Neurocysticercosis in non-endemic regions: The experience of Qatar.

Objective: To describe the occurrence and features of Neurocystircercosis (NCC) in Qatar. Background: Qatar has a mixed population of natives and expats. NCC is not endemic to the region, but clinical practice suggests its occurrence in large numbers. Design/ methods: A database was created to summarize information retrospectively collected on patients with NCC seen through the national health system (HMC) between 2013 and 2018. We identified demographic and disease related variables (clinical manifestations, investigative findings, treatment and outcome) for all patients. Results: Out of 420 identified NCC patients, 393 (93.6%) were men, and 98.3% were immigrants from NCC endemic countries such as Nepal (63.8%) and India (29.5%). Eighty percent of patients presented with seizures, with the majority (69%) experiencing generalized tonic-clonic seizures. Five percent presented with status epilepticus. Headaches, the second most common complaint, were reported in 18% of subjects. On imaging, 50% had a single lesion while 63% included pathology at the calcified stage. The lesions were parenchymal in 99.5% of cases, predominantly in the frontal lobe (59%). Thirteen percent were diagnosed incidentally on imaging, mainly in the form of isolated calcified non enhancing lesions. Albendazole was received by 55% of patients, and phenytoin was the most prescribed anti-seizure drug (57%). When long term follow up was available, 70% of the patients presenting with seizures were completely seizure free. Conclusion: NCC is prevalent in Qatar, mainly within the large Southeast Asian immigrant population. NCC is currently a significant contributor to the epilepsy burden in Qatar, often with a good outcome regarding seizure control. NCC with intraparenchymal single lesion shares a large proportion of our cohort.

Cohen syndrome and early-onset epileptic encephalopathy in male triplets: two disease-causing mutations in VPS13B and NAPB.

Cohen syndrome (CS) is a rare multisystem autosomal recessive disorder associated with mutations in VPS13B (vacuolar protein sorting homolog 13B). The NAPB-related neurodevelopmental disorder is characterized mainly by early-onset epileptic encephalopathy (EOEE) and is associated with mutations in NAPB that encodes for SNAP-beta (soluble NSF attachment protein beta). Here we describe male triplets, clinically presenting with the phenotype of subtle but distinctive facial features, intellectual disability, increased body weight, neonatal EOEE, and prominently variable abnormal behaviors of autism and sexual arousal. The EEG showed multifocal epilepsy, while the brain MRI showed no abnormalities. Diagnostic exome sequencing (ES), the applied next-generation sequencing approach, revealed the interesting finding of two novel homozygous variants in two genes: VPS13B missense variant (c.8516G > A) and NAPB splice-site loss (c.354 + 2 T > G). Sanger sequencing verified the segregation of the two recessive gene variants with the phenotype in family members. The prediction algorithms support the pathogenicity of these variants. Homozygosity mapping of ES data of this consanguineous family revealed multiple chromosomal regions of homozygosity stretches with the residing of VPS13B (chr8: 100830758G > A) and NAPB (Chr20: 23,375,774 A > C) variants within the largest homozygous blocks further supporting the disease-genes causal role. Interestingly, the functions of the two proteins; VPS13B, a transmembrane protein involved in intracellular protein transport, and SNAP-beta involved in neurotransmitters release at the neuronal synaptic complexes, have been associated with Golgi-mediated vesicular trafficking. Our ES findings provide new insights into the pathologic mechanism underlying the expansion of the neurodevelopmental spectrum in CS and further highlight the importance of Golgi and Golgi-membrane-related proteins in the development of neurodevelopmental syndromes associated with early-onset non-channelopathy epilepsy. To our knowledge, this is the first report documenting multifocal EOEE in CS patients with the association of a pathogenic NAPB variant.

Effect of Reperfusion Therapies on Incidence of Early Post-Stroke Seizures.

Objective: This study aimed to determine the effect of reperfusion therapies on the occurrence of early post-stroke seizures (PSS) in patients with acute ischemic stroke (AIS). Background: Reperfusion therapies are paramount to the treatment of stroke in the acute phase. However, their effect on the incidence of early seizures after an AIS remains unclear. Design and Methods: The stroke database at Hamad Medical Corporation was used to identify all patients who received reperfusion therapies for AIS from 2016 to 2019. They were matched with patients of similar diagnosis, gender, age, and stroke severity as measured by National Institutes of Health Stroke Scale (NIHSS) who did not receive such treatment. The rates of early PSS were calculated for each group. Results: The results showed that 508 patients received reperfusion therapies (342 had IV thrombolysis only, 70 had thrombectomies only, and 96 had received both), compared with 501 matched patients receiving standard stroke unit care. Patients who received reperfusion therapies were similar to their matched controls for mean admission NIHSS score (9.87 vs. 9.79; p = 0.831), mean age (53.3 vs. 53.2 years; p = 0.849), and gender distribution (85 vs. 86% men; p = 0.655). The group receiving reperfusion therapies was found to have increased stroke cortical involvement (62 vs. 49.3%, p < 0.001) and hemorrhagic transformation rates (33.5 vs. 18.6%, p < 0.001) compared with the control group. The rate of early PSS was significantly lower in patients who received reperfusion therapies compared with those who did not (3.1 vs. 5.8%, respectively; p = 0.042). When we excluded seizures occurring at stroke onset prior to any potential treatment implementation, the difference in early PSS rates between the two groups was no longer significant (2.6 vs. 3.9%, respectively; p = 0.251). There was no significant difference in early PSS rate based on the type of reperfusion therapy either (3.2% with thrombolysis, 2.9% with thrombectomy, and 3.1% for the combined treatment, p = 0.309). Conclusions: Treatment of AIS with either thrombectomy, thrombolysis, or both does not increase the risk of early PSS.

Eslicarbazepine-induced severe hyponatremia resulted in generalized tonic-clonic seizure.

Although eslicarbazepine is an anti-seizure medication, it may result in seizure worsening if its use is complicated by severe hyponatremia, even long time after commencing this medication. The treatment is a replacement for another ASM.

24-Hour video EEG in the evaluation of the first unprovoked seizure.

OBJECTIVE: To assess the gain in detection of epileptiform abnormalities in 24-hour EEG recordings following the first seizure. METHODS: We identified patients who underwent 24-hour video EEG (VEEG) with "first seizure" as an indication. We noted the presence or absence of epileptiform discharges (EDs) in the VEEG study and the latency for the appearance of such discharges. We compared the rate of EDs during the initial 60 min with those occurring only later during the recording. RESULTS: Data from 25 patients, aged 15 to 59, were included. Of the 11 patients with EDs, eight (73%) appeared only after 60 min of recording. This equates to a 32% absolute increase in the detection of EDs across all patients. The latency to first EDs varied from one to 1080 min with a median of 170 min. In four cases, actual subtle seizures were recorded. CONCLUSION: This study suggests an increase in the detection of EDs with the 24-hour studies compared to the traditional shorter recordings, in the context of a first seizure. SIGNIFICANCE: A standard EEG can be performed close to the seizure, followed by a longer up to 24-hour recording if the initial shorter study is unrevealing.

A Suggested Approach of Managing Excessive Maxillary Gingival Display in Terminal Dentition.

The aim of this paper is to report a suggested approach for the management of excessive maxillary gingival display with terminal dentition. A segmental osteotomy of the maxillary process was performed, and the latter used as grafting material for lateral sinus augmentation that was performed simultaneously. Following the graft maturation period, implants were inserted and rehabilitated with a fixed dentogingival prosthesis. Consequently, the mandible was prosthetically restored following the new occlusal plane dictated by the rehabilitated maxilla. Clinically, the procedure showed a drastic improvement in the patient's appearance, eliminating the excessive gingival display. Radiologically, it led to a vertical translation of the maxillary process level in an apical direction. Nevertheless, the resected process used as grafting material was noticed to have a suboptimal behavior as long as it showed increased intrasinusal resorption, barely sufficient for a regular implant accommodation. The described therapy concept seems to be a plausible approach when it comes to manage excessive maxillary gingival displays in edentulous patients or those presenting a terminal dentition. However, at the time of sinus augmentation, authors recommend to graft a mixture of resected maxillary process and a bone substitute material, in order to get more stable results.

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.

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.

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.

Recurrent status epilepticus as the primary neurological manifestation of CADASIL: A case report.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) often presents with a history of migraine with aura and eventual manifestations of dementia with unrelenting, repeated cerebral vascular insults. Only 6-10% of patients with CADASIL have been reported to develop seizures, and status epilepticus (SE) is exceedingly rare. Here, we describe a patient who presented with recurrent SE, with eventual biopsy diagnosis of CADASIL. An 80-year-old woman presented to our hospital three times in two years with decreased level of consciousness and subtle intermittent right-sided upper extremity and facial twitching. There was no known significant family history and no past medical history for seizures, stroke, migraine headache, or overt dementia. Electroencephalography revealed recurrent focal seizures with left hemispheric onset and evolution, fulfilling the criteria for focal SE each time. All three admissions required sedation with midazolam to control seizure activity, in addition to high doses of multiple antiepileptic drugs. Brain MRI repeatedly showed extensive abnormalities in the periventricular and deep white matter, subcortical white matter, and bilateral basal ganglia. Skin biopsy was obtained on the third admission, and electron microscopy showed numerous deposits of granular osmiophilic material, which are pathognomonic for CADASIL. Detailed investigations failed to reveal any other etiology for the patient's condition. This case illustrates the potential for nonconvulsive SE to be the sole manifestation of CADASIL. With the appropriate brain MRI findings, CADASIL should be added to the list of rare causes of SE.

Enhanced automated sleep spindle detection algorithm based on synchrosqueezing.

Detection of sleep spindles is of major importance in the field of sleep research. However, manual scoring of spindles on prolonged recordings is very laborious and time-consuming. In this paper, we introduce a new algorithm based on synchrosqueezing transform for detection of sleep spindles. Synchrosqueezing is a powerful time-frequency analysis tool that provides precise frequency representation of a multicomponent signal through mode decomposition. Subsequently, the proposed algorithm extracts and compares the basic features of a spindle-like activity with its surrounding, thus adapting to an expert's visual criteria for spindle scoring. The performance of the algorithm was assessed against the spindle scoring of one expert on continuous electroencephalogram sleep recordings from two subjects. Through appropriate choice of synchrosqueezing parameters, our proposed algorithm obtained a maximum sensitivity of 96.5% with 98.1% specificity. Compared to previously published works, our algorithm has shown improved performance by enhancing the quality of sleep spindle detection.

Telemedicine for patients with epilepsy: a pilot experience.

We aimed to describe our preliminary experience with the telemedicine (TM) seizure clinic. A retrospective database analysis for the TM seizure visits between January 2009 and January 2012 was performed. Each subject's age, gender, epilepsy syndrome, seizure types, and outcome were identified. The antiepileptic drug (AED) regimen at each visit was noted, as well as instances where surgical therapies and admission for monitoring were discussed. We identified a total of 74 encounters with 24 patients. Fifteen subjects (62.5%) had focal epilepsy, whereas seven (29%) had generalized epilepsy. Seven patients (29%) experienced one seizure type, 14 (58.5%) had two seizure types, and five (12.5%) had three or more seizure types. Thirty-two out of the 74 encounters (43%) resulted in some change in the AED regimen. Surgical therapeutic options were discussed in 35% of the visits. Two-thirds of subjects were either seizure-free or improved by the last encounter. The no-show rate was only 11%. We were able to deliver follow-up care through a TM model to patients with epilepsy with a wide spectrum of syndromes and severity. We believe that TM improves access to specialized care for patients with epilepsy living in rural areas.

New Onset Refractory Status Epilepticus in a Young Man with H1N1 Infection.

Objective. To report a case of refractory status epilepticus (SE) as an unusual early manifestation of H1N1 influenza infection. Introduction. H1N1 neurological complications have been reported and consist mainly of seizures or encephalopathy occurring in children. However, we only found a single report of an adult developing complex partial SE with H1N1 infection. Case Report. A 21-year-old previously healthy man was brought to the emergency room (ER) after a witnessed generalized tonic clonic seizure (GTCS). He was fully alert and afebrile upon ER arrival, but a second GTCS prompted treatment with Lorazepam and Fosphenytoin. The initial EEG showed diffuse slowing, but a repeat one requested as the patient failed to regain consciousness revealed recurrent focal seizures of independent bihemispheric origin, fulfilling the criteria for nonconvulsive SE. Chest X-ray, followed by chest CT scan, showed a left upper lobe consolidation. H1N1 infection was confirmed with PCR on bronchoalveolar lavage material. Despite aggressive treatment with Midazolam, Propofol, and multiple high dose antiepileptic drugs, the electrographic seizures recurred at every attempt to reduce the intravenous sedative drugs. The patient died two weeks after his initial presentation. Conclusion. H1N1 should be added to the list of rare causes of refractory SE, regardless of the patient's age.

Improved spindle detection through intuitive pre-processing of electroencephalogram.

BACKGROUND: Numerous signal processing techniques have been proposed for automated spindle detection on EEG recordings with varying degrees of success. While the latest techniques usually introduce computational complexity and/or vagueness, the conventional techniques attempted in literature have led to poor results. This study presents a spindle detection approach which relies on intuitive pre-processing of the EEG prior to spindle detection, thus resulting in higher accuracy even with standard techniques. NEW METHOD: The pre-processing techniques proposed include applying the derivative operator on the EEG, suppressing the background activity using Empirical Mode Decomposition and shortlisting candidate EEG segments based on eye-movements on the EOG. RESULTS/COMPARISON: Results show that standard signal processing tools such as wavelets and Fourier transforms perform much better when coupled with apt pre-processing techniques. The developed algorithm also relies on data-driven thresholds ensuring its adaptability to inter-subject and inter-scorer variability. When tested on sample EEG segments scored by multiple experts, the algorithm identified spindles with average sensitivities of 96.14 and 92.85% and specificities of 87.59 and 84.85% for Fourier transform and wavelets respectively. These results are found to be on par with results obtained by other recent studies in this area.

Quantification of fetal magnetoencephalographic activity in low-risk fetuses using burst duration and interburst interval.

OBJECTIVE: To identify quantitative MEG indices of spontaneous brain activity for fetal neurological maturation in normal pregnancies and examine the effect of fetal state on these indices. METHODS: Spontaneous MEG brain activity was examined in 22 low-risk fetal recordings with gestational age (GA) ranging from 30 to 37 weeks. As major quantitative characteristics of spontaneous activity, burst duration (BD) and interburst interval (IBI) were studied in correlation with GA and fetal state. RESULTS: IBI showed a decrease with gestational age (-0.21 s/week, P=0.0031). This trend was only maintained in the quiet-sleep state. With respect to BD, no significant trends were detected with GA and state. CONCLUSION: IBI can be quantified as a fetal brain maturational parameter. The decrease in IBI over gestation was similar to the trend reported in the preterm neonatal EEG studies. Quiet sleep could be the optimal state to study such MEG maturational indices. SIGNIFICANCE: With further investigation, indices extracted from spontaneous fetal brain activity may serve as an early warning for fetal neurological distress.

Spectral power differences in the brain activity of growth-restricted and normal fetuses.

Using non-invasive fetal magnetoencephalography (fMEG), we investigated spontaneous brain activity in 28 fetuses diagnosed with intrauterine growth restriction (IUGR) and compared the results to 47 normal-growth fetuses. The fetal gestational age ranged from 28 to 39 weeks with post-natal recordings obtained on 17 of the IUGR fetuses. Power spectrum was computed and was divided into four frequency bands. A significant difference in the relative spectral power in delta, theta and beta bands (P<0.01) was observed only in the 28-32 week gestation age group with alpha band showing a similar trend (P=0.054). This observation suggests that growth restriction may have a more pronounced effect on the fetal brain in early gestation. Larger population studies could reveal the potential value of fMEG as an additional surveillance tool for growth-restricted fetuses.

Correlation between fetal brain activity patterns and behavioral states: an exploratory fetal magnetoencephalography study.

The fetal brain remains inaccessible to neurophysiological studies. Magnetoencephalography (MEG) is being assessed to fill this gap. We performed 40 fetal MEG (fMEG) recordings with gestational ages (GA) ranging from 30 to 37 weeks. The data from each recording were divided into 15 second epochs which in turn were classified as continuous (CO), discontinuous (DC), or artifact. The fetal behavioral state, quiet or active sleep, was determined using previously defined criteria based on fetal movements and heart rate variability. We studied the correlation between the fetal state, the GA and the percentage of CO and DC epochs. We also analyzed the spectral edge frequency (SEF) and studied its relation with state and GA. We found that the odds of a DC epoch decreased by 6% per week as the GA increased (P = 0.0036). This decrease was mainly generated by changes during quiet sleep, which showed 52% DC epochs before a 35 week GA versus 38% after 35 weeks (P = 0.0006). Active sleep did not show a significant change in DC epochs with GA. When both states were compared for MEG patterns within each GA group (before and after 35 weeks), the early group was found to have more DC epochs in quiet sleep (54%) compared to active sleep (42%) (P = 0.036). No significant difference in DC epochs between the two states was noted in the late GA group. Analysis of SEF showed a significant difference (P = 0.0014) before and after a 35 week GA, with higher SEF noted at late GA. However, when both quiet and active sleep states were compared within each GA group, the SEF did not show a significant difference. We conclude that fMEG shows reproducible variations in gross features and frequency content, depending on GA and behavioral state. Fetal MEG is a promising tool to investigate fetal brain physiology and maturation.

Localization of spontaneous magnetoencephalographic activity of neonates and fetuses using independent component and Hilbert phase analysis.

The fetal magnetoencephalogram (fMEG) is measured in the presence of large interference from maternal and fetal magnetocardiograms (mMCG and fMCG). These cardiac interferences can be attenuated by orthogonal projection (OP) technique of the corresponding spatial vectors. However, the OP technique redistributes the fMEG signal among the channels and also leaves some cardiac residuals (partially attenuated mMCG and fMCG) due to loss of stationarity in the signal. In this paper, we propose a novel way to extract and localize the neonatal and fetal spontaneous brain activity by using independent component analysis (ICA) technique. In this approach, we perform ICA on a small subset of sensors for 1-min duration. The independent components obtained are further investigated for the presence of discontinuous patterns as identified by the Hilbert phase analysis and are used as decision criteria for localizing the spontaneous brain activity. In order to locate the region of highest spontaneous brain activity content, this analysis is performed on the sensor subsets, which are traversed across the entire sensor space. The region of the spontaneous brain activity as identified by the proposed approach correlated well with the neonatal and fetal head location. In addition, the burst duration and the inter-burst interval computed for the identified discontinuous brain patterns are in agreement with the reported values.

Localizing the neonatal and fetal spontaneous brain activity by Hilbert phase analysis.

We propose a novel method to characterize the spontaneous brain signals using Hilbert phases. The Hilbert phase of a signal exhibits phase slips when the magnitude of the successive phase difference exceeds pi. To this end we use standard deviation (sigmaDeltatau) of the time (Deltatau) between successive phase slips to characterize the signals. We demonstrate the application of this approach to neonatal and fetal magnetoencephalographic signals recorded using a 151-sensor array to identify the sensors containing the neonatal and fetal brain signals. To this end we propose a spatial filter using sigma(Deltatau) as weights to reconstruct the brain signals.