Andrea E. Cavanna

The prevalence and clinical characteristics of punding in Parkinson's disease†

Background: Punding (the display of stereotyped, repetitive behaviors) is a relatively recently discovered feature of Parkinsons disease (PD). Little is known about the prevalence and clinical characteristics of punding in PD. Methods: In this review, four large scientific databases were comprehensively searched for literature in relation to punding prevalence and clinical correlates in the context of PD. Results: Prevalence was found to vary greatly (between 0.34 to 14%), although there were large disparities in study populations, assessment methods, and criteria. We observed an association between punding, dopaminergic medications, and impulse control disorder. Other characteristics, which may be more common among punders, include a higher severity of dyskinesia, younger age of disease onset, longer disease duration, and male gender. Discussion: More research in large clinical datasets is required in many areas before conclusions are drawn. The pathophysiology behind the punding phenomenon is also poorly understood at present, rendering it difficult to develop targeted therapy. The current mainstay of treatment is the reduction in the dose of dopaminergic medications, the evidence for other suggested therapies being purely empirical.

Ictal consciousness in epilepsy and nonepileptic attack disorder

Exploration of subjective experiences during seizures may enhance knowledge of the differing natures of epilepsy and nonepileptic attack disorder (NEAD). We performed a quantitative evaluation of both the general level of awareness and the specific contents of consciousness during seizures using the Ictal Consciousness Inventory (ICI). Ninety-five adult outpatients attending general neuropsychiatry and epilepsy clinics with established diagnoses of either epilepsy (n = 66) or NEAD (n = 29) completed one ICI for each witnessed seizure recalled. Patients with a dubious/dual diagnosis were excluded. ICI Level (ICI-L) and ICI Content (ICI-L) scores were calculated for the 167 questionnaires generated by patients with epilepsy (n = 119, of which 58 from patients with temporal lobe epilepsy, 14 frontal lobe epilepsy, and 47 idiopathic 30 generalized epilepsy) and patients with NEAD (n = 48). Mann-Whitney U tests revealed statistically significant higher ICI-L and ICI-C scores for patients with NEAD (both P = 0.01). Subjective reports of consciousness experiences varied between epilepsy and NEAD, with patients with NEAD reporting significantly greater levels of general awareness/responsiveness and more vivid subjective experiences during attacks. The ICI is proposed as a potentially useful self-report instrument to supplement clinical and instrumental tests for the differential diagnosis of epilepsy and NEAD.

Corpus callosum abnormalities in Tourette syndrome: an MRI-DTI study of monozygotic twins

Background Tourette syndrome (TS) is a chronic neurodevelopmental disorder characterised by the presence of multiple motor and phonic tics. Recent brain imaging investigations with diffusion tensor imaging (DTI) techniques found reduced measures of connectivity in the corpus callosum of children with TS compared with healthy controls, thus raising the hypothesis that the reduced interhemispherical connectivity in TS reflects neural plasticity processes. Methods We assessed corpus callosum white-matter connectivity with fractional anisotropy (FA) index from magnetic resonance-DTI in two monozygotic twins (male sex; age 20) discordant for the diagnosis of TS. Results Both conventional morphological magnetic resonance images and fibre-tracking reconstruction failed to show any difference between the two twins. On the other hand, mean corpus callosum FA values were significantly lower in the affected twin than in the unaffected twin (p<0.01). The differences in FA values were highest in the posterior portions of the corpus callosum, and lowest in the central area. Conclusions Our findings of reduced interhemispherical white-matter connectivity in the affected twin support the hypothesis that plastic remodelling in the corpus callosum possibly represents an adaptation mechanism in TS.

Altered subjective fear responses in Huntington’s disease

Patients with Huntingtons 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.

Trousseau's Disease: A Description of the Gilles de la Tourette Syndrome 12 Years Before 1885

French neurologist Georges Gilles de la Tourette first described the syndrome which earned him eponymous fame in 1885. However, a publication dated 1873 by Armand Trousseau included a detailed account of what is currently know as Gilles de la Tourette syndrome (GTS). In Gilles de la Tourettes celebrated 1885 paper, there is a brief mention of the clinical picture described earlier by Trousseau, but Gilles de la Tourette somewhat disregarded it. We present the first English translation of Trousseaus description and argue that this description is more akin to modern conceptualization of GTS than the description of Gilles de la Tourette himself.

Pharmacotherapeutic and Non-Pharmacological Options for Refractory and Difficult-to-Treat Seizures

It is currently estimated that about 20%–30% of adults and 10%–40% of children diagnosed with epilepsy suffer from uncontrolled or poorly controlled seizures, despite optimal medical management. In addition to its huge economic costs, treatment-refractory epilepsy has a widespread impact on patients’ health-related quality of life. The present paper focuses on the concepts of refractory and difficult-to-treat seizures and their pharmacological management. Evidence on efficacy and tolerability of rational pharmacotherapy with antiepileptic drug combinations and of non-pharmacological treatment options such as epilepsy surgery, neurostimulation, metabolic treatment and herbal remedies is reviewed. The importance of early identification of the underlying etiology of the specific epilepsy syndrome is emphasized, to inform early prognosis and therapeutic strategies.

The prevalence and clinical characteristics of hypersexuality in patients with Parkinson's disease following dopaminergic therapy: A systematic literature review

INTRODUCTION A range of impulse control disorders have been identified as possible behavioural effects of brain dopamine replacement therapy (DRT) in patients with Parkinsons disease (PD). Among the behavioural problems associated with dysregulation of dopaminergic pathways underlying reward processing, hypersexuality carries significant social and legal repercussions, in addition to embarrassment for the patient with PD and his/her family. The present article evaluates the prevalence and characteristics of hypersexuality in the context of PD, focusing on the best available evidence. METHODS We conducted a systematic literature review according to the Prisma guidelines on large-scale epidemiological studies (n > 250) assessing hypersexuality in patients with PD treated with DRT. RESULTS Our systematic literature review identified 10 relevant studies characterised by medium-to-large sample sizes (n = 268-3090). Average lifetime prevalence of hypersexuality in patients with PD on DRT was found to be 2.7% (7.4% in patients on dopamine agonists). In general, hypersexuality was associated with male gender and higher doses of dopamine agonists. Other clinically relevant associations included younger age, earlier PD onset and history of behavioural symptoms prior to dopamine agonist use. CONCLUSION Hypersexuality is not rare in patients with PD treated with DRT, particularly in those on dopamine agonists. These findings indicate that PD specialists should regularly screen and monitor for hypersexuality, paying particular attention to younger male patients, with an early PD onset and previous history of behavioural problems.

Impact of video-ambulatory electroencephalography on the medical management of epilepsy

Video-ambulatory electroencephalography (video-AEEG) is increasingly being used in secondary care centres for the diagnostic work-up of new cases with suspected epilepsy and for the review of known cases with active seizures despite medical treatment. We reviewed how the outcome of video-AEEG influenced the medical management of patients who underwent this investigation at a neurophysiology department within a secondary care centre. Out of a total of 171 consecutive video-AEEG studies performed over a period of two years, 111 could be included in our retrospective analysis, based on availability and completeness of relevant clinical information pre- and post-investigation. In our sample, 55.9% of patients had typical clinical events captured on video-AEEG and diagnostic yield was higher in patients with a previously established diagnosis of epilepsy (n=62; diagnostic yield 62.9%). A total of 27 patients (24.3%) had changes in medical treatment following video-AEEG, most frequently antiepileptic drug introduction/increase when epileptic seizures were captured. This proportion was similar between patients with or without a previously established diagnosis of epilepsy. Our findings in a real-life setting confirm the usefulness of video-AEEG in influencing the clinical attitude towards complex patients with suspected or longstanding history of epilepsy.

Video-ambulatory EEG in a secondary care center: A retrospective evaluation of utility in the diagnosis of epileptic and nonepileptic seizures.

The development and optimization of protocols using simultaneous video recording alongside long-term electroencephalography (EEG), such as ambulatory EEG (AEEG), expanded the range of available techniques for the investigation of paroxysmal clinical events. In particular, video-AEEG has received increasing attention over the last few years because of its potential to further improve diagnostic utility in the differential diagnosis between epileptic and nonepileptic seizures. We retrospectively evaluated 88 video-AEEG studies in order to assess the diagnostic utility of video-AEEG in 87 patients consecutively referred to a neurophysiology department. Typical clinical events occurred during 55 studies (62.5%). In 26 of these, at least one event was also clearly seen on video recording, contributing to a confident diagnosis. Clinical events were classified according to three diagnostic categories: epileptic seizures (6 studies, 6.8%), physiologic nonepileptic events (13 studies, 14.8%), or psychogenic nonepileptic seizures (36 studies, 40.9%). Of the studies with an event not recorded on video, a confident diagnosis could be reached in 55.2% of cases. The main reason for unsuccessful video recording was failure to activate the camcorder by the patient or carer. We found an overall diagnostic utility of 67.0%, which confirms the findings of previous reports evaluating the diagnostic yield of AEEG. Implementation of video-AEEG protocols in a secondary care center appears to have high diagnostic utility, particularly for patients with psychogenic nonepileptic seizures. Our findings prompt further research into the potential applications of video-AEEG, in consideration of important implications for successful patient management and healthcare resource allocation.

Histaminergic modulation in Tourette syndrome

ABSTRACT Introduction: Tourette syndrome is a neurodevelopmental disorder characterized by multiple motor tics and at least one vocal/phonic tic. Clinical phenotypes show a wide variability, often incorporating behavioral symptoms. The exact pathophysiology of Tourette syndrome is unknown, however genetic vulnerability and alterations in dopaminergic neurotransmission have consistently been reported. Other biochemical pathways, including histaminergic neurotransmission, are likely to be involved but have received relatively little attention until recently. Areas covered: We conducted a systematic literature review focusing on the role of histaminergic neurotransmission and its pharmacological modulation in Tourette syndrome. We identified a number of relevant original studies published over the last five years, mainly focusing on genetic aspects. Expert opinion: There is converging evidence from recent studies supporting the hypothesis that histaminergic neurotransmission may play a role in the pathophysiology of Tourette syndrome. Most studies focused on the role of the histidine decarboxylase gene and the potential usefulness of histidine decarboxylase knockout mice as an experimental model for studying neurochemical function in Tourette syndrome. There have been no large scale studies assessing the use of histaminergic medications in the management of Tourette syndrome. This would be an important area for future research, with direct implications for the clinical management of selected phenotypes.