Alan R. Jacobs

The Effect of Menopause and Perimenopause on the Course of Epilepsy

Summary: Purpose: The purpose of this study was to obtain preliminary information about the effect of menopause and perimenopause on the course of epilepsy, and to determine whether seizure type, use of hormone‐replacement therapy (HRT), or a history of catamenial seizure pattern would influence this course.

Interictal EEG discharges, reproductive hormones, and menstrual disorders in epilepsy

We evaluated reproductive endocrine function in women with unilateral temporolimbic epilepsy and normal control subjects to assess the effects of epilepsy, epilepsy laterality, and antiepileptic drug use on the cerebral regulation of hormonal secretion. The findings indicate that reproductive endocrine function differs between women with epilepsy and normal control subjects. Significant differences exist at all levels of the reproductive neuroendocrine axis, that is, hypothalamus, pituitary, and peripheral gland. Differences show significant relationships to the epilepsy itself as well as to medication use. Reproductive neuroendocrine changes occur in a stochastic manner such that the laterality of unilateral temporolimbic discharges is associated with predictable directional changes in hormonal secretion at all levels of the reproductive neuroendocrine axis. These directional changes are consistent with the finding that different reproductive disorders may develop in relation to left‐ and right‐sided temporolimbic epilepsy. Hormonal changes can show close temporal relationship to the occurrence of interictal epileptiform discharges and may vary in relation to the laterality of the discharges. Antiepileptic drugs differ in their effects on reproductive hormone levels. There are notable differences between enzyme‐inducing and noninducing drugs. Menstrual disorders are more common among women with interictal discharges as well as women with abnormal hormonal findings. Ann Neurol 2003;54:625–637

Testosterone versus testosterone and testolactone in treating reproductive and sexual dysfunction in men with epilepsy and hypogonadism

Antiepileptic drug-induced reductions in serum levels of biologically active testosterone and elevations in serum estradiol (E2) may contribute to sexual dysfunction among men with epilepsy. Treatment using a combination of testosterone and the aromatase inhibitor testolactone may have significantly better effects on sexual function and also seizure frequency than testosterone alone.

Relationship of sexual dysfunction to epilepsy laterality and reproductive hormone levels in women

Sexual dysfunction has been reported to be common among women with epilepsy. Controlled studies, quantitative data, and investigations of potentially contributory factors, however, have been few. The purpose of this investigation was to determine if (1) sexual dysfunction is unusually common among women with partial seizures of temporal lobe origin (TLE), and (2) sexual dysfunction varies in relation to the laterality of EEG epileptiform discharges, antiepileptic drug use, and serum gonadal steroid levels. This controlled prospective investigation used a quantitative sexual rating scale and reproductive hormone measures to compare sexual dysfunction in women with left and right unilateral temporolimbic epilepsy and controls. Sexual dysfunction scores were significantly higher in women with TLE, and sexual dysfunction affected substantially more women with epilepsy than controls. Women with right-sided foci were affected more than women with left-sided foci. There was a significant inverse correlation between sexual dysfunction and bioactive testosterone levels in women with epilepsy as well as in controls. Serum estradiol was lower in women with TLE but did not correlate significantly with overall sexual dysfunction. The findings suggest that sexual dysfunction is significantly more common in women with right-sided epileptiform discharges than in controls and is inversely correlated with bioactive testosterone levels. The value of hormonal replacement or supplementation remains to be explored.

Hormones and cognition: current concepts and issues in neuropsychology.

This article provides an extensive and comprehensive review of the effects of hormones on cognition. Studies detailing specific neurocognitive functions affected by variation in hormone levels across the life span are presented. Dysregulation of hormone levels is considered from models of both normal and diseased functioning. Patterns of cognitive dysfunction are described for a range of syndromes involving the neuroendocrine system, and evidence of specific neurophysiological mechanisms that can account for these findings is outlined. This review includes discussion of treatment outcomes and the permanency of endocrine-related cognitive dysfunction. The authors present a set of guidelines for clinical neuropsychologists to use for assessment of patients with neuroendocrine system dysfunction. Clinical and methodological issues in research and treatment settings are discussed.

Late-onset congenital adrenal hyperplasia: a treatable cause of anxiety

BACKGROUND Some intermediaries of cortisol synthesis, especially the sulfated ester of dehydroepiandrosterone (DHEAS), are picrotoxin-like antagonists of the gamma-aminobutyric acid A (GABA-A) receptor and exert potent anxiogenic effects. We report 5 men and 7 women with refractory anxiety disorders, who had late-onset congenital adrenal hyperplasia (CAH), and in whom interactions between neuroactive steroids and anomalous brain substrates may have participated in the pathophysiology and treatment of anxiety. METHODS Twelve patients with refractory anxiety disorders as defined by DSM-IV had elevated DHEAS and specific enzyme deficiencies diagnostic of CAH. All were treated with adrenal suppressive therapy using ketoconazole or low (physiologic) dose glucocorticoids. Anxiety was rated by the Tension Scale of the Profile of Mood States (POMS Tension) questionnaire before and during hormonal treatment. RESULTS Reduction of DHEAS was associated with lower anxiety scores in all twelve cases. POMS Tension scores decreased by 55%. Hormonal treatment, which failed to lower DHEAS, was ineffective. CONCLUSIONS These findings suggest that late onset CAH can contribute to anxiety disorders and that adrenal suppressive therapy or inhibition of steroidogenesis with ketoconazole may be efficacious as adjuvant therapy.

Isolated global amnesia associated with autoimmune thyroid disease

One week after developing a gastrointestinal illness, a 32-year-old man with a 15-year history of Hashimoto thyroiditis, with no previous cognitive or comportment changes, presented with confusion and extreme forgetfulness over 3 days. He repeated himself in conversations and lost memories from his recent past. There were no headaches, fevers, seizures, or focal elementary neurologic or systemic symptoms or signs. His judgment, personality, language, and reasoning abilities remained normal by history and mental status testing. Brain MRI on day 3 of his amnesia, with and without gadolinium, was normal. An EEG 3 weeks later was also normal. Ten days later, tests for antinuclear and anti-Hu antibodies were negative, CSF leukocyte count was 3/mm3, protein concentration was 20 mg/dL, and viral and bacterial cultures were negative. At this time, the serum thyroid peroxidase antibody concentration was 1,860 IU/mL (reference range, 0.0 to 2.0 IU/mL). Based …