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Biomedical subjects

S D Lhatoo

Publications and source records attributed to S D Lhatoo.

18 recordsLinked to original sources
PubMed2003

The treatment of epilepsy in developing countries: where do we go from here?

Epilepsy is the most common serious neurological disorder and is one of the world's most prevalent noncommunicable diseases. As the understanding of its physical and social burden has increased it has moved higher up the world health agenda. Over four-fifths of the 50 million people with epilepsy are thought to be in developing countries; much of this condition results from preventable causes. Around 90% of people with epilepsy in developing countries are not receiving appropriate treatment. Consequently, people with epilepsy continue to be stigmatized and have a lower quality of life than people with other chronic illnesses. However, bridging the treatment gap and reducing the burden of epilepsy is not straightforward and faces many constraints. Cultural attitudes, a lack of prioritization, poor health system infrastructure, and inadequate supplies of antiepileptic drugs all conspire to hinder appropriate treatment. Nevertheless, there have been successful attempts to provide treatment, which have shown the importance of community-based approaches and also indicate that provision for sustained intervention over the long term is necessary in any treatment programme. Approaches being adopted in the demonstration projects of the Global Campaign Against Epilepsy--implemented by the International League Against Epilepsy, the International Bureau for Epilepsy, and the World Health Organization--may provide further advances. Much remains to be done but it is hoped that current efforts will lead to better treatment of people with epilepsy in developing countries.

Anticonvulsants↗
PubMed2002

Sudden unexpected death in epilepsy.

Sudden unexpected death in epilepsy is the most common category of seizure-related death for patients who develop chronic epilepsy, accounting for up to 17% of epilepsy deaths. Sudden unexpected death in epilepsy is defined as a sudden, unexpected, non-accidental death in an individual with epilepsy with or without evidence of a seizure having occurred (excluding documented status epilepticus) and where autopsy does not reveal an anatomical or toxicological cause of death. Incidence rates range between 0.35 and 2.70 per 1000 person-years in the population-based studies and between 1.50 and 9.30 per 1000 person-years in selected cohorts. Seizure frequency appears to be an important factor in sudden unexpected death in epilepsy, although the exact pathogenetic mechanisms involved are unclear.

Cause of Death↗
PubMed2001

A pharmacoepidemiologic study of factors influencing the outcome of treatment with lamotrigine in chronic epilepsy.

PURPOSE: To identify prognostic factors for freedom from seizures and long-term retention of treatment in patients receiving lamotrigine (LTG). METHODS: A multicenter, retrospective, case record study of 1,050 patients with chronic epilepsy was carried out. Logistic regression and Cox regression analyses were used to identify clinical features associated with freedom from seizures and retention of treatment, respectively. Long-term retention rates of LTG therapy were estimated using Kaplan-Meier survival analysis. RESULTS: The 1,050 patients with chronic epilepsy were included in the study. Patients with generalized epilepsy (p = 0.01), who were not receiving carbamazepine (CBZ; p = 0.02) were more likely to become seizure-free. Sixty percent of patients continued on LTG therapy >1 year and estimated retention at 8 years was 38%. Patients with generalized epilepsy (p = 0.002), patients receiving concurrent sodium valproate (VPA; p < 0.0001), those not previously exposed to gabapentin and vigabatrin (p < 0.0001), and those in whom the starting dose was lower (p < 0.0012), were more likely to remain on long-term treatment with LTG. The relationships with exposure to other antiepileptic drugs remained significant in patients with focal and with generalized epilepsy when considered separately. CONCLUSIONS: The best results from LTG treatment in terms of freedom from seizures and long-term retention of treatment were obtained in patients with generalized epilepsy. Retention of treatment was enhanced by VPA not only in generalized but also in focal epilepsy. The importance of a low starting dose of LTG was again confirmed. The apparent negative effect of CBZ in patients taking LTG merits further investigation.

Anticonvulsants↗
PubMed2001

The dynamics of drug treatment in epilepsy: an observational study in an unselected population based cohort with newly diagnosed epilepsy followed up prospectively over 11-14 years.

OBJECTIVES: To study prospectively long term dynamics and patterns of treatment in a population based cohort of patients with newly diagnosed epilepsy. METHODS: 564 patients with definite epilepsy entered the UK National General Practice Study of Epilepsy (NGPSE), between 1984 and 1987, and were prospectively followed up for between 11-14 years. RESULTS: Treatment was started in 433 (77%) patients. Only 15% of single seizure patients had medication prescribed initially, although due to high seizure recurrence, more than 70% ultimately received antiepileptic medication. 209/564 patients (37%) were on drug therapy for epilepsy at the time of last follow up. 168/564 patients (30%) have stayed continuously on medication and another 41/564 patients (7%) restarted drug therapy because of seizure recurrence, having withdrawn medication. 98/209 (47%) of those on treatment are known to be in 5 year terminal remission. Phenytoin (29%) and carbamazepine (27%) were the most commonly preferred first line drugs followed by valproate (15%). Less than half of treated patients with partial seizures received carbamazepine as a first line drug and less than a third with generalised seizures were prescribed valproate as first choice drug. Nine out of 31 (29%) patients with one or more seizures a week at last follow up had never tried a second drug and only seven (23%) had tried four or more drugs. 11% of all treatment changes involved a new antiepileptic drug. Treatment changes were associated with low terminal remission rates. CONCLUSIONS: Out of 30 000 patients with newly diagnosed epilepsy every year in the United Kingdom, about 6000 have inadequate seizure control in the long term. About a third of the patients in this group have one or more seizures every month. Only two thirds of these patients with frequent seizures are likely to switch medication to try and achieve better seizure control. There is probably still considerable room for improvement in prescribing practice in the United Kingdom.

Adolescent↗
PubMed2001

Mortality in epilepsy in the first 11 to 14 years after diagnosis: multivariate analysis of a long-term, prospective, population-based cohort.

The United Kingdom National General Practice Study of Epilepsy is a prospective, population-based study of newly diagnosed epilepsy. A cohort of 792 patients has now been followed for up to 14 years (median follow-up [25th, 75th percentiles] 11.8 years, range 10.6-11.7 years), a total of 11,400 person-years. These data are sufficient for a detailed analysis of mortality in this early phase of epilepsy. Over 70% of patients in this cohort have developed lasting remission from seizures, although the mortality rate in the long term was still twice that of the general population. The standardized mortality ratio (SMR), the number of observed deaths per number of expected deaths, was 2.1 (95% confidence interval [CI] = 1.8, 2.4). Patients with acute symptomatic epilepsy (SMR 3.0; 95% CI = 2.0, 4.3), remote symptomatic epilepsy (SMR 3.7; 95% CI = 2.9, 4.6), and epilepsy due to congenital neurological deficits (SMR 25; 95% CI = 5.1, 73.1) had significantly increased long-term mortality rates, whereas patients with idiopathic epilepsy did not (SMR 1.3; 95% CI = 0.9, 1.9). This increase in mortality rate was noted particularly in the first few years after diagnosis. Multivariate Cox regression and time-dependent co-variate analyses were utilized for the first time in a prospective study of mortality in epilepsy. The former showed that patients with generalized tonic-clonic seizures had an increased risk of mortality. The hazard ratio (HR), or risk of mortality in a particular group with a particular risk factor compared to another group without that particular risk factor, was 6.2 (95% CI = 1.4, 27.7; p = 0.049). Cerebrovascular disease (HR 2.4; 95% CI = 1.7, 3.4; p < 0.0001), central nervous system tumor (HR 12.0; 95% CI = 7.9, 18.2; p < 0.0001), alcohol (HR 2.9; 95% CI = 1.5, 5.7; p = 0.004), and congenital neurological deficits (HR 10.9; 95% CI = 3.2, 36.1; p = 0.003) as causes for epilepsy and older age at index seizure (HR 1.9; 95% CI = 1.7,2.0; p < 0.0001) were also associated with significantly increased mortality rates. These hazard ratios suggest that epilepsy due to congenital neurological deficits may carry almost the same risk of mortality as epilepsy due to central nervous system tumors and that epileptic seizures subsequent to alcohol abuse may carry almost the same risk of mortality as epilepsy due to cerebrovascular disease. The occurrence of one or more seizures before the index seizure (the seizure that led to the diagnosis of epilepsy and enrolment in the study) was associated with a significantly reduced mortality rate (HR 0.57; 95% CI = 0.42, 0.76; p = 0.00001). Time-dependent co-variate analysis was used to examine the influence of ongoing factors, such as seizure recurrence, remission, and antiepileptic drug use, on mortality rates in the cohort. Seizure recurrence (HR 1.30; 95% CI = 0.84, 2.01) and antiepileptic drug treatment (HR 0.97; 95% CI = 0.67, 1.38) did not influence mortality rate. There were only 5 epilepsy-related deaths (1 each of sudden unexpected death in epilepsy, status epilepticus, burns, drowning, and cervical fracture), suggesting that death directly due to epileptic seizures is uncommon in a population-based cohort with epilepsy.

Adolescent↗
PubMed2000

Long-term retention rates of lamotrigine, gabapentin, and topiramate in chronic epilepsy.

PURPOSE: We sought to determine the long-term retention rates of lamotrigine (LTG), gabapentin (GBP), and topiramate (TPM) therapy for patients at a tertiary referral clinic for chronic, refractory epilepsy. METHODS: We analyzed 424 consecutive patients with chronic, refractory partial and/or generalized epilepsy who were started on LTG, 158 patients who were started on GBP, and 393 patients who were started on TPM. The percentages of patients who continued therapy with LTG, GBP, and TPM were estimated with the use of Kaplan-Meier survival analysis. Factors that influence retention were analyzed with the use of Cox regression analysis. RESULTS: Kaplan-Meier survival analysis showed that at 3 years, 30% continued therapy on TPM compared with 29% on LTG and fewer than 10% on GBP. Adverse events resulted in therapy withdrawal in 40% of patients on TPM compared with GBP (37%) and LTG (22%). Perceived lack of efficacy led to treatment withdrawal in 39% of patients on GBP compared with 34% on LTG and 19% on TPM. Cox regression estimated that a fourth or fewer of patients with chronic partial epilepsy are likely to continue therapy with a new antiepileptic drug beyond 5 years. CONCLUSIONS: The impact of these new antiepileptic drugs on the long-term course of chronic partial epilepsy is likely to be small, as approximately three of four patients will discontinue therapy. More patients appear to continue on TPM compared with LTG or GBP, with a possible reason being better perceived efficacy of TPM, despite having the highest incidence of adverse events.

Acetates↗
PubMed2000

Prognostic factors affecting long-term retention of topiramate in patients with chronic epilepsy.

PURPOSE: To determine the long-term retention rate of topiramate (TPM) therapy in patients with chronic epilepsy and to identify the relevant prognostic factors that influence retention. METHODS: All patients with chronic epilepsy (n = 393) prescribed TPM between October 1, 1995, and December 31, 1998, at a tertiary referral centre for epilepsy were analysed. The retention rate for TPM was calculated by using Kaplan-Meier survival analysis, and the prognostic factors influencing retention were analysed by using Cox regression. RESULTS: Of patients prescribed TPM, 30% continued taking the drug beyond 3 years. Discontinuation was mainly due to adverse events and lack of efficacy. Use of more than one new concurrent antiepileptic drug (AED) and lower maximal daily doses were more likely to result in treatment discontinuation due to adverse events. Older age at onset of epilepsy, a history of having previously taken more than one new AED [lamotrigine (LTG), gabapentin (GBP), or vigabatrin (VGB)], and lower maximal daily doses were more likely to lead to discontinuation due to lack of efficacy. CONCLUSIONS: A third of patients with chronic epilepsy started on TPM therapy will continue on treatment for >3 years. Absence of learning disabilities, late age at onset of seizures, previous use of more than one new AED, two or more concurrent AED use, and low maximal daily doses of TPM are more likely to result in discontinuation of medication. These factors should be taken into account when considering the use of TPM for the treatment of chronic epilepsy.

Adolescent↗
PubMed2000

Adverse reactions to new anticonvulsant drugs.

A lack of systematic pharmacoepidemiological studies investigating adverse drug reactions (ADRs) to anticonvulsants makes it difficult to assess accurately the incidence of anticonvulsant-related ADRs. Most of the available information in this regard stems from clinical trial experience, case reports and postmarketing surveillance, sources that are not, by any means, structured to provide precise data on adverse event epidemiology. For various ethical, statistical and logistical reasons, the organisation of structured clinical trials that are likely to provide substantial data on ADRs is extremely difficult. This review concentrates on current literature concerning serious and life-threatening ADRs. As with the older anticonvulsants, the majority of ADRs to newer anticonvulsants are CNS-related, although there are several that are apparently unique to some of these new drugs. Gabapentin has been reported to cause aggravation of seizures, movement disorders and psychiatric disturbances. Felbamate should only be prescribed under close medical supervision because of aplastic anaemia and hepatotoxicity. Lamotrigine causes hypersensitivity reactions that range from simple morbilliform rashes to multi-organ failure. Psychiatric ADRs and deterioration of seizure control have also been reported with lamotrigine treatment. Oxcarbazepine has a safety profile similar to that of carbamazepine. Hyponatraemia associated with oxcarbazepine is also a problem; however, it is less likely to cause rash than carbamazepine. Nonconvulsive status epilepticus has been reported frequently with tiagabine, although there are insufficient data at present to identify risk factors for this ADR. Topiramate frequently causes cognitive ADRs and, in addition, also appears to cause word-finding difficulties, renal calculi and bodyweight loss. Vigabatrin has been reported to cause seizure aggravation, especially in myoclonic seizures. There have been rare reports of other neurological ADRs to vigabatrin, such as encephalopathy, aphasia and motor disturbances. Vigabatrin-induced visual field constriction is the latest and most worrying ADR. Many questions regarding the nature of this potentially serious ADR remain unanswered, as no prospective controlled study examining the phenomenon has been published. Rare cases of behavioural ADRs and IgA and IgG2 deficiency associated with the use of zonisamide have been reported. However, relatively few patients so far have been exposed to this drug, and therefore more postmarketing information is required. The relatively late establishment of aplastic anaemia and hepatic failure as potentially fatal ADRs of felbamate, and of visual field constriction with vigabatrin, should serve as ample reminders that ADRs can appear at any time.

Animals↗
PubMed2000

Stopping drug therapy in epilepsy.

In most of the epilepsies and epileptic syndromes, the decision to initiate antiepileptic drug (AED) therapy is often a far simpler one than the decision to stop it. The primary factor that drives a patient to want to discontinue therapy, and a doctor to endorse or recommend this, is a fear of long-term adverse events, a consideration that may be entirely justified as the side effects of vigabatrin and felbamate have proved. On the other hand, seizure recurrence with the attendant implications in employment, driving regulations and social stigmatization is a strong deterrent that discourages withdrawal of therapy. The absence of a clearer understanding of the natural history and prognosis of many individual epilepsy syndromes somewhat hampers the resolution of this dilemma. Hopefully, as our understanding of the epilepsies grows and the prediction of the chances of seizure relapse becomes a more precise science, stopping medication will become a less fraught exercise for both the patient and the doctor.

Animals↗
PubMed2000

Effect of alcohol dependence on the levels of duodenal disaccharidases in human subjects.

BACKGROUND: The aim of the study was to detect the duodenal enzyme activity in patients of alcohol dependence and to compare with non-alcoholic patients of non-ulcer dyspepsia. METHODS: Disaccharidases (lactase, sucrase, maltase) were estimated in 20 non alcoholic patients of non-ulcer dyspepsia and 20 alcoholics admitted to the drug de-addiction and treatment centre of PGIMER, Chandigarh, India. RESULTS: No significant influence of alcohol on enzyme levels in patients of alcohol dependence when compared to patients of non-ulcer dyspepsia was observed. However, a significant decrease in lactase level was noted in patients consuming more than 125 gm/day of alcohol. CONCLUSION: Amount of consumption of alcohol showed decrease in lactase enzyme, but not in maltase and sucrase. There was no effect of duration of alcohol consumption on dissacharidases in the two groups.

Adult↗
PubMed1999

Sudden unexpected death in epilepsy.

The majority of persons with epilepsy develop lasting remission from seizures, although mortality is significantly greater than that of the age-matched general population. Of the deaths that are thought to be directly related to seizures, sudden unexpected death in epilepsy is probably the commonest category; more so than status epilepticus or seizure-related accidents. Annual incidence rates vary from 1 in 200 patients with chronic epilepsy to about 1 in 1000 in more population-based studies. Young adults with severe, intractable epilepsy appear to be the most frequently affected group and may have even higher incidence rates. Other risk factors may also be important. An area of great research interest, several pathogenetic mechanisms have been postulated, centering mainly around cardiac rhythm and central hypoventilation. Given the frequent devastation caused by sudden unexpected death in epilepsy, the importance of seizure control is emphasised.

Death, Sudden↗