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.

Evaluation of one-year effectiveness of clobazam as an add-on therapy to anticonvulsant monotherapy in participants with epilepsy having uncontrolled seizure episodes: An Indian experience.

OBJECTIVES: To prospectively study the effectiveness and safety of clobazam as an add-on therapy in patients with epilepsy whose seizures are not adequately controlled with antiseizure medicine (ASM) monotherapy. METHODS: We conducted a prospective, observational study at 28 neurology outpatient clinics in India from June 2017 to October 2019. Consecutive patients with epilepsy (older than 3 years) with inadequate seizure control with ASM monotherapy were initiated on clobazam. Patients were followed up at 1, 3, 6, 9, and 12 months. Seizure control and adverse events were assessed through personal interviews and seizure diaries. RESULTS: Out of 475 eligible patients, data of 429 patients (men: 65.5%) were evaluated (46 excluded due to protocol deviations). The median age was 25 (range, 3-80 years) years and the median duration of epilepsy was 3 (0.1-30) years. The majority of patients had focal epilepsy (55.0%) and genetic generalized epilepsy (40.1%). The one-year follow-up was completed by 380 (88.5%) patients. At one-year follow-up, 317 (83.4%; N = 380) patients in the study remained seizure free. These 317 patients who were seizure free at 12 months comprised 73.9% of the evaluable population (N = 429). In 98.8% of patients, the primary reason for adding clobazam was inadequate control of seizures with treatment. During one-year follow-up, a total of 113 (22.6%) patients experienced at least one adverse event which included 103 (20.6%) patients who experienced 386 episodes of seizures. CONCLUSION: The study provides preliminary evidence that clobazam is effective and well-tolerated as add-on therapy for a period of one year among patients with epilepsy inadequately stabilized with monotherapy. TRIAL REGISTRATION NUMBER: CTRI/2017/12/010906.

Current Concepts in the Management of Idiopathic Generalized Epilepsies.

Idiopathic generalized epilepsies (IGEs) are a group of epilepsies characterized by an underlying genetic predisposition and a good response to antiseizure medicines (ASMs) in the majority of the patients. Of the various broad-spectrum ASMs, valproate is the most effective medicine for the control of seizures in IGEs. However, with the availability of many newer ASMs and evidence showing the high teratogenic potential of valproate, the choice of ASMs for IGEs has become increasingly difficult, especially in women of the child-bearing age group. In this article, we review the current evidence regarding the efficacy and safety of various ASMs in patients with IGEs and provide practical guidelines for choosing appropriate ASMs in various subgroups of patients with IGEs.

Utility of 18F-fluorodeoxyglucose positron emission tomography in presurgical evaluation of patients with epilepsy: A multicenter study.

OBJECTIVE: 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) is widely used in presurgical assessment in patients with drug-resistant focal epilepsy (DRE) if magnetic resonance imaging (MRI) and scalp electroencephalography (EEG) do not localize the seizure onset zone or are discordant. METHODS: In this multicenter, retrospective observational cohort study, we included consecutive patients with DRE who had undergone FDG-PET as part of their presurgical workup. We assessed the utility of FDG-PET, which was defined as contributing to the decision-making process to refer for resection or intracranial EEG (iEEG) or to conclude surgery was not feasible. RESULTS: We included 951 patients in this study; 479 had temporal lobe epilepsy (TLE), 219 extratemporal epilepsy (ETLE), and 253 epilepsy of uncertain lobar origin. FDG-PET showed a distinct hypometabolism in 62% and was concordant with ictal EEG in 74% in TLE and in 56% in ETLE (p < .001). FDG-PET was useful in presurgical decision-making in 396 patients (47%) and most beneficial in TLE compared to ETLE (58% vs. 44%, p = .001). Overall, FDG-PET contributed to recommending resection in 78 cases (20%) and iEEG in 187 cases (47%); in 131 patients (33%), FDG-PET resulted in a conclusion that resection was not feasible. In TLE, seizure-freedom 1 year after surgery did not differ significantly (p = .48) between patients with negative MRI and EEG-PET concordance (n = 30, 65%) and those with positive MRI and concordant EEG (n = 46, 68%). In ETLE, half of patients with negative MRI and EEG-PET concordance and three quarters with positive MRI and concordant EEG were seizure-free postsurgery (n = 5 vs. n = 6, p = .28). SIGNIFICANCE: This is the largest reported cohort of patients with DRE who received presurgical FDG-PET, showing that FDG-PET is a useful diagnostic tool. MRI-negative and MRI-positive cases with concordant FDG-PET results (with either EEG or MRI) had a comparable outcome after surgery. These findings confirm the significance of FDG-PET in presurgical epilepsy diagnostics.

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.

Antiepileptic drugs and serotonin syndrome- A systematic review of case series and case reports.

Serotonin syndrome (SS) is a drug­induced, potentially fatal, clinical syndrome resulting from drugs that have serotonergic properties. Several antiepileptic drugs (AEDs) are known to have serotonergic properties and it can be hypothesized that such AEDs can cause SS. This study aims to review the literature on SS in patients receiving AEDs. We performed a systematic review of Scopus and MEDLINE/PUBMED for case reports and case series of SS where patients had received at least one AED at the onset of symptoms. The cases published in the English literature between 1 January 1991 and 1 April 2021 were included. Initial search identified 1263 articles of which 63 (76 patients) were included in the final analysis. Most of the included cases (53 cases, 70%) have been published in the last 10 years. The mean age of the 76 patients was 40.6 ± 17.8 years, and 51% of cases were females. These patients had been exposed to a total of 8 different types of AEDs. Valproic acid was the most common drug (29, 38%), followed by lamotrigine (22, 29%), gabapentin (16, 21%), pregabalin (seven, 9%), topiramate (five, 7%) and carbamazepine (two, 3%). There has been one case each with phenytoin and oxcarbazepine. Seven (9%) patients received more than one AEDs. Most patients (67, 88%) also received other serotoninergic agents. Only nine (12%) patients were on AEDs alone. The most common clinical condition for using AEDs was psychiatric disorders (36 patients, 47.3%), followed by migraine (17, 22.4%), other painful conditions (15, 19.7%), epilepsy (7, 9.2%), and perioperative conditions (8, 10.5%). Death was reported in two patients. We suggest that AEDs, because of their serotonergic properties, may induce SS, especially in patients who are on another serotonergic agent.

Chronic serotonin syndrome: A retrospective study.

BACKGROUND: Serotonin syndrome (SS) is an underdiagnosed drug-induced clinical syndrome resulting from the excess intrasynaptic concentration of serotonin. Very limited information is available about chronic SS. AIM: To evaluate the epidemiological, clinical, and other aspects of the insidious onset SS. METHODS: We retrospectively evaluated 14 consecutive adult patients (> 18 years) who had complaints for more than 6 wk at the time of consultation and met the Hunter criteria for SS. RESULTS: The mean age was 41.1 years (range: 21-61 years), with a male preponderance (64%). Although tremors were observed in all patients, this was a presenting complaint in only 43% of patients. Generalized body pain, insomnia, and restlessness were common presenting features (50% each). Other common clinical features were stiffness of the limbs (43%), diaphoresis (43%), gait disturbances (36%), bowel disturbances (36%), dizziness (29%), sexual dysfunctions (21%), incoordination (14%), and fatigue (14%) The mean duration of symptoms before the diagnosis of SS was 13.5 ± 5.8 wk (range: 6-24 wk). Amitriptyline was the most common drug (n = 6, 43%), followed by tramadol (n = 5, 36%) and sodium valproate (n = 5, 36%). All patients received cyproheptadine, a 5- hydroxytryptamine2A antagonist, as treatment and noted an excellent response over the course of 4-14 d. CONCLUSION: This study represents the largest study on chronic SS. We suggest that patients receiving serotonergic drugs should be physically examined for the presence of SS upon the development of new symptoms.

The prevalence of serotonin syndrome in an intensive care unit: A prospective observational study.

PURPOSE: In spite of life-threatening nature of serotonin syndrome (SS), it remains an under-diagnosed condition. The availability of epidemiological data about SS, especially in the ICU setting, may help physicians make early diagnoses and interventions. MATERIALS AND METHODS: This was a 6-month prospective study in a medical ICU of a tertiary hospital to find out the prevalence of SS. All consecutive adult patients admitted to the medical ICU were evaluated to see if they fulfilled the Hunter criteria of SS. Patients who met the Hunter criteria were evaluated further for other details. RESULTS: Overall, 309 patients were identified of which 24 (7.8%) met the Hunter criteria. The mean age was 52.4 years, and 75% were male. Most patients received two or more serotonergic drugs. Ondansetron was the most common serotonergic drug (58%), followed by tramadol (38%), and cough syrup (dextromethorphan or chlorpheniramine, 21%). None of the patients received a diagnosis of SS by the treating physicians. Chronic obstructive pulmonary disease exacerbation with respiratory failure and metabolic encephalopathy were the two most common admission diagnoses (17% each). Twenty-two patients received cyproheptadine. There were no fatalities. CONCLUSION: SS is not uncommon in the ICU setting. There is a need to increase awareness among physicians.

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.

Prevalence of benign epileptiform variants from an EEG laboratory in India and frequency of their misinterpretation.

OBJECTIVE: To prospectively study the prevalence of benign epileptiform variants (BEVs) and their impact on epilepsy misdiagnosis. METHODS: Consecutive patients, older than one year, who underwent EEG from January 2016 to December 2019 were prospectively studied for the presence of BEVs. We used descriptions of Klass and Westmoreland (1985) to categorize the BEVs. We reviewed old EEG reports and records in patients with BEV to determine whether they were interpreted as abnormal. RESULTS: Of the 1862 subjects included, 1474 (79 %) patients had epilepsy while 388 (21 %) had other diagnoses. The mean age of the subjects was 23.1 ± 15.3 years and 1111 (60 %) were males. BEVs were noted in 223 (12 %) subjects undergoing EEG. The most common BEVs were wicket waves (n = 127, 6.8 %) and small sharp spikes (n = 69, 3.7 %) while 6 Hz spike-wave discharges (0.9 %), 14 and 6 Hz positive spikes (0.6 %), rhythmic mid-temporal theta burst of drowsiness (0.4 %) and subclinical rhythmic epileptiform discharges in adults (0.2 %) were less common. Patients with BEVs were older and were more likely to have normal EEG (68.2 % vs. 55.8 %; p < 0.001). BEVs were not mentioned in any of the 282 previous EEG reports. BEVS were considered to be over-interpreted as epileptiform abnormalities in 31 of 101 (30 %) records available for review. CONCLUSION: BEVs are present in 12 % of subjects undergoing EEG. BEVS are largely unrecognized and are misdiagnosed as epileptiform discharges in one third of the patients by the general neurologists.

Fatal serotonin syndrome: a systematic review of 56 cases in the literature.

INTRODUCTION: Serotonin syndrome (SS) is a drug-induced potentially life-threatening clinical condition. There is a paucity of data on the risk factors, clinical course, and complications associated with fatal SS. OBJECTIVE: To characterize the epidemiological profile, clinical features, and risk factors associated with fatal SS through a systematic review. METHODS: We performed a systematic review of MEDLINE and Google Scholar for case reports, case series, or cohort studies of fatal SS. RESULTS: Initial database search identified 2326 articles of which 46 (56 patients) were included in the final analysis. The mean age was 42.3 years (range 18-87 years) with female predominance (57%). North America and Europe constitute 80% of the reported fatal SS. The symptoms evolved very rapidly, within 24 h after the administration of serotonergic drugs in 59% of the cases. Fever (61%) was the most common symptom, followed by seizure (36%) and tremors (30%). The mean temperature in the reported cases (25 patients) was 41.6 ± 1.3 °C (range 38.3-43.5 °C). SS was reported to occur with the maintenance dosage of serotonergic agents, after initiation of the drug for the first time, and addition of the drugs for the development of another unrelated illness. Creatine kinase (CK) activities were elevated (>3 times of the upper limit of normal) in eighteen patients, and it was very high (>25,000 IU/L) in four patients. Presence of high grade fever, seizures, and high CK activities may be associated with severe SS. Nine patients (16%) received 5-HT2A antagonists as a therapy. About 50% of patients died within 24 h of the onset of symptoms. CONCLUSIONS: While fatal SS is rare, frequently observed features include hyperthermia, seizures, and high CK activities. Cyproheptadine use appears infrequent for these patients.

Posterior reversible encephalopathy syndrome in a patient with serotonin syndrome.

Serotonin syndrome (SS) is a drug-induced clinical syndrome, characterised by a triad of cognitive impairment, autonomic hyperactivity and neuromuscular abnormalities. Hypertension, one of the common autonomic manifestations in SS, may lead to lead to several life-threatening conditions. Herein, we report a case of SS who had posterior reversible encephalopathy syndrome (PRES) because of high blood pressure.A young male with a 5-month history of chronic tension-type headache and depression had been receiving amitriptyline and paroxetine. Increment of paroxetine led to the development of various new clinical features, fulfilling the Hunter criteria of SS. MRI brain revealed high-signal intensity lesions on T2 fluid-attenuated inversion recovery, and T2-weighted imaging in the posterior regions of the occipital, parietal, temporal and cerebellum lobes, suggestive of PRES. The patient responded to cyproheptadine. Autonomic hyperactivity, due to SS, is the most likely explanation of this association.

Prevalence of photoparoxysmal response in patients with epilepsy: Effect of the underlying syndrome and treatment status.

OBJECTIVE: To prospectively study the prevalence of photoparoxysmal response (PPR) and its determinants in epilepsy patients. METHODS: Consecutive patients, older than 2 years, undergoing EEG from January 2016 to December 2019 were prospectively studied for the presence of PPR. Patients with emergent EEG and those with only sleep record were excluded. Intermittent photic stimulation was performed as per standard techniques with frequencies from 1-30 Hz. RESULTS: Of the 1893 subjects included, 1492 (78%) patients had epilepsy while 401 (22%) had other diagnoses. In epilepsy group, 1028 (68.7%) had focal epilepsy, 343 (21.6%) had generalized epilepsy, while (9.7%) patients had unclassified epilepsy. Overall, 36 (2.2%) patients with epilepsy had PPR. The mean age of these patients was 19.5 ± 9.4 years and 75% were females. PPR was noted in 5 (0.5%) patients with focal epilepsy and 31 (9%) patients with generalized epilepsies [p < 0.0001; Odds ratio: 20.3 (95% CI, 7.8 - 52.7)]. PPR was noted in 1.5% of treated and 18% of untreated patients with genetic generalized epilepsy (n = 145) and 22% of untreated patients with juvenile myoclonic epilepsy (n = 86). Patients with untreated epilepsy had 17 times higher odds of having PPR [p < 0.0001; Odds ratio: 17.6 (95% CI, 4.1 - 75.6)]. CONCLUSION: Underlying epilepsy syndrome and treatment status are the two most important determinants of PPR. Variability in these two factors is largely responsible for the variable reported prevalence of PPR.