Subject epilepsy

Phosphorus MRS studies of depressed subjects strongly indicate that this disorder arises from altered brain energy metabolism 944 Hydrogen MRS has revealed unique and consistent metabolic characteristics in the brains of patients with probable AD 944 Hydrogen and phosphorus MRS have proven to be useful tools in the characterization of several epilepsies 944... 

The success of drug therapy in the treatment of epilepsy is singularly difiScult to assess owing to the extreme variability of the disorder, both in type of seizure pattern and the frequency with which attacks occur. The natural history of the disorder is also notoriously variable, further increasing the difficulties of assessing the contribution made by therapeutic agents. Moreover, the therapeutic aim varies from patient to patient. In one subject, for example, successful therapy may mean complete seizure control, while in another a reduction in seizure frequency from daily to weekly attacks may be considered adequate. 

Elderly No overall differences in safety were observed between subjects 65 years of age or older and younger subjects. There were insufficient numbers of elderly subjects in controlled trials of epilepsy to adequately assess the efficacy of levetiracetam in these patients. Because elderly patients are more likely to have decreased renal function, take care in dose selection it may be useful to monitor renal function. 

Sudden unexplained death In epilepsy Sudden and unexplained deaths were recorded among a cohort of treated patients (2,796 subject years of exposure). This represents an incidence of 0.0035 deaths per patient year. 

Kastner et al. (1993) evaluated valproic acid in 18 children and adults (mean age, 19.7 years) with self-injury or aggression, irritability, sleep disorder, and evidence of cycling. Fourteen (78%) responded positively as assessed by the CGI in this uncontrolled study. The authors found that 11 subjects with established or suspected epilepsy responded significantly better than participants with no evidence of epilepsy. 

As Mark Solms points out in his recent book, the dreams of patients with temporal lobe epilepsy are more intense than those of normals. They are more frequently intensely unpleasant or nightmarish, and this is presumably a function of higher levels of anxiety mediated by the hyperexcit-able amygdala of the epileptic patients. These hypotheses are testable in two ways. One is to confirm the anecdotal reports of patients by studying the subjects in sleep labs, as Jose Calvo and his group have done in Mexico City. Compared to age- and sex-matched controls, the epileptic subjects had measurably higher levels of anxiety in their dream reports. 

Recent studies of dream emotion prove Kliiver and Bucy s point. They support the idea that it is the brain itself—and more specifically the limbic brain—that may generate fear (the number one dream affect), cosmic elation (number two), and anger (number three). To round out the picture, there are reports that an intensification of these same emotions colors the dreams of patients with temporal lobe epilepsy. Subjects may indeed evince rapid heart action, increases in blood pressure, and rises and falls of breathing efforts in REM sleep, but these are not sensed as part of the subjective experience of dream emotion. 

Fig. 10.2 Chemical structures of NMDA and AMPA antagonists used for the treatment of ischemic injury, epilepsy and head injury in human subjects. Eliprodil (a) ifenprodil (b) remacemide (c) selfotel (d) and aptiganel (e)...

A large number of epidemiology and case-control studies have examined the potential association between oral aluminum exposure and Alzheimer s disease. A number of these studies have been criticized for flawed patient selection, poor comparability of exposed and control groups, poor exposure assessment, poor assessment of health outcomes, and weak statistical correlations (Nieboer et al. 1995 Schupf et al. 1989). Studies conducted by Martyn et al. (1989), McLachlan et al. (1996), and Michel et al. (1990) have found an association between oral exposure to aluminum and an increased risk of Alzheimer s disease. In a survey study conducted by Martyn et al. (1989), the incidence of Alzheimer s disease in individuals under the age of 70 was estimated from computerized tomographic (CT) records. The 1,203 subjects lived in 88 county districts within England and Wales. Data on aluminum concentrations in the municipal water over a 10-year period were obtained from water authorities and water companies. The subjects were classified as having probable Alzheimer s disease, possible Alzheimer s disease, other causes of dementia, or epilepsy. The relative risks of Alzheimer s disease were elevated in the subjects living in districts with aluminum water concentrations of >0.01 mg/L. However, the relative risk exceeded unity only in the subjects with aluminum water concentrations of >0.11 mg/L (relative risk of 1.5, 95% confidence interval of 1.1-2.2). 

Of the more recently introduced methods for smoking cessation, bupropion (an antidepressant with dopaminomimetic properties) has recently been introduced. Clinical trial data, in which the nicotine patch, bupropion at 300 mg, and a combination of the two drugs were compared with placebo treatment, have shown cessation of smoking rates of 36% for the patch, 49% for bupropion and 58% for the combined treatments following 7 weeks of treatment. The placebo response rate was 23%. All subjects received relapse prevention therapy. Thus bupropion appears to be a reasonably safe and effective treatment for nicotine dependence. It is however contraindicated in those subject to epilepsy its main side effects are dry mouth and insomnia. 

Three antiepileptic drugs have now been FDA approved as mood stabilizers for the prevention of recurring episodes of mania divalproex sodium (Depakote), extended-release carbamazepine (Equetro), and lamotrigine (Lamictal). Many of these drugs are prescribed to children for the control of epilepsy and, increasingly, for bipolar disorder. A critical question is their effect on the developing mental and emotional function of children, but there is little research on the subject (Loring, 2005). 

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