The cost-effectiveness of a real-time seizure detection application for people with epilepsy.

OBJECTIVES: Automated seizure detection modalities can increase safety among people with epilepsy (PWE) and reduce seizure-related anxiety. We evaluated the potential cost-effectiveness of a seizure detection mobile application for PWE in Singapore. METHODS: We used a Markov cohort model to estimate the expected changes to total costs and health outcomes from a decision to adopt the seizure detection application versus the current standard of care from the health provider perspective. The time horizon is ten years and cycle duration is one month. Parameter values were updated from national databases and published literature. As we do not know the application efficacy in reducing seizure-related injuries, a conservative estimate of 1% reduction was used. Probabilistic sensitivity analysis, scenario analyses, and value of information analysis were performed. RESULTS: At a willingness-to-pay of $45,000/ quality-adjusted life-years (QALY), the incremental cost-effectiveness ratio was $1,096/QALY, and the incremental net monetary benefit was $13,656. Probabilistic sensitivity analyses reported that the application had a 99.5% chance of being cost-effective. In a scenario analysis in which the reduction in risk of seizure-related injury was 20%, there was a 99.8% chance that the application was cost-effective. Value of information analysis revealed that health utilities was the most important parameter group contributing to model uncertainty. CONCLUSIONS: This early-stage modeling study reveals that the seizure detection application is likely to be cost-effective compared to current standard of care. Future prospective trials will be needed to demonstrate the real-world impact of the application. Changes in health-related quality of life should also be measured in future trials.

Change in Mortality of Generalized Convulsive Status Epilepticus in High-Income Countries Over Time: A Systematic Review and Meta-analysis.

IMPORTANCE: Status epilepticus (SE) is associated with significant morbidity and mortality. Since the late 1990s, a more aggressive management of prolonged convulsive seizures lasting longer than 5 minutes has been advocated. OBJECTIVE: To determine if convulsive SE mortality has decreased during a time of increasing advocacy for out-of-hospital treatment and escalating and earlier treatment protocols for prolonged seizures and SE. DATA SOURCE: This systemic review and meta-analysis on studies focused on the mortality of convulsive status epilepticus was conducted by searching MEDLINE, Embase, PsychINFO, CINAHL Plus, and the Cochrane Database of Systematic Reviews between January 1, 1990, and June 30, 2017. STUDY SELECTION: Studies were excluded if they had fewer than 30 participants (<20 for refractory SE), were limited to SE of single specific etiology or an evaluation of a single treatment modality, or were studies of nonconvulsive SE. DATA EXTRACTION AND SYNTHESIS: Data were abstracted and their quality was assessed via a modified Newcastle-Ottawa scale independently by 2 reviewers (A.N. and T.D.G.) using the Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines. Data were pooled using a random-effects model. MAIN OUTCOMES AND MEASURES: The main outcome measure was in-hospital mortality or 30-day case fatality expressed as proportional mortality. RESULTS: Sixty-one studies were included in the analysis. The pooled mortality ratios were 15.9% (95% CI, 12.7-19.2) for adult studies, 13.0% (95% CI, 7.2-19.0) for all-age population studies, 3.6% (95% CI, 2.0%-5.2%) for pediatric studies, and 17.3% (95% CI, 9.8-24.7) for refractory SE studies, with very high between-study heterogeneity. We found no evidence of a change in prognosis over time nor by the definition of SE used. CONCLUSIONS AND RELEVANCE: The mortality of convulsive SE is higher in adults than in children and there was no evidence for improved survival over time. Although there are many explanations for these findings, they can be explained by aetiology of SE being the major determinant of mortality. However, there are potential confounders, including differences in case ascertainment and study heterogeneity. This meta-analysis highlights the need for strict international guidelines for the study of this condition.

Revisiting the public awareness, attitudes, and understanding towards epilepsy among Singapore residents.

A survey to assess the familiarity, attitudes, and knowledge about epilepsy was done using a questionnaire identical to the one used in 1999. Two hundred forty-six people participated in our survey in 2017 as compared with 214 in the 1999 survey. In terms of familiarity about epilepsy, 76% had heard or read about epilepsy, 55.7% had witnessed a seizure, and 35.8% knew someone with epilepsy (85%, 56%, and 36% respectively in 1999). Forty point five percent were not familiar with or did not know what to do if they witnessed a seizure (44% in 1999); 25.6% would put something in the mouth of a person having a seizure (32% in 1999). In terms of attitudes towards epilepsy, 14.6% would object to their children associating with one with epilepsy while 19.9% would object to their children marrying a person with epilepsy (13% and 36% respectively in 1999). Only 43.1% would employ a person with epilepsy while 68.3% would employ if seizures do not interfere with the job (42 and 66% respectively in 1999). In terms of knowledge of seizures and epilepsy, 66.3% associated epileptic attack with convulsion (68% in 1999). Only 37.5% were aware of nonconvulsive forms of epilepsy (25% in 1999). Twenty-six point eight percent did not know what treatment to recommend to relatives/friends with epilepsy while 60.6% recommend western medicine (22% and 60% respectively in 1999). CONCLUSION: The awareness, attitudes, and understanding towards epilepsy does not seem to show any significant difference when compared with that in 1999. Reluctance to marry and employ a person with epilepsy persists. The awareness about first aid of a patient having a seizure, attitudes towards marrying a person with epilepsy, and the understanding of cause of epilepsy have shown some positive changes over 17 years.

Low conversion rate of ocular to generalized myasthenia gravis in Singapore.

INTRODUCTION: Ocular myasthenia gravis (OMG) is a common condition of the neuromuscular junction that may convert to generalized myasthenia gravis (GMG). Our aim in this study was to determine the conversion rate and predictive factors for generalization in OMG, in an Asian population. METHODS: The investigation consisted of a retrospective study of OMG patients with a minimum 2 years of follow-up. RESULTS: Among 191 patients with OMG, 155 had the minimum 2-year follow-up. The conversion rate at median follow-up (40.8 months) was 10.6% (95% confidence interval 7.9%-13.3%), and at the 2-year follow-up it was 7.7% (95% confidence interval 5.6%-9.8%). At baseline, the predictive factors for generalization were positive acetylcholine receptor antibodies (hazard ratio 3.71, P = 0.024), positive repetitive nerve stimulation (RNS) studies (hazard ratio 4.42, P = 0.003), and presence of radiologically presumed or pathologically confirmed thymoma (hazard ratio 3.10, P = 0.013). DISCUSSION: The conversion rate of OMG to GMG in Asian patients is low, as predicted by presence of acetylcholine receptor antibodies, presence of thymoma, and positive RNS studies. Muscle Nerve 57: 756-760, 2018.

Ictal and interictal EEG patterns in patients with nonconvulsive and subtle convulsive status epilepticus.

BACKGROUND: Electroencephalography findings in nonconvulsive or subtle convulsive status epilepticus (NCSE and SCSE, respectively) can be heterogenous. We aimed to study the different patterns on EEG in our cohort of patients. OBJECTIVE: Our objective was to study ictal and interictal EEG patterns in patients with NCSE and SCSE. METHODS: From January 2012 to December 2013, EEGs recorded from patients admitted for altered mental status suspected of having NCSE or SCSE were reviewed retrospectively. Electroencephalography status was defined as having (a) continuous ictal discharges lasting >5 min or (b) >2 discrete bursts of ictal discharges, each lasting <5 min, without returning to previous background rhythm in between these bursts. RESULTS: Among 1698 EEGs recorded for at least 30 min from hospitalized patients, 55 (3.23%) satisfied the criteria of EEG SE. The ictal onset was regional in 37 (67.2%) EEGs, multiregional independent in 8 (14.5%), and generalized in 10 (18.4%). The EEG seizure duration was >5 min in 24 (43.6%) EEGs, between 1 and 5 min in 14 (25.4%), and less than 1 min in 17 (30.8%). Twenty (36.3%) EEGs showed one continuous prolonged seizure episode of >5-minute duration, 15 (27.2%) had 10 or less discrete episodes, 20 (36.3%) had more than 10 episodes, and 11 (20%) had 2 or more ictal patterns. Thirty (54.5%) EEGs had onset ictal frequency of >8 Hz whereas the rest had <8-Hz ictal frequency. In the interictal segment, 29 patients had continuous generalized slow waves, while 12 had intermittent generalized slow waves. Eleven patients had continuous slow waves lateralized to one hemisphere, and these were ipsilateral to the ictal focus in 10 but contralateral in 1. Other interictal waves seen were PLEDS (6), sharp waves (3), suppression (5), and triphasic waves (1). The background alpha rhythm was absent in 36 patients and slow in 14, and normal background alpha was seen in the interictal period in 5 patients. CONCLUSION: The ictal and interictal EEG patterns in NCSE and SCSE can be varied. Further study to look for etiologic and clinical correlates of each pattern could add to its clinical value. This article is part of a Special Issue entitled "Status Epilepticus".

Central pontine myelinolysis presenting as isolated sixth nerve palsy in third trimester of pregnancy.

A 30-year-old primigravida presented with isolated left sixth nerve palsy at 38 weeks gestation. Her MRI showed a lesion consistent with central pontine myelinolysis (CPM). Extensive investigations did not reveal any secondary cause for the CPM. She recovered spontaneously in 2 weeks with complete resolution of her MRI changes. To our knowledge, this is the first report of CPM occurring in third trimester in the absence of identifiable secondary causes and of CPM presenting as an isolated sixth nerve palsy. We discuss the reported causes of CPM in pregnancy, possible pathophysiologic mechanisms involved and the anatomic basis of the unique clinical presentation of sixth nerve palsy in our case.

Predictive Value of Electrophysiology for Presence of Thymic Pathology in Myasthenia Gravis.

OBJECTIVE: Single fibre electromyography (SFEMG) and repetitive nerve stimulation (RNS) are routinely performed investigations in evaluation of patients with myasthenia gravis (MG). Significant number of MG patients have a thymic pathology. We aimed to explore the relationship between the SFEMG and RNS findings with the presence of thymic pathology. METHODS: We studied 159 consecutive patients with MG over a 10 year period. The SFEMG parameters - mean jitter (MJ) and percentage of abnormal fibres (POAF) and the RNS result were correlated with the thymic findings. RESULTS: As compared to patients with normal thymus (MJ:58.3 µsec; POAF:63.5%), patients with thymic pathology had a significantly higher MJ (80.9 µsec; p < 0.0005) and POAF (83.5%; p < 0.0005). MG patients with thymic hyperplasia had the highest MJ (87.6 µsec) and POAF (84.4%) followed by patients with thymoma (MJ:78.6 µsec; POAF:83.2%). The MJ and POAF did not correlate with the stage of thymoma. Mean jitter values above 34.9 µsec and POAF above 31% had 100% sensitivity for the presence of thymic pathology. A positive RNS increased the risk of thymic pathology (OR = 3.9, CI = 1.8-8.5) and thymoma. (OR = 3.5; CI = 1.5-8.1). CONCLUSION: Electrophysiology could be valuable complimentary tool to identify MG patients at high risk for thymic pathology. However, it does not aid us to identify the exact thymic pathology and does not correlate with the stage of thymoma. All OMG patients with higher MJ and PAOF values should also be screened for thymoma. The results reinforce the immunological role of thymic pathology in neuromuscular transmission interference.

Methotrexate induced leucoencephalopathy: A stroke mimic.

With increasing usage of thrombolysis in the treatment of acute ischemic strokes within 4.5- hour window, it is becoming more important to recognize stroke mimics. Though the incidence of stroke mimics being thrombolysed is less than 3%, it is essential to diagnose them so as to avoid wrong thrombolytic treatment which carries potential complications of bleeding. We describe the case of a 17 year old girl with acute lymphoblastic leukemia, who developed stroke like episodes on two consecutive challenges with a chemotherapeutic regime which included intravenous and intrathecal methotrexate. She had MRI changes consistent with acute ischemic stroke on both occasions. Her deficits recovered completely and spontaneously, as did the MRI changes. She did not have any further episodes when methotrexate was excluded from the chemotherapeutic regime.

Methotrexate-induced myelopathy mimicking subacute combined degeneration of the spinal cord.

Methotrexate (MTX), a folate antagonist, is widely used to treat hematological malignancies. Although it is known to cause myelopathy, little is known about the pathophysiology and natural history of this myelopathy. We describe a 42-year-old woman with acute lymphoblastic leukemia who was treated with chemotherapy consisting of intrathecal MTX who developed a progressive myelopathy. The myelopathy mimicked, radiologically, subacute combined degeneration (SACD) of the spinal cord. This myelopathy mimicking SACD could be explained by the folate antagonism of MTX. The progressive clinical signs and serial MRI in this patient further our understanding of the natural progression of this myelopathy.