Dosage, time, and polytherapy dependent effects of different levetiracetam regimens on cognitive function.

OBJECTIVE: Cognitive impairment is a potential drawback of antiseizure medications. This study aimed to evaluate the impact of different levetiracetam drug regimens on cognitive function. METHODS: A retrospective analysis identified 221 patients diagnosed with seizures who underwent cognitive screening. Patients were categorized into four groups: no medications, non-levetiracetam medications, high and low dose levetiracetam. Composite scores determined low and high levetiracetam groups whereby one point was added for each increment in dosage, duration since uptake, and concurrent anti-seizure medication. Variables known to affect cognition were recorded and classified as demographic, seizure-related, diagnosis-related, and psychopathology. Logistic regression was used to identify variables associated with cognitive scores below cut-off. RESULTS: Multivariable analysis found being male, non-active in the community, less than 12 years of education, left temporal lobe epilepsy, high seizure frequency, and depression were associated with poor cognitive performance. In a final regression analysis, the high levetiracetam group exhibited a 4.5-fold higher likelihood of scoring below cut-off than the medication-free group (OR 4.5, CI 1.5-13.6, p<.08). Depression (OR 2.1, CI 1.1-3.9, p<.03), being male (OR 2.2, CI 1.1-4.3, p<.02), and not being active in the community (OR 3.8, 1.6-8.7, p <.003) remained significant contributors to the model. Language (p<.05), attention (p<.05), and delayed recall (p<.001) were the most affected cognitive domains. SIGNIFICANCE: When taken in small doses, for brief periods as monotherapy, levetiracetam minimally influences cognition. At higher doses, as part of long-term seizure management, in conjunction with multiple ASMs, LEV is associated with cognitive impairment.

Drug-resistant epilepsy: Definition, pathophysiology, and management.

There are currently >51 million people with epilepsy (PWE) in the world and every year >4.9 million people develop new-onset epilepsy. The cornerstone of treatment in PWE is drug therapy with antiseizure medications (ASMs). However, about one-third of PWE do not achieve seizure control and do not respond well to drug therapy despite the use of appropriate ASMs [drug-resistant epilepsy (DRE)]. The aims of the current narrative review are to discuss the definition of DRE, explain the biological underpinnings and clinical biomarkers of this condition, and finally to suggest practical management strategies to tackle this issue appropriately, in a concise manner.

Seizure clusters.

Acute repetitive seizures, also called seizure clusters, are common phenomena in patients with epilepsy. They are a burden on patients and their caregivers and may be very disruptive to the patients' lives. They may progress to prolonged seizures or status epilepticus if they are not aborted as soon as possible. However, their definition, recognition, and classification still suffer from a lack of consensus among healthcare professionals in the field. This review aims to shed light on various aspects of seizure clusters with particular attention to their treatments.

Prevalence and Incidence of Drug-Resistant Temporal Lobe Epilepsy in Qatar.

BACKGROUND: Information on the epidemiology of temporal lobe epilepsy associated with hippocampal sclerosis (TLE-HS) from Qatar and the developing countries is scarce. To acquire knowledge on the incidence and prevalence of drug-resistant TLE-HS in Qatar, we designed this analytical and extrapolative systematic review of the existing literature. MATERIAL AND METHODS: We searched the electronic database PubMed from 1947 until April, 2018, using the following search terms in the title: "epilepsy" OR "temporal lobe" OR "hippocampal sclerosis" AND "epidemiology" OR "incidence" OR "prevalence." Relevant original studies, reviews, and their references, were included. We extrapolated from the previous international literature to estimate the epidemiology of drug-resistant TLE-HS in Qatar. RESULTS: The estimated Qatar incidence of epilepsy varies from 50 to 61 per 100 000 persons per year, and the estimated prevalence of epilepsy is 6.54 per 1000 population; the estimated incidence of TLE varies from 9.5 to 11.6 patients per 100 000 population per year and the estimated prevalence of TLE is 1.76 patients per 1000 people, with 4721 patients having TLE in Qatar. Finally, the reviewed studies also helped in making an estimate of the Qatar prevalence of drug-resistant TLE-HS to be between 0.3 and 0.6 cases per 1000 people (804-1609 current patients) and the Qatar incidence of drug-resistant TLE-HS (2.3-4.3 cases per 100 000 people, per year) with 62 to 116 new patients per year. CONCLUSION: Our study suggests that 804 to 1609 current patients (with 62-116 additional patients per year) in Qatar are suffering from drug-resistant TLE-HS; emphasis should be placed on the surgical aspect of the current Qatar Comprehensive Epilepsy Program.

Unexpected brain imaging findings in patients with seizures.

New imaging technologies have advanced our ability to localize the epileptogenic zone in patients with epilepsy. As a result of the constant improvement of the image quality, magnetic resonance imaging (MRI) has become the most important ancillary tool in the management of patients with epilepsy. Magnetic resonance imaging for the evaluation of patients with epilepsy should be done using a special temporal lobe protocol and read by physicians experienced with the findings in patients with epilepsy. On the other hand, in the healthy populations, incidental structural brain abnormalities have been reported in 18% of people. Incidental, subtle, or unexpected structural brain abnormalities have also been reported in many patients who were investigated because of having seizures. In the current narrative review, we will discuss some of these instances, where structural brain abnormalities are discovered unexpectedly, are subtle (but important) and/or may be considered as incidental.

Current status of stroke in Qatar: Including data from the BRAINS study.

BACKGROUND: Qatar is located on the north-eastern coast of the Arabian Peninsula. Qatari natives account for less than 15% of the population while the largest migrant group comprising 60% derives from South Asia. Despite projections that stroke burden in Qatar will increase with population ageing, epidemiological studies focusing on stroke in Qatar are relatively scarce. METHOD: We reviewed the available epidemiological publications relating to Qatar. In addition, we have added to this knowledge by incorporating Qatari data from the on-going Bio-Repository of DNA in Stroke, an independent multinational database of stroke patients. RESULTS: Qatar has low reported incidence and mortality rates of 58 and 9.17 per 100,000 per year, respectively, which may be explained by its middle-aged migrant worker majority population. Correspondingly, South Asian migrants in Qatar suffered younger strokes than Qatari natives (48.7 vs 63.4 years, P < 0.001). Among the most common risk factors identified in stroke patients were hypertension (77.9%), diabetes (43.8%) and hypercholesterolemia (28.5%). Ischaemic stroke was the most frequent subtype amongst migrant South Asians (71.1%). The majority of stroke cases had computed tomography and/or magnetic resonance imaging scans, but only 11.1% of ischaemic strokes were thrombolysed. Qataris on one-year follow up were more often found to have died (6.5% vs 0.3%) and had further stroke/transient ischaemic attack events (17.4% vs 6.4%, P = 0.009) compared to South Asians. CONCLUSION: The burden of stroke is increasing in Qatar, and considerable disparities are observed between the native and migrant populations which likely will require different approaches to management by its healthcare system.

Electroencephalography in epilepsy: look for what could be beyond the visual inspection.

Since its starting point in 1929, human scalp electroencephalography (EEG) has been routinely interpreted by visual inspection of waveforms using the assumption that the activity at a given electrode is a representation of the activity of the cerebral cortex under it, but such a method has some limitations. In this review, we will discuss three advanced methods to obtain valuable information from scalp EEG in epilepsy using innovative technologies. Authors who had previous publications in the field provided a narrative review. Spike voltage topography of interictal spikes is a potential way to improve non-invasive EEG localization in focal epilepsies. Electrical source imaging is also a complementary technique in localization of the epileptogenic zone in patients who are candidates for epilepsy surgery. Quantitative EEG simplifies the large amount of information in continuous EEG by providing a static graphical display. Scalp electroencephalography has the potential to offer more spatial and temporal information than the traditional way of visual inspection alone in patients with epilepsy. Fortunately, with the help of modern digital EEG equipment and computer-assisted analysis, this information is more accessible.

Oral disease-modifying therapies for multiple sclerosis in the Middle Eastern and North African (MENA) region: an overview.

BACKGROUND: The introduction of new disease-modifying therapies (DMTs) for remitting-relapsing multiple sclerosis (RRMS) has considerably transformed the landscape of therapeutic opportunities for this chronic disabling disease. Unlike injectable drugs, oral DMTs promote patient satisfaction and increase therapeutic adherence. REVIEW: This article reviews the salient features about the mode of action, efficacy, safety, and tolerability profile of approved oral DMTs in RRMS, and reviews their place in clinical algorithms in the Middle East and North Africa (MENA) region. A systematic review was conducted using a comprehensive search of MEDLINE, PubMed, Cochrane Database of Systematic Reviews (period January 1, 1995-January 31, 2018). Additional searches of the American Academy of Neurology and European Committee for Treatment and Research in Multiple Sclerosis abstracts from 2012-2017 were performed, in addition to searches of the Food and Drug Administration and European Medicines Agency websites, to obtain relevant safety information on these DMTs. CONCLUSIONS: Four oral DMTs: fingolimod, teriflunomide, dimethyl fumarate, and cladribine have been approved by the regulatory agencies. Based on the number needed to treat (NNT), the potential role of these DMTs in the management of active and highly active or rapidly evolving RRMS is assessed. Finally, the place of the oral DMTs in clinical algorithms in the MENA region is reviewed.

Characteristics of patients with confirmed epilepsy and psychogenic nonepileptic seizures in Qatar.

OBJECTIVE: The Middle Eastern country of Qatar opened its first epilepsy monitoring unit (EMU) in late 2015. This study compared demographic and clinical characteristics of patients with confirmed epilepsy to those of patients with confirmed psychogenic nonepileptic seizures (PNES). METHODS: Data were collected via retrospective chart review on 113 patients admitted for evaluation to the Qatar national health system EMU between November 2015 and May 2017. RESULTS: Seventy-one patients had a confirmed diagnosis (20 had PNES, 46 had epilepsy, 5 had both PNES and epilepsy). Evaluation in 33 patients was inconclusive, and 9 had other medical conditions. Patients with PNES were significantly more likely to be primary Arabic speakers (p = 0.003), and this difference was not explained by education or employment status. The most common referral request in patients with PNES was for recurrent/refractory seizures (p = 0.011), and there was a trend for patients with PNES to have more frequent seizures compared with patients with epilepsy (daily to several per week versus several times a month or less, p = 0.051). Depression was identified in 47% of patients with epilepsy and 65% of patients with PNES, and patients with PNES had higher mean depression scores on the PHQ-9 than patients with epilepsy (p = 0.014). Patients with PNES experienced significantly more fatigue (p = 0.021). Seventy percent of patients with PNES and 50% of patients with epilepsy reported sleep problems. CONCLUSIONS: The characteristics of patients with epilepsy and PNES at the EMU in Qatar were generally similar to those found worldwide. Patients with PNES more often suffered from frequent depression, sleep problems, and fatigue than those with epilepsy, but these were significant concerns for both groups.

Clinical presentation, epidemiology, neurophysiological findings, treatment and outcome of nonconvulsive status epilepticus: a 3-year prospective, hospital-based study.

Objective: This study reports the prevalence of Nonconvulsive Status Epilepticus (NCSE) in patients with altered mental status (AMS), and describes the clinical presentation, etiology, neurophysiological findings, neuroimaging, treatment, and outcome of NCSE in Qatar. Recording duration of continuous EEG monitoring was also discussed. Methods: This was a 3-year, prospective, hospital-based study involving patients with AMS and continuous EEG monitoring admitted to the Emergency and ICUs of Hamad Hospital, Qatar. Patients with confirmed diagnosis of NCSE were compared to the patients who did not show EEG and clinical features compatible with NCSE. Descriptive statistics in terms of mean with standard deviation, as well as frequency and percentages for categorical variables, were calculated; Student's t test as well as Chi-square tests or Fisher's exact tests were applied. Logistic regressions NSCE was performed using significance level 0.05 for independent variables at univariate analysis. Results: Number of patients with AMS and continuous EEG monitoring was 250. Number of patients with EEG compatible with NCSE: 65 (age range, 12-79 ys; m, 37; f, 28). Number of controls (defined as patients with EEG not compatible with NCSE): 185 (age range, 12-80 ys; m, 101; f, 84). Rate of occurrence of NCSE in patients with AMS: 26%. NCSE group was younger than controls (p < .001). Twenty patients with NCSE (31%) and 35 patients in the control group (19%) died. Death was more frequent in comatose NCSE compared to controls (p < .0007). NCSE proper and comatose NCSE had longer hospital stays than controls (p < .02 and p < .03, respectively). Complete recovery occurred in 26 NCSE patients (40%) and in 98 controls (53%) (p < .08). Twenty-one patients (31%) presented with refractory NCSE: 12 patients survived, 9 died. Conclusion: This was the first prospective study reporting a high number of NCSE in Qatar, a small country in the MENA region. This prevalence (26%) was in the middle range. NCSE patients did not perform better than controls, outcome being worse with comatose NCSE. NCSE is an emergent condition warranting expedited diagnosis and management. Three days of continuous EEG monitoring were able to diagnose most cases of NCSE.

Optimization and stratification of multiple sclerosis treatment in fast developing economic countries: a perspective from Qatar.

OBJECTIVE: The introduction of disease-modifying therapies (DMTs) - with varying degrees of efficacy for reducing annual relapse rate and disability progression - has considerably transformed the therapeutic landscape of relapsing-remitting multiple sclerosis (RRMS). We aim to develop rational evidence-based treatment recommendations and algorithms for the management of clinically isolated syndrome (CIS) and RRMS that conform to the healthcare system in a fast-developing economic country such as Qatar. RESEARCH DESIGN AND METHODS: We conducted a systematic review using a comprehensive search of MEDLINE, PubMed, and Cochrane Database of Systematic Reviews (1 January 1990 through 30 September 2016). Additional searches of the American Academy of Neurology and European Committee for Treatment and Research in Multiple Sclerosis abstracts from 2012 through 2016 were performed, in addition to searches of the Food and Drug Administration and European Medicines Agency websites to obtain relevant safety information on these DMTs. RESULTS: For each of the DMTs, the mode of action, efficacy, safety and tolerability are briefly discussed. To facilitate the interpretation, the efficacy data of the pivotal phase III trials are expressed by their most clinically useful measure of therapeutic efficacy, the number needed to treat (NNT). In addition, an overview of head-to-head trials in RRMS is provided as well as a summary of the several different RRMS management strategies (lateral switching, escalation, induction, maintenance and combination therapy) and the potential role of each DMT. Finally, algorithms were developed for CIS, active and highly active or rapidly evolving RRMS and subsequent breakthrough disease or suboptimal treatment response while on DMTs. The benefit-to-risk profiles of the DMTs, taking into account patient preference, allowed the provision of rational and safe patient-tailored treatment algorithms. CONCLUSIONS: Recommendations and algorithms for the management of CIS and RRMS have been developed relevant to the healthcare system of this fast-developing economic country.

Epilepsy in Qatar: Causes, treatment, and outcome.

OBJECTIVE: Qatar is a small country on the Eastern coast of the Arabian Peninsula. Its population is a unique mixture of native citizens and immigrants. We aimed to describe the features of epilepsy in Qatar as such information is virtually lacking from the current literature. METHODS: We summarized information retrospectively collected from 468 patients with epilepsy seen through the national health system adult neurology clinic. RESULTS: Epilepsy was classified as focal in 65.5% of the cases and generalized in 23%. Common causes of epilepsy were as follows: stroke (9%), hippocampal sclerosis (7%), infections (6%), and trauma (6%). Sixty-six percent of patients were receiving a single antiepileptic drug, with levetiracetam being the most frequently prescribed drug (41% of subjects). When the patients were divided by geographical background, remote infections caused the epilepsy in 15% of Asian patients (with neurocysticercosis accounting for 10%) but only in 1% of Qatari and 3% of Middle East/North African subjects (with no reported neurocysticercosis) (p<0.001). Cerebrovascular and neurodegenerative etiologies were the most prominent in Qataris, accounting for 14% (p=0.005) and 4% (p=0.03) of cases, respectively. The choice of antiepileptic drugs varied also according to the regional background, but the seizure freedom rate did not, averaging at 54% on the last clinic visit. SIGNIFICANCE: To our knowledge, this is the first detailed information about epilepsy in Qatar. The geographical origin of patients adds to the heterogeneity of this disorder. Neurocysticercosis should be in the etiological differential diagnosis of epilepsy in patients coming from Southeast Asian countries, despite the fact that it is not endemic to Qatar. The choice of antiepileptic drugs is influenced by the availability of individual agents in the patients' native countries but had no bearing on the final seizure outcome.

Prevalence, demographics and clinical characteristics of multiple sclerosis in Qatar.

No published epidemiologic data on multiple sclerosis (MS) in Qatar exist. Our objectives were to determine the prevalence, demographics and clinical characteristics of MS in the Middle Eastern country of Qatar. We analyzed data for Qatari MS patients fulfilling the McDonald diagnostic criteria. A total of 154 patients fulfilled the inclusion criteria. On 31 April 2010, the crude prevalence of MS in Qatar was 64.57 per 100,000 inhabitants (95% CI: 58.31-70.37). The female-to-male ratio was 1.33:1. A positive family history was found in 10.4% of included MS patients. We conclude that Qatar is now a medium-to-high risk area for MS, with some important differences in clinical characteristics as compared to other countries in the region.

Hypothalamic hamartoma presenting with gelastic seizures, generalized convulsions, and ictal psychosis.

We report a case of hypothalamic hamartoma in an adult female who presented with gelastic seizures, generalized convulsions, and ictal aggressive psychotic behavior. Anticonvulsant treatment was ineffective in controlling the epileptic seizures. Surgical excision after accurate imaging diagnosis 3 decades after the onset of symptoms markedly ameliorated her condition. Delayed and erroneous diagnosis had unnecessarily prolonged the suffering of our patient.

Scleredema Diabeticorum with unusual presentation and fatal outcome.

We present a case of Scleredema Diabeticorum (SD) in a patient with diabetic neuropathy and restrictive respiratory disease with unusual skin lesion distribution. The onset of dermatologic symptoms heralded a progressive respiratory disease with constrictive component. Painful diabetic neuropathy was noteworthy and difficult to relieve. Predominantly, distribution of the skin lesions on the thighs makes the case exceptional. T2-weighted MRI showed abnormal hyperintensities along the muscles of the thighs in correspondence with the skin lesions. Gait and respiratory symptoms progressively worsened. After a transient remitting period, he developed sudden shortening of breath, arrested and expired at home.The atypical distribution of the skin lesions with further involvement of underlying muscles plus concomitant polyneuropathy and respiratory constrictive disease with sudden death is quite unusual and aggressive presentation of SD.

Short-term efficacy and safety of valproate sustained-release formulation in newly diagnosed partial epilepsy VIPe-study. A multicenter observational open-label study.

OBJECTIVE: To evaluate the efficacy and safety of valproate (VPA) sustained-released in monotherapy across all ages in newly-diagnosed epileptic patients with partial seizures (PS) with or without secondary generalization. METHODS: This was a multicenter, prospective, observational, open-label, non-comparative study involving the Gulf Cooperation Council (GCC) countries except the Kingdom of Saudi Arabia, and was performed between November 2004 and May 2006. Adults and children (6 years or older with newly diagnosed partial epilepsy [PE]) with or without secondary generalization were enrolled. The primary efficacy parameter was 6 month-remission rate (proportion of seizure-free patients in relation to total number of retained patients). Secondary efficacy parameters included: 6 month-retention rate, investigator's clinical global impression rating, maximal effective dose and safety profile. RESULTS: Seventy-seven patients were enrolled; 56% adults and 44% children, with average duration of epilepsy of 5 months in the pediatric and 17 months in the adult group. Seizures type distribution: PS with secondary generalization (62%), complex PS (53%) and simple PS (14%). The majority had idiopathic seizures (48%). Sixty-six patients completed the study (treatment retention rate 80.5%). At 6 months, 87% of patients became seizure free with VPA sustained-release monotherapy (average dose 22 mg/kg/day). Adverse drug reactions (hair loss and tremor) were recorded in <20% of patients, mostly affecting adults. CONCLUSION: In this population, short-term treatment with VPA sustained-release in monotherapy provides good seizure control and is well tolerated.

Irreversible papillitis and ophthalmoparesis as a presenting manifestation of neurobrucellosis.

A 35-year-old man presented with a meningeal syndrome and acute onset of visual blurring. Clinical investigations revealed bacterial meningitis with bilateral papillitis and ophthalmoparesis. Serum and cerebrospinal fluid serology confirmed the diagnosis of chronic active neurobrucellosis. Following therapy there was no improvement and he developed optic atrophy. Extensive literature review revealed, one case of bilateral irreversible papillitis resulting from neurobrucellosis. However no cases of neurobrucellosis have been reported with meningitis, irreversible papillitis and ophthalmoparesis. This case demonstrates that in endemic areas, acute meningitis is a potential manifestation of neurobrucellosis and that bilateral irreversible papillitis with ophthalmoparesis can be a potential serious complication.

Central nervous system demyelination associated with etanercept in a 51 years old woman.

There are few case reports documenting a new onset of demyelinating processes in patients receiving anti-tumour necrosis factor alpha therapy (anti-TNF alpha) for chronic inflammatory arthropathies. Whether anti-TNF alpha therapy induces new onset demyelination or just exacerbates pre-existing latent multiple sclerosis is not fully understood. We are reporting a 51-year-old woman without a prior history of multiple sclerosis, who developed demyelinating brain lesions three months after starting Etanercept. Her symptoms partially resolved on cessation of the drug. Our case was unusual compared to some previous case reports, as the patient's age at presentation was beyond that for idiopathic multiple sclerosis. This may strengthen the hypothesis of a causal relationship between new onset demyelination and Etanercept; however, exacerbation of pre-existing demyelinating process by Etanercept in this patient still cannot be totally excluded. We recommend doing magnetic resonance imaging (MRI) of the brain before starting patients on anti-TNF alpha therapy to exclude latent demyelination. In addition, new onset demyelination following anti-TNF alpha therapy should be reported and studied thoroughly as this may yield a significant advancement in our understanding of the pathogenesis of multiple sclerosis. Long-term follow-up of these cases is also important to determine the long-term prognosis and the rate of relapse of demyelinating process in this group of patients.

Ethnic variations in risk factor profile, pattern and recurrence of non-cardioembolic ischemic stroke.

BACKGROUND: Ischemic stroke is influenced by ethnic and geographical variations. The aim of this study was to identify the risk factor profiles, subtypes and recurrence of non-cardioembolic ischemic stroke for the two largest subpopulations, the Arab and South Asians, at the only stroke-admitting hospital in Qatar. METHODS: Data on stroke patients admitted to Hamad Medical Corporation from January through December 2001 were reviewed in January 2005. Only patients with non-cardioembolic ischemic stroke and complete work-up were included. RESULTS: A total of 303 patients with ischemic non-cardioembolic stroke fit the entry criteria. Sixty seven percent of the overall patient population (sex ratio 2:6, M/F) was of Arab origin, and 32% were South Asians. Hypertension was the most commonly encountered risk factor followed by dyslipidemia, diabetes mellitus, and obesity. Significant differences between the Arab and South Asian subgroup of patients were observed with respect to number of risk factors and occurrence of obesity and diabetes. Carotid artery stenotic lesions, ventricular wall motion abnormalities and stroke recurrence were observed with a higher frequency in the Arab subgroup of patients compared with the South Asians. The majority of strokes were lacunar hemispheric strokes (68%), followed by lacunar brainstem strokes (15%) and large-vessel hemispheric infarctions (10%). Patients with a previous history of stroke had a higher frequency of carotid artery stenosis (p = 0.05) and risk of stroke recurrence (p = 0.04). CONCLUSIONS: Unlike in other studies originating from the Arabian Gulf, lacunar stroke is the most common subtype of non-cardioembolic ischemic stroke in both the Arabs and South Asians in Qatar. Significant ethnic differences in age of occurrence, risk factor profile, and cardiovascular variables were observed.

"Man-in-the-barrel" syndrome as delayed manifestation of extrapontine and central pontine myelinolysis: beneficial effect of intravenous immunoglobulin.

"Man-in-the-barrel" syndrome has been rarely described following osmotic myelinolysis. We report a case of a 45-year-old woman admitted with septicemia and severe hyponatremia. She presented with a "man-in-the-barrel" syndrome which developed more than 10 days after rapid correction of the hyponatremia. There was radiological evidence of central pontine and extrapontine myelinolysis. Three days after completing a course of intravenous immunoglobulin therapy (0.4 g/kg body weight/day for 5 days) there was considerable improvement (Expanded Disability Status Scale score improved 30%). This case, reported for its peculiar mode of development, unusual presentation and challenging therapeutic response to intravenous immunoglobulin, highlights the enigmatic and unpredictable aspects of osmotic myelinolysis.