Using McGurk effect to detect speech-perceptional abnormalities in refractory epilepsy.

BACKGROUND: McGurk effect is a perceptual phenomenon that demonstrates an interaction between hearing and vision in speech perception. A wide range of neuropsychological deficits have been described in people with long-standing epilepsy, which affect multimodal integration in speech perception and hence refractory epilepsy patients are ideal for testing the McGurk effect. MATERIALS AND METHODS: We studied the McGurk effect in 50 patients diagnosed with medically refractory left or right hemispheric epilepsy based on clinical, radiological, and electrophysiological data. RESULTS: The McGurk effect was better perceived (p = 0.006) in patients with left hemispheric epilepsy (n = 12, 71%) compared to right (n = 5, 29%). The other factors which compromised the perception of the McGurk effect were impairments in visual memory (p = 0.041), facial emotion recognition (p = 0.001), and lip-reading (p = 0.006). Perception of the McGurk effect reduced significantly (p = 0.006) when the epilepsy duration was 10 years or beyond. CONCLUSION: The McGurk effect can be used in refractory epilepsy patients, to detect subtle abnormalities in speech perception, before significant irreversible speech and language dysfunction become evident.

Predictors of outcome in super refractory status epilepticus.

PURPOSE: We conducted this study to determine the clinical, electrophysiological and radiological predictors of outcome in Super Refractory Status Epilepticus (SRSE). METHODS: Data of patients treated for SRSE between January 2000 and November 2019, archived prospectively in our SE registry were analyzed. Functional outcome was measured by Glasgow outcome score (GOS) at the time of hospital discharge and was divided into: good i.e. GOS ≥ 3 and bad outcome i.e. GOS < 3. The predictors of outcome were determined using appropriate statistical tests by univariate and multivariate analysis, p < 0.05 was considered as statistically significant. RESULTS: Of the 384 patients with status epilepticus (SE) identified during the study, 28 (8%) were diagnosed as SRSE and were included in the final analysis. Acute symptomatic SE comprising 15 (53.6%) patients was the most common etiology of SRSE. Thirteen patients (three patients with viral encephalitis and 10 patients with clinically possible autoimmune encephalitis) had New Onset Refractory Status Epilepticus (NORSE) like clinical presentation.12 patients (42.9%) had good outcome and 16 patients (57.1%) had bad outcome. Multivariate logistic regression analysis showed that independent predictors of poor outcome were: duration of ICU stay (p < 0.001); EEG findings such as non-convulsive SE in coma (0.032), spontaneous burst suppression (0.001) and postictal diffuse attenuation (<0.001); delay in starting anesthesia (0.002); and delay in starting immunotherapy in NORSE due to autoimmune encephalitis (0.002). CONCLUSION: We could determine independent therapeutic and electrophysiological prognostic factors for SRSE. Early initiation of treatment and stringent management of these factors especially in an younger age-group, aided by continuous EEG monitoring and a thorough etiological work-up can result in good outcomes in more than one-third of cases.

Intracranial hypertension in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating and life-threatening condition with high mortality and morbidity. Even though there is an association with intracranial pressure (ICP) raise and aSAH, there is a lack of recommendations regarding the indications for ICP monitoring in patients with aSAH. Defining what patients are at a higher risk to develop intracranial hypertension and its role in the functional outcome and mortality in patients with aSAH will be the purpose of the following systematic review and meta-analysis. The primary endpoint is to determine the prevalence and impact on mortality of ICP in patients with aSAH. Secondary endpoints aim to describe the variables related to the development of ICP and the relationship between traumatic and aneurysmal etiology of intracranial hypertension. PubMed, Embase, Central Cochrane Registry of Controlled Trials, and research meeting abstracts were searched up to August 2019 for studies that performed ICP monitoring, assessed the prevalence of intracranial hypertension and the mortality, in adults. Newcastle Ottawa scale (NOS) was used to assess study quality. The statistical analysis was performed using the Mantel-Haenszel methodology for the prevalence and mortality of intracranial hypertension for reasons with a randomized effect analysis model. Heterogeneity was assessed by I2. A total of 110 bibliographic citations were identified, 20 were considered potentially eligible, and after a review of the full text, 12 studies were considered eligible and 5 met the inclusion criteria for this review. One study obtained 7 points in the NOS, another obtained 6 points, and the rest obtained 5 points. Five studies were chosen for the final analysis, involving 793 patients. The rate of intracranial hypertension secondary to aSAH was 70.69% (95% CI 56.79-82.84%) showing high heterogeneity (I2 = 92.48%, p = < 0.0001). The results of the meta-analysis of mortality rate associated with intracranial hypertension after aSAH found a total of four studies, which involved 385 patients. The mortality rate was 30.3% (95% CI: 14.79-48.57%). Heterogeneity was statistically significant (I2 = 90.36%; p value for heterogeneity < 0.001). We found that in several studies, they reported that a high degree of clinical severity scale (Hunt and Hess or WNFS) and tomographic (Fisher) were significantly correlated with the increase in ICP above 20 mmHg (P < 0.05). The interpretation of the results could be underestimated for the design heterogeneity of the included studies. New protocols establishing the indications for ICP monitoring in aSAH are needed. Given the high heterogeneity of the studies included, we cannot provide clinical recommendations regarding this issue.

Status epilepticus in pregnancy - Can we frame a uniform treatment protocol?

BACKGROUND: There is lack of uniform treatment protocol for status epilepticus (SE) in pregnancy, with majority of data being limited to individual cases or case series. Devising a uniform treatment protocol will facilitate prompt control of SE in pregnancy and reduce adverse maternal and fetal outcomes. METHODS: Literature search was done in various databases including PubMed, CINAHL, EMBASE, TRIP, and the gray literature, including relevant organizational websites, for the topics "Status Epilepticus" and "Pregnancy". English language original research articles, case reports, and systematic reviews that were published in the last 18 years (2000-2018) and addressed SE in relation to pregnancy (i.e., antepartum, labor, or postpartum) were considered for inclusion. RESULTS: Over the past 15 years, a total of seven articles reporting 29 cases of SE related to pregnancy, satisfying the inclusion criteria were analyzed. The most common cause of SE was posterior reversible encephalopathy syndrome (PRES)/reversible cerebral vasoconstriction syndrome (RCVS) spectrum (n = 11, 38%), followed by cortical venous sinus thrombosis (CVT) and autoimmune encephalitis (n = 5, 17%). Twenty-three out of 29 cases (79%) had good maternal outcomes in terms of recovery to baseline. Seventeen fetuses (58%) were delivered at term and seven at preterm (2.4%). First-line agent used was lorazepam in 15 patients (52%) and midazolam in two patients (7%). The most common antiepileptic drug (AED) and anesthesia used for treatment of SE and refractory SE were phenytoin/fosphenytoin (n = 21, 72%) and midazolam (n = 12, 52%), respectively. In all cases due to eclampsia (n = 5), magnesium sulfate was the preferred first-line drug. CONCLUSION: Management of SE in pregnancy is influenced by etiology of SE and duration of pregnancy. It carries a good prognosis if detected early and treated appropriately. Large-scale multicentric studies are warranted for formulating definite guidelines for management of SE in pregnancy. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".

Status epilepticus related to pregnancy: Devising a protocol for use in the intensive care unit.

BACKGROUND: Status epilepticus (SE) related to pregnancy is rare and carries a significant risk to both the mother and the fetus. OBJECTIVES: We conducted this study to devise a protocol for the management of SE related to pregnancy in a cohort of female patients admitted with SE during pregnancy. MATERIALS AND METHODS: All women who developed SE related to pregnancy (gestation, labor, and puerperium) between January 2000 and December 2016 were included. Data was collected using a structured proforma. RESULTS: There were 17 women who had SE related to pregnancy, of whom 10 had refractory SE. The various causes of refractory SE were eclampsia (N = 2), posterior reversible encephalopathy syndrome (PRES) due to various causes other than eclampsia (N = 3), cortical venous thrombosis (CVT) [N = 3], subarachnoid hemorrhage (SAH) [N = 1], and N-methyl-D-aspartate (NMDA) receptor antibody-mediated encephalitis (N = 1). Six out of 10 women with refractory SE (60%) and five out of 10 fetuses (50%) had a good outcome. CONCLUSION: There is a dearth of literature with regards to SE related to pregnancy and little or no guidelines exist for its management. Awareness about the diverse etiologies other than eclampsia is important. A protocol-based approach to the diagnosis and management of SE is necessary to ensure best outcomes.

Status epilepticus in pregnancy: Etiology, management, and clinical outcomes.

BACKGROUND: Status epilepticus (SE) in pregnancy carries significant risk to both mother and fetus. There is limited literature available on SE occurring in pregnancy world-over, with majority being from obstetric centers. METHODS: All women who developed SE related to pregnancy (gestation, labor, or puerperium) between January 2000 and December 2016 were included in the study. Data were collected from our SE registry, maintained, and archived in the institute. The variables influencing the maternal and fetal outcome were compared using Student's t-test for continuous variables and Fisher's exact test for discrete variables. RESULTS: During the 16-year study period, a total of 348 SE events were recorded in 294 patients. Among these, there were 138 women, of which 17 had SE related to pregnancy. The etiology of SE was remote symptomatic in two and acute symptomatic in 15 patients. The various causes detected after initial evaluation for acute symptomatic SE were eclampsia (n=4), posterior reversible encephalopathy syndrome due to various causes other than eclampsia (n=6), cortical venous thrombosis (n=3), subarachnoid hemorrhage (n=1), and NMDA receptor antibody-mediated encephalitis (n=1).13 of 17 women with SE (76%) had good outcome. Majority of the fetuses had good outcomes, i.e., Category 1 (n=9, 57%). Duration of intensive care unit stay (p=0.029) and Status Epilepticus Severity Score (p=0.0324) at admission, were found to be significantly associated with poor outcomes. CONCLUSION: In any patient presenting with SE occurring in pregnancy, though eclampsia is presumed to be the most common overall cause; it is relevant to consider other etiologies such as posterior reversible encephalopathy syndrome, cortical venous thrombosis, and autoimmune encephalitis especially in cases presenting with refractory SE. Posterior reversible encephalopathy may occur in pregnancy due to diverse etiologies other than eclampsia.

Bilateral--otitis media, dacroadenitis, parotitis and left sided infranuclear facial palsy: unusual manifestations of Wegener's granulomatosis.

Wegener's granulomatosis is a systemic vasculitis of unknown aetiology. Although it classically involves the upper respiratory tract, lungs and kidneys, virtually any organ may be affected. We report a rare case of a 45 year old female who presented with bilateral-dacroadenitis, otitis media, parotid enlargement and left sided lower motor neuron type of facial palsy as the initial manifestations of Wegener's granulomatosis.

Women's issues.

Special considerations are required for women with epilepsy. These include issues such as catamenial exacerbation, concerns for contraception, teratogenesis (including both anatomical and neurodevelopmental effects), and other concerns for pregnancy complications such as increased seizures or adverse obstetric outcomes. In this manuscript, several cases are presented and discussed addressing some of the important issues in the management of women with epilepsy.

Anti-epileptic drug and folic acid usage during pregnancy, seizure and malformation outcomes: Changes over two decades in the Kerala Registry of Epilepsy and Pregnancy.

BACKGROUND: This study was carried out to determine changes over time in use of folic acid, anti-epileptic drugs (AED), seizures during pregnancy and malformation rate over two decades in women with epilepsy enrolled in the Kerala registry of Epilepsy and Pregnancy (KREP). METHODS: All completed pregnancies with known outcome between 1998 and 2017 (n = 1962) were analyzed for the use of folic acid and AEDs in the first trimester, seizure count for the entire pregnancy and the presence of major congenital malformation (MCM). The results were presented for three epochs (1998-2004, 2005-2011 and 2012-2017). RESULTS: There was significant increase (p = .001) in the use of folic acid 5 mg/day or more in pre-pregnancy month (43.9 to 81 %) and first trimester (52.7 to 86.6 %). Occurrence of seizures during pregnancy had declined significantly (57.2 to 32.9 %, p = 0.001) over time. Those who were off AEDs during pregnancy declined from 17.4 to 8.5 % (p = .001). Newer AEDs - lamotrigine, levetiracetam, oxcarbazepine and topiramate) were increasingly preferred in the last seven years instead of older AEDs (phenobarbitone, phenytoin and clonazepam). There was no significant change in the use of carbamazepine or valproate. MCM rates did not show any significant change (7.5 to 7.3 %). CONCLUSION: Seizure control and high dose folic acid usage during pregnancy had improved over two decades. Despite the changes in the AED usage over time the MCM rates had remained unchanged probably due to continued use of valproate, increased use of topiramate and clobazam that are associated with higher MCM rates and lack of reduction in polytherapy.

Risk of Seizures after Endovascular Management of Ruptured Intracranial Aneurysms: A Systematic Review and Meta-analysis.

Seizures in aneurysmal subarachnoid haemorrhage (aSAH) have been described secondary to SAH, changes in cortical function, vasospasm and as a result of treatment effects. Seizures are one of the important clinical determinants in neurological outcome of aSAH. Various studies support the notion of less risk of future seizures in endovascular treatment as compared to the microsurgical clipping, yet there is no conclusive evidence in favour or against the seizure occurrence in aSAH patients after endovascular treatment as compared to the microsurgical treatment. To carry out a systematic review and meta-analysis of the risk of seizures after endovascular management (coiling) of ruptured intracranial aneurysms. A literature search was performed in electronic database of PubMed, MEDLINE, Embase, and Scopus from inception to February 2020, using the terms Seizure, Intracranial aneurysms, embolization, with no constraints applied. Data were pooled using a random-effect model, results were abstracted as odds ratios (ORs) and 95% confidence interval (CI), and heterogeneity was reported as Chi-square. Five studies involving 3,077 patients were included in the meta-analysis. After endovascular management of aSAH, seizure risk was increased by a worse clinical severity (World Federation of Neurosurgery scale or Hunt and Hess) (OR, 3.34; 95% CI, 2.69-4.16; p<0.00001), severe vasospasm (OR, 2.20; 95% CI, 1.67-2.92; p<0.00001), cerebral infarction (OR, 5.19; 95% CI, 3.23-8.35; p<0.00001), and cerebral edema (OR, 1.79; 95% CI, 1.37-2.34; p<0.0000). Worse clinical severity, vasospasm, cerebral infarction and cerebral oedema are significant risk factors for the development of seizures after endovascular intervention in aSAH. The mechanism for this correlation is not clear.

How safe is bone health in patients on newer or enzyme inhibitor antiepileptic drugs?

BACKGROUND: Data on the effect of enzyme inhibitors and newer anti-epileptic drugs (AEDs) on bone health is limited with conflicting results. AIM: We compared the effects on bone health of patients exposed to enzyme inducer versus enzyme inhibitor AEDs and newer versus older AEDs. METHODS: We prospectively studied 51 patients on AEDs for more than two years and equal age and sex matched controls from March 2017 to September 2018. Biochemical bone mineral markers and bone mineral density (BMD) were measured and analysed between patients versus controls and between various sub-groups based on enzymatic effect, generation and number of AEDs. RESULTS: Of 51 patients,11(21.5%) had osteopenia and 3(5.9%) had osteoporosis. T-score (-0.75 ±â€¯1.22 versus 0.004 ±â€¯1.0, p < .001) and Z-score at femur neck (-0.38 ±â€¯1.08 versus0.002 ±â€¯0.81, p < .001) were found to be significantly lower in patients compared to controls. Relative risk for low BMD was higher in patients on polytherapy compared to monotherapy (RR = 1.37,CI = 0.69-2.74).Higher relative risk for low BMD was noted with; clobazam (RR = 1.51,CI = 0.82-2.78), oxcarbazepine (RR = 1.33,CI = 0.68-2.59), phenobarbitone (RR = 1.31,CI = 0.26-6.7) and leviteracetam (RR = 1.18,CI = 0.45-3.06) mono or polytherapy and valproate monotherapy (RR = 3.5,CI = 1.09-11.29). No significant difference was noted with regards to mean dosage or metabolic or radiological markers of bone health between patients on enzyme inducer versus inhibitors and newer versus older AEDs. A significant negative correlation was found between cumulative drug load and femur T-score (r2 = -0.27, p = .04). CONCLUSION: Bone health in epilepsy is adversely affected by chronic exposure to AEDs; irrespective of the enzymatic effect or generation of AEDs. Complex pharmacodynamic mechanisms of AEDs as well as pharmacokinetic interactions between various AED polytherapies affects bone health.

Teratogenicity of antiepileptic dual therapy: Dose-dependent, drug-specific, or both?

OBJECTIVE: To determine the relative risk (RR) of major congenital malformations (MCMs) in infants with antenatal exposure to antiepileptic drug (AED) dual therapy and to explore the influence of specific AEDs vs dose. METHODS: All completed pregnancies prospectively enrolled in the Kerala Registry of Epilepsy and Pregnancy from 1998 until December 2013 on AED dual therapy exposure during the first trimester were analyzed for the outcome, MCMs. Dose was expressed as ratio of prescribed to daily defined dose (PDD/DDD), and the RR for malformation was referenced to lamotrigine monotherapy. RESULTS: Of 1,688 completed pregnancies, 368 women were on dual therapy. The risk of MCM with dual therapy was 1.6 times more than with monotherapy (p = 0.0015). The frequency of renal, alimentary, and skeletal malformations was higher with dual therapy, while cardiac malformations were more common with monotherapy. The risk of MCM was highest with topiramate dual therapy (14.82, 95% confidence interval [CI] 1.88-113.83). No MCMs were seen with levetiracetam or lamotrigine dual therapy. There was a marked reduction in the risk of MCM when dual therapies involving topiramate or valproate were excluded (RR 1.78, 95% CI 1.00-3.15). The risk of MCM with dual therapy was higher even at lower doses (8.2%, PDD/DDD 0.5-1), and the subsequent dose-dependent increment was less profound than with monotherapy. CONCLUSIONS: Our data indicate that the excess risk of dual therapy over monotherapy is contributed largely by topiramate or valproate. The complex pharmacokinetic and pharmacodynamic effects of dual therapy adversely influence MCM risk.

An audit of the predictors of outcome in status epilepticus from a resource-poor country: a comparison with developed countries.

Status epilepticus is a neurological emergency with significant morbidity and mortality. This study describes the clinical profile, treatment, and predictors of outcome of status epilepticus in a tertiary referral centre in a developing country and aims to highlight the similarities and differences from data available from the western world. A retrospective analysis of data of patients treated for status epilepticus was conducted from prospectively maintained records, between January 2000 and September 2010. The demographic data, clinical profile and investigations (including neuroimaging and EEG), aetiology, treatment, and outcomes were studied and compared with data available from the western world. The analysis included 108 events in 84 patients. A single episode of status epilepticus was treated in 72 patients (86%) and multiple status epilepticus events, ranging from two to six per patient, were managed in 12 patients (14%). Mean age was 24.1±20.3 years and 63% were males. The types of status epilepticus included convulsive status in 98 (90.7%), non-convulsive status in seven (6.5%), and myoclonic status in three (2.8%). The majority of events (60%) were remote symptomatic, 16% were acute symptomatic, 16% were of unexplained aetiology, and 8% were progressive symptomatic. In 85 events (79%), status epilepticus could be aborted with first and second-line drugs. The remaining 23 events (21%) progressed to refractory status epilepticus, among which, 13 (56%) were controlled with continuous intravenous midazolam infusion. Case fatality rate was 11%, neurological sequelae were reported in 22%, and 67% returned to baseline. Acute symptomatic status, older age, altered sensorium at the time of admission, and delayed hospitalisation were predictors of poor outcome. Aetiology was the most important determinant of outcome of status epilepticus, as in reports from the western world, with remote symptomatic aetiology secondary to gliosis being the most common. Treatment delay was frequent and adversely affected the outcome.