G. Devigili

Clinical outcome of deep brain stimulation for dystonia: constant-current or constant-voltage stimulation? A non-randomized study.

Bilateral globus pallidus deep brain stimulation (GPi‐DBS) represents an effective and relatively safe therapy for different forms of refractory dystonia. The aim of this study was to assess, retrospectively, the effect of two different stimulation settings during GPi‐DBS in 22 patients affected by primary generalized or multi‐segmental dystonia.

Botulinum neurotoxin serotype D is poorly effective in humans: An in vivo electrophysiological study

OBJECTIVE Botulinum neurotoxins act on nerve endings and block neurotransmitter release. Their potency is due to their enzymatic activity and high affinity binding to neurons. Botulinum toxin type A is used in the treatment of human diseases characterized by hyperactivity of peripheral cholinergic nerve terminals, but some patients are or become resistant to it. This can be overcome by using other botulinum toxins, and studies have been performed with different toxin serotypes. Botulinum neurotoxin type D has never been tested in humans in vivo, and, therefore, we investigated the action of this toxin in mouse and human muscles. METHODS Botulinum toxin type D potency was determined on mouse hemidiaphragm and on rat neuronal cultures. From these experiments, doses to be injected in human volunteers were decided. The compound muscle action potential of toxin-injected Extensor Digitorum Brevis muscle was measured at different times points after injection in human volunteers. RESULTS Botulinum toxin type D is poorly effective in inducing human skeletal muscle paralysis. CONCLUSIONS Botulinum toxin type D is very potent in mice and almost ineffective in humans in vivo. SIGNIFICANCE The results shed new light on the mechanism of toxin type D binding to the neuronal surface receptors.

Microsubthalamotomy improves sleep in patients affected by advanced Parkinson's disease.

BACKGROUND Deep brain stimulation of the subthalamic nucleus (STN-DBS) improves sleep in patients affected by Parkinsons disease (PD). Since microsubthalamotomy (mSTN) shows positive effects on motor symptoms, it could improve sleep in PD patients. Our goals were: to assess the effects of mSTN on sleep in patients affected by advanced PD; and to look for a correlation between sleep and motor features after the neurosurgical procedure. METHODS Fifteen patients who underwent bilateral STN-DBS were enrolled. Subjective sleep evaluation was assessed using the Parkinsons Disease Sleep Scale (PDSS). Data on sleep schedule and presence of restless legs syndrome (RLS) were obtained. Objective sleep features were investigated by polysomnography (PSG). To evaluate the mSTN effect, we compared motor state and sleep features before and after the neurosurgical procedure, before the programmable pulse generator was switched on. RESULTS mSTN had beneficial effects on motor state and sleep features. After the surgery, the mean total PDSS score increased from 84.0±25.2 to 115.2±16.6 (P<0.001). PD patients reported longer total sleep time duration, decreased daytime sleepiness, and improvement in RLS symptoms. PSG data showed an increase in total sleep time and sleep efficiency with a decrease in wakefulness after sleep onset and arousal index. No correlation between motor improvements and sleep features modifications was observed after mSTN. CONCLUSIONS mSTN improves sleep quality and ameliorates several sleep complaints, as well as motor symptoms, in advanced PD patients who have undergone STN-DBS.

The epidemiology of Parkinson’s disease in the Italian region Friuli Venezia Giulia: a population-based study with administrative data

Parkinson’s disease is known to pose a relevant burden to society in industrialized countries. However, not much research has been conducted on the epidemiology of this disease in Italy. Our aim was to estimate the incidence rate and prevalence of Parkinson’s disease in the Italian Friuli Venezia Giulia region using administrative health-related databases. Five regional administrative databases (hospitalizations, exemptions from medical charges, drug prescriptions, nursing homes, and home visits) were individually linked with one another through an anonymous stochastic univocal key. Using a pre-defined algorithm, incident and prevalent cases of Parkinson’s disease were identified for the year 2016. The estimated regional incidence rate was 0.28 new cases/1000 person-years; prevalence was 3.89/1000 inhabitants. Both increased with increasing age and were higher among males than among females. A considerable proportion of prevalent cases was admitted to the hospital or nursing home in 2016, whereas only a few received home visits by health professionals. The incidence and prevalence of the disease were considerable, especially in the older population, indicating the need to develop multidisciplinary models to care for patients living in the region.

Identification and characterization of the novel m.8305C>T MTTK and m.4440G>A MTTM gene mutations causing mitochondrial myopathies

We report on two novel mtDNA mutations in patients affected with mitochondrial myopathy. The first patient, a 44-year-old woman, had bilateral eyelid ptosis and the m.8305C>T mutation in the MTTK gene. The second patient, a 56-year-old man, had four-limb muscle weakness and the MTTM gene m.4440G>A mutation. Muscle biopsies in both patients showed ragged red fibers and numerous COX-negative fibers as well as a combined defect of complex I, III and IV activities. The two mutations were heteroplasmic and detected only in muscle tissue, with a higher mutation load in COX-negative fibers. Additionally, both mutations occurred in highly conserved mt-tRNA sites, and were not found by an in silico search in 30,589 human mtDNA sequences. Our report further expands the mutational and phenotypic spectrum of diseases associated with mutations in mitochondrial tRNA genes and reinforces the notion that mutations in mitochondrial tRNAs represent hot spots for mitochondrial myopathies in adults.

1. Laser evoked potential in clinical practice: The diagnostic field in small fiber neuropathy

Small fiber neuropathy (SFN) is frequently encountered in clinical practice. Due to the small nerve fiber characteristics, the diagnosis requires the use of not conventional tests like skin biopsy, Quantitative sensory testing (QST) and Laser Evoked Potentials (LEPs). The aim of this study was to evaluate the diagnostic value of A-delta LEPs in clinical practice in a large cohort of patients with diagnosis of “definite” SFN. We screened 296 patients evaluated in our institution with confirmed diagnosis of sensory neuropathy. We collected 140 patients with pure SFN and 79 patients with mixed fiber neuropathy (MFN). All underwent clinical evaluation, sensory, painful thermal and mechanical detection thresholds, and quantification of somatic intraepidermal nerve fibers (IENF) by skin biopsy to define the diagnosis. Then, all SFN and MFN patients underwent LEPs. The sensitivity and specificity were calculated compared with our normative data on 67 healthy age-matched subjects. A-delta LEPs at dorsal foot showed 76% sensitivity and 80% specificity in SFN diagnosis, and, if performed bilaterally, the sensitivity and specificity increased (81% and 84%). We did not find any correlation between LEPs and entity of skin denervation, but we found good concordance with warm, heat pain thresholds and pinprick perception.

9. Navigated transcranial magnetic stimulation (nTMS) for preoperative mapping in motor areas tumor surgery: Comparison with functional magnetic resonance imaging (fMRI) and intraoperative direct cortical stimulation

Navigated transcranial magnetic stimulation (nTMS) is a novel technology in the field of neurosurgery for noninvasive delineation of cortical functional topography. Recent studies show that it can detect eloquent cortical areas directly, comparable to intraoperative direct cortical stimulation (DCS). The aim of this study was to evaluate the nTMS in comparison with functional magnetic resonance imaging (fMRI) in the setting of brain tumors involving motor areas. Thirteen consecutive patients affected by frontal lobe brain tumors were enrolled in the study. All patients received an fMRI and nTMS examination preoperatively. Consistency of preoperative mapping with intraoperative DCS was assessed off-line by means of the neuronavigation system: as result, nTMS produced statistically significant higher accuracy scores of the motor area localization than fMRI. Moreover, nTMS has fewer restrictions for preoperative functional mapping than fMRI and requires only a limited level of compliance: so it represents an useful and reliable technique during preoperative planning for surgical decision making in the clinical setting.