Efficacy of pulse intravenous methylprednisolone in epileptic encephalopathy: a randomised controlled trial.

BACKGROUND: High-level evidence for using steroids in epileptic encephalopathy (EE), other than West syndrome (WS), is lacking. This study investigated the efficacy and safety of pulse intravenous methylprednisolone (IVMP) in EE other than WS. METHODS: This is an open-label evaluator-blinded randomised controlled study. Children aged 6 months or more with EE other than WS were included. Eighty children were randomised into intervention and non-intervention groups with 40 in each group. At the first visit (T1) seizure frequency, electroencephalographic (EEG) and Vineland Social Maturity Scale (VSMS) were obtained, and antiseizure medication (ASM) were optimised. After 1 month (T2), subjects were randomised to intervention (ASM+3 months IVMP pulse) or non-intervention group (only ASM) with 40 subjects in each group. They were followed up for 4 months (T3) and assessed. RESULTS: After 4 months of follow-up, 75% of patients receiving IVMP had >50% seizure reduction versus 15.4% in control group (χ2=28.29, p<0.001) (RR 4.88, 95% CI 2.29 to 10.40), median percentage change in seizure frequency (91.41% vs 10%, p<0.001), improvement in EEG (45.5% vs 9.4%, χ2=10.866, p=0.001) and social age domain of VSMS scores (Z=-3.62, p<0.001) compared with baseline. None of the patients in the intervention group had any serious side-effects. DISCUSSION: Three-month pulse IVMP therapy showed significant improvement in seizure frequency, EEG parameters and VSMS scores, with no steroid-related serious adverse effects. It can be considered as a safe and effective add on treatment in children with EE other than WS. TRIAL REGISTRATION NUMBER: CTRI/2019/02/017807.

Posterior Quadrant Disconnection for Childhood Onset Sub-Hemispheric Posterior Head Region Epilepsy: Indications in an Indian Cohort and Outcome.

BACKGROUND: Posterior quadrant disconnection (PQD) is an under-utilized surgical technique in the management of refractory epilepsy. There is a dearth of data pertinent to post-PQD seizure outcomes. METHODS: This retrospective study analyzed patients with drug-resistant childhood-onset epilepsy who underwent PQD at our center from 2009 to 2018. The clinical, imaging, and electrophysiological data were reviewed. The seizure outcome was noted from the latest follow-up in all patients. RESULTS: Fifteen patients underwent PQD, with a mean age at onset of epilepsy of 3.3 ± 4.6 years. All patients had seizure onset in childhood with focal onset of seizures, and in addition, 5 had multiple seizure types. All cases underwent presurgical workup with MRI, video-EEG, psychometry, while PET/MEG was done if required. Engel Ia and ILAE I outcomes were considered to be favorable. The histology of the specimen showed 9 patients (60%) had gliosis, 4 (26.7%) had focal cortical dysplasia (FCD), while 1 patient had nodular heterotopia and another had polymicrogyria-pachygyria complex. Postoperative follow-up was available in 14 cases. One patient was lost to follow-up. Mean follow-up duration for the cohort was 45 + 24 months. At last, follow-up (n = 14), 66.7% (10 cases) had favorable outcome (Engel Ia). At the end of 1-year follow-up, up to 73% (n = 11) of the patients were seizure-free. Four patients developed transient hemiparesis after surgery which improved completely by 3-6 months. CONCLUSIONS: Gliosis was more common etiology requiring PQD in our series than Western series, where FCD was more common. PQD is a safe and effective surgical modality in childhood-onset epilepsy with posterior head region epileptogenic focus.

Cardiac Rhythm Aberrations in Subacute Sclerosing Panencephalitis: Insights From Heart Rate Variability Analysis.

PURPOSE: Subacute sclerosing panencephalitis (SSPE) is a fatal neurological disorder resulting from persistent measles virus infection within the brain. Although neurological manifestations have been well-documented, the impact of SSPE on cardiac autonomic function, assessed through heart rate variability (HRV), remains understudied. METHODS: In this prospective single-center study conducted from January 2022 to March 2023 in Southern India, 30 consecutive SSPE patients and age- and sex-matched controls underwent electrocardiogram recordings for HRV analysis. Various HRV parameters were assessed, including time-domain metrics (SD of normal-to-normal intervals, root mean square of successive differences between normal heartbeats, percentage of successive normal interbeat intervals greater than 50 msec), SD1 and SD2 for Poincaré plot analysis, and frequency-domain metrics (low frequency %, high frequency %, low frequency:high frequency ratio). RESULTS: In the study, SSPE patients exhibited markedly reduced HRV. Specifically, SD of normal-to-normal intervals (P = 0.003), percentage of successive normal interbeat intervals greater than 50 msec (P = 0.03), and SD2 (P = 0.0016) were significantly lower compared with controls. Frequency-domain analysis did not reveal significant distinctions. Correlation analysis demonstrated a negative relationship between percentage of successive normal interbeat intervals greater than 50 msec and SSPE severity (r = -0.37, P = 0.042). Heart rate variability did not significantly differ between SSPE stages or with clinical variables. The interbeat interval range showed a narrower distribution in SSPE subjects. CONCLUSIONS: Our study highlights the clinical relevance of HRV analysis in SSPE and autonomic dysfunction throughout the disease course underscoring its importance in SSPE. This investigation provides valuable insights into cardiac autonomic dysfunction probably because of affliction of the central autonomic networks caused by the disease process and may be a contributing factor to mortality in SSPE.

Phenotypic features of epilepsy due to sodium channelopathies - A single center experience from India.

Objectives: Nearly 40% of pediatric epilepsies have a genetic basis. There is significant phenotypic and genotypic heterogeneity, especially in epilepsy syndromes caused by sodium channelopathies. Sodium channel subunit 1A (SCN1A)-related epilepsy represents the archetypical channel-associated gene that has been linked to a wide spectrum of epilepsies of varying severity. Subsequently, other sodium channels have also been implicated in epilepsy and other neurodevelopmental disorders. This study aims to describe the phenotypes in children with sodium channelopathies from a center in Southern India. Materials and Methods: This is a retrospective, descriptive, and single-center study. Out of 112 children presenting with epilepsy who underwent genetic testing between 2017 and 2021, 23 probands (M: F = 12:11) were identified to have clinically significant sodium channel mutations. Clinical presentation, electroencephalography, and imaging features of these patients were recorded. The utility of genetic test results (e.g., in planning another child, withdrawal of medications, or change in treatment) was also recorded. Results: Age at onset of seizures ranged from day 4 of life to 3.5 years. Clinical epilepsy syndromes included generalized epilepsy with febrile seizures plus (n = 3), Dravet syndrome (n = 5), early infantile epileptic encephalopathy (n = 7), drug-resistant epilepsy (n = 5), and epilepsy with associated movement disorders (n = 3). The most common type of seizure was focal with impaired awareness (n = 18, 78.2%), followed by myoclonic jerks (n = 8, 34.78%), epileptic spasms (n = 7, 30.4%), bilateral tonic-clonic seizures/generalized tonic-clonic seizures (n = 3, 13%), and atonic seizures (n = 5, 23.8%). In addition to epilepsy, other phenotypic features that were discerned were microcephaly (n = 1), cerebellar ataxia (n = 2), and chorea and dystonia (n = 1). Conclusion: Sodium channelopathies may present with seizure phenotypes that vary in severity. In addition to epilepsy, patients may also have other clinical features such as movement disorders. Early clinical diagnosis may aid in tailoring treatment for the given patient.

Corpus Callosotomy for Non-Localizing Drug Resistant Epilepsy with Drop Attacks.

BACKGROUND: Corpus callosotomy (CC) is a surgical palliative procedure done for a selected group of patients with drug resistant epilepsy (DRE) to stop drop attacks and prevent falls. METHODS: We performed a retrospective chart review of consecutive patients who underwent CC for DRE with drop attacks at our center between 2015 and 2019. Clinical, imaging details and surgical findings were noted. Clinical outcomes and functional status were evaluated. RESULTS: During the study period, 17 patients underwent corpus callosotomy (Male: Female 14:3). The mean age at surgery was 10.3 years (standard deviation - 5.85, interquartile range [IQR] = 6.5). The mean age at onset of seizure was 2.23 years (standard deviation - 3.42, IQR = 1.5). Preoperative seizure frequency ranged from 2 to 60 attacks per day (median: 20, IQR= 36). All patients had atonic seizures/drop attacks. One patient underwent anterior CC and 16 underwent complete CC. Three patients had complications in the postoperative period. The median follow-up was 26 months. All patients had cessation of drop attacks immediately following surgery. One patient with anterior CC had a recurrence of drop attacks for which she underwent completion CC. Another patient had recurrent drop attacks 3 years later and was found to have a residual callosal connection. Three patients had complete seizure freedom and 4 patients had a <50% reduction in seizure frequency. CONCLUSIONS: Our study lends additional support to the efficacy of CC in patients with DRE, with the cessation of drop attacks. It also provided a reasonable reduction in seizure frequency. Complete CC led to better control of drop attacks.

Intravenous methylprednisolone is a potential add on therapy for Ring chromosome 20 syndrome.

Ring 20 syndrome is a rare cause of refractory epilepsy and non-convulsive status epilepticus in children. We report a patient with Ring 20 syndrome with refractory focal seizures and non-convulsive status epilepticus who showed good treatment response with intravenous steroids. We wish to highlight that intravenous pulse methylprednisolone is a useful treatment strategy in this setting.

Spectrum and Evolution of EEG Changes in Anti-NMDAR Encephalitis.

BACKGROUND: NMDA receptor encephalitis (NMDARE) is the most prevalent autoimmune encephalitis and it encompasses a spectrum of clinical features. It is most commonly associated with alteration in consciousness, seizures, neuro-psychiatric symptoms, and movement disorders. Electroencephalography (EEG) plays a vital role and can give clues to diagnosis in a subset of patients. METHODS: We retrospectively characterized the clinical and EEG findings in our NMDARE patients (n = 48). A total of 131 EEGs were analyzed. RESULTS: We observed that patients with seizures had a younger age of onset (p < 0.001). The most common EEG pattern that was noted was diffuse slowing (n = 20) followed by generalized rhythmic delta activity (n = 9), focal spikes and slowing (n = 8 each). Delta brush pattern was seen in only 3 EEGs. Focal ictal rhythms were seen in 3 EEGs. There was no significant difference in outcomes such as seizure recurrence, modified Rankin score (mRS) at follow up/discharge or relapse between groups of patients who had EEG abnormalities in the first EEG and with those who did not. CONCLUSIONS: NMDARE has varied EEG findings, most of them being non-specific. When combined with clinical presentation, EEG is a useful tool in the diagnosis and management of NMDARE.

Role of pulse methylprednisolone in epileptic encephalopathy: A retrospective observational analysis.

OBJECTIVES: To study the effect of monthly pulses of intravenous methylprednisolone (IVMP) on seizure and global outcomes in children with epileptic encephalopathy (EE). METHODS: This retrospective study was undertaken in a tertiary care epilepsy center in India. Consecutive patients with EE who had received IVMP as adjunctive therapy for a minimum of 3 months and had at least one pre-and post-steroid EEG each, were identified and a structured questionnaire was used to collect information including outcomes at 3 months post-steroid course completion and beyond, as available. RESULTS: Ninety-seven patients (M:F=71:26) fulfilling the inclusion criteria with a mean age at onset of seizures being 20.52 ± 25.69 months were included. Commonest seizure types were myoclonic (66%); Lennaux-Gastaut and West Syndromes accounted for 57 % and 24 % patients respectively. The etiology was unknown in 52 %. All children were on a combination of standard anti-seizure drugs. The duration of IVMP pulse therapy was 7.72 ± 6.25 months. One-fourth (26 %) patients experienced minor adverse events. Greater than 50 % seizure burden reduction was seen in 66 % patients at 3 months with seizure-freedom in 25 %. A total of 45 (46 %) patients became seizure-free in the cohort eventually with continuation of steroids beyond 3 months. Children with idiopathic EEs, normal neuroimaging, myoclonic jerks, and West syndrome showed the best response. The presence of burst-suppression and generalized paroxysmal fast activity (GPFA) predicted inadequate response. CONCLUSIONS: Adjunct pulse doses of IVMP are safe, well-tolerated, and effective in reducing seizures and improving global outcomes in children with idiopathic EEs, West syndrome, normal neuroimaging, and myoclonic jerks. Seizure freedom might be delayed in a subset of these patients, hence duration of therapy beyond 3 months may be warranted.

Genetic analysis of ATP7B in 102 south Indian families with Wilson disease.

Wilson disease (WD) is an autosomal recessive disorder, characterized by excessive deposition of copper in various parts of the body, mainly in the liver and brain. It is caused by mutations in ATP7B. We report here the genetic analysis of 102 WD families from a south Indian population. Thirty-six different ATP7B mutations, including 13 novel ones [p.Ala58fs*19, p.Lys74fs*9, p.Gln281*, p.Pro350fs*12, p.Ser481*, p.Leu735Arg, p.Val752Gly, p.Asn812fs*2, p.Val845Ala, p.His889Pro, p.Ile1184fs*1, p.Val1307Glu and p.Ala1339Pro], were identified in 76/102 families. Interestingly, the mutation analysis of affected individuals in two families identified two different homozygous mutations in each family, and thus each affected individual from these families harbored two mutations in each ATP7B allele. Of 36 mutations, 28 were missense, thus making them the most prevalent mutations identified in the present study. Nonsense, insertion and deletion represented 3/36, 2/36 and 3/36 mutations, respectively. The haplotype analysis suggested founder effects for all the 14 recurrent mutations. Our study thus expands the mutational landscape of ATP7B with a total number of 758 mutations. The mutations identified during the present study will facilitate carrier and pre-symptomatic detection, and prenatal genetic diagnosis in affected families.

The Tale of the Storyteller and the Painter: The Paradoxes in Nature.

INTRODUCTION: Brain as the seat of behavior is acknowledged from the times of Charaka, however where neurology ends and philosophy begins remains an enigma. It is certainly every neurologist's observation that there is loss of function either region based or domain based in progressive diseases of the nervous system making it the seat of all useful activities. However, there are references to occurrence of new skills seen during various illnesses causing progressive cognitive dysfunction. This serves as a pharmaco-sparing agent in behavior management and therefore serves as a rehabilitatory tool. However, its pathomechanism is not clear. PATIENT AND METHODS: Two patients comprising one male and one female who were being evaluated for progressive cognitive dysfunction and were found to have interesting creative skills and are being described. RESULTS: The first patient is a case of young onset behavioral variant frontotemporal dementia and the second patient is a case of neurosarcoidosis. CONCLUSION: The emergence of these skills could be due to disinhibition of some of the innate skills of the patients during degeneration or establishment of new data linking circuits with creative potential during attempted repair.

Subacute Noninfective Inflammatory Encephalopathy: Our Experience and Diagnostic Problems.

INTRODUCTION: Immune dysregulation associated encephalopathies present with significant psychiatric manifestations and only a few soft neurological and general systemic features. They are generally resistant to treatment with psychiatric medications. Generalized orthostatic myoclonus and faciobrachial dystonic seizures are mistaken as Creutzfeldt-Jakob disease and subacute sclerosing panencephalitis. PATIENTS AND METHODS: Forty-two patients seen during 2010-2015 and diagnosed as noninfective encephalopathy were analyzed. Those patients with infective causes and those who had significant features of systemic manifestations of vasculitis and other disorders of central nervous system were excluded from the study. They were investigated with cerebrospinal fluid imaging, electroencephalogram (EEG), and antibody profile. RESULTS: More than 70% patients had psychiatric manifestation as presenting features and reported to psychiatrist. Three patients had paraneoplastic and others N-methyl-D-aspartate, voltage-gated potassium channel, thyroid peroxidase, antinuclear antibody related, and few were due to unknown antibody. CONCLUSION: Serious diagnostic errors are common and early diagnosis is based on high degree suspicion in patients presenting with new-onset refractory psychosis. Soft neurological features should be looked for and EEG serves as a very sensitive tool in establishing organicity.

Syndromes of Rapidly Progressive Cognitive Decline-Our Experience.

BACKGROUND: Dementias are fairly slowly progressive degenerative diseases of brain for which treatment options are very less and carry a lot of burden on family and society. A small percentage of them are rapidly progressive and mostly carry a different course outcome. However, there are no definite criteria other than the time line for these patients. AIMS: The aim of this was to identify and categorize the causes and course of rapidly progressive dementias seen in our center. SETTINGS AND DESIGN: Patients who presented with rapid deterioration of cognitive functions within weeks to 1 year between 2011 and December 2016 were evaluated. PATIENTS AND METHODS: All patients underwent all mandatory tests for dementia including brain imaging. Complete vasculitis workup, autoimmune encephalitis profile including Voltage Gated Potassium Channel, N-methyl-D-aspartic acid receptor, glutamic acid-decarboxylase, thyroid-peroxidase antibody, cerebrospinal fluid, and other special tests such as duodenal biopsy and paraneoplastic workup were done based on clinical indications. RESULTS AND CONCLUSIONS: Out of 144 patients 42 had immune-mediated encephalopathy, 18 had Creutzfeldt-Jakob disease, 3 had Vitamin B12 deficiency, 63 had infection with neurocysticercosis, 7 had tuberculosis, 2 had HIV, 1 had herpes simplex encephalitis, 1 had neurosyphilis, 1 Whipples disease, 1 had Subacute Sclerosing Panencephalitis, 1 had Mass lesion, 3 had Frontotemporal dementia, and 3 had small vessel disease. Good majority of these patients have infective and immune-mediated causes and less number belong to degenerative group. Therefore, caution is needed to look for treatable cause as it carries a different treatment options and outcome.

Sporadic Hyperekplexia Plus Syndrome.

A disorder of infants and children with pathological startle response, features of other system involvement, falls, and stiffness with retained consciousness. It should be differentiated from conditions such as myoclonic epilepsy, psychogenic movement disorder, Isaac syndrome, Schwartz-Jampel syndrome, Gilles de la Tourette, and culture-specific startle syndromes such as jumping Frenchman of Maine. A 5-year-old child symptomatic with repeated falls spontaneously as well as by sound and activities since neonatal period. He was having hyperalert facies, intelligent, cooperative with mild dysmorphism. His investigations were noncontributory except giant somatosensory evoked potentials and skeletal abnormalities. He showed excellent response to clonazepam and no complications on withdrawing the antiepileptic drugs. Proper diagnosis is of great therapeutic relevance and is based on high degree of suspicion.