Muscle spasms as presenting feature of Nivelon-Nivelon-Mabile syndrome.

Hedgehog acyltransferase gene (HHAT)-associated Nivelon-Nivelon-Mabile syndrome (NNMS) is a rare genetic disorder of multiple system involvement with microcephaly, central nervous system malformations, skeletal dysplasia, and 46,XY sex reversal. Other variable and inconsistent features reported in this disorder are muscle spasms, facial dysmorphism, prenatal onset growth restriction, microphthalmia, and holoprosencephaly. This is the sixth postnatal reported patient with biallelic variants in HHAT gene, who presented with microcephaly, short stature, muscle hypertrophy, muscle spasms, and facial dysmorphism. The most prominent and presenting finding in this patient were muscle hypertrophy and muscle spasms which had a clinical response to phenytoin and acetazolamide treatment. Our report emphasizes the phenotypic variability of NNMS and further reiterates muscle spasms as an important clinical manifestation of this extremely rare condition.

Current practices in epilepsy monitoring units (EMU) in India.

AIM: As an initial step to develop guidelines for epilepsy monitoring units (EMUs) appropriate for developing countries, we inquired the existing practices in EMUs in India. METHODS: After checking for the content and face validity as well for clarity, we sent a 52-item online non-anonymized questionnaire to all the 52 EMUs in India. RESULTS: The questionnaire was completed by 51 of the 52 EMUs (98% response rate). The majority of the EMUs are located in major cities and 51% are located in non-governmental corporate hospitals. There are total of 122 prolonged video-EEG monitoring (PVEM) beds in India and 70% EMUs have ≤2 beds. Approximately two-thirds of the EMUs have defined protocols for pre-procedure consent and risk assessment, management of seizure clusters and status epilepticus, continuous observation of patients, and peri­ictal testing. Only one-third of the EMUs have protocols for management of post-ictal psychosis, anti-suffocation pillows, and protected environment within bathrooms. The waiting period for PVEM is more (49.9 ± 101 vs. 4.9 ± 10.9 days; p = 0.04) and mean cost for 3-day PVEM is less (INR 8311 ± 9021 vs. 30,371 ± 17,563; p <0.0001) in public as compared to private hospitals. There was a negative correlation between cost of PVEM and the waiting period (r=-0.386; p = 0.01). Safety practices are similar in public and private hospitals. CONCLUSIONS: Although practices in EMUs in India vary widely, they are comparable to those in developed countries. India has severe shortage of EMUs and long waiting lists for affordable PVEM.

Impact of COVID-19 pandemic on epilepsy practice in India: A tripartite survey.

OBJECTIVE: To assess the impact of ongoing COVID-19 pandemic on epilepsy care in India. METHODS: We conducted a three-part survey comprising neurologists, people with epilepsy (PWE), and 11 specialized epilepsy centers across India. We sent two separate online survey questionnaires to Indian neurologists and PWE to assess the epilepsy practice, seizures control, and access to care during the COVID-19 pandemic. We collected and compared the data concerning the number of PWE cared for and epilepsy procedures performed during the 6 months periods preceding and following COVID-19 lockdown from epilepsy centers. RESULTS: The survey was completed by 453 neurologists and 325 PWE. One third of the neurologist reported >50 % decline in outdoor visits by PWE and EEG recordings. The cumulative data from 11 centers showed 65-70 % decline in the number of outdoor patients, video-EEG monitoring, and epilepsy surgery. Working in a hospital admitting COVID-19 patients and use of teleconsultation correlated with this decline. Half of PWE had postponed their planned outpatient visits and EEG. Less than 10 % of PWE missed their antiseizure medicines (ASM) or had seizures due to the nonavailability of ASM. Seizure control remained unchanged or improved in 92 % PWE. Half of the neurologists started using teleconsultation during the pandemic. Only 4% of PWE were afflicted with COVID-19 infection. CONCLUSIONS: Despite significant decline in the number of PWE visiting hospitals, their seizure control and access to ASMs were not affected during the COVID-19 pandemic in India. Risk of COVID-19 infection in PWE is similar to general population.

Patterns of peripheral neuropathy in Sjogren's syndrome in a tertiary care hospital from South India.

INTRODUCTION: Sjogren's syndrome (SS) is a systemic autoimmune disease that apart from involving the exocrine glands can affect any organ. Involvement of the peripheral nervous system results in a wide spectrum of neuropathic manifestations. OBJECTIVE: To evaluate the clinico-electrophysiological patterns as well as pathological characteristics of neuropathy in SS patients presenting to a neuromuscular clinic in a tertiary hospital from South India. MATERIALS AND METHODS: This is a retrospective study from the Departments of Neurology, Rheumatology, and Pathology from Nizam's Institute of Medical Sciences. Twenty-one patients with the diagnosis of SS and peripheral neuropathy, seen between 2010 and 2016 were analyzed. Clinical records, conventional nerve conduction studies, and lip and nerve biopsy reports were collected. RESULTS: Twenty one patients with SS had associated neuropathy. Female-to-male ratio was 2:1. In 14 (66.7%) patients, neuropathy was the initial manifestation, while in 4 (20%), exocrinopathy preceded neuropathy. The patterns of neuropathy included mononeuropathy multiplex (MNM) in 7 patients (30%), ganglionopathy in 4 (20%), length-dependant trigeminal autonomic neuropathy, and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in 2 (10%), and cranial neuropathy in 1 (10%). Eighteen (86%) were seropositive with either anti Ro/SS-A or anti La/SS-B antibodies. Schirmer's test was positive in 13 (61.9%) patients. Nerve biopsy showed vasculitis in 5 patients and demyelinating and axonopathy in 2 patients each. CONCLUSIONS: We conclude that neuropathy is frequently the initial presentation of SS. MNM is the most common pattern followed by ganglionopathy. The pattern of neuropathy helps in arriving at the diagnosis of SS. Serology is a useful initial laboratory test. However,confirmation of SS is not by mere serology. Schirmer's test and lip biopsy are equally essential for the diagnosis, especially in seronegative patients when the clinical index of suspicion is high.

Levetiracetam-Associated Psychogenic Non-epileptic Seizures; A Hidden Paradox.

Objectives To study the clinical profile and outcome in patients with epilepsy who developed psychogenic non-epileptic seizures (PNES) associated with levetiracetam (LEV) use.   Methods In this prospective observational study, conducted over 1 year, 13 patients with epilepsy and PNES, documented by video electroencephalogram (VEEG) while on LEV, were included. Those with past history of psychiatric illnesses were excluded. VEEG, high-resolution magnetic resonance imaging, neuropsychological and psychiatric evaluation were performed. Patients in Group I (07) were treated with psychotherapy, psychiatric medications and immediate withdrawal of LEV while, those in Group II (06) received psychotherapy, anxiolytics and LEV for initial 2 months after which it was stopped. Follow-up period was six months. There was subsidence of PNES on discontinuation of LEV in these patients.   Results Mean (±SD) age of patients was 25 ± 12.28 years; there were 11 (84.62%) females. All were on antiepileptic agents which included LEV >1000 mg/day, except one. Mean dose of LEV was 1269.23 ± 483.71 mg/day. Three patient's scores were suggestive of depression or anxiety; one had both depression and anxiety. Eight patients had mood disorders; three had a history of emotional abuse or neglect. PNES subsided within 1-3 months and did not recur after withdrawal of LEV in any patient.   Conclusion LEV can induce PNES in susceptible populations. Awareness of this association is crucial for timely withdrawal of triggering factor and appropriate management. This will reduce inadvertent additional prescription of antiepileptic agents.

Adult-onset Leigh's disease: A rare entity.

Leigh syndrome (LS) is a heterogeneous familial or sporadic neurodegenerative disorder. It is typically seen in infancy or childhood, although rare cases of adult onset have been described. The authors describe a 37-year-old woman who presented with protracted gastrointestinal symptoms followed by acute brain stem syndrome with severe metabolic acidosis and who subsequently showed dramatic clinical and neuroradiological improvement.

Comparison of frequencies of non motor symptoms in Indian Parkinson's disease patients on medical management versus deep brain stimulation: A case-control study.

BACKGROUND: Non motor symptoms (NMS) of idiopathic Parkinson's disease (PD) are a major cause of disability and recognition of these symptoms and treatment is important for comprehensive health care. Deep brain stimulation of bilateral subthalamic nucleus deep brain stimulation (STN DBS) has been shown to improve motor symptoms in PD and effects on NMS are unknown. To investigate the NMS among PD patients who underwent STN DBS. METHODS: We recruited prospectively 56 patients with PD, who had undergone bilateral STN DBS and 53 age and duration of illness matched PD patients on dopaminergic therapy (controls). NMS were assessed using 30 item questionnaire NMS Quest. These questions evaluated 9 domains, gastrointestinal, urinary, cardiovascular, sexual, cognition (apathy/attention/memory), anxiety/depression, hallucinations/delusions, sleep and miscellaneous. Comparison was done on individual symptoms as well as in various domains. This study was carried at Nizam's Institution of Medical Sciences and study period was from January 2011 to December 2012. RESULTS: Patients who underwent STN DBS had a significantly lower mean total score on NMS quest (6.7 ± 3.8) compared to controls (8.4 ± 3.7) (P < 0.00100). Symptoms in the domains of cardiovascular, gastrointestinal, sleep were significantly less frequent while sexual disturbances were significantly more frequent among patients compared to controls. On individual symptom analysis, nocturia  (P < 0.00010), unexplained pains (P < 0.00010), nausea and vomiting, constipation, lightheadedness, depression, and insomnia were less prevalent, while sexual disturbances were significantly more common in STN DBS group compared to controls. CONCLUSION: Bilateral STN DBS not only improves the motor symptoms but also improves many NMS in PD patients.

Fulminant subacute sclerosing panencephalitis presenting with acute ataxia and hemiparesis in a 15-year-old boy.

BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a delayed and fatal manifestation of measles infection. Fulminant SSPE is a rare presentation in which the disease progresses to death over a period of 6 months. The clinical features are atypical and can be misleading. CASE REPORT: We report herein a teenage boy who presented with acute-onset gait ataxia followed by right hemiparesis that evolved over 1 month, with left-hemispheric, delta-range slowing on the electroencephalogram (EEG). Magnetic resonance imaging disclosed multiple white-matter hyperintensities, suggesting a diagnosis of acute disseminated encephalomyelitis. He received intravenous steroids, and within 4 days of hospital admission he developed unilateral slow myoclonic jerks. Repeat EEG revealed Rademecker complexes, pathognomonic of SSPE, and an elevated titer of IgG antimeasles antibodies was detected in his cerebrospinal fluid. The disease progressed rapidly and the patient succumbed within 15 days of hospitalization. The diagnosis of SSPE was confirmed by autopsy. CONCLUSIONS: This case illustrates the difficulty of recognizing fulminant SSPE when it manifests with asymmetric clinical and EEG abnormalities.

Safinamide for the treatment of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease caused by a complex interaction of loss of dopaminergic and non-dopaminergic neurotransmitter systems. Drugs acting on the dopaminergic pathways are the mainstay of treatment for motor symptoms today. Safinamide (NW-1015) is a novel drug with multiple actions. It is a monoamine oxidase B inhibitor and improves dopaminergic transmission. In addition, it has antiglutamatergic effects and can thus reduce dyskinesias, which is a side effect limiting most dopaminergic therapy. In Phase III trials, safinamide has been found to be a useful adjunctive to dopamine agonists in early PD and has been shown to increase time without increasing troublesome dyskinesias when used as an adjunct to levodopa in patients with advanced PD. A possible neuroprotective role in inhibiting PD disease progression is envisaged and warrants future studies.

Primary diffuse leptomeningeal gliomatosis: An autopsy case report.

Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare condition, characterized by infiltration of the meninges by glial cells without evidence of the primary tumor in the brain or spinal cord parenchyma. Glioma arising primarily from the leptomeninges is extremely rare and often diagnosed only in post mortem examination and the diagnosis may be missed in meningeal biopsy. We describe a young female who presented with symptoms of raised intracranial pressure with imaging evidence of diffuse leptomeningeal enhancement in whom autopsy confirmed the diagnosis of PDLG. Our case illustrates the diagnostic difficulties in making the pre-mortem diagnosis even with multiple cerebrospinal fluid cytologies and leptomeningeal biopsy.

Epilepsy with myoclonic absences in siblings.

BACKGROUND: Epilepsy with myoclonic absences (EMAs) is a distinct form of childhood epilepsy characterized by a peculiar seizure type that identifies this condition. PURPOSE: To describe the clinical, electroencephalographic features, treatment strategies and outcome in this first case series of two siblings with normal intelligence presenting with EMAs. MATERIALS AND METHODS: Both siblings underwent video-polygraphic investigations (simultaneous recording of electroencephalogram [EEG] and electromyogram [EMG] from deltoids), high-resolution magnetic resonance imaging (MRI), karyotyping, neuropsychological evaluation and language assessment. RESULTS: Both the children had a mean age of onset of prototype seizures by 3.5 years. Myoclonic absences (MAs) were characterized by rhythmic, bilateral, synchronous, symmetric 3-Hz spike-wave discharges, associated with EMG myoclonic bursts at 3 Hz, superimposed on a progressively increasing tonic muscle contraction. The interictal EEG showed a normal background activity with bursts of generalized spike and waves (SWs) as well as rare focal SWs independently over bilateral temporal and frontal regions. Increase in the seizure frequency from 5 to 100/day was observed due to use of carbamazepine and phenobarbitone which decreased with its withdrawal and introduction of valproate. Though lamotrigine was given as an add on to valproate, it did not benefit them and was therefore replaced by topiramate at 3.5 mg/kg/day which has maintained them on remission at one year follow up. CONCLUSIONS: Recognition of this ictal pattern allows identification and differentiation of EMAs from other seizure types. Idiopathic and symptomatic EMAs need to be differentiated from childhood absence epilepsy with myoclonia. MAs are worsened by drugs like carbamazepine while valproate either alone or in combination with topiramate (preferred to lamotrigine) gives excellent outcome.

Cryptoccocal menigitis as a primary manifestation in a patient with intestinal lymphangictasia.

Opportunistic infections usually occur in patients with an immunocompromised state, and can be severe. Cryptoccocal meningitis is a fatal condition if left untreated, and is usually found in such patients. We report the case of an adult patient with cryptoccocal meningitis secondary to intestinal lymphangiectasia. A 30 year old female was admitted to our hospital for meningitis. Biochemical and radiological investigations were performed. A cerebrospinal fluid latex agglutination test showed positive cryptoccocal antigen. In addition, there were features of humoral and cell mediated immunity deficiency (lymphopenia, hypoalbuminemia, hypogammaglobulinemia), with a negative human immunodeficiency virus (HIV) test by enzyme linked immunosorbent assay and polymerase chain reaction. An upper gastroduodenoscopy was performed, which showed multiple lymphangiectasias, and a biopsy confirmed the diagnosis of primary intestinal lymphangiectasia (PIL). The patient was treated with intravenous amphotericin B and oral flucytosine, and the meningitis resolved. PIL should be suspected in patients with cryptoccocal meningitis, combined with humoral and cell mediated immunity with a negative HIV test. The management issues, in addition to antifungal therapy, include nutritional supplements for the protein losing enteropathy.