A survey-based approach on restless legs syndrome: practices and perspectives among Italian neurologists.

INTRODUCTION: Restless Legs Syndrome (RLS) is a widely prevalent and complex neurological disorder. Despite notable advancements in managing RLS, the disorder continues to face challenges related to its recognition and management. OBJECTIVE: This study seeks to gain comprehensive insights into the knowledge and clinical practices among Italian neurologists regarding RLS diagnosis, management, and treatment, comparing approaches among general neurologists, movement disorder specialists, and sleep experts. METHODS: Members of the Italian Society of Neurology, the Italian Society of Parkinson and Movement Disorders, and the Italian Association of Sleep Medicine were invited to participate in a 19-question online survey. RESULTS: Among the 343 surveyed neurologists, 60% categorized RLS as a "sleep-related movement disorder." Forty% indicated managing 5-15 RLS patients annually, with sleep specialists handling the highest patient volume. Of note, only 34% adhered strictly to all five essential diagnostic criteria. The majority (69%) favored low-dosage dopamine agonists as their first-line treatment, with movement disorder specialists predominantly endorsing this approach, while sleep experts preferred iron supplementation. Regular screening for iron levels was widespread (91%), with supplementation typically guided by serum iron alterations. In cases of ineffective initial treatments, escalating dopamine agonist dosage was the preferred strategy (40%). CONCLUSIONS: These findings underscore a lack of a clear conceptualization of RLS, with a widespread misconception of the disorder as solely a movement disorder significantly influencing treatment approaches. Disparities in RLS understanding across neurology subspecialties underscore the necessity for improved diagnostic accuracy, targeted educational initiatives, and management guidelines to ensure consistent and effective RLS management.

Dystonia, chorea, hemiballismus and other dyskinesias.

Hyperkinesias are heterogeneous involuntary movements that significantly differ in terms of clinical and semeiological manifestations, including rhythm, regularity, speed, duration, and other factors that determine their appearance or suppression. Hyperkinesias are due to complex, variable, and largely undefined pathophysiological mechanisms that may involve different brain areas. In this chapter, we specifically focus on dystonia, chorea and hemiballismus, and other dyskinesias, specifically, levodopa-induced, tardive, and cranial dyskinesia. We address the role of neurophysiological studies aimed at explaining the pathophysiology of these conditions. We mainly refer to human studies using surface and invasive in-depth recordings, as well as spinal, brainstem, and transcortical reflexology and non-invasive brain stimulation techniques. We discuss the extent to which the neurophysiological abnormalities observed in hyperkinesias may be explained by pathophysiological models. We highlight the most relevant issues that deserve future research efforts. The potential role of neurophysiological assessment in the clinical context of hyperkinesia is also discussed.

Relationship between risk and protective factors and clinical features of Parkinson's disease.

BACKGROUND: Non-genetic risk factors play a relevant role in Parkinson's disease (PD) development but the relationship between these factors and PD clinical features is unknown. OBJECTIVE: The aim of the present multicenter study was to investigate possible relationship between risk factors and clinical motor and non-motor features in a large sample of PD patients. METHODS: Six hundred ninety-four patients with PD participated. Patients underwent a clinical evaluation assessing motor symptoms and motor complications as well as non-motor symptoms severity. Information regarding pharmacological treatment was also collected. Risk and protective factors were previously identified in the present population and included coffee consumption, cigarette smoking, and physical activity as protective factors and a family history of PD, dyspepsia, exposure to toxic agents and general anesthesia as risk factors. Multiple regression models were used to investigate the relationship between risk factors and clinical variables. RESULTS: Coffee consumption predicted older age at onset (B: 0.527; CI: 0.195; 0.858) and milder motor symptom severity (B: 1.383; CI: 2.646; -0.121). Non-motor symptom severity was more severe in patients with dyspepsia before PD (B: 13.601; CI 5.019; 22.182) and milder in patients who performed physical activity before PD (B: 11.355; CI: 16.443; -6.266). We found no relationship between risk factors and motor complications, motor subtype and pharmacological treatment. CONCLUSIONS: Risk and protective factors of PD development may influence PD clinical features. This finding may represent the first step in the development of new preventive approaches able to delay disease onset and mitigate the extent of clinical manifestations.

The Effectiveness of Equine Therapy Intervention on Activities of Daily Living, Quality of Life, Mood, Balance and Gait in Individuals with Parkinson's Disease.

OBJECTIVES: The objective of this study was to evaluate the efficacy of equine therapy (ET) to detect changes in the activities of daily living, quality of life, mood, balance, and gait in individuals with Parkinson's disease (PD). MATERIAL AND METHODS: In the study, 17 participants with PD were recruited to participate in 10 sessions of ET. The inclusion criteria of the study were: second and third stages of the Hoehn and Yahr scale, Mini-Mental State Examination (MMSE) greater than or equal to 24 points, and age up to 85 years. The outcome measures administered at the beginning and the end of treatment relied on measurements from the Rivermead ADL scale, Parkinson's Disease Questionnaire-39 (PDQ-39), Zung Self-Rating Depression Scale (SDS), unified Parkinson's disease rating scale (UPDRS), and Tinetti balance assessment. Data from the stabilometric platform were also collected to objectify the value obtained by the Tinetti balance assessment. The ET program included 10 biweekly 45 min sessions. RESULTS: The results obtained included statistically significant increases in measurements from the Rivermead ADL, PDQ-39, UPDRS, SDS, and Tinetti balance assessment scales. The stabilometric platform did not report significant changes in data. CONCLUSION: ET that was used as a supportive therapy for traditional treatments resulted in statistically significant improvements in the occupational performance, mood, quality of life, gait, and balance of the participants. Data from the stabilometric platform did not show significant changes.

Review of Available Data for the Efficacy and Effectiveness of Nabiximols Oromucosal Spray (Sativex®) in Multiple Sclerosis Patients with Moderate to Severe Spasticity.

BACKGROUND: Sativex (USAN: nabiximols [NAB]) oromucosal spray is indicated for treatment of multiple sclerosis (MS) patients with moderate to severe spasticity and inadequate response to other antispasticity medications who demonstrate clinically significant improvement during an initial trial of therapy. This narrative review investigated the efficacy and effectiveness of NAB oromucosal spray for moderate to severe MS spasticity by examining spasticity 0-10 numerical rating scale (NRS) data from interventional and observational studies which featured a 4-week trial period as per the European Union-approved label. SUMMARY: Across both study types, clinically relevant and statistically significant reductions in mean MS spasticity 0-10 NRS scores were measured soon after treatment start and were maintained in the mid- to long term in treatment responders. Initial responder rates (≥20% NRS improvement from baseline at week 4) ranged from 47.6% to 81.4%, tending lower in the randomized clinical trials setting. Clinically relevant responder rates (≥30% NRS improvement from baseline at week 12) were similar between study types (range 30-41%) except for one outlier (74% in an observational study). Two open studies reported treatment continuation for ≥18 months in approximately half of patients who initiated treatment. In most longer term studies, symptomatic improvement in MS spasticity was maintained at mean daily dosages of about 6-7 sprays/day. Safety was consistent with the known profile of NAB. KEY MESSAGES: Experimental and observational studies of NAB oromucosal spray recorded similar findings. About half to two-thirds of MS patients who begin treatment will perceive initial symptomatic relief of spasticity within the 4-week trial period. About 40% of patients who initiate treatment will reach the ≥30% NRS improvement threshold at 3 months, comprising the majority of patients who continue long-term treatment. A trial of therapy with NAB is useful to identify patients most likely to gain longer term improvement in spasticity symptoms and discontinue those with insufficient benefit.

The effect of aquatic physical therapy on patients with multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: The aquatic environment has unique properties, such a buoyancy, turbulence, hydrostatic pressure, and resistance, which can be used to gain a range of exercise benefits. During the last decade, hydrotherapy has spread in a very heterogeneous rehabilitation field. However, the efficacy of this kind of rehabilitation is not clear in scientific literature. The purpose of this study is to conduct a systematic review with meta-analysis to evaluate the qualitative and quantitative results of physical therapy treatments in an aquatic setting for individuals with Multiple Sclerosis. METHOD: PRISMA guidelines were used to carry out the systematic review and meta-analysis. Three bibliographic databases were searched: MEDLINE, PEDro, and the Cochrane Library. Papers included in the study have the following characteristics: (a) a randomized controlled trial design of research and (b) published in English. The quality of the clinical trials included were evaluated according to a Jadad score and through meta-analysis. RESULTS: After the elimination of duplicates, 116 records were screened. Among these, 11 Randomized Controlled Trials (RCTs) were included in the systematic review. Ten of these were involved in the meta-analysis. From the qualitative analysis, a larger number of studies were found with a high level of quality. Most of the results of the quantitative analysis were statistically significant (p< 0.05). CONCLUSION: Aquatic physical therapy is a valid means of rehabilitation for people with Multiple Sclerosis. The integration of this methodological approach with conventional physical therapy is recommended. Nevertheless, more studies, a larger number of participants, and short-, medium-, and long-term follow-up are required to confirm current results.

Deep grey matter involvement and altered sensory gating in multiple sclerosis.

BACKGROUND: Somatosensory temporal discrimination threshold (STDT) is altered in multiple sclerosis (MS). In healthy subjects (HS), voluntary movement modulates the STDT through mechanisms of subcortical sensory gating. OBJECTIVE: With neurophysiological and magnetic resonance imaging (MRI) techniques, we investigated sensory gating and sensorimotor integration in MS. METHODS: We recruited 38 relapsing-remitting multiple sclerosis (RR-MS) patients with no-to-mild disability and 33 HS. We tested STDT at rest and during index finger abductions and recorded the movement kinematics. Participants underwent a 3T MRI protocol. RESULTS: Patients exhibited higher STDT values and performed slower finger movements than HS. During voluntary movement, STDT values increased in both groups, albeit to a lesser extent in patients, while the mean angular velocity of finger movements decreased in patients alone. Patients had a smaller volume of the thalamus, pallidum and caudate nucleus, and displayed higher mean diffusivity in the putamen, pallidum and thalamus. STDT correlated with thalamic volume while mean angular velocity correlated with putaminal volume. Changes in mean angular velocity during sensorimotor integration inversely correlated with mean diffusivity in the thalamus and pallidum. Changes in STDT and velocity were associated with fatigue score. CONCLUSION: Altered STDT and sensorimotor integration are related to structural damage in the thalamus and basal ganglia in MS and likely to affect motor performance.

Neurophysiological studies on atypical parkinsonian syndromes.

There have been a relatively large number of experimental investigations using neurophysiological techniques in patients with atypical parkinsonian syndromes (APs), including progressive supranuclear palsy, cortico-basal syndrome and multiple system atrophy. Earlier studies focused on the startle, blink and trigemino-cervical reflexes and showed several brainstem abnormalities. Studies using transcranial magnetic stimulation have revealed a number of abnormalities in primary motor cortex and inter-hemispheric connectivity. More recent studies have highlighted the role of cerebellar dysfunction and have reported altered movement kinematics. Neurophysiological abnormalities in APs reflect degeneration or functional changes at multiple brain levels. In the majority of cases, APs share common abnormalities even though some neurophysiological changes differ among the various APs. Evidence of a correlation between neurophysiological abnormalities and clinical signs and symptoms in APs is limited. This paper provides an update on the results of experimental investigations using neurophysiological techniques in APs and also reviews similarities and differences between APs and Parkinson's disease. The potential role of neurophysiological abnormalities in the clinical context of APs is also discussed.

Cerebellar continuous theta burst stimulation in essential tremor.

The pathophysiological mechanisms of essential tremor (ET) are still not entirely clear. In the present study, we aimed to investigate the cerebello-thalamo-cortical connectivity in ET using the cerebellar continuous theta burst stimulation (cTBS) and possible effects on tremor and reaching movements. Sixteen patients with ET and 11 healthy subjects underwent two experimental sessions: (i) cTBS over the right cerebellar hemisphere (real cerebellar cTBS) and (ii) cTBS over the neck muscles (sham cerebellar cTBS). The two sessions were performed at least 1 week apart. The effects of real and sham cerebellar cTBS were quantified as excitability changes on contralateral primary motor cortex, as well as possible changes of postural tremor and reaching movements on the ipsilateral arm. Primary motor cortex excitability was assessed by recording the input/output curve of the motor-evoked potentials from the right first dorsal interosseous muscle. Tremor was rated clinically. Objective assessment of tremor and reaching movements was performed using kinematic techniques. Real cerebellar cTBS reduced the excitability in the contralateral primary motor cortex in healthy subjects though not in patients with ET. There was no significant change in tremor severity and reaching movements, as assessed by clinical examination or kinematic techniques, after real or sham cerebellar cTBS in patients with ET. Finally, there was no correlation between individual changes of M1 excitability and kinematic measures of tremor and reaching movement abnormalities in patients with ET. The results suggest that functional cerebello-thalamo-cortical connectivity tested by cTBS is abnormal in ET and that cerebellar cTBS does not ameliorate tremor in this condition.

Psychopathological and cognitive effects of therapeutic cannabinoids in multiple sclerosis: a double-blind, placebo controlled, crossover study.

OBJECTIVES: To study possible psychopathological symptoms and cognitive deficits, abuse induction, as well as general tolerability and effects on quality of life, fatigue and motor function in cannabis-naïve patients with multiple sclerosis (MS) treated with a free-dose cannabis plant extract (Sativex). METHODS: In an 8-week, randomized, double-blind, placebo-controlled, parallel group crossover trial, 17 cannabis-naïve patients with MS were assessed at baseline and at the end of the cannabis and placebo phases of the trial (each of 3 weeks) by means of Symptom Checklist-90 Revised, Self-rating Anxiety Scale, Multiple Sclerosis Functional Composite (of which 1 dimension is the Paced Auditory Serial Additional Test that was used to evaluate cognition), Visual Analogue Scale on health-related quality of life, Multiple Sclerosis Impact Scale-29, and Fatigue Severity Scale. RESULTS: Postplacebo versus postcannabinoid scores showed that no significant differences could be detected on all the variables under study. A significant positive correlation was found between Delta-9-tetrahydrocannabinol blood levels and scores at the General Symptomatic Index and at the "interpersonal sensitivity," "aggressive behaviour," and "paranoiac tendencies" subscales of the Symptom Checklist-90 Revised. No serious adverse events, abuse tendencies, or direct withdrawal symptoms were reported. Increased desire for Sativex with secondary depression was reported in 1 subject. CONCLUSIONS: Cannabinoid treatment did not induce psychopathology and did not impair cognition in cannabis-naïve patients with MS. However, the positive correlation between blood levels of Delta-9-tetrahydrocannabinol and psychopathological scores suggests that at dosages higher than those used in therapeutic settings, interpersonal sensitivity, aggressiveness, and paranoiac features might arise, although greater statistical power would be necessary to confirm this finding.