Lois E. Krahn

Gambling and increased sexual desire with dopaminergic medications in restless legs syndrome

Objectives: Do patients with restless legs syndrome (RLS) report gambling or other abnormal behaviors as previously reported in Parkinson disease. Methods: This survey study was sent to 261 idiopathic RLS patients, and it included the Gambling Symptoms Assessment Scale, Altman Self-Rating Mania Scale, and questions pertaining to sexual activity and novelty-seeking behaviors. Results: Ninety-nine patients responded to the survey, and 77 were actively taking 1 or more dopaminergic medications. Of the 70 respondents who answered the gambling questions, 5 (7%) noted a change in gambling, with 4 (6%; 95% confidence interval, 2%-14%) stating that increased urges and time spent gambling occurred specifically after the use of dopaminergic medications (2 on pramipexole, 1 on ropinirole, and 1 on levodopa and pramipexole). Increased sexual desire was reported by 4 (5%) of the 77 respondents, 3 (4%; 95% confidence interval, 1%-11%) reported that this occurred specifically after the use of dopaminergic medications (1 on pramipexole, 1 on ropinirole, and 1 on levodopa). One patient reported both an increase in gambling and sexual habits. Conclusions: This exploratory survey study revealed the development of gambling and/or increased sexuality in patients with RLS. These data raise the possibility that, as in Parkinson disease, RLS patients should be cautioned about potential behaviors that may occur with the use of dopaminergic medications. Further prospective studies are needed to assess the relationship between these medications and compulsive behaviors associated with the treatment of RLS.

Delirium in Elderly Patients: Evaluation and Management

OBJECTIVE To review the evaluation and management of delirium in elderly patients for primary-care providers. DESIGN We summarize the clinical features, course, pathophysiologic aspects, predisposing factors, causes, and differential diagnosis of delirium and discuss approaches to affected patients and various management strategies. RESULTS Delirium, an altered mental state, occurs more frequently in elderly than in younger patients. The pathophysiologic changes associated with aging and the higher occurrence of multiple medical problems and need for medications contribute to the higher frequency of delirium in elderly patients. Evaluation should begin with a consideration of the most common causes, such as a change in or addition to prescribed medications, a withdrawal from alcohol or other sedative-hypnotic drugs, an infection, or a sudden change in neurologic, cardiac, pulmonary, or metabolic state. Finally, management of delirium is threefold: (1) identifying and treating underlying causes, (2) nonpharmacologic interventions, and (3) pharmacologic therapies to manage symptoms of delirium. CONCLUSION Elderly patients frequently experience delirium. Delirious symptoms can produce devastating consequences if they are not recognized and appropriately treated.

Movement Disorders Associated with the Use of Gabapentin

Summary: Purpose: We report two cases of unusual movement disorders associated with the use of gabapentin (GBP) in patients being treated for epilepsy who were otherwise neuro‐logically intact.

Long-term survival of patients with anorexia nervosa: a population-based study in Rochester, Minn.

OBJECTIVE To estimate long-term survival of unselected patients with anorexia nervosa from Rochester, Minn. PATIENTS AND METHODS In this population-based retrospective cohort study, all 208 Rochester residents who presented with anorexia nervosa (193 women and 15 men) for the first time from 1935 through 1989 were monitored for up to 63 years. Subsequent survival was compared with that expected for Minnesota white residents of similar age and sex, and standardized mortality ratios were determined on the basis of age- and sex-specific death rates for the US population in 1987. RESULTS Survival was not worse than expected in this cohort (P = .16). The estimated survival 30 years after the initial diagnosis of anorexia nervosa was 93% (95% confidence interval, 88%-97%) compared with an expected 94%. During 5646 person-years of follow-up (median, 22 years per patient), 17 deaths occurred (14 women and 3 men) compared with an expected 23.7 deaths (standardized mortality ratio, 0.71; 95% confidence interval, 0.42-1.09). One woman died of complications of anorexia nervosa, 2 women committed suicide, and 6 patients (5 women and 1 man) died of complications of alcoholism. Other causes of death were not increased. CONCLUSIONS Long-term survival of Rochester patients with anorexia nervosa did not differ from that expected. This finding suggests that overall mortality was not increased among the spectrum of cases representative of the community.

Narcolepsy associated with other central nervous system disorders

The authors identified patients with the coexistence of narcolepsy and another CNS disorder seen between 1975 and 1998 at their institution. Eighteen patients were identified, nine with narcolepsy commencing within 1 year before or after the other disorder. Seven patients (39%) had hypothalamic–pituitary syndromes. When they occur together, narcolepsy and other CNS disorders frequently emerge at about the same time, suggesting a causative relationship. Hypothalamic–pituitary pathology was the most common association.

Psychiatric and psychosocial aspects of liver transplantation

Liver transplantation (LT) has increasingly been accepted as the standard of care for patients with irreversible advanced liver disease. Due to an expanded list of diseases that are accepted as indications for transplantation, for example, specific criteria for hepatocellular carcinoma (HCC), coupled with a finite number of available organs, the national waiting list of patients has steadily grown. Nonetheless, the supply of donor organs has not kept pace, with currently 16% of patients dying on the waiting list without obtaining a transplant.1 This mortality rate has indicated a need to develop effective selection criteria for the more suitable candidates. Efforts to prepare patients so they are in the optimal state of physical and emotional health to adapt successfully after transplantation remain a priority. Recognizing the potential impact of psychiatric disorders, including addictions, on the liver transplant patient’s outcome is essential. The aim of this article is to provide an overview the psychiatric disorders and issues with which the transplant hepatologist must be knowledgeable. In particular, this review evaluates how psychiatric and chemical dependency disorders may interfere with optimal adherence to recommended treatment and social support. In these complicated cases, psychiatric consultation can aid in the determination of the relative importance of a patient’s psychiatric history and assist in preparing these individuals for transplantation.

Major depression in medically ill patients

Major depression is one of the most common psychiatric problems complicating the treatment and prognosis of patients with active medical illness. Recognizing and treating major depressive conditions in this population can often be challenging, even for the most seasoned clinicians. This article reviews the medical and neurologic conditions that have been associated with the high prevalence rates of major depression. Highlights of the evaluation process that help confirm this suspected diagnosis are addressed, and management issues are discussed. Brief reviews of supportive psychotherapeutic tools that the clinician may find helpful are included, as well as current advances in pharmacologic interventions.

Studies of humoral immunity to preprohypocretin in human leukocyte antigen DQB1*0602-positive narcoleptic subjects with cataplexy

BACKGROUND Canine models for narcolepsy have mutations of the hypocretin receptor 2 gene, and preprohypocretin knockout murine lines exhibit narcoleptic-like behaviors. Human narcolepsy with cataplexy is associated with human leukocyte antigen DQB1*0602 and reduced hypocretin levels in cerebrospinal fluid, suggesting an autoimmune diathesis. We tested the hypothesis that DQB1*0602-positive narcoleptic subjects with cataplexy have immunoglobulin (Ig)G reactive to human preprohypocretin and its cleavage products. METHODS Serum samples of 41 DQB1*0602-positive narcoleptic subjects with cataplexy and 55 control subjects were studied, as were 19 narcoleptic and 13 control samples of cerebrospinal fluid. We tested for IgG reactive to preprohypocretin and its major cleavage products (including hypocretin 1 and 2), using immunoprecipitation assays (IP), immunofluorescence microscopy (IF) of Chinese hamster ovarian cells expressing preprohypocretin, and Western blots. RESULTS There was no evidence for IgG reactive to preprohypocretin or its cleavage products in CSF of subjects with narcolepsy as measured by IPs, Western blots, and IF. Although the IP with CSF and the C-terminal peptide showed significant differences by two methods of comparison, the control subjects had higher counts per minute than narcoleptic subjects, which was opposite to our hypothesis. CONCLUSIONS The hypothesis that DQB1*0602-positive narcoleptic subjects with cataplexy have IgG reactive to preprohypocretin or its cleavage products was not supported.

Examining serotonin function: A modified technique for rapid tryptophan depletion

Tryptophan (TRP) depletion was used to study serotonin because the ratio of TRP to large neutral amino acids (TRP/LNAA) determines the quantity of TRP that enters the brain. Because TRP is not universally available, a modified technique of TRP depletion was developed where a 1/4 strength preparation of an amino acid mixture (AAM) replaces TRP as the placebo. Seven healthy subjects could not differentiate between the preparations in this double-blind, placebo-controlled study. Urinary 6-hydroxymelatonin sulfate (6-MS) was monitored as a biochemical marker of serotonin. The TRP/LNAA ratio (GG = 0.0001) and 6-MS secretion (GG = 0.024) were decreased, but placebo TRP levels (GG = 0.062) were not altered significantly. This modified technique facilitates the sue of TRP depletion in clinical research.

Narcolepsy: New Understanding of Irresistible Sleep

Recently, low levels of a newly identified neuropeptide, hypocretin 1, were described in the cerebrospinal fluid of patients with narcolepsy. This neurochemical finding furthers our understanding of this enigmatic sleep disorder typically characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations. Narcolepsy appears to be fundamentally related to abnormally regulated rapid eye movement sleep. The diagnosis of this disorder remains challenging because of multiple other conditions that can cause daytime sleepiness and the difficulties in recognizing cataplexy based on patient report. The role of hypocretins in narcolepsy is unclear but intriguing because the cell bodies are restricted to the lateral hypothalamus, a brain region long associated with sleep regulation, with neuronal widespread projections to areas including the locus ceruleus, ventral tegmental area, amygdala, and dorsal raphe. Hypocretins potentially modulate the activity of monoamines and acetylcholine, and therefore their absence leads to the multiple symptoms of narcolepsy. This article reviews the current understanding of the diagnosis and treatment of narcolepsy and discusses the possible implications of the hypocretin discovery.