Genetic polymorphisms of microsomal epoxide hydrolase and UDP-glucuronosyltransferase (UGT) and its effects on plasma carbamazepine levels and metabolic ratio in persons with epilepsy of South India: A cross-sectional genetic association study.

OBJECTIVES: Carbamazepine (CBZ), an anti-seizure drug, is widely prescribed for the management of focal seizures. At a given therapeutic dose, CBZ exhibits marked interindividual variation in the plasma CBZ levels. The aim wasto study the influence of EPHX1 c.337 T>C and UGT2B7*2 genetic polymorphisms on plasma carbamazepine (CBZ) levels in persons with epilepsy (PWE) from South India. METHODS: 115 PWE belong to South India origin who are on carbamazepine monotherapy were recruited. Genotyping of the two variants weredone using RT-PCR method. PWE who had seizure freedom for one year and their last dose which was not changed for one year duration were included and their plasma levels of CBZ and its active metabolite CBZ 10,11 epoxide were analysed by reverse phase HPLC. RESULTS: In EPHX1 c. 337 (T>C) polymorphism, the PWE carrying CC had lower plasma CBZ levels when compared to CT genotype (2.45 µg/ml vs 3.15 µg/ml. In UGT2B7*2, PWE carrying homozygous mutant TT had higher levels when compared with CT (3.09 µg/ml vs 2.74 µg/ml) genotype but found no statistical significance. Mutant genotype of EPHX1 (CC) had higher metabolic ratio compared to TT genotype (1.33 vs 1.17) but not found to be statistically significant. Mutant genotype of UGT2B7*2 (TT) was found to be having lower metabolic ratio when compared with CC genotype (1.18 vs 1.35; p value =0.08). CONCLUSION: PWE carrying EPHX1 c.337 T>C (rs1051740) and UGT2B7*2 (rs7439366) genetic polymorphisms did not affect the plasma CBZ levels and metabolic ratio of PWE of South Indian origin. However, this finding should be confirmed in a larger sample size which may help in optimization and personalized CBZ therapy in South Indians.

Assessment of auditory perception abilities using temporal envelope and fine structure processing in children with self-limited epilepsy with centrotemporal spikes.

OBJECTIVES: Children with self-limited epilepsy with centrotemporal spikes (SeLECTS) exhibit difficulty processing spoken messages without hearing loss. The temporal envelope and fine structure processing abilities are the fundamental aspects of the normal listening process. There is limited literature on the temporal envelope and fine structure processing in children with SeLECTS. We evaluated the temporal envelope and fine structure processing in children with SeLECTS. DESIGN: The study included 35 children with SeLECTS and 50 typically developing children (TDC). The temporal envelope processing was measured using the temporal modulation transfer function (TMTF) and temporal fine structure using the temporal fine structure low-frequency (TFS LF) test. The TMTF was measured for the modulation rates 4, 8, 16, 32, 64 and 128 Hz. The TFS LF was done for 250, 500 and 750 Hz. RESULTS: The difference in modulation detection thresholds at 4 Hz was not found to be significant, whereas there was a significant difference in modulation detection thresholds observed for all the other modulation frequencies (p < 0.05) between the children with SeLECTS and TDC. The thresholds at 250, 500 and 750 Hz were higher (poorer) for children with SeLECTS than the TDC and was significant (p < 0.05). CONCLUSIONS: The TMTF and TFS LF tests were of practical use in evaluating temporal envelope and fine structure processing abilities in children with SeLECTS. The results suggest that children with SeLECTS have a poor temporal envelope and fine structure processing compared to the TDC.

Hyperglycemia and steroid use increase the risk of rhino-orbito-cerebral mucormycosis regardless of COVID-19 hospitalization: Case-control study, India.

BACKGROUND: In the ongoing COVID-19 pandemic, an increased incidence of ROCM was noted in India among those infected with COVID. We determined risk factors for rhino-orbito-cerebral mucormycosis (ROCM) post Coronavirus disease 2019 (COVID-19) among those never and ever hospitalized for COVID-19 separately through a multicentric, hospital-based, unmatched case-control study across India. METHODS: We defined cases and controls as those with and without post-COVID ROCM, respectively. We compared their socio-demographics, co-morbidities, steroid use, glycaemic status, and practices. We calculated crude and adjusted odds ratio (AOR) with 95% confidence intervals (CI) through logistic regression. The covariates with a p-value for crude OR of less than 0·20 were considered for the regression model. RESULTS: Among hospitalised, we recruited 267 cases and 256 controls and 116 cases and 231 controls among never hospitalised. Risk factors (AOR; 95% CI) for post-COVID ROCM among the hospitalised were age 45-59 years (2·1; 1·4 to 3·1), having diabetes mellitus (4·9; 3·4 to 7·1), elevated plasma glucose (6·4; 2·4 to 17·2), steroid use (3·2; 2 to 5·2) and frequent nasal washing (4·8; 1·4 to 17). Among those never hospitalised, age ≥ 60 years (6·6; 3·3 to 13·3), having diabetes mellitus (6·7; 3·8 to 11·6), elevated plasma glucose (13·7; 2·2 to 84), steroid use (9·8; 5·8 to 16·6), and cloth facemask use (2·6; 1·5 to 4·5) were associated with increased risk of post-COVID ROCM. CONCLUSIONS: Hyperglycemia, irrespective of having diabetes mellitus and steroid use, was associated with an increased risk of ROCM independent of COVID-19 hospitalisation. Rational steroid usage and glucose monitoring may reduce the risk of post-COVID.

Risk factors of intracranial haemorrhage in preeclampsia: a case-control study.

Intracranial haemorrhage (ICH) is an uncommon but one of the most devastating and potentially fatal complications of preeclampsia. Most ICHs in pregnancy are reported in the absence of a vascular lesion, and severe systolic hypertension is thought to be an important risk factor even though many reports suggest that ICH can complicate preeclampsia even at lower blood pressure levels. In this case-control study of preeclamptic women, risk factors associated with ICH were compared in women who did and did not develop ICH. During the study period, ICH occurred in 1.8% (42/2167) pregnancies with preeclampsia, with 45.2% (n = 19/42) resulting in maternal mortality. HELLP syndrome (OR = 11.5; 95% CI 3.8-34.8), multiparity (OR 3.2; 95% CI 1.4-7.7), nausea/vomiting (OR = 3.6; 95% CI 1.4-9.3), and lower educational attainment (OR = 38.2; 95% CI 3.5-423.6) were associated with the increased probability of ICH. The incidence of caesarean birth (n = 29, 74.4% vs. n = 161, 34.5%) and neonatal mortality (n = 4, 13.3% vs. n = 17, 4.0%) were higher among preeclamptic who have ICH compared to those who did not have it. Improving awareness as well as early identification of those at risk of preeclampsia and complications can limit the impact of ICH among pregnant women with preeclampsia, especially in low- to middle-income countries.

Risk factors for posterior reversible encephalopathy syndrome in hypertensive pregnant women presenting with seizures.

Pregnant women developing generalised tonic-clonic seizures in the absence of a prior neurological disorder are often diagnosed as eclamptic. Posterior reversible encephalopathy syndrome (PRES) is a distinct neuroimaging condition associated with long-term sequelae, which may occur in pregnancy. Some reports suggested PRES to be the pathophysiological process leading to eclampsia, whereas others observed PRES and eclampsia to have varying clinical severity and risk factors. In this case-control study, risk factors associated with PRES were compared to those for eclampsia in women with hypertension presenting with seizures who had undergone neuroimaging. PRES was noted to occur in 22.5% (51/227) hypertensive pregnant women presenting with seizures that otherwise would have been classified as eclampsia. An additional 51 women with eclampsia underwent neuroimaging. Women who had PRES had higher systolic (155.3 vs 144.5, p = 0.04), diastolic (99.2 vs 93.4, p = 0.006) and mean (117.9 vs 110.4, p = 0.001) blood pressure at admission compared to those with eclampsia. Eclampsia and PRES may occur through a similar pathophysiological mechanism, resulting in the same spectrum of neurological complications of preeclampsia, with PRES being the severest form of the disease process. PRES is difficult to differentiate from eclampsia based on clinical and laboratory investigation, except for high blood pressures, without adjunctive MRI/CT neuroimaging. Future studies should assess the role of biomarkers as well as long-term neurological sequelae in pregnant women with a diagnosis of PRES.

CYP2C19 & UGT1A6 genetic polymorphisms and the impact on Valproic acid-induced weight gain in people with epilepsy: Prospective genetic association study.

OBJECTIVES: To study the association between CYP2C19*2 (681 G > A) and UGT1A6*2 (552A > C) polymorphisms on Valproic acid (VPA)-induced weight gain in People with epilepsy (PWE). METHODS: We recruited PWE on VPA monotherapy and genotyped for CYP2C19 and UGT1A6 polymorphisms. Association between CYP2C19 polymorphism and weight gain was the primary outcome parameter. We followed them up monthly for six months and recorded Body mass index (BMI), drug compliance, side effects, food frequency, physical activity. RESULTS: Of 108 participants recruited, we assessed the association between the polymorphism and weight gain in 101 PWE for CYP2C19*2 and 103 PWE for UGT1A6*2 polymorphism. The proportion of participants with weight gain was higher in those with poor and intermediate metabolizer genotypes of CYP2C19 (*1/*2 and *2/*2) compared to extensive metabolizers (*1/*1) [53.3 % vs 31.7 %, RR 1.68, 95 % CI (1.01-2.79), P = 0.03]. However, CYP2C19*2 allele did not show an increased risk of weight gain over the CYP2C19*1 allele. No association could be demonstrated with UGT1A6 genotypes and weight gain. In logistic regression analysis, CYP2C19*2 carrier genotype was the independent predictor of weight gain. OR 2.89 [95% CI (1.07-7.84)]. There were no significant association with serum TSH, fT4, testosterone, and valproate levels with CYP2C19 or UGT1A6 polymorphisms. SIGNIFICANCE: People with epilepsy carrying CYP2C19 polymorphisms (*1/*2) and (*2/*2) had 3 times higher risk of VPA-induced weight gain compared to wild type (*1/*1).

Association of serum calprotectin with peripheral neuropathy in patients with type 2 diabetes mellitus.

INTRODUCTION: Peripheral neuropathy is a common microvascular complication in patients with type 2 diabetes mellitus with a prevalence of around 50%. OBJECTIVES: This prospective observational cross-sectional study was done to assess serum calprotectin levels among diabetic patients with peripheral neuropathy as compared to those without neuropathy. METHODS: This cross-sectional study was conducted in 126 diabetic patients attending the out-patient department of JIPMER Hospital, Pondicherry from July 2017 to January 2019. The subjects were divided into two groups (with and without peripheral neuropathy) and underwent nerve conduction study of both the lower limbs. Blood samples were collected and stored at -80°C for estimation of serum calprotectin. Serum calprotectin levels were compared between diabetic patients with and without peripheral neuropathy. RESULTS: Serum calprotectin levels were increased in patients with diabetic peripheral neuropathy (DPN) as compared to those without DPN. However, there was no significant difference in the mean value of serum calprotectin among the various sub-groups of DPN. CONCLUSION: Serum calprotectin, an inflammatory biomarker is elevated in patients with diabetic peripheral neuropathy as compared to those without neuropathy.

Video teleconsultation services for persons with epilepsy during COVID-19 pandemic: An exploratory study from public tertiary care hospital in Southern India on feasibility, satisfaction, and effectiveness.

PURPOSE: During the COVID-19 pandemic, there is a large unmet need for follow-up services, particularly for chronic diseases such as epilepsy. Alternative methods to reach these people have become necessary. We assessed the feasibility, satisfaction, and effectiveness of video teleconsultation using mobile phones for managing persons with epilepsy (PWEs) on follow-up at a tertiary care center in the southern part of India. PATIENTS AND METHODS: We included PWEs aged 18 years and over who have been evaluated in person within the past six months, with details available in electronic health records (EHRs), and advised regular follow-up after getting telephonic consent. We excluded those requiring emergency care and those seeking teleconsultation for new symptoms. Participants were sent a message in English and in the local language about the possibility of a video teleconsultation. If willing, they were informed about the date, time, and technical requirements such as smartphones, browsing facilities, etc. Feasibility and effectiveness were assessed. Satisfaction/acceptability was assessed using Telemedicine Satisfaction Questionnaire. RESULTS: From June 2020 to October 2020, we selected 336 PWEs after screening 1100 records, and we tried video teleconsultation in 141 (41.8%) PWEs. We achieved successful video connections in 95 (28.2%) and audio consultations in 46 (13.6%). The median duration for calling the participants, making successful connections, and consultation was 8 (5-14) min. The majority required two (47.4%) or three (32.6%) attempts. Sixty-five PWEs (68.4%) used caretaker's mobile phones. We gave prescriptions to all, and 18 received new drugs. Out of 95 PWEs, 90% either 'agreed' or 'strongly agreed' on 12 out of 14 telemedicine satisfaction questions. CONCLUSION: Although we need to make video teleconsultation more feasible, our synchronous mobile video teleconsultation model is an effective and acceptable method to follow up PWEs. This real-time model has the advantage that it does not require any mobile application to be downloaded and installed. Further studies are needed to evaluate methods to improve the reach of these services particularly to vulnerable groups of the population.

Comparison of proximal and distal corticosteroid injections for carpal tunnel syndrome.

INTRODUCTION: Evidence for the efficacy of distal corticosteroid injection compared with proximal injection in carpal tunnel syndrome (CTS) is inadequate. METHODS: We conducted a randomized, double-blind noninferiority trial of 131 wrists with CTS. Forty milligrams of methylprednisolone was injected medial to the palmaris longus tendon 2 cm proximal to the wrist crease, or at the volar aspect, 2 to 3 cm distal to the wrist crease. Proximal & distal groups received a placebo. The primary outcome was difference in CTS Symptom Severity Scale (SSS) score at 1 month. Secondary outcome measures included the difference in SSS score at 3 months, Functional Status Scale (FSS) score at 1 and 3 months, and pain of injections. RESULTS: No significant differences were noted between groups in scores on the SSS and FSS. Pain was lower in the proximal group compared with the distal group. DISCUSSION: Corticosteroid injections for CTS distal to the wrist are not inferior to proximal injections, yet they are more painful.

Adrenoleukodystrophy presenting as glue sniffing.

Adrenoleukodystrophy classically presents in childhood with bronze skin, spastic tetraparesis, dysphagia, behavioural abnormalities and adrenal insufficiency. However, atypical presentations are known. Here we report an adolescent with adrenoleukodystrophy who first sought medical attention for glue sniffing.

Telemedicine in epilepsy: How can we improve care, teaching, and awareness?

Telemedicine (TM) is the use of telecommunications' technologies to provide medical information and services. Telehealth (TH) permits broader and psychosocial support for patients and their families. We aimed to highlight the importance of the use of TH for all aspects of epilepsy, either for the scientific aspects (e.g., research, education, care, management, etc.) or for the social matters (e.g., education, sensitization, association support, etc.). There is a deep gap in knowledge and use of TH in the developing and developed countries. Epilepsy is a condition responsible for 1% of the global burden of disease. More than 50 million people have epilepsy, and barriers to care include shortage of human resources, medical facilities, and resources. Eighty (80) percent of people with epilepsy (PWE) live in low- and middle-income countries. Telehealth has the potential of addressing limited resources and improving access to PWE across the globe.

Complete recovery in Wernicke's encephalopathy complicating hyperemesis gravidarum.

Wernicke's encephalopathy (WE) is an uncommon neurological complication in pregnancies complicated with hyperemesis due to thiamine deficiency. In women with hyperemesis, inadvertent glucose administration prior to thiamine supplementation triggers the development of neurological manifestations. Delay in the diagnosis can lead to maternal morbidity, and in one-third of cases may lead to persistence of some neurological deficit. With early recognition and thiamine supplementation, complete recovery is reported. We report a case of WE complicating a case of triplet pregnancy with hyperemesis gravidarum, which highlights the importance of early recognition and treatment, resulting in complete recovery as in the index case.

Role of Ultrasound to Monitor Patients With Carpal Tunnel Syndrome Treated With a Local Corticosteroid.

OBJECTIVES: Carpal tunnel syndrome (CTS) is an entrapment neuropathy resulting from compression of the median nerve at the carpal tunnel (CT). We assessed the role of high-resolution ultrasound (US) in monitoring patients with CTS treated with corticosteroid injection. METHODS: We performed high-resolution US evaluations of the wrists of patients with CTS before and after treatment with local corticosteroid. Thirty-nine and 17 wrists were included for analysis at the end of 1 and 3 months, respectively. The cross-sectional area (CSA) and anteroposterior diameter (APD) of the median nerve at the CT and clinical and electrophysiologic data were recorded. We assessed whether changes in US measurements before and after the treatment correlated with clinical and electrophysiologic parameters. RESULTS: The Boston symptom severity scale (p < .01), Boston functional status scale (p < .01), median nerve motor latency (p = .017), median nerve sensory velocity (p = .003), and difference in motor latencies (p = 0.03) and difference in sensory latencies (p = .03) between median and ulnar nerves showed significant changes over 1 or/and 3 months compared to baseline values. Changes in the CSA and APD correlated with changes in some clinical and electrophysiologic parameters. However, measurements of the CSA and APD at 1 or 3 months were not significantly different from baseline values. CONCLUSIONS: High-resolution US parameters such as the APD and CSA of the median nerve at the CT inlet were not useful to monitor patients with CTS treated with corticosteroid injections.

New-onset interictal headache in Persons with epilepsy (PWE): A case-control study.

PURPOSE: In our personal experience, headache is a frequent complaint in Persons with epilepsy (PWE) receiving antiepileptic drugs (AEDs), carbamazepine (CBZ) in particular. There is hardly any systematic study on AEDs-associated headache. We assessed the association of new-onset interictal headache in PWE with CBZ compared with other AEDs and factors associated with it. METHODS: Two thousand PWE on AEDs were screened, and 165 persons having new-onset interictal headache were identified. Eight persons were excluded because of comorbid illnesses that could potentially contribute to a headache. Finally, 157 were recruited for the study. One hundred fifty-seven age- and sex-matched PWE on AEDs, without headache, were recruited as controls. Headache questionnaire based on the International Classification of Headache Disorders (ICHD-II) criteria was used. Demographic factors, seizure characteristics, type and dose of AEDs, findings on electroencephalogram (EEG), and magnetic resonance imaging (MRI)/computerized tomography (CT) were recorded. RESULTS: Among PWE with headache, the majority [88 (56.1%)] were on CBZ compared with other AEDs but not significantly different from controls. In 71 (45%) persons, the headache had migrainous character. In both univariate and multivariate analyses, lower seizure frequency and fewer EEG abnormalities were found to be independent predictors of headache. CONCLUSIONS: New-onset interictal headache is a significant issue in PWE; nonmigrainous headache is more common than the migrainous type. Carbamazepine was not found to have any predilection for new-onset interictal headache compared with other AEDs. A lower frequency of seizures and EEG abnormalities in PWE with headache may suggest that seizures contribute less to the development of headache and may further support the hypothesis that AEDs may be significant contributing factors for the headache.

High Frequency of Depressive Symptoms among Adults with Epilepsy: Results from a Hospital-based Study.

CONTEXT: Assessment of comorbid burden of depression and associated factors among adult people living with epilepsy (PWE) has the potential to inform clinical evaluation and management to improve outcomes. AIM: The aim of this study is to determine frequency of depressive symptoms and factors associated with it among PWE attending a tertiary care hospital. SETTING AND DESIGN: This was a cross-sectional observational study conducted in the outpatient clinic of a tertiary care center. SUBJECTS AND METHODS: One hundred and fifty patients with epilepsy were recruited between May 2016 and August 2016. For assessing depression, Tamil validated version of Patient Health Questionnaire-12 was used. Frequency of depression and its association with various sociodemographic and clinical factors were assessed. STATISTICAL ANALYSIS USED: Student t-test and Chi-square test for univariate analysis and logistic regression for multivariate analysis were used for statistical analysis. RESULTS: Of the 150 subjects, 89 (59.3%) were males. Generalized tonic-clonic seizures were present in 131 people (87.3%). Genetic and unknown epilepsies contributed higher proportion (44.7%) as compared to structural epilepsies (37.3%). Majority (88%) were on one or two antiepileptic drugs. Thirty-one people (20.3%) had less than one seizure per year. Depressive symptoms were present in 95 patients (63.3%). In multivariate regression analysis, secondary generalized seizures and seizure frequency >1/month emerged as significant predictors of depression ([OR]: 5.48 [95% (CI): 1.35-22.28] and OR: 2.53 [95% CI: 1.11-5.75], respectively). CONCLUSION: Depression is prevalent in a majority of adult PWE. Hence, a routine screening for depression as part of comprehensive epilepsy care is advisable for PWE attending the outpatient clinic.

Sporadic Creutzfeldt-Jakob disease (sCJD) with asymmetric findings.

We report a case of a patient with probable Creutzfeldt-Jakob disease (CJD) who had psychiatric manifestation in the form of withdrawn depressive behaviour at the onset, followed by rapidly progressive ataxia, parkinsonism, mutism and cognitive decline with generalised asynchronous multifocal myoclonic jerks. His EEG exhibited focal (lateralised) periodic triphasic sharp waves on the background of generalised delta slowing, which later on became more generalised. MRI of the brain showed hyperintensity in basal ganglia with cortical ribbon sign in bilateral frontal region. Clinical course showed progressive deterioration to an akinetic-abulic stage. He died 2 months after the onset of symptoms.

Refractory status epilepticus complicated by drug-induced involuntary movements.

New onset refractory status epilepticus (NORSE) is a neurological emergency and difficult to treat condition. We report a case of involuntary movements resulting from thiopentone sodium infusion during the management of refractory status epilepticus. A young woman was admitted with fever and NORSE in the neurology intensive care unit. In addition to supportive measures, she was treated with intravenous lorazepam, phenytoin sodium, sodium valproate, midazolam and thiopentone sodium. While on thiopentone sodium, she developed involuntary twitches involving her upper limbs and face with EEG showing no evidence of ongoing status epilepticus. Because of the temporal relationship with thiopentone infusion, we tapered the dose of thiopentone sodium, which resulted in the disappearance of the movements. The patient recovered well with no recurrence of the seizures during the hospital stay.