Is Epilepsy a Progressive Disease? The Neurobiological Consequences of Epilepsy

Summary: While primary, or idiopathic, epilepsies may exist, in the vast majority of cases epilepsy is a symptom of an underlying brain disease or injury. In these cases, it is difficult if not impossible to dissociate the consequences of epilepsy from the consequences of the underlying disease, the treatment of either the disease or the epilepsy, or the actual seizures themselves. Several cases of apparent complications of epilepsy are presented to illustrate the range of consequences encountered in clinical practice and the difficulty in assigning blame for progressive symptomatology in individual cases. Because of the difficulty in interpreting clinical material, many investigators have turned to epilepsy models in order to address the potential progressive consequences of recurrent seizures. The authors review experimental data, mainly from animal models, that illustrate short-, medium-, and long-term morphological and biochemical changes in the brain occurring after seizures, and attempt to relate these observations to the human condition.     

Anxiety disorders and major depression, together or apart.

This paper will discuss the relationship between anxiety and depression. We will begin with a brief historical perspective. We will then move into the twentieth century, with a focus on the 1950s, at which time the introduction of pharmacological treatment options revolutionized the field of psychiatry. The use of psychiatric medications and the observation of treatment response provided an additional means of understanding the relationship between anxiety and depression. From the late 1970s to the 1990s, it became apparent that various medications possessed wider therapeutic profiles than were previously recognized. For example, many medications were found to be efficacious in both anxiety and depressive disorders. These expanded therapeutic profiles provided additional clues to fuel our thinking about the relationship between anxiety and depression. The two major objectives of this paper are, first, to describe and formalize a process of pharmacological dissection and, second, to consider how this process might contribute to our search for a better understanding of the relationship between anxiety and depression.     

Breast Cancer Treatment of Women with Schizophrenia and Bipolar Disorder from Philadelphia, PA: Lessons Learned and Suggestions for Improvement

Treating cancer in patients with concurrent severe mental illness is complex and challenging for patients, families, and health care providers. Two such illnesses include schizophrenia and bipolar disorder. In this review, cases of women with breast cancer and severe mental illness from Philadelphia, PA illustrate the obstacles these women face in maintaining adequate cancer care. Barriers to receiving cancer treatment include understanding their disease, continuing medications and appointments, and experiencing complications of their psychiatric disorders. Learning from these cases is critical for health care providers and allows for innovation in treating and educating this difficult population. Increasing patient visit time, using social support services, and psychiatrist and psychiatrist-liaisons are necessary to improve care. In addition, family or caregivers should be included in discussions when possible. These techniques will assist in educating patients, improve insight into their disease and treatment, and allow them to benefit from cancer therapy.     

Metabolic effects of low dose angiotensin converting enzyme inhibitor in dietary obesity in the rat

Background and aimsGiven the recent observation of a local renin-angiotensin system (RAS) in adipose tissue, and its association with obesity-related hypertension, the metabolic effects of treatment with a low dose angiotensin converting enzyme inhibitor (ACEI) were investigated in a rodent model of diet-induced obesity.Methods and resultsMale Sprague Dawley rats were exposed to either standard laboratory chow (12% calories as fat) or palatable high fat (30% calories as fat) diet for 12 weeks. A subset from both dietary groups was given low dose ACEI in drinking water (perindopril, 0.3 mg/kg/day) throughout the study. The high fat diet increased body weight, adiposity, circulating leptin and insulin and in the liver we observed fat accumulation and increased tissue ACE activity. Treatment with perindopril decreased food intake and circulating insulin in both diet groups, and hepatic ACE activity in high fat fed animals only. Decreased plasma leptin concentration with ACE inhibition was only evident in chow fed animals. These effects were independent of any blood pressure lowering effect of ACE inhibition.ConclusionChronic low dose ACEI treatment reduced circulating insulin and leptin levels with some reduction in food intake in chow fed rats. Fewer beneficial effects were observed in obesity, and further work is required to investigate higher ACEI doses. Our data suggest a reduction in hepatic ACE activity may affect lipid accumulation and other inflammatory responses, as well as improving insulin resistance. Our findings may have implications for maximizing the clinical benefit of ACEI in patients without overt cardiovascular complications.     

Brain injury: Analysis of outcome in a post-acute rehabilitation system. Part 2: Subanalyses

The basic findings of brain-injured patients who underwent treatment within a co-ordinated system of post-acute brain-injury rehabilitation programmes have already been reported. The changes in function during the course of treatment by this post-acute sequence of rehabilitation were obtained and reported. A defined total population of N=192 was examined, with exclusions for appropriate causes (e.g. patients seen only for evaluation) producing a study population of N=173; of these, follow-up was achieved in 145 cases, a follow-up rate of 83.8%. Time from date of injury to date of admission, severity of deficit at time of admission to programme, and other appropriate independent variables were used to characterize the population. A single-blind interview methodology was employed in obtaining dependent measures of outcome at 6, 12 or 24 month periods post-discharge. Measures of outcome included residential status, level of productivity activity, and hours per day of attendant care or supervision required. In the work reported in this paper dependent variables are analysed for various subgroups of the total population. The subgroups analysed are: patients with traumatic brain injury only; mild moderate and severe grades of disability; and comparisons of outcomes at 6 months, 1 year, and 2 years post-discharge from treatment. The results are presented in terms of percentage change in dependent measures from point of admission to follow-up. Appropriate parametric and non-parametric statistical analyses of significance are carried out. Additionally, an analysis of cost associated with treatment, and some analysis of cost-benefit is provided. The results document substantial improvements in function during post-acute rehabilitation for both traumatic brain injury and brain dysfunction of other etiologies. Significant improvements are seen to occur in all grades of severity of dysfunction examined, and such improvements are robust and persist without evidence of decrement over the 2-year follow-up period. In addition, economic considerations suggest the potential for the recouping of costs of treatment within a reasonable period of time.