Prevalence and Diagnosis of Sexual Dysfunction in People with Epilepsy.

Even though sexual dysfunction occurs in about half of people with epilepsy (PWE), it is mostly under-reported, under-recognized, and under-treated. Sexual dysfunctions are more common in patients with uncontrolled epilepsy, frequent seizures, and those receiving enzyme-inducing antiseizure medicines (ASMs). The presence of underlying anxiety or depression is associated with a higher frequency of sexual dysfunction in PWE. Even though the evidence is limited, the newer and non-enzyme-inducing ASMs do not largely cause sexual dysfunction. A multidisciplinary and multipronged approach is required for the comprehensive evaluation and management of sexual dysfunction in PWE.

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.

Treatment outcomes in drug resistant juvenile myoclonic epilepsy: Valproate resistance may not be the end of the road.

OBJECTIVE: To determine treatment responses to various antiseizure medicines (ASMs) in patients with drug resistant juvenile myoclonic epilepsy (DRJME) METHODS: We reviewed records of all JME patients attending epilepsy clinics at 5 centers during a 5-year period. We used International Consensus Criteria to diagnose JME and International League Against Epilepsy Criteria to define drug resistance and sustained seizure freedom. We only used broad spectrum medicines which included valproate, lamotrigine, topiramate, levetiracetam, clobazam, phenobarbitone, clonazepam, and zonisamide. We considered an ASM successful if patient achieved seizure freedom within 3 months of attaining maintenance dose. RESULTS: We studied 116 patients (61 males) with DRJME. At terminal followup, 82 (70.7%) patients had achieved sustained seizure freedom with a mean followup of 3.2 ± 1.3 years after last dose change. In patients where valproate failed as first- or second-line ASM (n=70; 60.3%), 49(70%) became seizure-free. In this group, 33(67%) patients became seizure-free after addition of lamotrigine. Success rate of lamotrigine and valproate combination was 69% as compared to 9% with all other combinations (p = 0.001). In patients who were not exposed to valproate as initial therapy (n=46), 33 (71.7%) became seizure-free, 30 (91%) after adding valproate. At last follow-up, 75 (90%) seizure-free patients were receiving valproate including 45 (55%) patients with a combination of valproate and lamotrigine. Only one of 24 patients became seizure-free after failing valproate and lamotrigine combination. CONCLUSION: Seizure freedom can be achieved in two-thirds of patients with DRJME. A combination of valproate and lamotrigine is the most effective duotherapy.

Is the antiseizure effect of ketogenic diet in children with drug-resistant epilepsy mediated through proinflammatory cytokines?

In order to understand whether the antiseizure mechanism of ketogenic diet (KD) is mediated through its anti-inflammatory effect, we measured the serum concentrations of cytokines IL- 1ß and IL-6 in 21 children with drug-resistant epilepsy. We found a significant reduction in the levels of serum IL- 1ß and IL-6 levels at one-year of KD therapy compared to baseline. However, we did not find any correlation between decrease in the serum concentrations of these interleukins with the reduction in seizure frequency at one-year of KD therapy, which may be due to the small sample size and heterogeneous patient population we studied. Future studies should try to overcome these limitations.

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.

Can change in gut microbiota composition be used as a surrogate marker of treatment efficacy of ketogenic diet in patients with drug-resistant epilepsy?

To answer the question posed in the title of the manuscript, we critically examined the connection between ketogenic diet (KD), gut microbiota (GM), and epilepsy. We conclude that although the evidence for a KD-GM-epilepsy link is fairly robust in rodent epilepsy models, it is very hard to draw meaningful conclusions in humans. The limitations of human studies that have investigated the KD-microbiota-epilepsy relationship include small sample size, a heterogeneous patient population with regard to age and epilepsy type, failure to account for the effect of dietary habits, antiseizure drugs (ASDs) and comedications on GM composition, variability in the KD administered and in the duration of the intervention, and different approaches used in sequencing the microbiome. Although alteration in the GM composition may be a potential indicator of responsiveness/resistance to a KD, we need well-designed randomized case-control and cohort studies involving a large number of a fairly homogenous population of patients with epilepsy adjusted to their habitual dietary habits and region of residence before labeling it as a surrogate marker. Research in this direction may also help us to unravel the mysteries of GM-brain axis not only concerning epilepsy but also in other neurological diseases.

Socioeconomic consequences of drug-resistant epilepsy in an adult cohort from southern India.

OBJECTIVE: The objective of this study was to describe the socioeconomic consequences of drug-resistant epilepsy (DRE). METHODS: This study comprised 132 (equal males and females) consecutive patients aged ≥18 years, who fulfilled the International League Against Epilepsy (ILAE) definition for DRE, prospectively seen in a tertiary care center in South India. We used a structured questionnaire to gather relevant information. RESULTS: The mean age was 31 (range 18-70) years. Mean age of onset of epilepsy was 17 years and mean duration of epilepsy 14 years. The most common epilepsy type and etiology were focal epilepsy and gliotic lesions secondary to perinatal insults, respectively. The average out of the pocket expenditure on antiseizure drugs annually amounted to 19% of the gross national product (GNP)/capita, which was borne by family members in more than two-thirds of the subjects. Almost 60% reported epilepsy having affected their education, 40% their employment, and 90% their marital prospects. Female patients were less often employed outside their homes and had more marital problems compared with males. CONCLUSIONS: In addition to high seizure burden, DRE adversely affects the pursuit of higher education, employment, and marriage. Besides the direct cost of epilepsy, these issues augment both the patient and the caregiver's liability. Socioeconomic consequences of DRE are widely prevalent in developing countries, and this study highlights the need to address them.

Early versus late antiepileptic drug withdrawal following temporal lobectomy.

PURPOSE: To compare the seizure outcome following early and late complete antiepileptic drug (AED) withdrawal following anterior temporal lobectomy (ATL) for mesial temporal lobe epilepsy (MTLE). METHOD: All the patients who were seizure free for one year following ATL were offered early or late AED withdrawal. AEDs were discontinued starting at one year in those who opted for early withdrawal. Patients who opted for late withdrawal were continued on single AED for three years following surgery before attempting complete discontinuation. RESULTS: Of the 135 study patients, 65 opted for early AED withdrawal and 70 for late withdrawal. The mean postoperative follow-up duration was 10.4 ± 1.3 (Range, 8-12) years. At three years following surgery, seizure recurrence occurred in 23 (35.4 %) patients in the early withdrawal group and in 10 (14.3 %) patients in late withdrawal group (p = 0.005; relative risk [RR], 2.48; 95 % confidence interval [CI], 1.28-4.80). At last follow-up, 27 (41.5 %) patients in the early withdrawal group and 26 (37.1 %) in late withdrawal group had recurrence (p = 0.60; RR, 1.12, 95 % CI, 0.74-1.70). At last followup, 80 (59.3 %) patients were off AEDs. During the terminal one year, 123 (91 %) patients were seizure free, similar in the two groups. CONCLUSIONS: This nonrandomized controlled study suggests that early complete AED withdrawal starting one year following ATL is associated with a higher risk of early seizure recurrence. However, long term seizure outcome is similar in early and late AED withdrawal groups.

Sexual dysfunction in people with epilepsy.

Sexual dysfunction is a common comorbidity in people with epilepsy (PWE) that adversely affects their quality of life. Nearly one-half of men and women with epilepsy have sexual dysfunction, but in the majority, this often goes unnoticed. The wide variation in the reported prevalence of sexual dysfunction in PWE is due to the significant heterogeneity among the studies with regard to patient population, type and severity of epilepsy, number and type of antiseizure drugs (ASDs) used, and the tools used for assessing sexual dysfunction. Generally, patients with uncontrolled epilepsy, longer duration of epilepsy, focal epilepsy, higher seizure frequency, and those receiving enzyme-inducing and multiple ASDs are more likely to have sexual dysfunction. Women generally have dysfunction in the domains of desire, while males usually have arousal disorders such as erectile dysfunction and premature ejaculation. There is limited evidence to indicate that sexual function improves in patients rendered seizure-free following epilepsy surgery. Multiple mechanisms including direct effects of epilepsy, effects of ASDs, and psychosocial factors contribute to sexual dysfunction in epilepsy. Circumstantial evidence indicates that seizures and interictal epileptiform discharges can directly affect the hypothalamic-pituitary axis as well as production of gonadal steroids. Enzyme-inducing ASDs cause sexual dysfunction by affecting the metabolism of gonadal steroids. Limited data suggest that newer ASDs including oxcarbazepine, lamotrigine, and levetiracetam cause no or minimal sexual dysfunction. Depression and anxiety significantly contribute to sexual dysfunction in PWE. A multipronged and multidisciplinary approach is essential for optimizing the sexual functions. Every effort should be made to identify and treat reversible causes including changing to nonenzyme-inducing ASDs and to provide symptomatic relief. Large, prospective studies are required to improve our understanding on prevalence and mechanisms of sexual dysfunction in PWE.

Comparison of clinical and electrophysiological characteristics between ictal and cardiac asystole encountered during video-EEG monitoring.

Differentiation between syncope secondary to epileptic seizures and cardiac disease in patients displaying transient loss of consciousness associated with convulsive movements is a diagnostic challenge both for neurologists and cardiologists. In such patients, prolonged video-EEG monitoring not only helps in identifying asystole as the cause of syncope, but also in categorizing asystole as primarily cardiac in origin (cardiac asystole) and secondary to epileptic seizures (ictal asystole). We carried out this study to ascertain the prevalence of asystole in an epilepsy monitoring unit, and to contrast the clinical and electrophysiological characteristics between ictal asystole and cardiac asystole. Through a retrospective search, we identified patients who were shown to have had asystole using a database of patients who underwent prolonged video-EEG monitoring during a 68-month period. We compared the data of 18 consecutive patients; five with ictal asystole and 13 with cardiac asystole, with 121 and 64 events recorded from them, respectively. Of the 10,096 patients who underwent prolonged video-EEG monitoring during the study period, we identified 18 (0.17%) patients with asystole. Cardiac asystole was 2.6 times more frequent than ictal asystole. Older age at onset, heralding symptoms of presyncope, occurrence during wakefulness, and brief duration of the events supported the diagnosis of cardiac asystole. Ictal asystole events were more protracted, and prolonged asystole more frequently occurred in patients with extratemporal seizures compared to temporal lobe seizures. Asystole occurred in only half of the recorded seizures. The accurate categorization of asystole as seizure-related or heart disease-related has huge implications for management strategy and outcome. The necessity of permanent pacemaker implantation is more frequent and urgent in patients with cardiac asystole because of the greater risk of sudden death. Hence, in patients with an ominous diagnosis of cardiac asystole, a thorough cardiac evaluation should surpass neurological evaluation.

Persistent extreme delta brush in anti-NMDA-receptor encephalitis: Does it portend a poor prognosis?

We describe an adolescent girl with non-paraneoplastic anti-NMDA-receptor encephalitis (ANMDARE), who despite persistence of the extreme delta brush (EDB) pattern for nearly 2 years in her serial EEGs, she exhibited a speedy and sustained response to immunotherapy. To the best of our knowledge, our patient had the longest persistence of the EDB pattern on EEG reported to date. Our patient illustrates that, although presence of EDB supports the diagnosis of ANMDARE, its presence and persistence may not be a reliable predictor of response to immunotherapy and overall clinical prognosis.

Hyperbaric oxygen therapy in patients with hypoxic ischemic encephalopathy.

BACKGROUND AND AIM: To assess the efficacy of hyperbaric oxygen therapy (HBOT) in patients with hypoxic ischemic encephalopathy (HIE). DESIGN: Non-randomized case-control observational study. SETTING: Tertiary level neurorehabilitation unit. POPULATION: Twenty-five patients with HIE seen between 1 to 12 months after the injury and having a coma recovery scale-revised (CRS-R) score less than 7 at entry were recruited. METHODS: Out of the patients who received HBOT, 20 received 20 sessions of HBOT at two absolute atmosphere pressure (ATA), and two received 60 sessions at 2 ATA over three different treatment intervals. We compared the outcomes between cases (who received HBOT) and controls (who did not receive HBOT).Cases and controls were allocated to three groups based on the time interval after injury following which they were recruited to the study: 1-3 months (9 cases and 16 controls), 4-8 months (9 cases and 9 controls) and 9-12 months (8 cases and 3 controls). OUTCOME MEASURES: CRS-R, Karnofsky performance scale, and change in disorder of consciousness (DOC) at admission and discharge were assessed. RESULTS: We observed a significant difference in CRS-R favoring the HBOT group at time intervals of 1-3 and 4-8 months. More patients in the HBOT group improved in DOC than the control group. CONCLUSIONS: HBOT given in the first nine months post-HIE can result in a better recovery and functional outcome.

The comparative efficacy of theta burst stimulation or functional electrical stimulation when combined with physical therapy after stroke: a randomized controlled trial.

OBJECTIVE:: To study the long-term effectiveness of Theta Burst Stimulation (TBS) or Functional Electrical Stimulation (FES) combined with Physical therapy (PT) as compared to PT alone for improving arm functions in patients with acute stroke. DESIGN:: Single blind randomized controlled trial. SETTING:: Outpatient clinics and inpatient wards at tertiary care neurology center. SUBJECTS:: Adult patients with acute middle cerebral artery territory ischemic stroke. INTERVENTIONS:: 60 patients were randomized into three groups of 20 each: TBS+PT; FES+PT; and PT alone. TBS group received intermittent TBS of ipsilesional hemisphere and continuous TBS of contralesional hemisphere while FES group received FES of paretic limb, both for four weeks. All groups received supervised physical therapy for four weeks followed by home physiotherapy for one year. OUTCOME MEASURES:: Fugl Meyer Assessment upper limb score (FMA-UL) was primary outcome measure. Patients were evaluated at baseline and subsequently at one, three and six months and one year. RESULTS:: Compared to PT group, mean FMA-UL scores were higher in TBS and FES groups at all follow-ups ( P < 0.001). From baseline to one year, mean (SD) FMA-UL scores increased from 14.9(2.1) to 55.55(2.46) in TBS group, 15.5(1.99) to 55.85(2.46) in FES group, and 14.3(2.2) to 43.3(4.22) in PT group indicating an increase of 273%, 260%, and 203% respectively. There was no difference between FES and TBS groups. CONCLUSION:: A four-week intervention with TBS or FES combined with PT produces better long-term arm functions as compared to PT alone in patients with acute stroke.

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.

Sleep Apnea-Predictor of Functional Outcome in Acute Ischemic Stroke.

BACKGROUND: Sleep apnea is increasingly being recognized as 1 of the important, modifiable risk factors of stroke and cardiovascular diseases. Sleep apnea is thought to impair the functional recovery following stroke. Hence, we evaluated the patients with acute ischemic stroke for prevalence of sleep apnea and compared the functional outcomes of patients with and without sleep apnea, at 3rd month of acute ischemic stroke. METHOD: This study was conducted in Kasturba Medical College (KMC) hospital, Manipal, India, between May 2015 and August 2016. We included 102 consecutive patients of acute ischemic stroke with hemiplegic upper limb power of Medical Research Council (MRC) 3 or less. Sleep apnea was diagnosed in these patients using the sleep disordered Questionnaire, Berlin Questionnaire, and Epworth sleepiness scale. Functional outcome was measured using Barthel score on day 7 and at 3rd month following the onset of stroke. RESULT: Out of 102 patients, sleep apnea was present in 31 (30.6%) patients, more in males (67.7%) and elderly. Hypertension was present in 66.6% of patients with sleep apnea. NIHSS score at admission did not differ between the 2 groups. At 3rd month, the Barthel score calculated was better among patient with no apnea, but this was not statistically significant (P = .119). When mean Barthel score at baseline and 3rd month was calculated using repeated measure Analysis of Variance (ANOVA) between the 2 groups, gain in functional independence in no apnea group was statistically significant (P < .001). CONCLUSION: Sleep-disordered breathing is an independent risk factor for stroke, and sleep apnea is also associated with other known stroke risk factors like hypertension. In acute ischemic stroke, sleep apnea has a negative impact on functional recovery. Sleep apnea is amenable to treatment and should be considered in patients with acute ischemic stroke to improve the chance of recovery, and to reduce the risk of recurrence.

Predictors of seizure outcome following resective surgery for drug-resistant epilepsy associated with focal gliosis.

OBJECTIVEThe authors studied the clinical characteristics and postoperative outcomes of drug-resistant epilepsy associated with focal gliosis.METHODSFrom their epilepsy surgery database, the authors selected the patients with drug-resistant epilepsy and MRI-defined focal gliosis who underwent focal resective surgery. All patients underwent standard presurgical evaluation. Intracranial electroencephalography (EEG) was performed in patients with discordant presurgical data, ill-defined lesions, and lesions close to eloquent regions. Completeness of resection was defined on the basis of extraoperative and intraoperative electrocorticography studies. Favorable postoperative outcome was defined as Engel class I outcome during the last 2 years of follow-up.RESULTSSixty-six patients fulfilled inclusion criteria. An initial precipitating injury was present in 38 (57.6%) patients, mainly in the form of perinatal injury (n = 10), trauma (n = 10), and meningoencephalitis (n = 8). Gliosis involved a single lobe in 38 (57.6%) patients and 2 adjacent lobes in 14 (21.2%) patients; the remaining 14 (21.2%) patients had multilobar gliosis. In patients with unilobar or bilobar gliosis, the posterior region of the head was involved in 34 (65%) patients and the frontal lobes in 12 (23%) patients. During a median follow-up of 4 years (range 2-9 years), 41 (62.1%) patients had favorable outcome. On multivariate analysis, the presence of a well-defined aura (p = 0.019), electrocorticographically defined completeness of resection (p = 0.024), and normal postoperative EEG findings at 1 year (p = 0.003) were predictive of favorable postoperative seizure outcome.CONCLUSIONSFocal gliosis is a common etiology for drug-resistant extratemporal epilepsy in developing countries and is most often located in the posterior region of the head. The majority of these patients have perinatal injuries or neurological infections as initial precipitating injuries. Patients with focal gliosis have good postoperative seizure outcomes after well-planned resective surgery.

Marriage in people with epilepsy: A compelling theme for psycho-behavioral research.

People with epilepsy frequently experience problems in marriage including reduced marital prospects, poor marital outcomes and diminished quality of married life. Conversely, marriage might impact epilepsy self-management and quality of life in people with epilepsy. There is little in published literature on marriage and epilepsy, so there is a need for psycho-behavioral research. Here, we focus on arranged marriages which, although now rare in western cultures, are widely prevalent in South Asian communities. Arranged marriages, in which families rather than individuals choose marital partners, are particularly problematic because epilepsy is frequently hidden during marital negotiations as well as later. From the psycho-behavioral perspective, marital prospects, outcomes and satisfaction should be examined in relation to the type of marriage (arranged vs. love) and whether or not epilepsy is hidden. Additionally, culturally-relevant tools to appraise marital quality and epilepsy self-management within marriage should be developed. The main objective should be to develop a multi-sectorial action plan with interventions at several different levels involving different stakeholders to mitigate stigma associated with epilepsy in matrimony.

Optimal timing and differential significance of postoperative awake and sleep EEG to predict seizure outcome after temporal lobectomy.

OBJECTIVE: To evaluate the prognostic value of postoperative EEGs to estimate post anterior temporal lobectomy (ATL) seizure outcome. METHODS: We studied postoperative EEGs in 325 consecutive patients who had minimum five years of post-ATL followup. Interictal epileptiform discharges (IEDs) present only during sleep were classified as sleep IEDs. We defined favorable final-year outcome as no seizures during the final one year and favorable absolute-postoperative outcome as no seizures during the entire postoperative period. RESULTS: At mean follow-up of 7.3 ±â€¯1.8 years, 281 (86.5%) patients had favorable final-year outcome while 161 (49.5%) had favorable absolute-postoperative outcome. IEDs on three months and one year EEG were associated with unfavorable outcomes while IEDs at 7th day had no association with outcomes. Sleep record increased the yield of IEDs by 30% at each time-point without compromising predictive value. EEG at one year predicted the risk of seizure recurrence on drug withdrawal. CONCLUSION: While EEG at three months and at one-year after ATL predicted seizure outcome, EEG at 7th day was not helpful. Sleep record increases the sensitivity of postoperative EEG without compromising specificity. SIGNIFICANCE: Both awake and sleep EEG provide useful information in postoperative period following ATL.