Anti-epileptic drugs and hormonal treatments.

OPINION STATEMENT: Epilepsy and the medications used in its treatment are known to affect the menstrual cycle, aspects of contraception, and bone health in women. Adolescence is an important time to review the diagnosis of both epilepsy and the epilepsy syndrome because of the implications and decisions, which should be made regarding antiepileptic drug (AED) treatment. In girls, once they are on AED therapy, seizure free, and driving, it becomes difficult to change therapy because of the risk of breakthrough seizures and the fact that the new AED may not be as effective as the first. So a treatment choice made in adolescence is often life-long. Therefore, women need to be started on an AED that currently appears to be the most suitable for their seizure type, has a low teratogenic risk, and hopefully does not interact with contraception. There are no contraindications to the use of non-hormonal methods of contraception in women with epilepsy. Nonenzyme-inducing AEDs (valproate, benzodiazepines, ethosuximide, levetiracetam, tiagabine, and zonisamide) do not show any interactions with the combined oral contraceptive. There are interactions between the combined oral contraceptive and hepatic microsomal-inducing AEDs (phenytoin, barbiturates, carbamazepine, topiramate [dosages >200 mg/day], oxcarbazepine, eslicarbazepine and perampanel [dosages >12 mg/day]) and lamotrigine. Women taking enzyme inducing AEDs should be encouraged to use a method of contraception that is unaffected by their epilepsy medication. Interactions between AEDs and other hormonal therapies are less well studied. Studies have suggested that women with epilepsy are at increased risk of fractures, osteoporosis, and osteomalacia. No studies have been undertaken looking at preventative therapies for these comorbidities. This article will concentrate on current contraceptive treatment options in patients taking AEDs.

Geographical clustering of amyotrophic lateral sclerosis in South-East England: a population study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a degenerative disease of motor neurons that causes progressive paralysis and eventually results in death from respiratory failure. Environmental factors that trigger ALS might result in a pattern of geographical clustering of cases. We tested this hypothesis using the South-East England ALS population register, which covers south-east London, Kent and parts of neighbouring counties. METHODS: The register's catchment area was divided into postcode districts and sectors. The expected rates of ALS (adjusted for age and sex) were compared with the observed rates using a standardised residuals method and the SaTScan programme. RESULTS: There were 406 cases of ALS identified in the catchment area during the study period. Four of the 126 postcode districts, all in Greater London, had residuals >2.5 SDs from the mean. Similarly, there were 15 postcode sectors (out of 420) that had residuals >1.96 SDs from the mean. Nine of these were in Greater London. SaTScan identified an area that had a 5.61-km radius in which the relative risk of ALS was 1.70 (p = 0.012). This area overlapped with the postcode districts and some of the sectors identified using the residuals method. CONCLUSIONS: These findings suggest an excess of ALS cases in some postcode districts in south-east England.

Birth order and the genetics of amyotrophic lateral sclerosis.

The cause of ALS remains largely unknown for the 90% with no known family history, but spontaneous mutation to risk alleles of as yet unidentified genes is possible. It has long been recognized that genetic diseases may be more likely to occur in the last born children of a sibship because increased paternal age is associated with an increased spontaneous point mutation rate in sperm. To test the hypothesis that such a mechanism is responsible for sporadic ALS, we have performed a retrospective analysis of birth order position. We have analyzed sibships of size greater than four using a binomial test for birth position. The 478 pedigrees studied show no birth order effect, suggesting that any genetic contributions to sporadic ALS are more likely to be through deletion in large genes or interactions of common polymorphisms, rather than frequent spontaneous point mutation. This is encouraging for the prospect of finding sporadic ALS susceptibility genes using genome-wide association mapping.

A longitudinal study of diffusion tensor MRI in ALS.

In this study, we investigated whether diffusion tensor MRI (DTI) could detect progressive corticospinal tract degeneration in amyotrophic lateral sclerosis (ALS) and whether changes in diffusion variables reflected clinical deterioration. Twenty-three ALS patients and 25 healthy volunteers underwent whole brain DTI. Patients and a subset (n = 12) of controls returned for a second scan. Clinical measures of disease severity were assessed in the ALS group. Changes in fractional anisotropy (FA) and mean diffusivity (MD) were measured along the corticospinal tract using a region of interest approach. Adequate DTI data were available in 11 ALS patients and 11 controls at two time points. FA and MD differed significantly between ALS patients and controls at both time points, but neither changed significantly over time, while global measures of disease severity in patients increased with time. Although we confirmed that DTI detects corticospinal tract damage in ALS, there were no significant changes in diffusion measures over time. The sensitivity of DTI may be improved by advanced data analysis techniques, although the high dropout rate suggests that use of MRI as a biomarker in ALS may be restricted to earlier stages of disease.