Narcolepsy: a review

Narcolepsy is a lifelong sleep disorder characterized by a classic tetrad of excessive daytime sleepiness with irresistible sleep attacks, cataplexy (sudden bilateral loss of muscle tone), hypnagogic hallucination, and sleep paralysis. There are two distinct groups of patients, ie, those having narcolepsy with cataplexy and those having narcolepsy without cataplexy. Narcolepsy affects 0.05% of the population. It has a negative effect on the quality of life of its sufferers and can restrict them from certain careers and activities. There have been advances in the understanding of the pathogenesis of narcolepsy. It is thought that narcolepsy with cataplexy is secondary to loss of hypothalamic hypocretin neurons in those genetically predisposed to the disorder by possession of human leukocyte antigen DQB1*0602. The diagnostic criteria for narcolepsy are based on symptoms, laboratory sleep tests, and serum levels of hypocretin. There is no cure for narcolepsy, and the present mainstay of treatment is pharmacological treatment along with lifestyle changes. Some novel treatments are also being developed and tried. This article critically appraises the evidence for diagnosis and treatment of narcolepsy

Impulse Control Disorders Following Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease: Clinical Aspects

Parkinson's disease (PD) has been associated with the development of impulse control disorders (ICDs), possibly due to overstimulation of the mesolimbic system by dopaminergic medication. Preliminary reports have suggested that deep brain stimulation (DBS), a neurosurgical procedure offered to patients with treatment-resistant PD, affects ICD in a twofold way. Firstly, DBS allows a decrease in dopaminergic medication and hence causes an improvement in ICDs. Secondly, some studies have proposed that specific ICDs may develop after DBS. This paper addresses the effects of DBS on ICDs in patients with PD. A literature search identified four original studies examining a total of 182 patients for ICDs and nine case reports of 39 patients that underwent DBS and developed ICDs at some point. Data analysis from the original studies did not identify a significant difference in ICDs between patients receiving dopaminergic medication and patients on DBS, whilst the case reports showed that 56% of patients undergoing DBS had poor outcome with regards to ICDs. We discuss these ambivalent findings in the light of proposed pathogenetic mechanisms. Longitudinal, prospective studies with larger number of patients are required in order to fully understand the role of DBS on ICDs in patients with PD

A Brief History of the European Society for the Study of Tourette Syndrome

The European Society for the Study of Tourette syndrome (ESSTS) was established in Denmark in 2000 by Mary Robertson and Anne Korsgaard. The aims of the organisation are to foster research activity and raise awareness of Tourette syndrome throughout Europe. The organisation went into abeyance in 2002 but was resurrected in 2007 in Bari, Italy. Since that time ESSTS has grown and prospered. We have established elected officers and a constitution. We have successfully applied for three large scale European research grants and have members throughout the European Union. We have held yearly meetings across Europe including two training schools and we have developed successful alliances with patient support groups. ESSTS has developed and published the first European guidelines on assessment, diagnosis and treatment of Tourette syndrome

Data-driven Huntington’s disease progression modelling and estimation of societal cost in the UK

We develop a Huntington’s disease (HD) progression model and integrate this with a novel economic model, accounting for the major factors of the HD’s societal cost. Data from the Enroll-HD observational study were used to fit a continuous-time hidden Markov disease progression model, which identified five distinct states. The number of disease states was determined using a cross-validated maximum likelihood approach. A novel data augmentation method was used to correct the biased life expectancy of the progression model. Multiple sources of cost data were then mapped to Enroll-HD variables using expert experience. A simulation of a synthetic patient population was used to show the feasibility of the approach in estimating population costs and the impact of hypothetical intervention scenarios. Our results confirm that early cognitive decline, which is not captured by the total functional capacity score currently used by clinicians but flagged up in HD integrated staging system, can be quantified from participants’ visits. Finally, the results of the UK cost modelling show that indirect costs of HD such as state benefits and lost gross domestic product contribution could be the driving factors for the societal cost, over and above health and social care costs

European clinical guidelines for Tourette Syndrome and other tic disorders

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Health state utility estimates for value assessments of novel treatments in Huntington’s disease:a systematic literature review

Background: Huntington’s disease (HD) is a progressive neurodegenerative disease with a devastating impact on patients and their families. Quantifying how treatments affect patient outcomes is critical for informing reimbursement decisions. Many countries mandate a formal value assessment in which the treatment benefit is measured as quality-adjusted life-years, calculated with the use of utility estimates that reflect respondents’ preferences for health states. Objective: To summarize published health state utility data in HD and identify gaps and uncertainties in the data available that could be used to inform value assessments. Methods: We conducted a systematic literature review of studies that used preference-based instruments (e.g., EQ-5D and SF-6D) to estimate utility values for people with HD. The studies were published between January 2012 and December 2022. Results: Of 383 articles screened, 16 articles reported utility values estimated in 11 distinct studies. The utility measure most frequently reported was EQ-5D (9/11 studies). Two studies reported SF-6D data; one used time trade-off methods to value health state descriptions (vignettes). Although utility scores generally worsened to a lower value with increased HD severity, the estimates varied considerably across studies. The EQ-5D index range was 0.89 − 0.72 for mild/prodromal HD and 0.71 − 0.37 for severe/late-stage disease. Conclusions: This study uncovered high variability in published utility estimates, indicating substantial uncertainty in existing data. Further research is needed to better understand preferences and valuation across all stages and domains of HD symptoms and the degree to which generic utility measures capture the impact of cognitive changes on quality of life

The evolving discipline and services of neuropsychiatry in the United Kingdom

Background: The last few decades have seen a renaissance in the development of neuropsychiatric services on a global scale.Methods: This paper reviews the existing literature on the changing role of the clinical neuropsychiatrist and discusses the evolving theory and practice of neuropsychiatry in the United Kingdom.Results: The rapidly evolving specialty of neuropsychiatry is currently facing a number of challenges. These include, but are not limited to, uncertainties about the curricular requirements for clinical neuropsychiatrists and the changing roles within the wider scenario of health-care service provision.Discussion: An informed historical perspective on this multifaceted discipline allows key insights into its future development.</jats:sec

Mutation-related magnetization-transfer, not axon density, drives white matter differences in premanifest Huntington disease:Evidence from in vivo ultra-strong gradient MRI

White matter (WM) alterations have been observed in Huntington disease (HD) but their role in the disease-pathophysiology remains unknown. We assessed WM changes in premanifest HD by exploiting ultra-strong-gradient magnetic resonance imaging (MRI). This allowed to separately quantify magnetization transfer ratio (MTR) and hindered and restricted diffusion-weighted signal fractions, and assess how they drove WM microstructure differences between patients and controls. We used tractometry to investigate region-specific alterations across callosal segments with well-characterized early- and late-myelinating axon populations, while brain-wise differences were explored with tract-based cluster analysis (TBCA). Behavioral measures were included to explore disease-associated brain-function relationships. We detected lower MTR in patients' callosal rostrum (tractometry: p = .03; TBCA: p = .03), but higher MTR in their splenium (tractometry: p = .02). Importantly, patients' mutation-size and MTR were positively correlated (all p-values < .01), indicating that MTR alterations may directly result from the mutation. Further, MTR was higher in younger, but lower in older patients relative to controls (p = .003), suggesting that MTR increases are detrimental later in the disease. Finally, patients showed higher restricted diffusion signal fraction (FR) from the composite hindered and restricted model of diffusion (CHARMED) in the cortico-spinal tract (p = .03), which correlated positively with MTR in the posterior callosum (p = .033), potentially reflecting compensatory mechanisms. In summary, this first comprehensive, ultra-strong gradient MRI study in HD provides novel evidence of mutation-driven MTR alterations at the premanifest disease stage which may reflect neurodevelopmental changes in iron, myelin, or a combination of these