Sara Rinaldo

Paroxysmal itch caused by gain-of-function Nav1.7 mutation

Summary A novel clinical syndrome is described, characterized by paroxysmal itch and ensuing burning pain triggered by warmth and spicy food associated with a gain‐of‐function Nav1.7 variant. ABSTRACT Itch is a common experience. It can occur in the course of systemic diseases and can be a manifestation of allergies or a consequence of diseases affecting the somatosensory pathway. We describe a kindred characterized by paroxysmal itch caused by a variant in SCN9A gene encoding for the Nav1.7 sodium channel. Patients underwent clinical and somatosensory profile assessment by quantitative sensory testing, nerve conduction study, autonomic cardiovascular reflex, and sympathetic skin response examination, skin biopsy with quantification of intraepidermal nerve fiber density, and SCN9A mutational analysis. The index patient, her mother, and a sister presented with a stereotypical clinical picture characterized by paroxysmal itch attacks involving the shoulders, upper back, and upper limbs, followed by transient burning pain, and triggered by environmental warmth, hot drinks, and spicy food. Somatosensory profile assessment demonstrated a remarkably identical pattern of increased cold and pain thresholds and paradoxical heat sensation. Autonomic tests were negative, whereas skin biopsy revealed decreased intraepidermal nerve fiber density in 2 of the 3 patients. All affected members harbored the 2215A>G I739V substitution in exon 13 of SCN9A gene. Pregabalin treatment reduced itch intensity and attack frequency in all patients. The co‐segregation of the I739V variant in the affected members of the family provides evidence, for the first time, that paroxysmal itch can be related to a mutation in sodium channel gene.

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.

Weight gain after STN-DBS: The role of reward sensitivity and impulsivity

Weight gain has been reported after deep brain stimulation of the subthalamic nucleus (STN-DBS), a widely used treatment for Parkinsons disease (PD). This nucleus has been repeatedly found to be linked both to reward and to inhibitory control, two key aspects in the control of food intake. In this study, we assessed whether weight gain experienced by patients with PD after STN-DBS, might be due to an alteration of reward and inhibitory functions. Eighteen patients with PD were compared to eighteen healthy controls and tested three times: before surgery, in ON medication and after surgery, respectively five days after the implantation in ON medication/OFF stimulation and at least three months after surgery in ON medication/ON stimulation. All participants were assessed for depression (Beck Depression Inventory), anhedonia (Snaith-Hamilton Pleasure Scale) and impulsiveness (Barratt Impulsiveness Scale). They performed a battery of tests assessing food reward sensitivity (Liking, Wanting and Preference) and a food go/no-go task. Results showed that body weight significantly increased after STN-DBS. A few days after surgery, patients were slower and more impulsive in the go/no-go task, showed a higher preference for high calorie (HC) foods and rated foods as less tasty. Months after subthalamic stimulation, the performance on the go/no-go task improved while no differences were observed in reward sensitivity. Interestingly, weight gain resulted greater in patients with higher levels of attentional impulsiveness pre-surgery, higher wanting for low calorie (LC) foods and impulsivity in the go/no-go task in ON medication/ON stimulation. However, only wanting and attentional impulsivity significantly predicted weight change. Furthermore, weight gain resulted associated with the reduction of l-Dopa after surgery and diseases duration. In conclusion, our findings are consistent with the view that weight gain in PD after STN-DBS has a multifactorial nature, which reflects the complex functional organization of the STN.

Levodopa/carbidopa intestinal gel (LCIG) therapy for advanced Parkinson's Disease: An early toxic effect for small nerve fibers?

Introduction: Peripheral neuropathy related to levodopa/carbidopa intestinal gel (LCIG) therapy for advanced Parkinson disease (PD) is under investigation and is debated in the literature. The purpose of the study was to detect whether small nerve fibers are damaged during LCIG infusion. Methods: Five advanced PD patients were enrolled prior to starting LCIG infusion. Six PD patients on oral levodopa (LD) treatment and 6 PD patients naïve to LD were also enrolled. Clinical examination, the Quantitative Sensory Testing battery testing, nerve conduction studies, and intraepidermal nerve fiber density examinations were collected at baseline and at 3, 6, and 12 months after LCIG infusion was started in the study cohort. Results: After 3, 6, and 12 months, severe skin denervation and increased thermal thresholds were observed in the LCIG group. Conclusions: Significant damage to small nerve fibers was detected in PD patients soon after LCIG infusion had started, suggesting careful monitoring of small fiber impairment during LCIG is needed. Muscle Nerve, 2016 Muscle Nerve 54: 970–972, 2016

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.

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.

P11.7 Effects of “dissociative” anaesthesia on subthalamic nucleus activity in Parkinsonian patients who underwent deep brain stimulation

Introduction: During cerebral aneurysms surgery, could appear isquemic complications because of an artery occlusion. The changes depend of the cerebrovascular auto regulation, collateral perfusion and systemic homeostasis parameters. Objective: Assess intraoperative neurophysiologic monitoring outcomes of patients whom were operated or cerebral aneurysms. Methods: We present a total of 17 patients with intracranial aneurysms, that was intraoperative monitored with somatosensory evoked potentials (SEP) and motor evoked potentials (MEP). Results: Isquemic time during temporal clip collocation was 4 minutes in 11 cases, and in 6 cases between 1 second and 25 minutes. In 3 patients there was a change in SEP and MEP during the clipping. Patient 1: absence of SEP after 30 seconds aneurysm clipping without posterior recover and postoperative left hemiplegic. MEP with no changes. Patient 2: 50% amplitude reduction of SEP and MEP, when the aneurysm clipping with posterior recover and not postquirugic neurological sequel. Patient 3: 50% amplitude reduction of SEP after 6.86 minutes aneurysm clipping and a second amplitude SEP reduction alter 1.10 minutes, both of them with posterior recover and not postoperative neurological sequel. No changes in MEP. Conclusions: In our knowledge, the most sensitive parameter to detect isquemia was the SEP. MEP is not reliable, probably because it can bypass isquemic site by distal stimulation. The clipping duration was not related with the changes on SEP and MEP, maybe because of the presence of collateral arteries. Nevertheless it would be required more number of cases to determine the time of clipping and sensitive parameters to define isquemic complications.