Optimal Use of Perampanel in Elderly Asian Patients with Epilepsy: Expert Opinion.

Managing epilepsy in the elderly remains complicated largely due to factors related to aging. In this population, management practices are increasingly shifting towards the use of newer-generation anti-seizure medications (ASMs) as they are generally associated with better tolerability and safety profiles than older ones. Perampanel is a new ASM with broad-spectrum efficacy and a favorable safety profile. However, because of the lack of information and experience in its use, the prescription of perampanel has not been optimized in the elderly in the real-world setting in Asia. A group of epilepsy experts across the region convened at a series of virtual meetings to share their experience and discuss recommendations on perampanel use in elderly patients, including dose optimization, considerations with treatment initiation, and strategies to manage adverse events and maximize tolerability. This article summarizes key clinical and real-world evidence for perampanel in the elderly and consolidates the experts' opinions on optimizing perampanel use in elderly Asian patients with epilepsy, providing practical guidance for clinicians to address challenges related to treatment initiation and tolerance.

Knowledge, Attitude, and Practice of epilepsy in Wayanad, Kerala.

OBJECTIVE: Epilepsy is a common neurological condition characterized by recurrent seizures. The aim of the study was to assess the level of Knowledge, Attitude, and Practices (KAP) in epilepsy in the district of Wayanad. METHODS: This study was conducted among adults residing in Wayanad. This was a community-based door-to-door survey conducted among adults residing in Wayanad District between August 2021 and November 2021. A semi-structured questionnaire was used for data collection. The questionnaire included 23 items that could define the information on the level of knowledge and attitude toward epilepsy. RESULT: A total of 394 subjects without epilepsy were included in this study. According to the results of this study, 68.8% of respondents were female and 85.3% of them had completed at least primary school education. 93.1% of participants had heard about epilepsy and 64.5% of participants were aware that epilepsy was a brain disorder. 30.5% of participants believed that a person with epilepsy could not get married. 73.9% of participants recommended allopathic treatment for epilepsy and only 9.9% of participants knew about surgical treatment option for epilepsy. CONCLUSION: Despite having a good understanding of the disease, there is a general tendency in the population to consider patients with epilepsy as incapable of leading a normal life. The choice of modern treatment methods over traditional is also a positive aspect.

Auditory aura from the hippocampus - Not all that 'rings' is neocortical temporal lobe epilepsy.

Epileptic auras provide the initial clues to identify the probable region of ictal onset. In temporal lobe epilepsies, auras are most commonly experiential or viscerosensory, when they arise from mesial structures. Whereas sensations such as vertigo and auditory hallucinations are more likely to occur from the lateral temporal lobe structures. Auditory auras have been described from the lateral temporal neocortex, Heschl's gyri, frontal operculum and posterior insula. We herein describe a patient with temporal lobe epilepsy with an auditory aura who was localized to have the onset of seizures from the hippocampus using stereotactic EEG (SEEG). Stimulation of the hippocampal contacts also reproduced the habitual auditory aura. Anterior temporal lobectomy with amygdalohippocampectomy resulted in complete seizure freedom for 3 years. This is an initial description of auditory aura elicited from the hippocampus using SEEG.

Need and Viability of Newborn Screening Programme in India: Report from a Pilot Study.

India, a country with the second largest population in the world, does not have a national newborn screening programme as part of its health policy. With funding support from the Grand Challenges Canada, a pilot newborn screening programme was implemented for the Udupi district of South India to study the need and viability of a national programme in India. Six disorders were selected for the study based on the availability of funding and recommendation from pediatricians in the district. Here, we report the observed incidence during the study. A cost-effectiveness analysis of implementing newborn screening in India was performed. It is evident from our analysis that the financial loss for the nation due to these preventable diseases is much higher than the overall expenditure for screening, diagnosis, and treatment. This cost-effectiveness analysis justifies the need for a national newborn screening programme in India.

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.

Role of Video-EEG in Children.

Routine electroencephalogram (EEG) has many limitations, especially the inability to capture reported habitual events in question. A prolonged EEG with synchronized video (video-EEG) overcomes some of these limitations by improving the sensitivity, specificity and the diagnostic yield by attempting to record the habitual events when they are frequent and when indicated. Video-EEG is employed commonly for the diagnosis and classification of epilepsy/epilepsy syndromes, to distinguish between seizures and seizures mimickers, for pre-surgical evaluation and in the management of critically ill children. The duration of recording would vary depending on the indication and frequency of events. Ambulatory EEG is another cost effective and convenient alternative in certain circumstances. However, availability of the machines and expertise, accessibility, affordability and labor intensive nature of the procedure limit widespread use in India. This review explores the role of video-EEG in the management of children with epileptic and non-epileptic paroxysmal events with respect to routine clinical practice in India.

Therapeutic Challenge in a Case of Recent Onset Refractory Cluster Seizures.

A dilemma exists in context to the timing of surgery in a case presenting with explosive onset seizures secondary to a focal cortical dysplasia (FCD). This case report highlights the challenges faced in the management of a 4-year-old child with recent onset cluster seizures refractory to anti-epileptic drugs. A 4-year-old girl presented with an acute onset of cluster seizures (up to 32 in a day), semiologically characterized by tonic upper limb extension and laughter lasting for few seconds with no response to multiple anti-epileptic drugs. The clinical, electrographic, neuroimaging and interictal positron emission tomography data were concordant and consistent with a left middle frontal gyrus dysplasia which was successfully resected under electrocorticographic guidance. Patient is seizure free at 2 months of follow up. (Engel Class 1). Surgical resection is feasible and potentially more effective in the early phase of clinical presentation of FCD.

Age- and gender-related reference ranges for thromboelastography from a healthy Indian population.

INTRODUCTION: Thromboelastography (TEG) is a whole blood clotting assay largely used in major surgeries and trauma to monitor patients' in vivo hemostatic status. Standardization of kaolin-activated citrated whole blood thromboelastography is not done in the Indian population. This study primarily aims to derive reference ranges of kaolin-activated TEG for healthy volunteers in the Indian population. Secondarily, it aims to study the age- and gender-related hemostatic changes in the study population. METHODS: A total of 120 healthy volunteers were enrolled (55 adult males, 32 adult females, and 33 children). The volunteers were interviewed for any bleeding history or drug intake which affects coagulation. Kaolin-activated TEG was performed on citrated whole blood, and parameters including R-time, K-time, angle, MA, LY30, and CI were analyzed. RESULTS: Derived reference range for total volunteers irrespective of age and sex were as follows: R-time: 3.8-10.6, K-time: 1.2-3.1, angle: 44.9-72.0, MA: 41.2-64.5, LY30: 0-9.9, and CI: -3.7 to 3.4. Statistically significant difference was observed in different age and sex groups for R-time, K-time, and angle. About 40% of the volunteers had at least one abnormal parameter according to the manufacturer's reference range which decreased to 12.5% when the derived reference ranges were considered. CONCLUSION: Gender- and age-related variances were observed in reference ranges of our population and which was also differed from the other ethnic population. Many of our healthy volunteers were categorized as coagulopathic when manufacturer's reference range was considered. So, it is important to derive the reference range of the target population before using the TEG into clinical practice.

Immunogenicity and lot-to-lot consistency of a ready to use liquid bovine-human reassortant pentavalent rotavirus vaccine (ROTASIIL - Liquid) in Indian infants.

BACKGROUND: A lyophilized bovine-human rotavirus reassortant pentavalent vaccine (BRV-PV, Rotasiil®) was licensed in 2016. A liquid formulation of this vaccine (LBRV-PV, Rotasiil - Liquid) was subsequently developed and was tested for non-inferiority to Rotasiil® and for lot-to-lot consistency. METHODS: This Phase II/III, open label, randomized study was conducted at seven sites across India from November 2017 to June 2018. Participants were randomized into four arms; Lots A, B, and C of LBRV-PV and Rotasiil® in 1:1:1:1 ratio. Three doses of study vaccines were given at 6, 10, and 14 weeks of age. Blood samples were collected four weeks after the third dose to assess rotavirus IgA antibody levels. Non-inferiority of LBRV-PV to Rotasiil was proven if the lower limit two-sided 95% confidence interval (CI) of geometric mean concentration (GMC) ratio was at least 0.5. Lot-to-lot consistency was proven if 95% CI of the GMC ratios of three lots were between 0.5 and 2. Solicited reactions were collected by using diary cards. RESULTS: Of the 1500 randomized infants, 1436 infants completed the study. The IgA GMC ratio of LBRV-PV to Rotasiil® was 1.19 (95% CI 0.96, 1.48). The corresponding IgA seropositivity rates were 60.41% (57.41, 63.35) and 52.75% (47.48, 57.97). The IgA GMC ratios among the three LBRV-PV lots were: Lot A versus Lot B: 1.34 (1.03, 1.75); Lot A versus Lot C: 1.22 (0.93, 1.60); and Lot B versus Lot C: 0.91 (0.69, 1.19). The 95% CIs for the GMC ratios were between 0.69 and 1.75. The incidence of solicited reactions was comparable across the four arms. Only one serious adverse event of gastroenteritis event in the Rotasiil® group was causally related. CONCLUSION: The immunological non-inferiority of LBRV-PV against Rotasiil® as well as lot-to-lot consistency of LBRV-PV was demonstrated. LBRV-PV had safety profile similar to Rotasiil®. TRIAL REGISTRATION NUMBER: Clinical Trials.Gov [NCT03474055] and Clinical Trial Registry of India [CTRI/2017/10/010104].

Improved Patient-Independent System for Detection of Electrical Onset of Seizures.

PURPOSE: To design a non-patient-specific system to detect the electrical onset of seizures in patients with temporal lobe epilepsy. METHODS: We used EEG data from 29 seizures of 18 temporal lobe epilepsy patients who underwent multiday video-scalp EEG monitoring as part of their presurgical evaluations. We segmented each data set into preictal and ictal phases, and identified spectral entropy, spectral energy, and signal energy as useful features for discriminating normal and seizure conditions. The performance of five different classifiers was analyzed using these features to design an automated detection system. RESULTS: Among the five classifiers, decision tree, k-nearest neighbor, and support vector machine performed with sensitivity (specificity) of 79% (81%), 75% (85%), and 80% (86%), respectively. The other two, linear discriminant algorithm and Naive Bayes classifiers, performed with sensitivity (specificity) of 54% (94%), 47% (96%), respectively. CONCLUSIONS: The support vector machine-based seizure detection system showed better detection capability in terms of sensitivity and specificity measures as compared to linear discriminant algorithm, Naive Bayes, decision tree, and k-nearest neighbor classifiers. CONCLUSIONS: Our study shows that a generalized system to detect the electrical onset of seizures in temporal lobe epilepsy using scalp-recorded EEG is possible. If confirmed on a larger data set, our findings may have significant implications for the management of seizures, especially in patients with drug-resistant epilepsy.

Effectiveness of a training program for bleeding disorders among accredited social health activists in Udupi District, Karnataka, India.

INTRODUCTION: Hemophilia and other bleeding disorders are underreported and cause significant morbidity and mortality in resource-constrained countries. Training and the creation of awareness among accredited social heath activists (ASHAs) will aid in the early detection of bleeding disorders at the community level. OBJECTIVE: To develop awareness and skills for the screening and identification of cases with bleeding symptoms among ASHAs in Udupi District, Karnataka, India. METHODS: An interventional study was undertaken in Udupi District, which has three taluks and approximately 233 villages. All ASHAs with a current role (586) from rural Udupi were provided a competency-based training program at the community health center using a specifically designed training manual for the identification of cases with bleeding disorders. A pre-test/post-test evaluation was performed to discover the training outcomes. RESULTS: Sixteen (2.7%) participants had average knowledge in the first post-test, and 570 (92.2%) participants had good knowledge. Thirty-nine (6.6%) participants had average knowledge in second post-test, and 547 (94.3%) participants had good knowledge. The effectiveness of the training program was assessed using Friedman's two-way test. A significant difference in knowledge scores (χ2 = 955.1) was found at baseline evaluation and end of the training test 1 and at 30 days of training test 2 among the ASHAs. CONCLUSION: Accredited social heath activists health care workers, who are the most important link between the community and health services, successfully created public awareness concerning the early detection of bleeding disorders.

A Study on Drug-Induced Tardive Dyskinesia: Orofacial Musculature Involvement and Patient's Awareness.

OBJECTIVE: Schizophrenia is a psychiatric disorder that requires long-term treatment. Long-term antipsychotic treatment is often associated with the emergence of tardive dyskinesia (TD), the severity of which is measured by Abnormal Involuntary Movement Scale (AIMS). This study examined the relationship among TD, orofacial musculature activity, and patient's awareness of AIM. The knowledge would help dentists to deliver oral care for schizophrenics with TD. MATERIALS AND METHODS: We identified 317 patients from a standard, data sharing initiative, of whom 38.3% exhibited AIM score of 2 to 15. The patient demographics, drug history, details of AIMS were subjected to descriptive and inferential statistical analysis using SPSS with P≤0.05 as significance. RESULTS: The mean of only orofacial features (n = 56) was 3.43 ± 2.68. Muscles of facial expression was involved in nine (7.9% of all TD), lip/perioral area in 27 (23.68%), jaw in 52 (45.61%), and tongue in 77 (67.54%). The patient's perception of AIM precipitated stress when involving jaw, tongue, limbs, and trunk was statistically significant (P≤0.05). The multiple regression model statistically significantly predicted TD for factors considered. CONCLUSION: Around 1% of global population is being diagnosed with schizophrenia, carry an inherent risk of developing TD. They might have orodental care requirements, including prosthodontic and restorative services. Primary physicians and dentists need to be aware of TD and its mechanism for appropriate patient management.

Intractable ictal vomiting: a new form of reflex epilepsy?

In this description of the clinical course of a young female with persistent and protracted vomiting along with occasional loss of consciousness and subtle motor manifestations, the differential diagnosis is debated. The epileptic origin of her symptoms was substantiated by the presence of interictal epileptiform discharges and dramatic response to valproate monotherapy. Possible lobar localizations are discussed with the support of existing literature on this rare ictal manifestation [Published with video sequence on www.epilepticdisorders.com].

Epileptic Angina.

PURPOSE: To investigate the probable ictal origin of unexplained episodic chest pain and if possible to lateralize and localize the epileptic focus. METHODS: A 14 year old boy presented with episodic short lasting localized chest pain. His cardiac and other systemic work-up were normal. MRI brain did not reveal any structural pathology. Video telemetry was done for characterization of the paroxysms. RESULTS: Interictal record showed left fronto-central epileptiform discharges. A left hemispheric, predominantly centroparietal ictal rhythm was identified. The possible localizations of this unusual semiology are somatosensory areas I and II, supplementary sensorimotor area, posterior insula and cingulate cortex. Patient responded remarkably to antiseizure drugs. CONCLUSION: Pain is a rare manifestation of epilepsy observed in less than 1% of patients. When present, it is usually accompanied by other focal features. This rare occurrence of epileptic seizures masquerading as angina is a novel observation.

A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A.

BACKGROUND: The development of neutralizing anti-factor VIII alloantibodies (inhibitors) in patients with severe hemophilia A may depend on the concentrate used for replacement therapy. METHODS: We conducted a randomized trial to assess the incidence of factor VIII inhibitors among patients treated with plasma-derived factor VIII containing von Willebrand factor or recombinant factor VIII. Patients who met the eligibility criteria (male sex, age <6 years, severe hemophilia A, and no previous treatment with any factor VIII concentrate or only minimal treatment with blood components) were included from 42 sites. RESULTS: Of 303 patients screened, 264 underwent randomization and 251 were analyzed. Inhibitors developed in 76 patients, 50 of whom had high-titer inhibitors (≥5 Bethesda units). Inhibitors developed in 29 of the 125 patients treated with plasma-derived factor VIII (20 patients had high-titer inhibitors) and in 47 of the 126 patients treated with recombinant factor VIII (30 patients had high-titer inhibitors). The cumulative incidence of all inhibitors was 26.8% (95% confidence interval [CI], 18.4 to 35.2) with plasma-derived factor VIII and 44.5% (95% CI, 34.7 to 54.3) with recombinant factor VIII; the cumulative incidence of high-titer inhibitors was 18.6% (95% CI, 11.2 to 26.0) and 28.4% (95% CI, 19.6 to 37.2), respectively. In Cox regression models for the primary end point of all inhibitors, recombinant factor VIII was associated with an 87% higher incidence than plasma-derived factor VIII (hazard ratio, 1.87; 95% CI, 1.17 to 2.96). This association did not change in multivariable analysis. For high-titer inhibitors, the hazard ratio was 1.69 (95% CI, 0.96 to 2.98). When the analysis was restricted to recombinant factor VIII products other than second-generation full-length recombinant factor VIII, effect estimates remained similar for all inhibitors (hazard ratio, 1.98; 95% CI, 0.99 to 3.97) and high-titer inhibitors (hazard ratio, 2.59; 95% CI, 1.11 to 6.00). CONCLUSIONS: Patients treated with plasma-derived factor VIII containing von Willebrand factor had a lower incidence of inhibitors than those treated with recombinant factor VIII. (Funded by the Angelo Bianchi Bonomi Foundation and others; ClinicalTrials.gov number, NCT01064284; EudraCT number, 2009-011186-88.).