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To investigate the opinions of physicians about brain surgery for drug-resistant epilepsy worldwide.Practicing neurologists, psychiatrists, and neurosurgeons from around the world were invited to participate in an online survey. The survey anonymously collected data about demographics, years in clinical practice, discipline, nation, work setting, and answers to the questions about beliefs and attitudes about brain surgery for drug-resistant epilepsy.In total, 1410 physicians from 20 countries and different world regions participated. The propensity to discuss brain surgery with patients, who have drug-resistant seizures, was higher among men (versus women) [Odds Ratio (OR) 1.67, 95% CI 1.20-2.31; p = 0.002]. In comparison to neurologists, psychiatrists were less likely (OR 0.28, 95% CI 0.17-0.47; p 0.001) and neurosurgeons were more likely (OR 2.00, 95% CI 1.08-3.72; p = 0.028) to discuss about it. Survey participants working in Africa, Asia, the Middle East, and the Former Union of Soviet Socialist Republics showed a lower propensity to discuss epilepsy surgery with patients.This study showed that on an international level, there is still a knowledge gap concerning epilepsy surgery and much needs to be done to identify and overcome barriers to epilepsy surgery for patients with drug-resistant seizures worldwide.

Objective: The objective of this study was to assess the levels of depression among patients with Parkinson’s Disease (PD), the factors influencing their levels, and determine their influence on their Quality of Life (QoL). Materials and Methods: The study was conducted at the movement disorders outpatient department, Rajiv Gandhi Government General hospital, where 50 patients with diagnosed PD were enrolled. They were interviewed for their levels of depression and QoL using respective standardized depression and QoL assessment questionnaires. Results: Patients with PD were mostly above the age of 50 and were male. Their levels of depression ranged between normal to mild and borderline depression and their QoL scores were also moderate. Among their QoL domains, the emotional well-being, and cognition of patients were found to be more affected when compared to other domains. Conclusion: The prevalence and severity of depression among patients with PD were mild, but they play an important role in determining their QoL, especially the emotional well-being and cognitive performance of patients.

To investigate the opinions and attitudes of neurologists on the counseling about sudden unexpected death in epilepsy (SUDEP) worldwide.Practicing neurologists from around the world were invited to participate in an online survey. On February 18th, 2021, we emailed an invitation including a questionnaire (using Google-forms) to the lead neurologists from 50 countries. The survey anonymously collected the demographic data of the participants and answers to the questions about their opinions and attitudes toward counseling about SUDEP.In total, 1123 neurologists from 27 countries participated; 41.5% of the respondents reported they discuss the risk of SUDEP with patients and their care-givers only rarely. Specific subgroups of patients who should especially be told about this condition were considered to be those with poor antiseizure medication (ASM) adherence, frequent tonic-clonic seizures, or with drug-resistant epilepsy. The propensity to tell all patients with epilepsy (PWE) about SUDEP was higher among those with epilepsy fellowship. Having an epilepsy fellowship and working in an academic setting were factors associated with a comfortable discussion about SUDEP. There were significant differences between the world regions.Neurologists often do not discuss SUDEP with patients and their care-givers. While the results of this study may not be representative of practitioners in each country, it seems that there is a severe dissociation between the clinical significance of SUDEP and the amount of attention that is devoted to this matter in daily practice by many neurologists around the world.

Background Neurocysticercosis is a parasitic infection of the central nervous system by the larval stage of the pork tapeworm and is a common cause of seizures and epilepsy in endemic areas. Anthelmintics (albendazole or praziquantel) may be given alongside supportive treatment (antiepileptics/analgesia) with the aim of killing these larvae (cysticerci), with or without corticosteroid treatment. However, there are potential adverse effects of these drugs, and the cysticerci may eventually die without directed anthelminthic treatment. Objectives To assess the effects of anthelmintics on people with neurocysticercosis. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, the WHO ICTRP, and ClinicalTrials.gov, up to 21 October 2020. Selection criteria Randomized controlled trials comparing anthelmintics and supportive treatment (+/‐ corticosteroids) with supportive treatment alone (+/‐ corticosteroids) for people with neurocysticercosis. Data collection and analysis Two review authors independently screened the title and abstract of all articles identified by the search. We obtained full‐text articles to confirm the eligibility of all studies that passed screening. One review author extracted data, which a second review author checked. Two review authors assessed the risk of bias of each trial and performed GRADE assessments. In cases of disagreement at consensus discussion stage between review authors, we consulted a third review author. We calculated risk ratios (RR) for dichotomous variables, with 95% confidence intervals (CIs) for pooled data from studies with similar interventions and outcomes. Main results We included 16 studies in the review. Only two studies investigated praziquantel and did not report data in a format that could contribute to meta‐analysis. Most results in this review are therefore applicable to albendazole versus placebo or no anthelmintic. The aggregate analysis across all participants with neurocysticercosis did not demonstrate a difference between groups in seizure recurrence, but heterogeneity was marked (RR 0.94, 95% CI 0.78 to 1.14; 10 trials, 1054 participants; I2 = 67%; low‐certainty evidence). When stratified by participants with a single cyst or multiple cysts, pooled analysis suggests that albendazole probably improves seizure recurrence for participants with a single cyst (RR 0.61, 95% CI 0.4 to 0.91; 5 trials, 396 participants; moderate‐certainty evidence). All studies contributing to this analysis recruited participants with non‐viable, intraparenchymal cysts only, and most participants were children. We are uncertain whether or not albendazole reduces seizure recurrence in participants with multiple cysts, as the certainty of the evidence is very low, although the direction of effect is towards albendazole causing harm (RR 2.05, 95% CI 1.28 to 3.31; 2 trials, 321 participants; very low‐certainty evidence). This analysis included a large study containing a highly heterogeneous population that received an assessment of unclear risk for multiple 'Risk of bias' domains. Regarding radiological outcomes, albendazole probably slightly improves the complete radiological clearance of lesions (RR 1.22, 95% CI 1.07 to 1.39; 13 trials, 1324 participants; moderate‐certainty evidence) and the evolution of cysts (RR 1.27, 95% CI 1.10 to 1.47; 6 trials, 434 participants; moderate‐certainty evidence). More adverse events appeared to be observed in participants treated with either albendazole or praziquantel compared to those receiving placebo or no anthelmintic. The most commonly reported side effects were headache, abdominal pain, and nausea/vomiting. Authors' conclusions For participants with a single cyst, there was less seizure recurrence in the albendazole group compared to the placebo/no anthelmintic group. The studies contributing to this evidence only recruited participants with a non‐viable intraparenchymal cyst. We are uncertain whether albendazole reduces seizure recurrence for participants with multiple cysts. We also found that albendazole probably increases radiological clearance and evolution of lesions. There were very few studies reporting praziquantel outcomes, and these findings apply to albendazole only., Plain language summary Anthelmintics for people with neurocysticercosis What is the aim of this review? The aim of this review was to explore whether treatment with anthelmintics (drugs that kill worms) can benefit people with neurocysticercosis (an infection of the brain caused by the pork tapeworm). The primary outcome of the review was the impact of treatment on seizures (epilepsy). We collected and analysed all relevant studies (trials) to answer this question and found 16 studies. The most commonly reported outcomes were those relating to seizures and also the number and appearance of lesions caused by viable or degrading cysts (dormant worms) on brain imaging. Key messages We found that the anthelmintic albendazole probably reduces the recurrence of seizures in people with neurocysticercosis with a single cyst (moderate‐certainty evidence). We are uncertain whether albendazole reduces seizure recurrence for people with neurocysticercosis with more than one cyst (very low‐certainty evidence). We found little information regarding another anthelmintic drug, praziquantel; therefore these results are applicable to albendazole only. Albendazole treatment also probably increases the clearance and evolution of cysts in people with neurocysticercosis (moderate‐certainty evidence). Evolution of a cyst is progression to a later cyst stage, which is thought to be an improvement towards clearance. What was studied in the review? Neurocysticercosis is an infection of the brain with the pork tapeworm Taenia solium, which is caused by eating food or drinking water contaminated with the eggs of the worm. The eggs can travel from the gut to the brain, forming cysts in the brain that can cause various symptoms, the most common of which is seizures/epilepsy. Neurocysticercosis is found mainly in areas where people keep pigs and have poor sanitation facilities, and is a common cause of seizures in areas where it is prevalent. People with neurocysticercosis may have single or multiple cysts, and their symptoms depend on the position and numbers of these cysts within the brain. Each cyst goes through the natural process of being alive and dormant (viable), degrading (non‐viable), and then it resolves or calcifies. This process can take many years. The number, type, and position of the cysts can be seen on brain imaging (lesions). Two anthelmintics (drugs to treat worm infections), albendazole and praziquantel, are often used to treat neurocysticercosis. However, it is uncertain whether they reduce or stop seizures and other symptoms, or make them worse. In theory, the body's immune response to cysts dying as a result of treatment could cause more swelling and damage to the brain. What are the main results of the review? We included 16 studies in the review. These studies compared treatment with an anthelmintic versus placebo (a mock tablet/pill resembling the anthelmintic) or no anthelmintic treatment in adults or children with neurocysticercosis diagnosed by brain imaging. For people with a single cyst, treatment with albendazole probably reduces seizure recurrence (moderate‐certainty evidence). Notably, all studies that contributed to this analysis only included people with non‐viable cysts. For people with multiple cysts, the evidence was of very low certainty, therefore we are uncertain whether or not albendazole reduces seizure recurrence for this group of patients. The studies contributing to this finding included participants with cysts that were both viable and non‐viable. We found very little information regarding praziquantel, therefore these results are apply to albendazole only. Treatment with albendazole probably increases complete clearance of lesions on brain imaging as well as the evolution of cysts (from viable to non‐viable to resolved or calcified) (moderate‐certainty evidence). The studies contributing to this evidence included people with single and multiple cysts, both viable and non‐viable. More side effects were reported by participants treated with either albendazole or praziquantel compared to those receiving placebo or no anthelmintic. The most commonly reported side effects were headache, abdominal pain, and nausea/vomiting. How up‐to‐date is this review? We searched for studies that had been published up to 21 October 2020.

Background: Migraine is a common primary headache disorder and Episodic migraine is characterized by the occurrence of up to 14 headache days in a month. The preventive treatment of migraine is useful in patients with frequent migraine attacks, impaired activities of daily living, failure of acute pain management, disabling aura and limitations in the use of acute treatment. It is aimed at reducing headache frequency and intensity, improve response to acute treatment of migraine and improve the quality of life. Aim: To analyze the evidence for the efficacy and tolerability of preventive oral drugs used in the management of episodic migraine. Methods: A narrative review of the references were reviewed by searching the literature for the articles published in PubMed in English language using all the following MeSH keywords “preventive treatment”, “preventive oral treatment”, AND “episodic migraine”, “migraine”. Results: Out of articles identified in the search, 38 articles were reviewed for evidence and summarized. The various oral drugs used in the prevention of episodic migraine are antihypertensives (beta-blockers, calcium channel blockers and Angiotensin-converting enzyme inhibitors/Angiotensin receptor blockers), antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors), antiepileptic drugs (valproic acid, topiramate, lamotrigine) and other miscellaneous agents. HURT questionnaire and HALT 30 index are useful in assessing response to treatment in the follow up of migraine patients. Conclusion: An appropriately chosen oral drug is useful in the preventive treatment of episodic migraine. In patients, who fail to respond to the preventive treatment, it is essential to review the diagnosis of migraine, titrate the dosage and duration of preventive treatment and ensure patient compliance. In those patients who fail to respond to monotherapy, polytherapy is a useful option to be considered.

Myasthenia gravis is a neuro-muscular junction disorder characterized by skeletal muscle weakness and fatiguability. It is due to a decrease in the number of available acetylcholine receptors at the neuromuscular junction as a result of antibody mediated autoimmune attack. Weakness of muscles may involve cranial and somatic musculatures. Weakness resembling myasthenia gravis may occur in other conditions as a result of drug, endocrine disease of thyroid, certain malignancies, bacterial toxins and also by non-autoimmune mechanisms involving the neuromuscular junction. The weakness may involve all the skeletal muscles of the body but the distribution of weakness has a characteristic pattern and there is a diurnal variation of symptoms. If the weakness of respiratory muscles becomes so severe as to require respiratory assistance, then it is called myasthenic crisis. The myasthenia may be generalized one involving all the groups of muscles or it may involve the extra ocular muscles and facial muscles. Sometimes the bulbar muscles alone may be involved and the condition is called bulbar myasthenia gravis. In some of the patients, (anti-AchR) Acetyl choline receptor antibodies may be positive and in some it will be negative. In some of the patients, anti-muscle specific tyrosine kinase antibodies will be positive and negative in some of the patients. CONCLUSION : 1. In our study, the commonest age group of presentation of myasthenic crisis is the fourth decade (36%). 2. Male predominance (56%) was noted in our study. 3. The most common predisposing factor is the respiratory infection (28%). 4. In three patients, the presenting symptoms of myasthenia gravis was crisis itself. 5. The mean duration of onset of myasthenia gravis to the onset of crisis was 439.36 days. 6. The duration of myasthenia gravis does not influence the occurrence of myasthenic crisis. 7. Our patients presented with predominant bulbar symptoms with respiratory distress. 8. Ventilator associated pneumonia and other respiratory complications influenced the outcome of treatment of myasthenic crisis. 9. 32% of thymectomised patients had myasthenic crisis. 10. Higher age is a risk factor and younger age is a favourable factor for good outcome. 11. Duration of myasthenia gravis have no role on the outcome of crisis. 12. The better survival rate in ventilated patients outweigh the preventable ventilator related complications.

Perampanel is a non-competitive antagonist at the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid) subtype of ionotropic glutamate receptor. It is approved as an adjunctive therapy in focal epilepsy with or without secondarily generalised seizures in patients aged >12 years. This in-depth review describes the structure, mechanism of action, pharmacokinetic profile, indications, dosage and efficacy, contraindications, possible drug interactions, adverse effect profile and its management with regards to Perampanel. It is one of the latest additions in the therapeutic armamentarium of an epileptologist being useful in focal as well as generalised epilepsies as an add-on. It has shown high rates of efficacy and a relatively good tolerability. Slow dose titration, patient education and bed time dosing along with downtitration of medications which may aggravate Perampanel associated adverse events improves the patients’ compliance and quality of life.

Neuroimaging in dementia has advanced several folds in the past decade. It has evolved from diagnosing secondary causes of dementia to the current use in identifying primary dementia and aid in clinically perplexing situations. There has been a leap in the imaging technology that can virtually dissect the brain with a high degree of radiopathological correlation. The neuroimaging in dementia is classified into structural, functional, and molecular imaging. Structural imaging includes voxel-based morphometry and diffusion tensor imaging. Functional imaging includes 18F-fluorodeoxy glucose positron emission tomography imaging, 99mTc hexamethylpropyleneamineoxime single photon emission computed tomography imaging, and functional magnetic resonance imaging studies. Molecular imaging includes amyloid imaging, tau imaging, and translocated protein imaging. These advancements have led to using neuroimaging as a biomarker in assessing the progression and also in deciphering prognosis of the disease. In this article, we discuss the current clinical relevance of these neurological advancements.

Objectives To evaluate the applications of mobile phones in the day to day care of epileptic patients as a diagnostic, prognostic and therapeutic tool. Methods Detailed search of various mobile applications in the field of epileptology was made in MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, LILACS and corresponding developer websites of mobile applications were also looked into regarding their technical specifications and user friendliness. Results A plethora of apps are available across various mobile platforms especially Android, iOS and Windows. Careful selection and application of such apps by both the healthcare providers, the epileptic patients and their caregivers with proper understanding of their potential benefits as well as limitations will result in better diagnosis, prognosis and treatment of epilepsy. Conclusion The field of medicine is rapidly inculcating advanced cutting edge technologies for better diagnosis of diseases and better targeted therapy to such diseases. Hi tech electronic gadgets, in particular, are now becoming part and parcel of patient care in many specialties. The advent of the modern portable computers has revolutionised almost every specialty. The field of mobile technology is advancing with a break neck pace, with increase in mobile subscribers, advanced handsets practically like digital personal assistants with advanced capabilities. The possibilities of using such rapidly evolving mobile technology in the field of medicine are endless. This article explores such possibilities in the field of epileptology after analysing the current and existing applications of mobile phones in care of the epileptic patients worldwide.

Background The risk of falls in people with Multiple Sclerosis (MS) is much greater than that of the general population due to impaired coordination, gait, sensation, muscle tone, strength, and cognition. These MS related falls hamper the day to day living of these individuals and are one of the prime factors aggravating the disease related morbidity. The fear of falling itself may make these individuals more dependent and hinder their professional and leisurely activities. Hence, the significance of identifying individuals who are at risk of falling and instituting preventive counter-measures cannot be overemphasized. Various simple clinical tests and questionnaires have been recommended for this purpose, but are far from ideal. Objective The objective was to find accurate measures to predict a future fall in MS patients. We also aimed to enquire about the prevalence of falls in MS population and its clinical profile which included detailed history about the past falls, Expanded disability status scale (EDSS) scores, Timed 25 foot walk (T25FW) scores, Activities specific balance confidence (ABC) scores, Falls efficacy scale international (FESI) scores, Multiple Sclerosis Walking Scale 12 (MSWS12) questionnaire. Design/Methods This was a prospective cohort study conducted at the Institute of Neurology, Chennai from January 2015 to August 2017. MS patients of any subtype attending Neurology OPD satisfying revised 2010 McDonald criteria were recruited. 134 subjects with MS consented to participate in this study and 113 of them who met the criteria were included. Baseline history was obtained about the number of falls in the previous year. EDSS, T25FW, ABC, FESI, and MSWS12 scores were obtained at the baseline. VEMP and SEP tests were done and the baseline P13/N23 cVEMP latencies, N10 oVEMP latency, and P37 lower limb SEP latency were obtained. These subjects were followed up for one year and were enquired if they had fallen during that period and the number of falls was recorded. Logistic regression models were used to compute the area under receiver operating characteristic curve (AUC) for each variable tested. Pearson correlation coefficients were calculated for each variable with the number of future falls. Results Among the 113 patients, 72% (n = 81) had one or more falls during follow-up. Among all variables tested P13 cervical VEMP latency had the highest predictive accuracy (AUC = 0.820) followed by N10 ocular VEMP latency (AUC = 0.794) and P37 SEP latency (AUC = 0.732). P13 latency also had the highest correlation coefficient (R = 0.689, R2 = 0.475) with the number of future falls. Conclusion P13, N10 and P37 latencies were the most accurate in predicting a future fall when compared to clinical measures.

Background Although cognitive fatigue plays a significant part in Multiple Sclerosis (MS) related impairment, knowledge regarding it is largely lacking. Until now, not many tools are available to a clinician to detect cognitive fatigue. The subjective tools of fatigue have never been reliable.tabl Objectives To assess the prevalence and clinical/ demographic profile of cognitive fatigue in MS using novel clinical and electrophysiological measures and to find their accuracy. We also aimed to test the three leading hypotheses - the temporal fatigue, cognitive load and cognitive domain hypotheses of cognitive fatigue in MS. Methods 50 consecutive MS patients attending the Neurology OPD in Madras Medical College, Chennai from May 2015 to February 2016 satisfying the 2010 revised McDonald criteria for MS with an equal number of matched controls were recruited. Modified versions (a shorter version, and longer and more demanding versions) of the Stroop test, symbol digit modalities test, and serial addition tests were used in addition to modified tests of P300 latency and amplitude each specifically tailored to reveal cognitive fatigue. Results Out of the seven measures of cognitive fatigue used, 46% (n=23) of MS patients had impairment in two or more of the scores compared to that of 8% (n=4) in the healthy control group. The Expanded disability status scale (EDSS) scores were significantly higher for MS patients with cognitive fatigue compared to those without. All the clinical and electrophysiological measures used in this study had a relatively high sensitivity and specificity. In addition, all the clinical measures correlated with the electrophysiological measures of cognitive fatigue in this study. Our data also supported all three hypotheses implying that cognitive fatigue in MS may be a multifaceted entity. Conclusion Cognitive fatigue is widely prevalent in MS and can be detected with specific tools. The tools developed and described in this study may be used as an effective means of detecting cognitive fatigue in MS patients and thus allowing patients to realise their limitations. Institution of appropriate remedial measures like advising such patients to break up a more cognitively demanding task into smaller subtasks may help to improve their quality of life.

Reason for Withdrawal This protocol has been withdrawn as the orginal review author team are unable to progress with the review. We hope to reallocate to another review author team in the near future. To view the published versions of this article, please click the 'Other versions' tab.

Atrial fibrillation is a common arrhythmia that increases the risk of stroke by 4.5 times. Anticoagulant/antithrombotic therapy in atrial fibrillation has been inconsistent and inappropriate. Warfarin enjoyed the monopoly of being the primary medication used to reduce the risk of thromboembolic events. Warfarin has many limitations in its use as an ideal anticoagulant. To overcome this difficulty, now there are two main alternative groups to warfarin namely, direct thrombin inhibitors (ximelagatran and dabigatran) and factor Xa inhibitors (apixaban, rivaroxaban, edoxaban, etc.). The advantages of the newer anticoagulants over the conventional warfarin are numerous. There are three landmark trials which have shown some light to the path of newer anticoagulant era, which include the following: RE-LY, ROCKET AF and ARISTOTLE. Head to head comparison of warfarin with newer anticoagulants showed the superiority of newer anticoagulants over warfarin in terms of efficacy and favorable side effect profile. After few decades of using warfarin, it‘s high time to enter into the era of newer anticoagulants and bid adieu to warfarin.

Zonisamide, a 1,2 benzisoxazole derivative is a structurally novel antiepileptic drug (AED) with a broad spectrum of antiseizure activity. [1,2 ]Zonisamide has been available in Japan since 1989, where it is widely used both as monotherapy and adjunctive therapy (i.e. as Add on) for various seizure types and syndromes in adults and children.[3,4] In the United States, clinical trials of zonisamide began in the early1980s. These studies provided clear evidence of zonisamide’s promise as an effective adjunctive therapy for refractory partial seizures. Leppik et al. observed a 52% reduction in seizure frequency in a historical-control, open-label, multicenter study. However, development of kidney stones in 3.7% of patients enrolled in this study led to the temporary termination of US development efforts. Testing resumed in the 1990s, and zonisamide was approved by the US Food and Drug Administration (FDA) in March 2000 as adjunctive treatment for refractory partialonset seizures in adults( aged>16years).5 Results from placebo-controlled, short-term studies, as well as baselineor historicalcontrolled, long-term studies, demonstrate that zonisamide is an effective adjunctive treatment for refractory partialonset seizures. Zonisamide efficacy did not decline over time, suggesting that most patients do not develop tolerance to the anticonvulsant effects of zonisamide. Findings from one of the long-term studies indicate that, for some patients, zonisamide can be effective as monotherapy.[7] Zonisamide was well-tolerated; most adverse events were mild to moderate, and their incidence declined as treatment continued. The few serious adverse events were all reversible with zonisamide dose reduction or discontinuation or the passage of time. US clinical trials show that zonisamide is a safe and effective AED for the treatment of refractory partial-onset seizures. Further studies are needed to establish monotherapy efficacy in epilepsy. The potential use of zonisamide in non epileptic conditions like neuropathic pain, migraine prophylaxis [2] and Parkinsonism [6] are briefly touched in this review.

Background The ideal objective of treating a person with epilepsy is to induce remission by usage of antiepileptic drugs (AEDs) and withdraw the AEDs without causing seizure recurrence. Prolonged usage of AEDs may have long-term side effects. Hence when a person with epilepsy is in remission (free of seizures for some time) it is logical to attempt to discontinue the medication. The timing of withdrawal and the mode of withdrawal arise while contemplating withdrawal of AEDs. This review proposes to examine the evidence for the rate of withdrawal of AEDs (whether rapid or slow tapering) and its effect on recurrence of seizure. This review also examines the effect of variables such as age of seizure onset, seizure types, presence of neurological deficits, mental subnormality, aetiology of epilepsy, type of AED, EEG findings or duration of seizure freedom on the risk of recurrence of seizures with the two tapering regimens. Objectives (1) To quantify risk of seizure recurrence after rapid (taper period of three months or less) or slow (taper period or more than three months) discontinuation of antiepileptic drugs in adults with epilepsy who are in remission. (2) To quantify the risk of seizure recurrence after rapid (taper period of three months or less) or slow (taper period of more than three months) discontinuation of antiepileptic drugs in children with epilepsy who are in remission. (3) To attempt to assess which variables modify the risk of seizure recurrence. Search methods We searched the Cochrane Epilepsy Group's Specialized Register (August 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to September 2004) and cross-references from identified studies. No language restrictions were imposed. Selection criteria Randomized controlled trials that evaluate withdrawal of AEDs in a rapid or slow manner after varying periods of seizure control in patients with epilepsy. Data collection and analysis Both review authors independently assessed the trials for inclusion and extracted the data. The outcomes assessed included seizure relapse (i.e. the percentage of patients experiencing seizure recurrence after withdrawal of AED); time to recurrence of seizure following withdrawal; occurrence of status epilepticus; mortality; morbidity due to seizure such as injuries, fractures, aspiration pneumonia; and quality of life (if assessed by validated scale). Main results One trial with weak methodology involving 149 children was included with a mean age of seizure onset of four years, mean age of 11 years at the time of starting the taper. The rapid taper group (six weeks) recruited 81 participants and the slow taper group (nine months) included 68 participants, out of whom 11 and 5 were lost to follow up even before the taper began respectively. The number of participants who were seizure free in the rapid and slow taper groups were 40 and 44 respectively at the end of one year follow up (OR 0.53, 95% CI 0.27 to 1.03); 30 and 29 respectively at the end of two years, (OR 0.79, 95% CI 0.41 to 1.53); 24 and 14 respectively at the end of three years (OR 1.62, 95% CI 0.76 to 3.46); 18 and 8 respectively at the end of four years (OR 2.14, 95% CI 0.87 to 5.3); 10 and 6 respectively at the end of five years (OR 1.46, 95% CI 0.5 to 4.23). Authors' conclusions In view of methodological deficiencies and small sample size, in the solitary study identified, we cannot derive any reliable conclusions regarding the optimal rate of tapering of AEDs. Further studies are needed in adults as well as in children to investigate the rate of withdrawal of AEDs and to study the effects of variables such as seizure types, its aetiology, mental retardation, EEG abnormalities, presence of neurological deficits and other co-morbidities on the rate of tapering.

Background Vitamins have been reported to be effective in controlling certain types of seizures and to prevent some of the harmful effects of antiepileptic drugs (AEDs). In this review we will summarize evidence from randomized controlled trials. Objectives To assess if vitamins improve seizure control, reduce adverse effects of AEDs or improve the quality of life in people with epilepsy. Search methods We searched MEDLINE from 1966 to October 2006, the Cochrane Epilepsy Group Specialized Register (December 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2006), and cross-references from identified studies. Selection criteria Randomized or quasi-randomized studies investigating the effects of one or more vitamins given alone or in addition to AEDs to people of any age with any type of epilepsy. Data collection and analysis Both review authors assessed the trials for inclusion and extracted the data. Outcomes assessed included seizure frequency, gingival hyperplasia, neuropathy, changes in bone mineral content, serum calcium, alkaline phosphatase, hemogram, serum levels of AEDs, neuropsychological and quality of life outcomes. Primary analyses were by intention to treat. Main results Fifteen studies met our inclusion criteria and were of poor methodological quality. None described randomization methods and most enrolled small numbers of participants. Nine studies (331 participants) investigated folic acid. Two studies (75 participants) found no effect for the outcome 50% or greater reduction in seizure frequency (OR 0.96; 95% CI 0.32 to 2.29). Also, no evidence was found for an effect on gingival health, intelligence, behavior, mental health or personality, or measures of red blood volume and hemoglobin content. Folic acid was not associated with any consistent changes in serum phenytoin or phenobarbitone levels or improvement in the mean motor conduction velocities of peripheral nerves. One small study (72 participants) found that thiamine improves neuropsychological functions related to psychomotor speed, visuospatial abilities, selective attention and verbal abstracting ability. One study (226 participants) found a significantly higher bone mineral content (BMC) among patients with epilepsy taking AEDs with vitamin D supplementation compared to controls who were not given supplementation (OR 3.6; 95% CI 2.48 to 4.72; p < 0.00001). The studies found no significant effects on serum calcium, alkaline phosphatase or general well-being. One small study (24 participants) found a significant decrease in seizure frequency in those treated with vitamin E compared to placebo (p = 0.00005; Peto OR 26.73; 95% CI 5.46 to 130.92). Authors' conclusions In view of methodological deficiencies and limited number of individual studies, we have found no reliable evidence to support the routine use of vitamins in patients with epilepsy. Further trials are needed, especially to assess the utility of vitamin D supplementation to prevent osteomalacia and the role of vitamin E on seizures and thiamine in improving cognitive functions.