Epileptic Patients are at Risk of Cardiac Arrhythmias: A Novel Approach using QT-nomogram, Tachogram, and Cardiac Restitution Plots

Background: Sudden death is reported in patients who had a history of epilepsy and some authors believed that is due to cardiac arrhythmias. Objectives: This study aimed to predict that the epileptic patients are at risk of serious cardiac arrhythmias by QT-nomogram, tachogram (Lorenz), and cardiac restitution plots. Methods: A total number of 71 healthy subjects (Group I) and 64 newly diagnosed epileptic patients (Group II) were recruited from Al-Yarmouk and Baghdad Teaching hospitals in Baghdad from March 2015 to July 2015 and included in this study. The diagnosis of epilepsy achieved clinically, electroencephalograph record and radio-images including computerized tomography and magnetic image resonance. At the time of entry into the study, an electrocardiography (ECG) was done, and the determinants of each ECG record were calculated. The QT-nomogram, tachogram, and cardiac restitution plots were used to identify the patients at risk of cardiac arrhythmias. Results: Significant prolonged corrected QT corrected (QTc) and JT corrected intervals were observed in female compared with male at age ≥50 years while the TQ interval was significantly prolonged in males of Group II. Eight patients of Group II had a significant pathological prolonged QTc interval compared with undetectable finding in Group I. QT nomogram did not disclose significant findings while the plots of Lorenz and restitution steepness disclose that the patients of Group II were vulnerable to cardiac arrhythmias. Abnormal ECG findings were observed in the age extremities (≤18 years and ≥50 years) in Group II compared with Group I. Conclusion: Utilization of QT-nomogram, restitution steepness, and tachogram plots is useful tools for detection subclinical vulnerable epileptic patient with cardiac arrhythmias

Split limb phenomenon in amyotrophic lateral sclerosis: electrophysiologic study

Abstract Background Amyotrophic lateral sclerosis (ALS) is a degenerative disease that affects the upper and lower motor neurons. The onset of the disease is frequently focal, usually involving the distal segments of the extremities. A dissociated pattern of muscle atrophy is commonly found in the hands and feet. This study aims to investigate the presence (if any) of split indices in ALS patients and to correlate these indices with confounding factors. A total of 48 people were studied. The control group consists of 24 ALS patients and another 24 age- and gender-matched patients. To assess functional status and muscle strength, the ALS functional rating scale (ALSFRS) and the Medical Research Council (MRC) were used, respectively. Sensory and motor nerve conduction, as well as compound muscle action potential (CMAP) amplitude, were recorded from the muscles of the upper and lower limbs. The electromyographic (EMG) activity of 20 motor unit action potentials (MUAPs) from four different areas was also studied. Results Distal CMAP amplitude was reduced in all tested muscles (especially noticed when comparing the reciprocal muscles). In ALS patients, the split foot index (SFI) is significantly higher, while the split elbow index (SEI) is significantly lower. The split foot index (SFI) was found to be negatively related to disease duration, but positively related to ALSFRS scores. The CMAP amplitude was found to be positively related to the MRC score. Conclusion Ankle dorsiflexion muscles are more involved (dissociated) than plantar flexor muscles, and elbow flexors are more involved than extensors. SFI correlates significantly with disease duration and ALSFRS scores

P300 event-related potentials in people with epilepsy: clinico-neurophysiologic study

Abstract Background There is increasing evidence that prolonged or recurrent seizures can cause or exacerbate cognitive impairment (CI) in memory, attention, orientation, and visuospatial and abstraction disabilities, all of which can jeopardize educational progress and achievement throughout life. The objectives of our study are to assess the cognitive functions in people with epilepsy (PwE) using P300 event-related potentials (ERPs), and correlate each P300 components with six explanatory variables (epilepsy type, seizure type, NHS3 score- seizure severity, disease duration, age at first seizure, and the number of anticonvulsant medications). Methods One hundred and two PwE [52 with focal epilepsy and 50 with generalized epilepsy, as classified by the International League Against Epilepsy in 2017]. They underwent electroencephalography (EEG) and P300. The Montreal Cognitive Assessment (MoCA) scale was used to assess baseline cognitive functions. Results Epileptic patients showed significant latency prolongation and amplitude reduction of P300 as compared to non-epileptic population. Longer P300 latency and lower amplitude were seen in patients with abnormal EEG records. P300 latency was longer in patients using poly-therapy. P300 components correlated well with age at presentation and disease duration but not with NHS3. According to epilepsy type, 50.98% of PwE had focal epilepsy and 49.02% had generalized epilepsy, 85.29% of them had abnormal EEG recording. Considering seizure type, 47.06% had a generalized tonic–clonic seizure, 38.24% had a focal to bilateral tonic–clonic seizure, 20.59% had a myoclonic seizure, 12.75% had a focal with impaired awareness seizure, 3.92% had a focal aware seizure, and 2.94% had an absence seizure. Seventy-seven PwE had one type of seizure, while 25 had more than one type of seizure. The NHS3 score was higher in those with a single seizure type than in those with multiple seizure types. Conclusion All seizure types had an abnormal P300 component, indicating cognitive function deficits. P300 may be a promising objective method for assessing cognitive function in PwE. The number of antiepileptic drugs used, the presence of EEG abnormalities, the age at presentation, and the duration of the disease are the factors that best correlate with cognitive impairment (CI)

A review of NeuroAiDTM II (MLC901) development in Alzheimer’s disease treatment: promises of a multimodal pathway

Background: Alzheimer’s disease (AD) is a clinical and economic burden on society. Without new treatment, the impact of AD on society could triple by 2050. Aim: After a brief overview of treatments and challenges of new drug developments for AD, we reviewed the preclinical and clinical development program of NeuroAiD (MLC901, MLC601). Method: A literature search was conducted by using different web sources. The initial screening was based on keywords contained in the subtitles of each corresponding paragraphs of this article. We sorted the reviewed publications by relevance and publication date selecting 74 references out of the 319 initially shortlisted for review. Review: Since 1998, only symptomatic drugs were marketed. Intensive research has continued, aimed at delaying the onset of the disease and/or slowing its progression. However, the predictive value of delaying the onset of AD remains debated. Since 2003, aducanumab is the first new treatment approved and registered by US-FDA as an amyloid beta-directed antibody indicated for the treatment of Alzheimer’s disease under post-marketing conditions. Traditional medicines (TM) have shown interesting results, but many of TM clinical studies leave much to be desired from a methodological point of view. Among TM, NeuroAiD (MLC901/601), a botanical-derived combination, acts in a multimodal pathway combining neuroprotective and neuroregenerative properties. It has demonstrated sustained symptomatic benefits, slowing the disease progression in AD with a good safety profile. Discussion/Conclusions: The discovery of treatments preventing or slowing down the disease progression, are necessary to get reliable diagnostic tools to confirm AD diagnosis, and follow its evolution and long-term therapy. A growing consensus is emerging on the need for a multi-factorial approach to the treatment and the development of suitable AD drug combinations. Such an approach has been that of TM for a long time. This is the case for NeuroAiD, that it may be integrated safely either after symptomatic treatments have failed or on top of symptomatic treatments

Safety and Efficacy of Disease Modifying Therapies After Switching from Natalizumab: A MENACTRIMS Observational Study

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Disease-Modifying Therapies, Outcomes, Risk Factors and Severity of COVID-19 in Multiple Sclerosis: A MENACTRIMS Registry Based Study

International audienceMultiple sclerosis (MS) patients have been considered a higher-risk population for COVID-19 due to the high prevalence of disability and disease-modifying therapy use; however, there is little data in our Middle East and North Africa region (MENA) identifying clinical characteristics of MS associated with worse COVID-19 outcomes

Disease-modifying therapies, outcomes, risk factors and severity of COVID-19 in multiple sclerosis: A MENACTRIMS registry based study

International audienceBackground: There is a lack information regarding risk factors associated with worse COVID-19 outcomes in patients with multiple sclerosis (MS) in the MENA region. Methods: This is a multicenter, retrospective cohort study that included all MS patients with a suspected or confirmed COVID-19 infection using the MENACTRIMS registry. The association of demographics, disease characteristics, and use of disease-modifying therapies (DMTs) with outcomes and severity of COVID-19 were evaluated by multivariate logistic model. Results: A total of 600 MS patients with confirmed (n = 542) or highly suspected (n = 58) COVID-19 were analyzed. Seventy-three patients (12.2 %) had a COVID-19 severity score of ≥3 on a 7-point ordinal scale (ranging from 1 [not hospitalized with no limitations on activities] to 7 [death] with a cutoff at 3 [hospitalized and not requiring supplemental oxygen]), and 15 patients (2.5 %) died. Out of 73 patients with a severity score ≥3, 90.4 % were on DMTs; 50.6 % of them were on anti-CD20, including ocrelizumab and rituximab. Multivariate logistic regression showed that older age (odds ratio per 10 years, 1.4 [95 %CI, 1.0-1.8]), disability (OR for EDSS 3.0-5.5, 2.9 [95 %CI. 1.5-5.7], OR for EDSS ≥6.0, 2.3 [95 %CI. 1.0-5.1]), obesity (OR, 3.0 [95 %CI, 1.5-6.0]), and treatment with rituximab (OR, 9.0 [95 %CI, 3.1-25.3]) or off-label immunosuppressive medications (OR, 5.6 [95 %CI. 1.1-27.8]) were risk factors for moderate or severe COVID-19.</div

Safety and effectiveness of disease-modifying therapies after switching from natalizumab

International audienceIntroduction: One strategy to mitigate progressive multifocal leukoencephalopathy (PML) risk is to switch to other highly effective disease-modifying therapies (DMTs). However, the optimal switch DMT following natalizumab (NTZ) discontinuation is yet to be determined. Objective: The objective of the study is to determine the most effective and tolerable DMTs to switch to following NTZ discontinuation due to John Cunningham virus (JCV) antibody positivity. Methods: This is a multicenter observational cohort study that included all stable relapsing-remitting multiple sclerosis (MS) patients who were treated with NTZ for at least 6 months before switching therapy due to JCV antibody positivity. Results: Of 321 patients, 255 switched from NTZ to rituximab/ocrelizumab, 52 to fingolimod, and 14 to alemtuzumab, with higher annualized relapse rate (ARR) in fingolimod switchers (0.193) compared with rituximab/ocrelizumab or alemtuzumab (0.028 and 0.032, respectively). Fingolimod switchers also had increased disability progression ( p = 0.014) and a higher proportion developed magnetic resonance imaging (MRI) lesions compared with rituximab/ocrelizumab (62.9% vs. 13.0%, p &lt; 0.001, and 66.6% vs. 24.0%, p &lt; 0.001, respectively). Mean drug survival favored rituximab/ocrelizumab or alemtuzumab over fingolimod ( p &lt; 0.001). Conclusion: Our study shows superior effectiveness of rituximab/ocrelizumab and alemtuzumab compared with fingolimod in stable patients switching from NTZ due to JC virus antibody positivity

Hamsi scoring in the prediction of unfavorable outcomes from tuberculous meningitis: results of Haydarpasa-II study

Predicting unfavorable outcome is of paramount importance in clinical decision making. Accordingly, we designed this multinational study, which provided the largest case series of tuberculous meningitis (TBM). 43 centers from 14 countries (Albania, Croatia, Denmark, Egypt, France, Hungary, Iraq, Italy, Macedonia, Romania, Serbia, Slovenia, Syria, Turkey) submitted data of microbiologically confirmed TBM patients hospitalized between 2000 and 2012. Unfavorable outcome was defined as survival with significant sequela or death. In developing our index, binary logistic regression models were constructed via 200 replicates of database by bootstrap resampling methodology. The final model was built according to the selection frequencies of variables. The severity scale included variables with arbitrary scores proportional to predictive powers of terms in the final model. The final model was internally validated by bootstrap resampling. A total of 507 patients' data were submitted among which 165 had unfavorable outcome. Eighty-six patients died while 119 had different neurological sequelae in 79 (16 %) patients. The full model included 13 variables. Age, nausea, vomiting, altered consciousness, hydrocephalus, vasculitis, immunosuppression, diabetes mellitus and neurological deficit remained in the final model. Scores 1-3 were assigned to the variables in the severity scale, which included scores of 1-6. The distribution of mortality for the scores 1-6 was 3.4, 8.2, 20.6, 31, 30 and 40.1 %, respectively. Altered consciousness, diabetes mellitus, immunosuppression, neurological deficits, hydrocephalus, and vasculitis predicted the unfavorable outcome in the scoring and the cumulative score provided a linear estimation of prognosis

Results of a multinational study suggest the need for rapid diagnosis and early antiviral treatment at the onset of herpetic meningoencephalitis

Data in the literature regarding the factors that predict unfavorable outcomes in adult herpetic meningoencephalitis (HME) cases are scarce. We conducted a multicenter study in order to provide insights into the predictors of HME outcomes, with special emphasis on the use and timing of antiviral treatment. Samples from 501 patients with molecular confirmation from cerebrospinal fluid were included from 35 referral centers in 10 countries. Four hundred thirty-eight patients were found to be eligible for the analysis. Overall, 232 (52.9%) patients experienced unfavorable outcomes, 44 died, and 188 survived, with sequelae. Age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.05), Glasgow Coma Scale score (OR, 0.84; 95% CI, 0.77 to 0.93), and symptomatic periods of 2 to 7 days (OR, 1.80; 95% CI, 1.16 to 2.79) and >7 days (OR, 3.75; 95% CI, 1.72 to 8.15) until the commencement of treatment predicted unfavorable outcomes. The outcome in HME patients is related to a combination of therapeutic and host factors. This study suggests that rapid diagnosis and early administration of antiviral treatment in HME patients are keys to a favorable outcome