New pharmacological and neuromodulation approaches for impulsive-compulsive behaviors in Parkinson's disease.

INTRODUCTION: A significant proportion of patients with Parkinson's disease (PD) display a set of impulsive-compulsive behaviors at some point during the course of illness. These behaviors range from the so-called behavioral addictions to dopamine dysregulation syndrome, punding and hoarding disorders. These behaviors have been consistently linked to the use of dopaminergic medications used to treat PD motor symptoms (dopamine agonists, levodopa, and other agents) and less consistently to neuromodulation techniques such as deep brain stimulation (DBS). Since there are still no approved treatments for these conditions, their pharmacological management is still a big challenge for clinicians. METHODS: We conducted an extensive review of current pharmacological and neuromodulation literature for the management of impulsive-compulsive disorders in PD patients. RESULTS: Pharmacological treatment approaches for impulsive-compulsive behaviors and DDS in PD patients include reduction of levodopa (LD), reduction/cessation of dopamine agonist (DA), and initiation of infusion therapies (apomorphine infusion and duodopa). Also, atomoxetine, a noradrenergic agent approved for the treatment of attention deficit hyperactivity disorder, showed some interesting preliminary results but there is still a lack of controlled longitudinal studies. Finally, while DBS effects on impulsive-compulsive disorders are still controversial, non-invasive techniques (such as transcranial magnetic stimulation and transcranial direct current stimulation) could have a potential positive effect but, again, there is still a lack of controlled trials. CONCLUSION: Managing impulsivity and compulsivity in PD patients is still a non-evidence-based challenge for clinicians. Controlled trials on promising approaches such as atomoxetine and non-invasive neuromodulation techniques are needed.

Late-onset Huntington disease: An Italian cohort.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG expansion greater than 35 triplets in the IT-15 gene, with a clinical onset usually in the forties. Late-onset form of HD is defined as disease onset after the age of 59 years. The aim of the present study is to investigate the clinical-demographic features of Late-onset HD population (LoHD) in comparison to Classic-onset patients (CoHD). We analyzed a well-characterized Italian cohort of 127 HD patients, identifying 25.2% of LoHD cases. The mean age of onset was 65.9 and the mean length of pathological allele was 42.2. The 53.1% of LoHD patients had no family history of HD. No significant differences were observed in terms of gender, type of symptoms at disease onset, and clinical performance during the follow-up visits. The non-pathological allele resulted longer among LoHD patients. There is evidence that longer non-pathological allele is associated with a higher volume of basal ganglia, suggesting a possible protective role even in the onset of HD. In conclusion, LoHD patients in this Italian cohort were frequent, representing a quarter of total cases, and showed clinical features comparable to CoHD subjects. Due to the small sample size, further studies are needed to evaluate the influence of non-pathological alleles on disease onset.

Impulsivity Markers in Parkinsonian Subthalamic Single-Unit Activity.

BACKGROUND: Impulsive-compulsive behaviors are common in Parkinson's disease (PD) patients. However, the basal ganglia dysfunctions associated with high impulsivity have not been fully characterized. The objective of this study was to identify the features associated with impulsive-compulsive behaviors in single neurons of the subthalamic nucleus (STN). METHODS: We compared temporal and spectral features of 412 subthalamic neurons from 12 PD patients with impulsive-compulsive behaviors and 330 neurons from 12 PD patients without. Single-unit activities were extracted from exploratory microrecordings performed during deep brain stimulation (DBS) implant surgery in an OFF medication state. RESULTS: Patients with impulsive-compulsive behaviors displayed decreased firing frequency during bursts and a larger fraction of tonic neurons combined with weaker beta coherence. Information carried by these features led to the identification of patients with impulsive-compulsive behaviors with an accuracy greater than 80%. CONCLUSIONS: Impulsive-compulsive behaviors in PD patients are associated with decreased bursts in STN neurons in the OFF medication state. © 2021 International Parkinson and Movement Disorder Society.

Raman profiling of circulating extracellular vesicles for the stratification of Parkinson's patients.

Parkinson's disease (PD) is a chronic neurodegenerative disorder, characterized by considerable clinical heterogeneity. Extracellular vesicles (EVs) were proposed as new biomarkers for PD because of their role as vehicles of multiple PD related molecules, but technical limitations exist in their detection and characterization in a clinical environment. We propose herein a Raman based protocol for the label-free analysis of circulating EVs as diagnostic and predictive tool for PD. After purification from serum of PD patients and healthy subjects, EVs were analyzed by Raman spectroscopy demonstrating the feasibility and reproducibility of the proposed biophotonic approach, its moderate accuracy in distinguishing PD patients from controls by their EV profile and the correlation between Raman data and clinical scales. Once validated, the Raman spectroscopy of circulating EVs could represent a reliable, automatable and sensitive method for the stratification of PD patients and for the evaluation of the effectiveness of rehabilitation and pharmacological treatments.

A case of recurrent progressive multifocal leukoencephalopathy after human stem cell transplant, with detection of John Cunningham virus and human herpesvirus 6 on cerebrospinal fluid, treated with Mirtazapine, Olanzapine and Foscarnet.

We reported the case of a John Cunningham virus (JCV) and human herpesvirus 6 (HHV-6) mediated progressive multifocal leukoencephalopathy (PML) after human stem cell transplant, reactivated 6 months later in absence of immunosuppressive therapy, successfully treated with anti-5HT2A receptors agents and antiviral therapy. Few cases of JCV and HHV-6 coinfection associated PML are described in literature and the role of HHV-6 in the pathogenesis and prognosis of PML is not completely clear. Our case suggests that, in a possible PML, the research of HHV-6 and JCV should be always performed on cerebrospinal fluid (CSF) and on blood samples and in case of detection of HHV-6 DNA a chromosomally integrated human herpesvirus 6(ciHHV-6) should be excluded. Furthermore we recommend to start an appropriate therapy with antiviral and anti-5HT2A receptors agents in case of possible PML due to JCV and HHV-6 coinfection.