Behavioral adverse effects of antiepileptic drugs in epilepsy.

Patient tolerability is a significant limiting factor in the treatment of epilepsy and adverse effect profiles often determine drug retention rates. A full appreciation of the behavioral effects of a wide range of antiepileptic drugs (AEDs) is therefore essential to make informed treatment decisions. In this timely review, we highlight key alterations in mood, emotional experience, and other behavioral/psychiatric features, which can exert a crucial impact on patients' quality of life and well-being. With a view to prescribing both in general and in relation to more specific clinical characteristics, the evidence reviewed indicates that the incidence and characteristics of behavioral effects may be related to age, epilepsy type, the presence of learning disability, and previous psychiatric history. Medication parameters including dosage, titration rate, efficacy in controlling seizures, and concurrent AEDs can also contribute to the occurrence of behavioral effects. However, there are a number of limitations in drawing conclusions from the available literature. These include variation in study design, treatment group, and assessment tools that lead to difficulties comparing findings across studies, and problems with the consistency of available information relating to the study methodology. Future longitudinal studies assessing the impact of tolerance or developmental change on behavioral effects and specific studies comparing the effects of commonly prescribed agents across subgroups of patients with epilepsy will make an informative contribution to the available literature. A valuable outcome of further research may be the development of specific instruments that are sensitive to the behavioral effects associated with particular AEDs.

Executive functions in uncomplicated Tourette syndrome.

Previous studies reporting executive deficits in Tourette syndrome (TS) often failed to control for co-morbid conditions. We investigated executive functions in forty patients with TS without co-morbid psychiatric diagnoses (uncomplicated TS). Patients exhibited executive deficits which were unrelated to tic severity, suggesting executive dysfunction may be a core component of TS.

What patients with gilles de la tourette syndrome should be treated with deep brain stimulation and what is the best target?

BACKGROUND: Gilles de la Tourette syndrome (GTS) is a chronic neurodevelopmental disorder characterized by tics and associated behavioral symptoms. Over the past decade, deep brain stimulation (DBS) has been increasingly advocated as a reversible and controllable procedure for selected cases of GTS. OBJECTIVE: We set out to answer 2 clinically relevant questions: what patients with GTS should be treated with DBS and what is the best target? METHODS: We conducted a systematic literature review of the published studies of DBS in GTS and critically evaluated the current evidence for both patient and target selection. RESULTS: Since 1999, up to 99 cases of DBS in GTS have been reported in the scientific literature, with varying selection criteria, stimulation targets, and assessment protocols. The vast majority of studies published to date are case reports or case series reporting successful outcomes in terms of both tic severity improvement and tolerability. The reviewed studies suggest that the best candidates are patients with significant functional impairment related to the tic symptoms, who did not respond to conventional pharmacological and behavioral interventions. The globus pallidus internus and thalamus appear to be the safest and most effective targets, especially for patients with "pure" GTS and patients with comorbid obsessive-compulsive symptoms, anxiety, and depression. CONCLUSION: DBS is a promising treatment option for severe cases of GTS. There is a need to reach consensus on the definition of "treatment-refractoriness" and to conduct larger double-blind randomized controlled studies on the most promising targets.

Altered subjective fear responses in Huntington's disease.

Patients with Huntington's disease (HD) have been shown to exhibit impairment in the recognition of facial expressions such as disgust, as well as deficits in disgust responses to olfactory and gustatory stimuli. The present study investigated whether HD is associated with changes in emotional responses to a variety of visual and verbal stimuli selected to elicit core disgust, moral disgust, fear and happiness. Thirteen patients with HD and twelve controls provided emotional ratings after both reading emotion eliciting scenarios and viewing pictures from the International Affective Picture System database. Patients with HD exhibited executive dysfunction. In comparison to controls, they gave similar ratings for happy stimuli and did not differ significantly in response to core disgust or moral disgust stimuli. However, they did exhibit lower fear ratings in response to both sets of fear stimuli (pictures and scenarios), and higher anger ratings than controls in response to fear pictures. These differences in fear response could reflect dysfunction within frontostriatal pathways involving the amygdala. Changes to fear responses in HD may impair decision making and lead to increased risk-taking behaviour with significant personal or social consequences.

Behavioral and cognitive effects of anti-epileptic drugs.

Anti-epileptic drugs (AEDs) have a variety of mechanisms of action which are reflected through different anticonvulsant activities and behavioral effects. Two categories of AEDs are considered based on psychotropic profile. The first group is characterized by potentiation of gamma-aminobutyric acid (GABA) inhibitory neurotransmission, and comprises of agents such as vigabatrin, tiagabine, and gabapentin. These agents are noted to have sedating effects ranging from cognitive slowing to anti-manic effects. On the other hand, the second group is typified by attenuation of glutamate excitatory neurotransmission and has activating effects including anxiogenic and antidepressant actions. Lamotrigine and felbamate feature in this latter group. Mechanisms of action, chief clinical indications, as well as behavioral profile including comment on chief cognitive effects of the newer AEDs are reviewed in accordance with this dual categorization. In clinical practice, assessment of an individual patient alongside consideration of AED behavioral profile primes for appropriate prescription according to patient mood profile, also permitting exposure of AED-induced behavioral disturbance.

Cognitive functioning in Tourette syndrome.

Tourette Syndrome (TS) is characterized by tics, which are thought to reflect striatal dysfunction. Changes in functioning of the striatum in TS could lead to dysfunction in frontostriatal pathways involving cortical regions such as the dorsolateral prefrontal and anterior cingulate cortex. This in turn could result in deficits in specific cognitive processes and impairment on particular cognitive tasks. The aim of this review is to summarize the major findings of key studies of cognitive functioning in TS. The limitations and neurological implications of the reported findings are also discussed. Although the methodological limitations associated with many studies compel further investigation, tentative conclusions may be drawn from the available literature. While co-morbidities such as attention deficit-hyperactivity disorder (ADHD) may be associated with more significant executive dysfunction, we can conclude that patients without co-morbidities exhibit milder deficits in attention and inhibition-related processes. These cognitive difficulties are likely to reflect dysfunction with frontostriatal pathways involving the anterior cingulate circuit.