Clinical Characteristics and Treatment Outcome of Eosinophilic Meningoencephalitis in South Indian Children: Experience From a Prospective Registry.

BACKGROUND: To describe the clinical features and therapeutic outcomes of a prospective cohort of children with eosinophilic meningoencephalitis. METHODS: Children admitted with clinical features suggestive of meningitis along with cerebrospinal fluid (CSF) eosinophilia during the period of 14 years (2008 to 2021) were included. Their baseline characteristics, epidemiologic associations, and treatment outcomes were analyzed and compared with the previous studies. RESULTS: We identified 25 children (13 males) satisfying the inclusion criteria. The median age at presentation was 3.9 years (range 0.8 to 17 years); 68% were aged less than two years. Fourteen (56%) children had a history of exposure to snails. Most of them presented with fever, headache, irritability, lateral rectus palsy, and early papilledema. Symptoms started three to 42 days (median duration: 14 days) before admission to our center. All children had peripheral eosinophilia, which ranged from 9% to 41%. The mean CSF white blood cell count was 416/mm3 (range 50 to 1245 cells/mm3) with CSF eosinophilia ranging from 11% to 80%. Brain magnetic resonance imaging was done in 24 children and was normal in 15 (62.5%). Leptomeningeal enhancement was seen in two (8.3%) children, and other nonspecific changes were noted in seven (29.1%) children. All children recovered without any neurological deficits with a standard treatment regimen of albendazole and oral steroids. All were asymptomatic at the last follow-up. None of them had any recurrence during the follow-up period. CONCLUSION: We report one of the largest clinical series of children with eosinophilic meningoencephalitis from an endemic area of South India.

Novel biallelic variants expand the SLC5A6-related phenotypic spectrum.

The sodium (Na+):multivitamin transporter (SMVT), encoded by SLC5A6, belongs to the sodium:solute symporter family and is required for the Na+-dependent uptake of biotin (vitamin B7), pantothenic acid (vitamin B5), the vitamin-like substance α-lipoic acid, and iodide. Compound heterozygous SLC5A6 variants have been reported in individuals with variable multisystemic disorder, including failure to thrive, developmental delay, seizures, cerebral palsy, brain atrophy, gastrointestinal problems, immunodeficiency, and/or osteopenia. We expand the phenotypic spectrum associated with biallelic SLC5A6 variants affecting function by reporting five individuals from three families with motor neuropathies. We identified the homozygous variant c.1285 A > G [p.(Ser429Gly)] in three affected siblings and a simplex patient and the maternally inherited c.280 C > T [p.(Arg94*)] variant and the paternally inherited c.485 A > G [p.(Tyr162Cys)] variant in the simplex patient of the third family. Both missense variants were predicted to affect function by in silico tools. 3D homology modeling of the human SMVT revealed 13 transmembrane helices (TMs) and Tyr162 and Ser429 to be located at the cytoplasmic facing region of TM4 and within TM11, respectively. The SLC5A6 missense variants p.(Tyr162Cys) and p.(Ser429Gly) did not affect plasma membrane localization of the ectopically expressed multivitamin transporter suggesting reduced but not abolished function, such as lower catalytic activity. Targeted therapeutic intervention yielded clinical improvement in four of the five patients. Early molecular diagnosis by exome sequencing is essential for timely replacement therapy in affected individuals.

New Onset Focal Seizure Clusters in Children: Expanding the Spectrum of Anti NMDAR Encephalitis.

INTRODUCTION: Anti-N-methyl-d-aspartate receptor (Anti-NMDAR) Encephalitis classically presents with polysymptomatic presentation of behavioral or cognitive changes, seizures, and focal deficits. Large series in adults and children have described the above features. Monosymptomatic presentation of Anti NMDAR encephalitis is rare and in literature single case reports in adults and children are available. Here we report a series of 6 children presenting with seizure alone and thus expanding the clinical spectrum of Anti NMDAR encephalitis. MATERIALS AND METHODS: This is a a retrospective case series of 6 cases of anti NMDAR encephalitis treated in our institute, which is a tertiary referral center between 2010 and 2014. All the patients with NMDA encephalitis were initially included. The baseline demographics, clinical presentations, investigations (CSF, MRI and EEG), course in the hospital, details of treatment, short and long term outcomes were documented from the available medical records. Children presenting with monosymptomatic seizure clusters were only included in the final analysis. RESULTS: Twenty eight children were diagnosed with ant NMDA R encephalitis during the study period. 22 children had classical polysymptomatic presentations and were not included in this analysis. The remaining 6 children (5 girls and one boy), who presented with only acute seizure clusters were included in the study. All children presented with acute cluster of focal seizures. Four out of six had focal status epilepticus while 2 out of six had recurrent focal seizures. Commonest semiology was clonic seizure in 4/6 and one child had dystonic seizure and one had tonic seizure. All patients were started on steroids and antiepileptic drugs. No other immunomodulators or immunosuppressants were used. On discharge all patients where seizure free and with no focal deficits. CONCLUSION: This is the first series of Anti NMDAR encephalitis presenting as new onset seizure clusters in children. Unlike the existing literature, these children did not develop any other symptoms. We propose that focal encephalitis could be the reason for this monosymptomatic presentation.

Two South Indian Children with KCNT1-Related Malignant Migrating Focal Seizures of Infancy - Clinical Characteristics and Outcome of Targeted Treatment with Quinidine.

KCNT1 gene encodes a sodium-gated potassium channel subunit that plays an important role in regulating excitability in neurons. Quinidine is a partial antagonist of this channel. We report the clinical characteristics of two south Indian children with KCNT1-related epileptic encephalopathy. Both of them had very high seizure burden which were resistant to antiepileptic and dietary therapy. Pharmacological response to quinidine in these children is described. Case 1 had 30% reduction in seizure burden at 20 mg/kg/day and 80% reduction at 36 mg/kg/day; case 2 had 30% reduction at 20 mg/kg/day. Serial electrocardiography was used to monitor the cardiotoxicity. Serum quinidine levels were not measured due to nonavailability. A critical review on the current status of targeted treatment of KCNT1-related epileptic encephalopathies with quinidine is attempted.

Mineralizing Angiopathy of Lenticulostriate Arteries with Infantile Basal Ganglia Infarct Following Minor Head Trauma: A Case Series.

Acute arterial ischemic stroke after minor head trauma has been reported in the past, mostly in infants. Most of these affected children had basal ganglia infarct on imaging. Investigations for other etiologies of stroke were noncontributory in most of the cases. Thin-slice computed tomography scan may show mineralizing angiopathy of lenticulostriate arteries. We report a clinical series of four infants who presented with the classical features of this distinct clinico-radiological entity. Clinical characteristics and risk factors at the time of stroke were described in detail. The long-term outcome on standard antiplatelet therapy is reported. None of the children had stroke recurrence during follow-up. The current literature on this clinico-radiological syndrome is reviewed in detail. In the typical cases, extensive etiological workup may not be warranted.

Delayed Orthostatic Hypotension: A Pilot Study from India.

INTRODUCTION: Orthostatic hypotension is defined as a sustained decrease in systolic blood pressure of 20 mm Hg or a decrease in diastolic blood pressure of 10 mm Hg within three minutes of standing compared with blood pressure from the sitting or supine position or by head-up tilt-table testing (1). When sustained blood pressure (BP) drop is after three minutes of upright posture it is called delayed orthostatic hypotension (delayed OH) (2). AIM OF THE STUDY: To detect the incidence of delayed orthostatic hypotension in patients referred to our autonomic lab. MATERIALS AND METHOD: BP was measured noninvasively at 1-minute intervals with an automated cuff sphygmomanometer over the right brachial artery for 45 minutes. The onset and duration of falls in blood pressure either systolic or diastolic or both were documented, and any associated symptoms were recorded. Only patients with sustained falls in BP were included. Drugs causing OH was stopped 48 hours before testing as per protocol followed in lab. We also looked into other autonomic function test abnormalities in patients with delayed OH. INCLUSION CRITERIA: Patients above age of 18 years referred for evaluation of autonomic function tests. EXCLUSION CRITERIA: Patients with severe cardiac failure and cardiac arrhythmias were excluded and patients with rapid fall in BP and bradycardia (Neurally mediated syncope) were excluded. RESULTS: Total 170 patients underwent tilt table testing. Orthostatic hypotension was seen within 3 minutes in seventy patients, fifty patients had delayed OH (BP fall after 3 minutes). There were twenty seven males and twenty three females in this group. Twenty nine of the 50 patients with delayed orthostatic hypotension, had symptoms during the tilt table procedure. Asymptomatic OH was more common in patients who developed OH after 10 minutes. CONCLUSION: This is a pilot study, first in India where we looked into the incidence of delayed orthostatic hypotension in patients undergoing tilt table testing in our autonomic lab. We found that fifty patients had delayed orthostatic hypotension which could have been missed on clinical evaluation. High clinical suspicion is needed to detect this disorder and tilt table testing should be done in suspicious cases since orthostatic hypotension is cause of high morbidity.

Hyperphosphatasia with Mental Retardation Syndrome Due to a Novel Mutation in PGAP3.

Hyperphosphatasia with mental retardation syndrome is a heterogeneous genetic condition. Two siblings aged 5 years and 3 years were evaluated for global development delay and facial dysmorphism. A novel missense variant, c.851A>G (p.H284R, NM_033419.3), in PGAP3 was identified using whole-exome sequencing. Assays for elevated alkaline phosphatase and exome sequencing can be useful for the diagnosis of hyperphosphatasia with mental retardation syndrome.

Clinical profile and treatment outcome of febrile infection-related epilepsy syndrome in South Indian children.

PURPOSE: To describe the clinical features and outcome of febrile infection-related epilepsy syndrome (FIRES), a catastrophic epileptic encephalopathy, in a cohort of South Indian children. MATERIALS AND METHODS: We performed a retrospective chart review of a cohort of children with previously normal development who presented with status epilepticus or encephalopathy with recurrent seizures following a nonspecific febrile illness during the period between January 2007 and January 2012. They were divided into two groups super refractory status epilepticus (SRSE) and refractory status epilepticus (RSE) depending on the duration and severity of the seizures. KEY FINDINGS: Fifteen children who met the inclusion criteria were included for the final analysis. The age of the children at presentation ranged 3-15 years (median 6.3 years). All the children presented with prolonged or recurrent seizures occurring 1-12 days (median 4 days) after the onset of fever. Eight children had SRSE while seven children had refractory seizures with encephalopathy. Cerebrospinal fluid (CSF) analysis was done in all the children in the acute phase, and the cell count ranged 0-12 cells/µL (median 2 cells/µL) with normal sugar and protein levels. Initial neuroimaging done in all children (MRI in 10 and CT in 5), and it was normal in 13 children. Treatment modalities included multiple antiepileptic drugs (AEDs) (4-9 drugs) (median 5 drugs). Midazolam (MDZ) infusion was administered in seven patients. Eight patients required barbiturate coma to suppress the seizure activity. The duration of the barbiturate coma ranged 2-90 days (median 3 days). Steroids were used in 14 children and intravenous immunoglobulin (2 g/kg) in 7 children. Three children died in the acute phase. All children were maintained on multiple AEDs till the last follow-up, the number of AEDs ranged 1-6 (median 5 AEDs). The patients with super refractory status in the acute phase were found to be more severely disabled at the follow-up; the median score of these patients on the Glasgow Outcome Scale (GOS) was 2 compared to 5 in the RSE group. SIGNIFICANCE: This study reports one of the largest single center cohorts from India, with an adverse long-term developmental and seizure outcome. The duration and severity of seizures in the acute period correlated directly with the short-term and long-term clinical outcomes. There is an urgent need for developing new effective therapeutic strategies to treat this acute catastrophic epileptic syndrome.

Clinical Characteristics and Follow-up of South Indian Children with Autoimmune Encephalopathy.

OBJECTIVE: To describe the clinical characteristics of a cohort of south Indian children with probable autoimmune encephalopathy from a tertiary care academic hospital and to compare this data with the existing literature. METHODS: Patients with encephalopathy plus one or more of neuropsychiatric symptoms, seizures, movement disorder or cognitive dysfunction were identified. Common infectious causes were excluded. Clinical characteristics, investigations, management and outcome were analyzed. RESULTS: Thirteen patients were included in the study; 12 were females (92.3 %) and mean age was 9.6 y. Most common presentation was behavior change (13 patients) followed by seizures (11 patients). Three patients showed lymphocytic pleocytosis in CSF and one patient had oligoclonal bands. Initial MRI was normal in all patients except in one. Most common EEG abnormality was mild background slowing. Only one child had ovarian tumor. S.NMDA receptor antibody was positive in 10 patients (83 %), and all of them received immunotherapy. Six out of 13 children were followed up for more than 1 y (mean - 21 mo). Recurrence was noted in 4 out of 6 patients (66 %). On last follow-up, good recovery was seen in 2 children (33 %), moderate disability in 3 (50 %) and severe disability in 1 (16 %). CONCLUSIONS: The clinical characteristics and outcome of one of the largest single center cohort of Indian children with autoimmune encephalopathy is reported. Autoimmune encephalopathy should be considered as a differential diagnosis in the acute and subacute encephalopathies of childhood and treating pediatrician should be aware of this entity.

Seizure outcome following primary motor cortex-sparing resective surgery for perirolandic focal cortical dysplasia.

OBJECTIVES: We present a case series of patients who underwent perirolandic resection for medically refractory focal epilepsy due to focal cortical dysplasia (FCD). Our aim was to specifically evaluate the outcome of a surgical strategy intended for seizure freedom while preserving primary motor cortex function. MATERIALS AND METHODS: Thirteen patients undergoing perirolandic resection for pharmacoresistant focal epilepsy between 2010 and 2015 who demonstrated histological evidence of FCD were selected from a prospectively maintained database. Presurgical evaluation included video EEG telemetry and 3T MRI brain for all patients. Eight patients underwent interictal FDG PET scan. Intracranial EEG monitoring was done for 8 patients - six by conventional subdural grid and depth electrodes and two by Stereo EEG. Additional techniques included extraoperative cortical stimulation mapping, intraoperative electrocorticography (ECoG), intraoperative motor cortex mapping and awake surgery in various combinations. In all cases (lesional and nonlesional), resection was intentionally limited for anatomic preservation of the primary motor cortex. RESULTS: Amongst the thirteen patients with age ranging 14-44 years (mean 26.8 ± 9.2) 62% of them had daily seizures. MRI abnormalities were identified in 8 patients (62%), PET showed concordant findings in 7 patients (88%). When utilized, the mean duration of intracranial EEG recordings was 8.0 ± 7.2 days (range 2-23 days). All patients underwent a primary motor cortex-sparing resection of the suspected epileptogenic cortex. The mean postoperative follow up period was 23 months (range 7.5-62 months). Twelve out of 13 (92%) were seizure free (Engel 1) outcome at the last follow-up assessment; one patient had Engel 2a outcome at 28 months. Six patients (46%) had immediate new focal neurological deficits, however all six patients had recovered completely within three months. CONCLUSION: The surgical strategy of a primary motor cortex-sparing resective surgery for perirolandic FCD is associated with an excellent early seizure-freedom rate and no permanent neurological deficits. Since the ultimate goal of resective epilepsy surgery is seizure freedom with simultaneous functional preservation, similar long term outcome studies should ultimately guide the resection strategy.

Idiopathic intracranial hypertension in pediatric population: case series from India.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a well described entity in adults. In pediatric age group the presentation of disease can vary depending on the age of patients and is less frequently reported. AIM: The aim of this study is to describe the clinical features, investigations, treatment and outcome of IIH in pediatric population (age <18 years). MATERIALS AND METHODS: This retrospective hospital based study was carried out on 25 children with diagnosis of IIH based on modified Dandys criteria. Their clinical, investigation, treatment, outcome and follow-up for 2 year period were analyzed. RESULTS: Out of the 25 children, the youngest child was 4-month-old infant. The commonest symptom was headache (76%) followed by vomiting and papilledema (72%). The mean cerebrospinal fluid (CSF) pressure was 330 mm of H 2 O. In Infants irritability and bulging anterior fontanelle was seen. A total of 24 patients showed a complete resolution of symptom. None of patient had recurrence over a period of 2 years follow-up. CONCLUSION: IIH can present at any age group. This is the largest series of IIH reported in pediatric population in India. The clinical features are similar to adult patients except in infants. Absence of papilledema does not exclude the diagnosis of IIH. CSF pressure monitoring is needed in suspected cases of IIH. Early and prompt treatment can prevent deficits.

Diabetic neuropathy: rare presentation as a painful pseudoabdominal mass.

Diabetic neuropathy has varied clinical presentations. As clinicians we should be aware of the common as well as rare manifestations of this syndrome. Diabetic truncal neuropathy presenting as a painful pseudoabdominal mass can easily mislead clinicians who are unaware of this problem. Subsequently, this can lead to unnecessary investigations and discomfort to the patient. A good blood sugar control and judicious use of drugs for neuropathic pain along with physiotherapy usually gives good relief. It is mostly a self-limiting condition.