vaccination.

Carbon dioxide induced cerebral vasomotor reactivity in moderate-to-severe cerebral venous thrombosis patients and its impact on prognosis: A transcranial doppler-based prospective exploratory study.

Hyperventilation-induced intracranial pressure reduction might be impaired in cerebral venous thrombosis (CVT) patients. Using transcranial Doppler, we assessed carbon dioxide-vasomotor reactivity (CO2-VMR) within 24 hours of admission in CVT patients and studied its correlation with patient outcomes. Adult moderate-severe CVT patients (participants of another large observational study) were included. CO2-VMR was calculated as the percentage change in peak flow velocities during maximal hypercapnia and hypocapnia. Outcome was assessed with the modified Rankin scale (mRS) at one - month post-discharge, dichotomized into favourable (mRS≤2) and unfavourable (mRS>2). Twenty patients' data was analysed. Impaired CO2-VMR (<70 %) was observed in 13 patients in the affected hemisphere; among them, 10 had impairments in both hemispheres. CO2-VMR correlated negatively with mRS (Rho = -0.688, p = 0.001). Odds for unfavourable outcomes were reduced by 92 % in patients with intact VMR on the ipsilateral hemisphere (Odds ratio (OR) 0.08, Confidence interval (CI) 0.006---0.636, p = 0.027) and by 94 % with VMR intact on the contralateral hemisphere (OR 0.063, CI 0.003---0.569, p = 0.03). Thus, impaired CO2-VMR in moderate to severe CVT patients is associated with unfavourable outcomes, and has the potential to prognosticate CVT patients objectively.

Spinal melanoma with optic neuropathy -rare manifestation of Neurocutaneous melanosis and PET-MRI findings.

Neurocutaneous melanocytosis (NCM) is a rare, sporadic neuroectodermal dysplasia characterized by the presence of large or multiple congenital cutaneous nevi and melanocytic deposits in the central nervous system. Hitherto, unreported we describe a case of NCM with optic neuropathy and spinal cord melanoma from India. A 20 year-old-lady had headache and vomiting for 3 months followed by consecutive profound painless visual impairment. Visual acuity was counting of fingers at 1 m distance in both eyes with normal fundus. There were no symptoms of spinal cord involvement. Clinical examination showed multiple small to large melanocytic nevi over the face and body. Muscle power was normal. Tendon reflexes were exaggerated. Visual evoked potential showed bilateral prolonged P100 latency (Right eye - 144 msec; Left eye - 151 msec). Brain MRI revealed leptomeningeal enhancement of brainstem, cerebellum, oculomotor and facial-abducent nerve complex without optic nerve involvement. MRI spine showed extensive dorsal thoracic cord epidural lesion extending along the entire thoracic cord segment with dorsal cord compression. Positron Emission Tomography (PET) imaging showed Fludeoxyglucose F18 (FDG) avidity along D1-D12 levels of spinal cord. Biopsy from the cord lesion was suggestive of meningeal melanoma. Here we document a rare case of late onset NCM with intracranial meningeal infiltration and asymptomatic large epidural lesion of spinal cord, expanding its phenotypic spectrum. Optic neuropathy in NCM has not been reported earlier. Periodic screening of brain and spine is recommended for early prognostication and lesion identification in NCM.

Bing Neel syndrome presenting as isolated cranial nerve palsies - a case report.

Background and aims: Waldenstroms macroglobulinemia (WM) is a low-grade B cell neoplasm. Bing Neel syndrome is a rare manifestation of WM characterized by infiltrative involvement of the central nervous system. Case report: 64-year-old man, presented with 4 years history of slowly progressive diplopia and ptosis of eyes. Examination showed left oculomotor (internal and external ophthalmoplegia), with trochlear, abducens, and right partial oculomotor and abducens nerve involvement. Evaluation showed anemia of hemoglobin 10.7 g/dL, raised erythrocyte sedimentation rate of 120 mm/h and plasma albumin:globulin reversal. Serum protein electrophoresis showed a paraprotein peak in the early gamma region with elevated IgM level (3810 mg/dL) and elevated free kappa light chain level (70.1 mg/L). Bone marrow aspiration from posterior iliac crest revealed mature small lymphocytes with positive immunohistochemical markers of CD5, CD10 negativity and MYD88 mutation positivity suggestive of WM. Patient was treated with bendamustine and rituximab regimen, with no neurological improvement at the end of one year. Conclusion: This case expands spectrum of paraproteinemic neuropathy to include cranial nerve palsy. Thus, plasma cell dyscrasias have to be considered in patients with isolated ophthalmoparesis especially in elderly patients, even with other comorbidities such as diabetes mellitus.

Adult Onset Episodic Encephalopathy Due to Citrin Deficiency-A Case Report.

Hyperammonemia is a rare cause of adult episodic encephalopathy. Citrin deficiency resulting in citrullinemia type 2 (CTLN2) can lead to recurrent delirium in adults. Here we report a case of adult onset episodic encephalopathy due to citrin deficiency. A 40 years old male presented with one-year history of episodic encephalopathy triggered by high protein and fat diet. He also had chronic pancreatitis and subacute intestinal obstruction which is a novel manifestation of CTLN2. Evaluation showed elevated blood liver enzymes, ammonia, and citrulline. MRI brain showed frontal hyperintensities and bulky basal ganglia which have not been reported. Diagnosis was confirmed by next-generation sequencing which showed a novel variant c. 1591G > A in exon15 of SLC25A13. Hyperammonemic syndromes should be considered in differential diagnosis of episodic encephalopathy in adults. This report shows novel features of subacute intestinal obstruction and MRI findings in CTLN2 expanding spectrum of manifestation.

Co-VAN study: COVID-19 vaccine associated neurological diseases- an experience from an apex neurosciences centre and review of the literature.

BACKGROUND: Recent studies have shown various neurological adverse events associated with COVID-19 vaccine. OBJECTIVE: We aimed to retrospectively review and report the neurological diseases temporally associated with COVID-19 vaccine. METHODS: We performed a retrospective chart review of admitted patients from 1st February 2021 to 30th June 2022. A total of 4672 medical records were reviewed of which 51 cases were identified to have neurological illness temporally associated with COVID-19 vaccination. RESULTS: Out of 51 cases, 48 had probable association with COVID-19 vaccination while three had possible association. Neurological spectrum included CNS demyelination (n = 39, 76.5 %), Guillain-Barré-syndrome (n = 3, 5.9 %), stroke (n = 6, 11.8 %), encephalitis (n = 2, 3.9 %) and myositis (n = 1, 2.0 %). Female gender had a greater predisposition (F:M, 1.13:1). Neurological events were more commonly encountered after the first-dose (n = 37, 72.5%). The mean latency to onset of symptoms was 13.2 ± 10.7 days after the last dose of vaccination. COVIShield (ChAdOx1) was the most commonly administered vaccine (n = 43, 84.3 %). Majority of the cases with demyelination were seronegative (n = 23, 59.0 %) which was followed by anti-Myelin oligodendrocyte-glycoprotein associated demyelination (MOGAD) (n = 11, 28.2 %) and Neuromyelitis optica (NMOSD) (n = 5, 12.8 %). Out of 6 Stroke cases, 2 cases (33.3 %) had thrombocytopenia and coagulopathy. At discharge, 25/51 (49.0 %) of the cases had favourable outcome (mRS 0 to 1). Among six patients of stroke, only one of them had favourable outcome. CONCLUSION: In this series, we describe the wide variety of neurological syndromes temporally associated with COVID-19 vaccination. Further studies with larger sample size and longer duration of follow-up are needed to prove or disprove causality association of these syndromes with COVID-19 vaccination.