Clare M. Eddy

The cognitive impact of antiepileptic drugs

Effective treatment of epilepsy depends on medication compliance across a lifetime, and studies indicate that drug tolerability is a significant limiting factor in medication maintenance. Available antiepileptic drugs (AEDs) have the potential to exert detrimental effects on cognitive function and therefore compromise patient wellbeing. On the other hand, some agents may serve to enhance cognitive function. In this review paper, we highlight the range of effects on cognition linked to a variety of newer and older AEDs, encompassing key alterations in both specific executive abilities and broader neuropsychological functions. Importantly, the data reviewed suggest that the effects exerted by an AED could vary depending on both patient characteristics and drug-related variables. However, there are considerable difficulties in evaluating the available evidence. Many studies have failed to investigate the influence of patient and treatment variables on cognitive functioning. Other difficulties include variation across studies in relation to design, treatment group and assessment tools, poor reporting of methodology and poor specification of the cognitive abilities assessed. Focused and rigorous experimental designs including a range of cognitive measures assessing more precisely defined abilities are needed to fill the gaps in our knowledge and follow up reported patterns in the literature. Longitudinal studies are needed to improve our understanding of the influence of factors such as age, tolerance and the stability of cognitive effects. Future trials comparing the effects of commonly prescribed agents across patient subgroups will offer critical insight into the role of patient characteristics in determining the cognitive impact of particular AEDs.

Quality of life in young people with Tourette syndrome: a controlled study

Quality of life (QoL) may be adversely affected by Tourette syndrome (TS). Although the core symptoms of this complex neurodevelopmental disorder are tics, patients often present with an array of behavioural difficulties, such as co-morbid obsessive compulsive disorder (OCD) or attention deficit hyperactivity disorder (ADHD). In this study we investigated whether young people with TS exhibited poorer QoL in comparison to healthy individuals and an epilepsy control group. We also analysed whether greater tic severity or co-morbid OCD and\or ADHD led to greater differences in perceived QoL. The Youth Quality of Life Instrument-Research Version (Edwards et al. in J Adolesc 25:275–286, 2002) was used to assess QoL and a range of clinical scales were administered to assess anxiety, depression and other behavioural symptoms. TS was associated with significant differences in aspects of QoL related to home and social activities, involving peer and family interactions. Patients with more severe tics reported a greater negative impact on QoL. Patients with TS and no associated diagnoses (pure TS) presented with lower QoL scores in the environment domain, poorer perceived QoL in general, and depressive features. Co-morbid OCD appeared to exert a greater impact on self and relationship QoL domains. The presence of both OCD and ADHD as co-morbidities led to more widespread problems. In conclusion, TS can be associated with poorer perceived QoL. Although social aspects of QoL may be more vulnerable to TS in general, co-morbid conditions make an important contribution in determining which aspects of QoL are most affected in the individual.

Treatment strategies for tics in Tourette syndrome.

Tourette syndrome (TS) is a chronic neurodevelopmental disorder characterized by tics: repetitive, involuntary movements and vocalizations. These symptoms can have a significant impact on patients’ daily functioning across many domains. Tics tend to be most severe in child and adolescent sufferers, so their presence has the potential to impact a period of life that is both critical for learning and is often associated with the experience of greater social tension and self-consciousness than adulthood. Furthermore, control over tics that lead to physical impairment or self-injurious behaviour is of vital importance in maintaining health and quality of life. There are numerous complicating factors in the prescription of treatment for tics, due to both the side effects associated with alleviating agents and patient characteristics, such as age and comorbid conditions. This review summarizes literature pertaining to the efficacy and safety of both traditionally prescribed and more modern medications. We also discuss the merits of behavioural and surgical techniques and highlight newer emerging treatments. Although treatment response is to some extent variable, there are a number of agents that are clearly useful as first-line treatments for TS. Other interventions may be of most benefit to patients exhibiting refractory tics or more specific symptom profiles.

Neuropsychological aspects of Tourette syndrome: A review

Tourette syndrome (TS) is assumed to result from frontostriatal dysfunction, which would be expected to result in impairments in neuropsychological functions. This possibility has been explored in a number of studies that have assessed the performance of patients with TS within major cognitive domains and on tests involving executive functioning. We aim to summarize the main findings of these studies while evaluating the influence of task limitations and potentially critical confounding factors such as the presence of comorbidity. Although there is clearly a need for improved study design, we tentatively suggest that there is considerable evidence for cognitive impairment in a subgroup of patients, and that some difficulties seem to be intrinsic to TS. These impairments may reflect dysfunction of the anterior cingulate network within the frontostriatal pathway.

Behavioral adverse effects of antiepileptic drugs in epilepsy.

Abstract 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.

An approach to deep brain stimulation for severe treatment-refractory Tourette syndrome: the UK perspective

Deep brain stimulation (DBS) is an emerging therapeutic option for severe, treatment-resistant Tourette Syndrome (TS), with about 40 cases reported in the scientific literature over the last decade. Despite the production of clinical guidelines for this procedure from both European and USA centres, a number of unresolved issues still persist, mainly in relation to eligibility criteria and brain targets. The present article illustrates the UK perspective on DBS in TS and proposes consensus-based recommendations for double-blind controlled trials.

Consciousness: A Neurological Perspective

Consciousness is a state so essentially entwined with human experience, yet so difficult to conceptually define and measure. In this article, we explore how a bidimensional model of consciousness involving both level of arousal and subjective awareness of the contents of consciousness can be used to differentiate a range of healthy and altered conscious states. These include the different sleep stages of healthy individuals and the altered states of consciousness associated with neurological conditions such as epilepsy, vegetative state and coma. In particular, we discuss how arousal and awareness are positively correlated in normal physiological states with the exception of REM sleep, while a disturbance in this relationship is characteristic of vegetative state, minimally conscious state, complex partial seizures and sleepwalking.

Premonitory Urges in Adults With Complicated and Uncomplicated Tourette Syndrome

Most patients with Tourette syndrome (TS) report experiencing subjective bodily sensations termed premonitory urges, before they have a tic. This study investigated relationships between premonitory urges and tic severity, depression, anxiety, obsessions, compulsions, and attention problems. We also explored possible differences between patients with and without comorbid conditions. Finally, we explored whether premonitory urges impacted on perceived quality of life (QoL). One hundred adult outpatients (70 males; mean age 32 years) were recruited from a specialist TS clinic. Fifty percent exhibited comorbid diagnoses, the most common of which were obsessive-compulsive disorder (23%), attention-deficit hyperactivity disorder (15%), anxiety (6%), and depression (5%). For the entire sample, premonitory urges were significantly related to clinical symptoms, especially obsessive-compulsive symptoms and anxiety, and were significantly negatively related to QoL scores. Premonitory urges had a strong negative correlation with QoL in patients with “pure” TS (no comorbidities), while this relationship was weaker for patients with comorbid conditions, who reported stronger or more frequent premonitory urges in association with greater anxiety. These findings may imply that slightly different psychological factors drive self-reported premonitory urge ratings in patients with and without comorbidities and that the perceived influence of distressing premonitory urges on wellbeing is less important in the context of comorbid symptomatology. As premonitory urges are related to QoL, they should be taken into account during evaluation of treatment efficacy, especially in cases with “pure” TS.

Is Huntington's disease associated with deficits in theory of mind?

People with Huntingtons disease (HD) can exhibit interpersonal difficulties and deficits in recognizing emotional facial expressions. We investigated whether individuals with HD exhibit impairments in the understanding of other peoples mental states, an aspect of Theory of Mind (ToM).

Impaired Comprehension of Nonliteral Language in Tourette Syndrome

ObjectiveTo investigate theory of mind and the understanding of nonliteral language in patients with Tourette syndrome (TS). BackgroundIn TS, striatal dysfunction could affect the functioning of the frontal cortex. Changes in frontal functioning could lead to impairments in theory of mind: the understanding of mental states, such as beliefs, emotions, and intentions. Poor understanding of a speakers mental state may also impair interpretation of their nonliteral remarks. MethodIn this study, patients with TS and healthy controls completed tasks to assess their understanding of sarcasm, metaphor, indirect requests, and theory of mind. These tasks were the Pragmatic Story Comprehension Task, the Hinting task, and a faux pas task. Inhibitory ability was also assessed through the use of the Hayling task and a black and white Stroop test. ResultsPatients with TS exhibited significant impairment on the faux pas task and Pragmatic Story Comprehension Task despite limited evidence of inhibitory impairment. ConclusionTS may be associated with changes in theory of mind.