Seizures in alcohol-dependent patients: epidemiology, pathophysiology and management

The relationship between alcohol and seizures is complex and multifaceted. The prevalence of epilepsy in alcohol-dependent patients of western industrialised countries may be at least triple that in the general population, whereas the prevalence of alcoholism is only slightly higher in patients with epilepsy than in the general population. The seizure threshold is raised by alcohol drinking and declines on cessation of drinking. As a result, during withdrawal from alcohol, usually 6-48 hours after the cessation of drinking, seizures may occur. Alcohol acts on the brain through several mechanisms that influence seizure threshold. These include effects on calcium and chloride flux through the ion-gated glutamate NMDA and GABA receptors. During prolonged intoxication, the CNS adapts to the effects of alcohol, resulting in tolerance; however, these adaptive effects seem to be transient, disappearing after alcohol intake is stopped. Although the relationship of seizures to alcohol use is likely to be dose dependent and causal, the available clinical data do not suggest that alcohol use results in seizure genesis. However, a genetic predisposition to alcohol withdrawal seizures is possible. Other seizures in alcohol-dependent individuals may be due to concurrent metabolic, toxic, infectious, traumatic, neoplastic and cerebrovascular diseases and are frequently partial-onset seizures. Alcohol abuse is a major precipitant of status epilepticus (9-25% of cases), which may even be the first-ever seizure type. Prompt treatment of alcohol withdrawal seizures is recommended to prevent status epilepticus. During the detoxification process, primary and secondary preventative measures can be taken. A meta-analysis of controlled trials for the primary prevention of alcohol withdrawal seizures demonstrated a highly significant risk reduction for seizures with benzodiazepines and antiepileptic drugs and an increased risk with antipsychotics. A meta-analysis of randomised, placebo-controlled trials for the secondary prevention of seizures after alcohol withdrawal showed lorazepam to be effective, whereas phenytoin was ineffective. Because withdrawal seizures do not recur if the patient remains abstinent, long-term administration of antiepileptic drugs is unnecessary in abstinent patients. The first seizure not related to alcohol withdrawal should not result in permanent drug treatment in an alcohol-dependent patient, because of poor compliance and the high likelihood of remission. The treatment of alcohol dependence is more important and should be prioritised before the prevention of further seizures.     

Depression and anxiety in individuals with amyotrophic lateral sclerosis: epidemiology and management

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease with no curative treatment. Considering the devastating nature of the disease, a high prevalence of depression and anxiety in affected patients would be expected. A review of the literature shows prevalence rates for depression in ALS patients ranging from 0% to 44%, but studies using the structured interview according to DSM-IV criteria find highly consistent rates of 9-11%. Prevalence rates for anxiety in ALS range from 0% to 30%. Depression and anxiety appear to be not always properly addressed aspects of ALS, as there are only a few references in the literature about psychological and pharmacological interventions. Additionally, pharmacological antidepressant therapy is often not continuously monitored and its effectiveness remains unevaluated. A review of the literature and our own experiences show that there is a lack of psychological care and, to our knowledge, there is no specific psychological intervention method for ALS patients. Concerning pharmacological treatment of depression in patients with ALS, there is broad consensus among clinical experts that SSRIs and TCAs are helpful, but there have been no controlled clinical studies of these medications in ALS patients. TCAs can be prescribed if anticholinergic effects are desired simultaneously for treating pseudohypersalivation or insomnia. Anxiety is usually treated with anxiolytics, but again there have been no systematic studies of these drugs in patients with ALS. For psychological intervention we suggest a cognitive behavioural approach, which has to be integrated into an intervention programme that includes teaching of appropriate coping strategies and reappraisal skills and encourages engagement in activities that are still practicable and pleasant. We propose that the treatment of depression and anxiety should involve both cognitive behavioural therapy and pharmacological intervention. Pharmacological treatment should be strictly monitored for effectiveness. To date, no clinical trials are available that would allow us to recommend pharmacotherapy over psychotherapy or vice versa; however, evidence from other patient groups, such as elderly patients diagnosed with major depressive disorder, suggests that a combination of both therapies has the potential to also improve depression and anxiety in patients with ALS.     

Psychiatric and substance use disorders in individuals with hepatitis C: epidemiology and management

Hepatitis C virus (HCV) infection is a major health concern in the US as well as in other countries worldwide. Treatment issues and disease management strategies are complicated by the extremely high rate of psychiatric and substance use disorders in those who have HCV. The majority of new and existing cases of HCV are related to injection drug use and, in this population, the prevalence of psychiatric comorbidity is high. Optimally, all patients with HCV should be screened for psychiatric and substance use disorders before initiation of antiviral therapy. If a patient screens positive, he or she should be referred to a mental healthcare provider or addiction specialist, assessed for the presence of a psychiatric or substance use disorder, and appropriately treated prior to initiation of antiviral (i.e. interferon) therapy. Although interferon-based therapies can lead to severe neuropsychiatric adverse effects, including in rare instances suicide, evidence suggests that many patients with comorbid psychiatric and substance use diagnoses can be treated safely and effectively using comanagement strategies. However, most patients with HCV are not treated with antiviral therapy. Therefore, we must expand our definition of HCV 'treatment' to include treatment of the comorbid psychiatric and substance use disorders that accompany HCV infection and precede antiviral therapy. This paper reviews the epidemiology and management of psychiatric and substance use disorders in patients with HCV, the issue of psychiatric and substance use disorders as contraindications for antiviral therapy, and current treatment strategies for HCV patients with these comorbid conditions.     

Seizures in HIV-seropositive individuals: epidemiology and treatment

Seizures are a relatively common occurrence in patients with HIV infection. They may be a result of HIV infection of the CNS or a manifestation of an opportunistic infection. Because seizures are likely to recur in patients infected with HIV and because they are a poor prognostic indicator, it is generally recommended that all HIV-seropositive patients experiencing a first seizure without a recognisable and reversible cause be treated. Clinicians faced with treating seizures in HIV-seropositive patients often encounter a therapeutic dilemma since few data exist in this area. In selecting appropriate anticonvulsant therapy, clinicians must consider both therapy-compromising drug-drug and drug-disease interactions. Ideal anticonvulsants for this setting are those that do not effect viral replication, have limited protein binding and have no effects on the cytochrome P450 system, such as gabapentin, topiramate and tiagabine. Unless the benefits outweigh the risks, valproic acid (sodium valproate) should be avoided as it has been shown to stimulate HIV replication. Since few data exist, controlled trials examining pharmacokinetic and pharmacodynamic interactions between anticonvulsants and antiretrovirals are needed. Until such time, clinicians caring for these patients should examine existing data carefully and employ vigilant monitoring.     

Erotomania : epidemiology and management

Erotomania is generally classified as a delusional disorder in contemporary classification systems (DSM-IV and ICD-10). The incidence of erotomania is not known, but that of delusional disorder in general has been reported as approximately 15 cases per 100,000 of the population per year, with a female : male ratio of 3 : 1. Both primary and secondary types of erotomania have been identified, the latter being associated with evidence of an aetiologically significant organic or psychiatric condition. The aetiology of primary erotomania is not yet fully understood, but neuroimaging, genetic studies and findings from evolutionary psychopathology hold considerable promise for a deeper and broader understanding of this condition.The initial management of secondary erotomania focuses on treating the underlying organic or psychiatric illness. The management of primary and secondary erotomania involves a combination of pharmacological treatments, psychosocial interventions and risk management strategies. In the past, the antipsychotic medication pimozide was commonly used, at least in certain countries (such as the US and Canada), despite a paucity of systematic studies of its use in this disorder. In recent years, there have been reports of positive therapeutic outcomes with atypical antipsychotics (risperidone, clozapine), which, as a result of their improved tolerability over older agents such as pimozide, will hopefully enhance patient acceptability and, thereby, improve clinical outcome. Despite this advance, there is still a strong need for controlled clinical trials of therapeutic strategies for primary erotomania and related syndromes.     

Interrelationship of hepatic function, thyroid activity and mood status in alcohol-dependent individuals

BACKGROUND: Alcohol-induced changes in thyroid function may contribute to the development of mood disorders such as depression and anxiety that almost invariably coexist in alcohol-dependent individuals. The aim of the present study was to investigate the severity of liver dysfunction and thyroid activity in correlation with anxiety and depressive-like symptomatology before and after a detoxification period. PATIENTS AND METHODS: In a sample of 100 alcohol-abusing/dependent subjects treated on an in-patient basis according to a standard detoxification protocol, measurements of the serum levels of hepatic enzymes (ASAT, ALAT, gammaGT) and thyroid hormones (T3, T4, TSH) as well as measures of anxiety, depression and global functioning were obtained at baseline and at weekly intervals over the period of 4-5 weeks. RESULTS: After completion of the alcohol detoxification, most measurements returned to normal levels and correlations were observed between the levels of hepatic enzymes and thyroid hormones. Additionally, a significant correlation was obtained between the levels of thyroid hormones and the mood status scales. CONCLUSION: Our results indicated a dysfunction of the hypothalamic-pituitary-thyroid axis in alcohol dependence with possible implications in the diagnosis and treatment of mood disorders associated with alcohol abuse.     

Otitis media: epidemiology and management

Otitis media is one of the most common disease entities in children worldwide. This critical review of the literature will focus on the demographics, pathophysiology, diagnosis, and medical and surgical management of the various types of otitis media.     

Neonatal sepsis: epidemiology and management

Neonatal sepsis is uncommon (2-4 per 1000 live births in developed countries), but the rate increases dramatically in premature newborns and those born to mothers with infections or prolonged rupture of the fetal membranes. While infections caused by organisms contracted from the mother at birth have decreased in the past two decades, there has been an increase in nosocomial infections. Today, most infants with sepsis have been hospitalized in neonatal intensive care units for weeks or months because of extreme prematurity, or because of a congenital malformation or surgical condition. Antimicrobial therapy is usually begun prior to the isolation of a pathogen and is based upon knowledge of the likely microbes in the particular clinical situation. The number of antimicrobial agents that can be safely used in neonates is relatively small, and dose administration usually needs to be adjusted based upon birthweight and post-gestational age. The decision whether to treat with antimicrobials should be made with consideration of the history, physical examination, and laboratory data. One should also consider the effects of the use of antimicrobials on the flora of the care unit. Bacterial resistance in the resident flora of the unit has become a major problem where there has been indiscriminate use of broad-spectrum agents.     

Evaluation of apolipoprotein E (apoE) and lipoprotein profile in severe alcohol-dependent individuals

BACKGROUND: Chronic alcohol consumption down-regulates the expression of sialytransferase genes resulting in impaired sialylation of apolipoprotein E (apoE) and decreased association with HDL. There are a limited number of studies with contradictory data on the effect of alcohol dependence on human plasma apoE. The aim of the present work is to determine and compare the levels of apoE in relation to the other lipoproteins in alcohol-dependent individuals in order to evaluate the possible role of apoE in lipoprotein metabolism in conditions of severe alcohol dependence. PATIENTS AND METHODS: The sample of our study comprised 43 DSM-IV diagnosed alcohol-dependent/abusing subjects (33 males and 10 females), treated on an inpatient basis according to a standard detoxification protocol, and 27 healthy people (9 males and 18 females, as a control group). Serum concentration of hepatic enzymes (AST, ALT, gammaGT), as well as measures of cholesterol and lipoproteins were obtained at baseline and at discharge after a detoxification period of 4-5 weeks. RESULTS: Upon admission, all alcohol-dependent individuals had significantly higher hepatic enzyme levels, apoE and HDL values compared to controls. After completion of alcohol detoxification, all the above parameters returned to normal levels. Additionally, a significant correlation was observed between alcohol consumption during the previous year of alcohol abuse and the apoE values both upon admission to and on discharge from the detoxification program. CONCLUSION: The statistical correlation between apoE on admission and discharge with alcohol consumption during the previous year suggests that apoE is dependent on alcohol consumption and can serve as a sensitive marker of severe alcohol abuse.     

Separating intentional inhibition of prepotent responses and resistance to proactive interference in alcohol-dependent individuals

Background

Impulsivity is a hallmark of addictive behaviors. Addicts’ weakened inhibition of irrelevant prepotent responses is commonly thought to explain this association. However, inhibition is not a unitary mechanism. This study investigated the efficiency of overcoming competition due to irrelevant responses (i.e., inhibition of a prepotent response) and overcoming competition in memory (i.e., resistance to proactive interference) in sober and recently detoxified alcohol-dependent individuals.

Methods

Three cognitive tasks assessing the inhibition of a prepotent response (Hayling task, anti-saccade task and Stroop task) and two tasks tapping into the capacity to resist proactive interference (cued recall, Brown-Peterson variant) were administered to 30 non-amnesic recently detoxified alcohol-dependent individuals and 30 matched healthy participants without alcohol dependency. In addition, possible confounds such as verbal updating in working memory was assessed.

Results

Alcohol-dependent subjects performed worse than healthy participants on the three cognitive tasks assessing the inhibition of irrelevant prepotent responses but group performance was similar in the tasks assessing overcoming proactive interference in memory, updating of working memory and abstract reasoning.

Conclusions

These findings suggest that alcohol-dependence is mainly associated with impaired capacity to intentionally suppress irrelevant prepotent response information. Control of proactive interference from memory is preserved. Theoretical and clinical implications are discussed.     

Sleep abnormalities during abstinence in alcohol-dependent patients. Aetiology and management

Virtually every type of sleep problem occurs in alcohol-dependent patients. Typically, these individuals take a longer time to fall asleep and show decreased sleep efficiency, shorter sleep duration and reduced amounts of slow wave sleep when compared with healthy controls. Their sleep patterns are fragmented, and the typical time course of electroencephalogram (EEG) delta wave activity is severely disrupted. The amount of rapid eye movement (REM) sleep may be reduced or increased. Sleep changes can persist during months or years of abstinence, and recent studies indicate that certain alterations in sleep architecture, as well as subjective sleep complaints, predict relapse to alcoholism. The mechanisms of action of short and long term alcohol administration on sleep are incompletely understood. They may arise from an interaction with gamma-aminobutyric acid (GABA), serotonin (5-hydroxytryptamine; 5-HT), adenosine or other neurotransmitter systems. While only a few pharmacological and nonpharmacological strategies to improve or normalise disturbed sleep in individuals who have recovered from alcoholism have been studied, the use of benzodiazepines, other hypnosedatives or selective serotonin reuptake inhibitors is not recommended. Therapies include sleep hygiene, bright light therapy, meditation, relaxation methods, and other nonpharmacological approaches. Further studies are needed to clarify the relationship between sleep, sleep abnormalities and alcoholism, and to establish new approaches to improve sleep in alcohol-dependent patients and to prevent withdrawal reactions that affect sleep during abstinence.     

Faecal incontinence in the elderly : epidemiology and management

Faecal incontinence occurs in up to 10% of community dwelling persons > or = 65 years of age and approximately 50% of nursing home residents. It is a vastly under-reported problem that has a devastating effect on those who experience it as well as their spouses and caregivers. There are three broad categories of faecal incontinence among the elderly: (i) overflow incontinence; (ii) reservoir incontinence; and (iii) rectosphincteric incontinence. The first two can be diagnosed based upon the patient's history and physical examination and the response to dietary and pharmacological interventions. The third is assessed by careful physical examination supplemented by diagnostic tests directed towards evaluation of anorectal continence mechanisms. The most important of these is anorectal manometry, which can be supplemented by studies of structure (anal ultrasonography or pelvic floor magnetic resonance imaging) and neuromuscular function (electromyogram). A variety of therapeutic interventions are employed in patients with rectosphincteric incontinence; these include dietary, behavioural, pharmacological and surgical modalities chosen on the basis of the results of diagnostic testing. For isolated internal anal sphincter weakness, a cotton barrier in the anal canal is often effective. Acute sphincter injury is best treated with sphincteroplasty but, otherwise, surgical procedures are of uncertain benefit. Peripheral neurogenic incontinence may be treated with antidiarrhoeal agents, biofeedback techniques and dietary manipulations. Sacral spinal nerve stimulation is a promising new technique for selected patients with neurogenic faecal incontinence and is currently undergoing testing in the US and Europe. Significant improvement in quality of life can be achieved in most elderly persons with faecal incontinence.     

Attention-deficit hyperactivity disorder in girls: epidemiology and management

Attention-deficit hyperactivity disorder (ADHD) in girls is a topic of growing research and clinical interest. For many years, girls with ADHD have been ignored and overshadowed by hyperkinetic and impulsive boys, but they are now attracting interest in an effort to understand the similarities and differences in the prevalence, symptoms, familial risk, comorbidities and treatment of ADHD in the two sexes. A review of past and current literature finds that the symptoms of ADHD are not sex specific, but that identification of girls with ADHD is hampered by parental and teacher bias, and confusion. Girls are more likely to be inattentive without being hyperactive or impulsive, compared with boys. Girls and boys share the same familial risk patterns, as well as similar, although not identical, comorbidity or impairment patterns. The risk of non-treatment is as great in girls as it is in boys; up to 70-80% of identified children will have persistent symptoms and impairment that extends into adolescence and adulthood. Treatment modalities are equally effective in girls and boys. Stimulants, non-stimulants and behavioural modalities are the mainstays of effective treatment.     

Sleep disorders in Parkinson's disease: epidemiology and management

Sleep problems are an under-emphasised cause of disability in Parkinson's disease (PD) and may be seen independently of PD, associated with primary PD pathology, or as a result of antiparkinsonian medications. Common sleep disorders include excessive daytime sleepiness, rapid eye movement (REM) sleep behaviour disorder, night-time wakefulness and restless legs syndrome. A number of strategies may be used to improve sleep cycle disturbances, and often these interventions do not require pharmacological manipulation. Restoring traditional mealtimes and scheduling activities during predicted periods of sleepiness may help alleviate daytime somnolence; the use of controlled-release levodopa preparations or administration of a catechol-O-methyl transferase (COMT) inhibitor with levodopa at bedtime may reduce periods of night-time wakefulness. Administration of clonazepam at bedtime may assist with REM sleep behaviour disorder but, because this agent can result in daytime somnolence, experimentation with dosage times is recommended. Sleep attacks are described as a sudden, unavoidable transition from wakefulness to sleep and, although rare, have been described with pramipexole, ropinirole and other dopamine agonists. Although the condition has yet to be recognised by the International Association of Sleep Disorders, patients with PD who report rapid sleep onset should be evaluated for the possibility of sleep attacks. If sleep attacks are suspected, it is reasonable to strongly caution patients regarding potentially risk-associated activities such as driving, and to consider careful withdrawal of dopaminergic therapy.     

Psychiatric disorders in Prader-Willi syndrome: epidemiology and management

Although people with intellectual disabilities are at increased risk for psychiatric disorders, the type and rate of these problems differ between those with different causes for their retardation. In this paper, we review behavioural and psychiatric problems in persons with Prader-Willi syndrome, a disorder caused by a paternally derived deletion at chromosome 15(q11-q13) in about 70% of affected patients, and by maternal uniparental disomy in the majority of the remaining patients. In addition to the syndrome's characteristic hyperphagia and food seeking, individuals with Prader-Willi syndrome also have increased risks of nonfood, compulsive behaviours. These include skin picking, which is highly prevalent, as well as more variable rates of hoarding, redoing and concerns with symmetry, exactness, cleanliness, ordering and arranging. Relative to others with mental retardation, persons with Prader-Willi syndrome are at a marked increased risk for developing full-blown, obsessive-compulsive disorder. In addition, many people with Prader-Willi syndrome show increased rates of tantrums, oppositionality and aggression. Recent findings suggest that they also have an increased risk of psychotic disorder or affective illness with a psychotic component, especially young adult patients and those with the maternal uniparental disomy as opposed to paternal deletion. Dietary approaches include a reduced-calorie diet and increased physical activity, as well as close supervision around food and keeping food locked away. To date, neither CNS stimulants nor anorectic agents have been effective in treating hyperphagia, in part because hyperphagia in Prader-Willi syndrome is attributed to decreased satiation as opposed to increased hunger. Treatment for compulsivity and maladaptive behaviours include: behavioural programming; a structured, predictable routine; extra help with transitions; family support; and pharmacotherapy. Although formal drug studies have yet to be conducted, SSRIs have been effective in reducing skin picking, compulsivity and aggressive episodes in some individuals with Prader-Willi syndrome. Atypical antipsychotics have also proven helpful in persons with psychotic features or extreme aggression and impulsivity. Largely on the basis of case studies, the risks and benefits of these and other drugs in Prader-Willi syndrome are reviewed. Drug trials that move beyond case studies and that assess the relative efficacy of behavioural treatments alone or in combination with pharmacotherapy are sorely needed.     

Subsensitive alpha-2-adrenoceptor function in male alcohol-dependent individuals during 6 months of abstinence

Postsynaptic alpha-2-receptor function, as assessed by growth hormone (GH) response to clonidine (CLON), has been shown to be downregulated in patients investigated in acute but also in late withdrawal after heavy alcohol intake. The results are however sometimes conflicting. The question whether this changed receptor function is a trait or state marker is not fully investigated so far. A total of seven male patients with alcohol dependence according to DSM-IV were assessed for the postsynaptic alpha-2-receptor function with the CLON/GH test (2.0 microg/kg body weight; i.v.) starting immediately after a period of heavy drinking. Neuroendocrine tests were repeated after 7 days, 2 and 6 months. A total of six healthy males were used as controls. The maximum GH responses to CLON were significantly lower on all four test occasions in the patient group as compared to the controls. Furthermore, in the patient group all neuroendocrine test results showed blunted GH responses to CLON. Thus, patients with downregulated alpha-2-receptor function during acute withdrawal after heavy alcohol intake showed similar subsensitive receptor function abnormality after a prolonged period of abstinence. The findings in this study indicate that alcohol dependent individuals have a persistent subsensitive alpha-2-adrenoceptor function which may constitute a trait factor for alcohol dependence.