Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: A network meta-analysis

This is the protocol for a review and there is no abstract. The objectives are as follows: We aim to compare the efficacy and acceptability of immunomodulators and immunosuppressants to treat participants with RRMS and to generate a clinically useful hierarchy of available immunotherapies according to their efficacy and acceptability

Dysphagia in multiple system atrophy consensus statement on diagnosis, prognosis and treatment.

Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by a combination of autonomic failure plus cerebellar syndrome and/or parkinsonism. Dysphagia is a frequent and disabling symptom in MSA and its occurrence within 5 years of motor onset is an additional diagnostic feature. Dysphagia can lead to aspiration pneumonia, a recognized cause of death in MSA. Guidelines for diagnosis and management of dysphagia in MSA are lacking. An International Consensus Conference among experts with methodological support was convened in Bologna to reach consensus statements for the diagnosis, prognosis, and treatment of dysphagia in MSA. Abnormalities of the oral and pharyngeal phases of swallowing, esophageal dysfunction and aspiration occur in MSA and worsen as the disease progresses. According to the consensus, dysphagia should be investigated through available screening questionnaires and clinical and instrumental assessment (videofluoroscopic study or fiberoptic endoscopic evaluation of swallowing and manometry) at the time of MSA diagnosis and periodically thereafter. There is evidence that dysphagia is associated with poor survival in MSA, however effective treatments for dysphagia are lacking. Compensatory strategies like diet modification, swallowing maneuvers and head postures should be applied and botulinum toxin injection may be effective in specific conditions. Percutaneous endoscopic gastrostomy may be performed when there is a severe risk of malnutrition and pulmonary complications, but its impact on survival is undetermined. Several research gaps and unmet needs for research involving diagnosis, prognosis, and treatment were identified

Dysphagia in multiple system atrophy consensus statement on diagnosis, prognosis and treatment

Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by a combination of autonomic failure plus cerebellar syndrome and/or parkinsonism. Dysphagia is a frequent and disabling symptom in MSA and its occurrence within 5 years of motor onset is an additional diagnostic feature. Dysphagia can lead to aspiration pneumonia, a recognized cause of death in MSA. Guidelines for diagnosis and management of dysphagia in MSA are lacking. An International Consensus Conference among experts with methodological support was convened in Bologna to reach consensus statements for the diagnosis, prognosis, and treatment of dysphagia in MSA. Abnormalities of the oral and pharyngeal phases of swallowing, esophageal dysfunction and aspiration occur in MSA and worsen as the disease progresses. According to the consensus, dysphagia should be investigated through available screening questionnaires and clinical and instrumental assessment (videofluoroscopic study or fiberoptic endoscopic evaluation of swallowing and manometry) at the time of MSA diagnosis and periodically thereafter. There is evidence that dysphagia is associated with poor survival in MSA, however effective treatments for dysphagia are lacking. Compensatory strategies like diet modification, swallowing maneuvers and head postures should be applied and botulinum toxin injection may be effective in specific conditions. Percutaneous endoscopic gastrostomy may be performed when there is a severe risk of malnutrition and pulmonary complications, but its impact on survival is undetermined. Several research gaps and unmet needs for research involving diagnosis, prognosis, and treatment were identified

Are patients with GBA-Parkinson disease good candidates for deep brain stimulation? A longitudinal multicentric study on a large Italian cohort

Background: GBA variants increase the risk of developing Parkinson disease (PD) and influence its outcome. Deep brain stimulation (DBS) is a recognised therapeutic option for advanced PD. Data on DBS long-term outcome in GBA carriers are scarce. Objective: To elucidate the impact of GBA variants on long-term DBS outcome in a large Italian cohort. Methods: We retrospectively recruited a multicentric Italian DBS-PD cohort and assessed: (1) GBA prevalence; (2) pre-DBS clinical features; and (3) outcomes of motor, cognitive and other non-motor features up to 5 years post-DBS. Results: We included 365 patients with PD, of whom 73 (20%) carried GBA variants. 5-year follow-up data were available for 173 PD, including 32 mutated subjects. GBA-PD had an earlier onset and were younger at DBS than non-GBA-PD. They also had shorter disease duration, higher occurrence of dyskinesias and orthostatic hypotension symptoms. At post-DBS, both groups showed marked motor improvement, a significant reduction of fluctuations, dyskinesias and impulsive-compulsive disorders (ICD) and low occurrence of most complications. Only cognitive scores worsened significantly faster in GBA-PD after 3 years. Overt dementia was diagnosed in 11% non-GBA-PD and 25% GBA-PD at 5-year follow-up. Conclusions: Evaluation of long-term impact of GBA variants in a large Italian DBS-PD cohort supported the role of DBS surgery as a valid therapeutic strategy in GBA-PD, with long-term benefit on motor performance and ICD. Despite the selective worsening of cognitive scores since 3 years post-DBS, the majority of GBA-PD had not developed dementia at 5-year follow-up

Hallucinations and sleep-wake cycle in PD: A 24-hour continuous polysomnographic study

Twenty-four-hour ambulatory polysomnography was performed in 20 patients with PD who were having visual hallucinations (12 men and 8 women, mean age 70 ± 6 years). Visual hallucinations were clearly related to daytime NREM sleep or nocturnal REM sleep in 33% of the instances. The data reinforce the hypothesis that neural mechanisms implicated in generating sleep and, in particular, in dream imagery play a role in the occurrence of visual hallucinations in PD

Underestimation of hypoglycaemia using patients' diaries compared with downloaded glucometer data: an ITAS post hoc analysis

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Study of genetic comorbidities in parkinson’s disease patients

Aims During these years many genetic studies using deep sequencing techniques have underlined genetic comorbidities in neurodegenerative disorders shaking the specific relationship between gene and pathology. Herein we have performed a genetic comorbidities study in Parkinson\u2019s Disease (PD) never described in literature. Our objective was to analyze a cohort of Italian Parkinson samples by screening the most relevant (PD) related genes together with hereditary neurodegenerative disorders genes, Peripheral Nervous System (PNS) genes and Inherited Neuromuscular Disorder genes. Method Next Generation Sequencing (NGS) analysis and Multiplex ligation-dependent probe amplification (MLPA) has been performed in a cohort of 83 idiopathic PD Italian patients. MLPA kit was composed by 8 PD genes while SureSelect Agilent platform by 100 neurodegenerative disease genes. Data collected from NGS experiments were analyzed in order to identify single nucleotide variants and small insertions/deletion. Results Data analysis showed the presence of non-synonymous mutations in 20 (24%) of PD patients. We observed new non-synonymous mutations in PD genes as GBA, LRRK2, PINK1, ATP13A2 and PARK2. The most interesting data concerned non-synonymous mutations found in non PD genes as MFN2 (related to Charcot-Marie-Tooth), CYP27A1 (related to Cerebrotendinous Xanthomatosis) and SPG11 (related to Spastic paraplegia). Conclusion NGS data report variations in non PD genes opening intriguing prospective in the genetics of PD whereit is clear that the old genotype-phenotype vision is very simplistic and that the approach to the neurodegenerative diseases must be change

Gait initiation in progressive supranuclear palsy: brain metabolic correlates

The initiation of gait is a highly challenging task for the balance control system, and can be used to investigate the neural control of upright posture maintenance during whole-body movement. Gait initiation is a centrally-mediated motion achieved in a principled, controlled manner, including predictive mechanisms (anticipatory postural adjustments, APA) that destabilize the antigravitary postural set of body segments for the execution of functionally-optimized stepping. Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by early impairment of balance and frequent falls. The neural correlates of postural imbalance and falls in PSP are largely unknown. We biomechanically assessed the APA at gait initiation (imbalance, unloading, and stepping phases) of 26 patients with PSP and 14 age-matched healthy controls. Fourteen of 26 enrolled patients were able to perform valid gait initiation trials. The influence of anthropometric and base-of-support measurements on the biomechanical outcome variables was assessed and removed. Biomechanical data were correlated with clinical findings and, in 11 patients, with brain metabolic abnormalities measured using positron emission tomography and 2-deoxy-2-[18F]fluoro-D-glucose. Patients with PSP showed impaired modulation of the center of pressure displacement for a proper setting of the center of mass momentum and subsequent efficient stepping. Biomechanical measurements correlated with “Limb motor” and “Gait and midline” subscores of the Progressive Supranuclear Palsy Rating Scale. Decreased regional glucose uptake in the caudate nucleus correlated with impaired APA programming. Hypometabolism of the caudate nucleus, supplementary motor area, cingulate cortex, thalamus, and midbrain was associated with specific biomechanical resultants of APA. Our findings show that postural instability at gait initiation in patients with PSP correlates with deficient APA production, and is associated with multiple and distinctive dysfunctioning of different areas of the supraspinal locomotor network. Objective biomechanical measures can help to understand fall-related pathophysiological mechanisms and to better monitor disease progression and new interventions

Monitoring subthalamic oscillations for 24 hours in a freely moving Parkinson's disease patient

Adaptive deep brain stimulation (DBS) devices aim to personalize stimulation delivery by following the current state of symptom-specific neural signals during different activities of daily living (walking, sleeping, etc.). This approach is not yet suitable for clinical practice, and groundwork is needed. The first essential steps for establishing adaptive DBS comprise the capacity for measurements in chronically implanted patients (to avoid the \u201cstunning effect\u201d) and for prolonged recordings not corrupted by artifacts