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Multiple sclerosis (MS) is a chronic, debilitating disease characterised by demyelination of the nerves of the central nervous system that results in patients progressively losing the ability to perform daily tasks. As there is no cure for this disease, rehabilitation therapy is an important aspect of care; assisting patients to regain or retain function and improve their physical, mental and social wellbeing. At present there is no current consistent model of care for MS, likely due to the variable symptom presentation. Various forms of rehabilitation therapy are available, and these include physical rehabilitation methods, such as balance and gait therapy, speech and respiration rehabilitation, and occupational therapy. Contrary to previous understanding, exercise-based therapies have shown various benefits for patients with MS, and in addition to improving MS-related physical symptoms, have been shown to reduce the risk of developing cardiovascular disease and can improve cognitive function. Cognition rehabilitation therapy specifically focuses on behavioural tasks and is divided into two main forms: compensatory rehabilitation, which offers cognitive functioning benefits, and restorative rehabilitation, which offers memory benefits. Excitation therapies include cranial stimulation and other stimulation rehabilitation methods such as focal muscle vibration therapy and these non-invasive techniques may improve patient's physical ability. Additionally, more novel rehabilitation methods include robot-assisted gait therapy and telerehabilitation, both of which are expected to play progressively more prominent roles in the future of rehabilitation therapy. The structure of the care team has been found to impact patient outcomes, and both in- and out-patient care settings have been found to be beneficial, dependant on the patient's circumstances, with certain patients better suited to a particular setting. While a single point of care is recommended for patients, a multidisciplinary care team and regular reassessment is recommended to manage changing symptoms and ensure continuity of care. The importance of the critical components of rehabilitation have been identified, and these are of vital importance in achieving beneficial outcomes. These components include the patients' participation in the treatment, goal setting with a multidisciplinary care team, a guiding-light purpose for the patient, which focusses on recognizing their personal potential and obtaining improvements through a tailored plan. The final critical component of rehabilitation is the results measurement, which highlights the need for a quantifiable reduction in impairment and improvement in activity and participation. Overall, a lack of standardisation in outcome measurements makes comparison challenging. This is particularly important when comparing standard methods of care with more novel rehabilitation techniques. However, within the broad area of rehabilitation therapies, it is clear that patients with MS can benefit from rehabilitation practices; physically, mentally and socially.

Background: In patients with Multiple Sclerosis (pwMS) disease-modifying therapies (DMTs) are known to affect immune response to antigens and possibly to SARS-CoV2 vaccine. Therefore, post-vaccination serological assessments are needed to evaluate the effect of the vaccine on SARS-CoV-2 antibody response. Methods: We designed a prospective multicenter cohort study enrolling pwMS who were scheduled for SARS-Cov-2 vaccination with mRNA vaccines (BNT162b2, Pfizer/BioNTech, Inc or mRNA-1273, Moderna Tx, Inc). A blood collection for the measure of SARS-CoV-2 antibody before the first vaccine dose and 4 weeks after the second dose was planned, with a centralized serological assessment (electrochemiluminescence immunoassay, ECLIA, Roche Diagnostics). Findings: 780 pwMS (76% BNT162b2 and 24% mRNA-1273) had pre- and 4-week post-vaccination blood assessments. 87 (11·2%) were untreated, 154 (19·7%) on ocrelizumab, 25 (3·2%) on rituximab, 85 (10·9%) on fingolimod, 25 (3·2%) on cladribine and 404 (51·7%) on other DMTs. 677 patients (86·8%) had detectable post-vaccination SARS-CoV-2 antibodies. At multivariate analysis, the antibody levels of patients on ocrelizumab (178-fold decrease, p

Charcot-Marie-Tooth (CMT) diseases are a clinically and genetically heterogeneous group of disorders. Different variants in the neurofilament heavy chain (NEFH) gene have been described to cause the CMT2CC subtype. Here we report the first Italian patient affected by CMT2CC, harboring a novel variant in NEFH. In describing our patient, we also reviewed previously CMT2CC individuals, and suggested to consider NEFH variant if patients have an axonal sensory-motor neuropathy with a prominent proximal muscles involvement with early requirement of walking aids or wheelchair, remembering a motor neuron disorder.

Background The SARS-CoV-2 pandemic impact on people with Multiple Sclerosis (pwMS) continues to worry. The disease modifying therapies in pwMS can add a more severe risk of infection when compared to the general population. Alemtuzumab is an anti-CD52 monoclonal antibody and it is one of the most immunosuppressive drugs used in Multiple Sclerosis (MS). Case Description We present a case of Covid-19 infection that occurred in a 24-year-old woman with MS and treated with alemtuzumab. The infection occurred 4 months after administration of the first course of alemtuzumab and had a benign course with subsequent development of antibodies. Furthermore, we present a brief review of the literature on similar published cases. Discussion We reviewed 17 articles concerning COVID-19 infection in MS patients in treatment with Alemtuzumab. In our case and all screened cases no severe course of disease was noted and no fatality was observed. Systematic compilation of this observation comforts clinicians about the course of Covid-19 infection despite alemtuzumab immunosuppressive treatment Conclusions The risk of serious COVID-19 disease in MS patients treated with alemtuzumab is unknown. Physicians need to monitor carefully pwMS treated with alemtuzumab and to consider COVID-19 infection related relapse in the MS patients. Further research is recommended to evaluate the beneficial-risk profile of alemtuzumab in pandemic era.

Background Clinical trials have shown the therapeutic effect of fingolimod in reducing disease activity in relapsing-remitting multiple sclerosis (RR-MS), but its influence on nervous conduction assessed by evoked potentials (EPs) has not been previously investigated. Methods EP data of 20 patients examined 12months prior to initiation of fingolimod ( t =−1), at treatment initiation ( t =0) and 1year later ( t =+1) were compared. Each EP (VEP, MEP, SEP) and EP sum score, a global evoked potential score as the sum score of the each EP score was evaluated and correlated with Expanded Disability Status Scale (EDSS). Results During pre-treatment period (1year) EDSS worsened while one year after fingolimod treatment EDSS remained stable. From t −1 to t 0 VEP, SEP, MEP and EP sum score worsened while from t 0 to t +1 VEP, SEP and EP sum score improved, and MEP score remain stable. VEP and SEP were related to EDSS at baseline ( t =−1), while MEP and total EP sum score were related to EDSS at all time points. Conclusion Fingolimod is able to improve visual and somatosensory evoked potential in RR-MS patients even if clinical disability scale remains stable. VEP and SEP could give eloquent information on pathway underweighted in EDSS. EPs are useful to evaluate fingolimod effects in clinical practice.

Cladribine is an approved drug for the treatment of highly active multiple sclerosis. We report a 28-years-old man with a poor response to previous treatments, elected to treatment with Cladribine. He developed a lichenoid rash two weeks after taking the first and second treatment cycles. This symptom regressed with specific therapy. A lichenoid drug eruption is a rare side effect which can occur following the administration of several different medications, but it has never been described after treatment with oral Cladribine.

Niemann-Pick disease type C (NPC) is a recessive lysosomal lipid storage disorder characterized by central nervous system involvement. Miglustat treatment might improve or stabilize neurological manifestations but there is still limited data on the long-term efficacy. The aim of our study was to report a four-year clinical, neuropsychological and electrophysiological follow-up of two sisters under treatment with miglustat. We report data at basal (T0) and after 4 years (T4) of treatment with miglustat from two sisters (P1 and P2) affected by NPC disease. During the follow-up period, P1 was not adherent to treatment. Both patients underwent neurological evaluation, neuropsychological assessment, nerve conduction study and motor (MEP), visual (VEP), somatosensory and brainstem auditory evoked potentials. In the patient P2, neurological and electrophysiological evaluations at T4 were stable. Instead, the patient P1, with poor adherence to therapy, developed spasticity, psychiatric disturbances and alterations of MEP and VEP. Neuropsychological examination showed in both patients a worsening of cognitive impairment. Our findings suggest that long-term therapy with miglustat does not arrest cognitive decline, otherwise it stabilizes other neurological manifestations.

In infantile and juvenile Niemann–Pick type C (NPC) disease electrophysiological studies have shown central (CNS) and peripheral (PNS) nervous system abnormalities. However, an extensive electrophysiological evaluation of CNS and PNS in adult form of NPC is still lacking. The aim of the study is to assess in adult-onset NPC disease the involvement of CNS and PNS by a multimodal electrophysiological approach. Three patients affected by adult form of NPC disease underwent electrophysiological evaluation including nerve conduction study (NCS), magnetic motor (MEPs), visual (VEPs), somatosensory (SSEPs) and brainstem auditory (BAEPs) evoked potentials. NCS, MEPs, VEPs and upper limb SSEPs were normal. Lower limb SSEPs were abnormal in all patients and abnormalities were consistent with a length-dependent process affecting the central somatosensory pathway. BAEPs were abnormal in all patients with both peripheral and central impairment of auditory pathway. Our electrophysiological findings suggest that auditory and lower limb somatosensory pathways are constantly affected in adult-onset form of NPC disease. The involvement of PNS, pyramidal, visual and upper limb somatosensory pathways might occur later during the course of disease.

Background Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) account for up to 13% of dominant familial Parkinson’s disease (PD) cases. The clinical and pathological features of LRRK2-PD are often indistinguishable from idiopathic PD (iPD). Recent evidence pointed out that LRRK2 acts directly at the secretory and endocytic molecular machinery. Importantly, in southern Italy the R1441C mutation is the most frequent mutation reported so far. Objective Based on the LRRK2-role on synaptic transmission, we aimed to investigate in vivo excitability and plasticity of the motor cortex by means of transcranial magnetic stimulation (TMS). Methods Paired pulse TMS was used to investigate cortical excitability by using short intracortical inhibition and facilitation and short afferent inhibition paradigm. Intermittent theta burst stimulation (iTBS) was used to test long-term potentiation-like cortical plasticity (LTP). Eight LRRK2-PD patients harboring the R1441C mutation and 11 iPD were tested on the more affected side in ON l-dopa therapy. Results We observed the lack of LTP-like motor cortex plasticity in R1441C-LRRK2 patients compared to healthy-subjects and with a similar profile observed for iPD patients. Motor cortex excitability profile did not exhibit any difference among the three groups. Conclusions R1441C mutation disrupts motor cortex LTP-like plasticity in Parkinson’s disease patients.

Small fiber pathology has been demonstrated in Parkinson Disease (PD). To verify if it is among the early non-motor features of PD, unrelated to Levodopa therapy, we assessed function and morphology of cutaneous sensory and autonomic nerves in 32 consecutive drug-naive PD patients (M/F = 16/16; age 57.3 ± 11.1 years) and 64 age and sex matched controls. Fifty-micron-thick sections of skin samples from thigh, leg and fingertip were processed by indirect immunofluorescence techniques. Digital images were acquired using a non-laser confocal microscope. Density of intrapapillar myelinated endings (IME), Meissner’s corpuscles (MC) and epidermal nerve fibers (ENFs) was calculated. Sudomotor, pilomotor and vasomotor nerves were assessed semi-quantitatively. Further evaluation included sural nerve conduction study, sympathetic skin response, quantitative sensory testing and dynamic sweat test. Nerve conduction was normal in all patients. Morphological analysis showed: a significant loss (p

Abnormalities of cholinergic circuitries may be at the basis of cognitive dysfunction, gait disorders, and falls and they may also be important for freezing of gait (FOG). Aim of this study is the evaluation of central cholinergic circuits by means of short latency afferent inhibition (SAI) technique in patients with Parkinson’s disease (PD) and freezing of gait (FOG+). We applied the SAI technique in 14 FOG+ patients, in 10 patients without freezing (FOG−) and in 11 age-matched normal controls. All PD patients also underwent a comprehensive battery of neuropsychological tests. Mean SAI was not significantly different in FOG+ patients when compared with FOG− patients and controls. Neuropsychological examination showed mild cognitive impairment (MCI) in 10 out of the 14 FOG+ patients, and in 1 out of the 10 FOG−. Notably, the pattern of cognitive impairment included a variable degree of deficits in executive and visuospatial domains. Our SAI findings suggest the integrity of cholinergic circuits in PD patients with FOG. In addition, neuropsychological findings provide further evidence of executive dysfunction in the pathogenesis of FOG.

In infantile and juvenile NPC disease electrophysiological studies have shown central (CNS) and peripheral (PNS) nervous system abnormalities. However, an extensive electrophysiological evaluation of CNS and PNS in adult form of NPC is still lacking. To assess in Niemann-Pick type C disease (NPC) the involvement of the central (CNS) and peripheral (PNS) nervous system by a multimodal electrophysiological approach. Three patients affected by adult form of NPC underwent electrophysiological evaluation including nerve conduction study (NCS), motor (MEPs) and somatosensory (SEPs) evoked potentials at upper and lower limbs, visual (VEPs) and brainstem auditory (BAEPs) evoked potentials. NCS, VEPs, MEPs and upper limb SEPs were normal. Lower limb SEPs were abnormal in all patients and abnormalities were consistent with a central somatosensory pathway involvement (CCT: 21.2 ± 0.6 ms). BAEPs were constantly abnormal with peripheral and central type lesions. Our electrophysiological findings are in keeping with pathological evidence of dysfunction at brainstem level between acoustic nerve and inferior colliculus/superior olivary nucleus for auditory pathways and at gracile nuclei for somatosensory pathways. Moreover, our results, unlike cases of infantile and juvenile NPC disease, suggest the sparing of PNS and of visual and corticospinal pathways.

Sensory symptoms in CMT1A are generally attributed to large fiber. However, an involvement of small fibers has been recently brought up. We performed an extensive clinical, morphological and functional study of cutaneous somatic and autonomic innervation in 10 patients affected by CMT 1A, in order to assess small fiber involvement in this condition. We used a 13 items questionnaire and QST to evaluate symptoms and function of somatic small fibers, DST, SSR and Ewing tests to evaluate autonomic function. Morphological analysis of cutaneous innervation included lENF density and sudomotor nerves assessment. Twenty age-and-sex-matched healthy subjects were used as controls for morphological data. All patients complained of at least 2 symptoms related to small fiber dysfunction. Nine out of ten patients had an increase in thermal/pain thresholds indicating an impairment of both C and A-delta fibers. DST revealed hypoidrosis in all patients (41.8 ± 22.8 vs 83.7 ± 17.3 sweat drops/cm 2 ). SSR amplitude at feet was significantly lower ( p p

Glatiramer acetate (GA) is an approved and well tolerated drug for the treatment of relapsing-remitting multiple sclerosis. We report a case of a 52 year-old man with psoriasis and relapsing-remitting multiple sclerosis who developed, after 21 months of GA treatment, an injection-site cutaneous necrosis that involved both subcutaneous and muscular tissue with massive edema, followed, 3 days later, by radial nerve palsy. After few days another similar lesion appeared in another injection-site. We hypothesize that cutaneous necrosis could be due to a local dis-immune reaction and, probably, psoriasis could have played an important role in its pathogenesis.