Vitamin D Receptor Gene Polymorphism Predicts the Outcome of Multidisciplinary Rehabilitation in Multiple Sclerosis Patients.

Better knowledge about the possible role of genetic factors in modulating the response to multiple sclerosis (MS) treatment, including rehabilitation, known to promote neural plasticity, could improve the standard of care for this disease. Vitamin D receptor (VDR) gene polymorphisms are associated with MS risk, probably because of the role played by vitamin D in regulating inflammatory and reparative processes. The aim of this study was to evaluate the association of the most important functional VDR SNPs (TaqI (T/C), ApaI (A/C), and FokI (C/T)) with functional outcome in MS patients undergoing multidisciplinary inpatient rehabilitation (MDR) treatment, in order to determine whether genetic profiling might be useful to identify subjects with a higher chance of recovery. To this end, 249 MS inpatients with a diagnosis of either progressive (pMS; n = 155) or relapsing remitting (RRMS; n = 94) disease who underwent MDR treatment (average duration = 5.1 weeks) were genotyped for VDR SNPs by real-time allelic discrimination. The rehabilitation outcome was assessed using the modified Barthel Index (mBI), Expanded Disability Status Scale (EDSS), and pain numerical rating scores (NRS) at the beginning and the end of MDR treatment. A positive correlation was observed in RRMS patients between the VDR TaqI major allele (TT) and mBI increase (i.e., better functional recovery), as assessed by the linear and logistic regression analysis adjusted for gender, age, disease duration, time of hospitalization, HLA-DRB1*15.01 positivity, and number of rehabilitative interventions (Beta = 6.35; p = 0.0002). The VDR-1 TaqI, ApaI, FokI: TCC haplotype was also associated with mBI increase in RRMS patients (Beta = 3.24; p = 0.007), whereas the VDR-2: CAC haplotype was correlated with a lower mBI increase (Beta = -2.18 p = 0.04) compared with the other haplotypes. VDR TaqI major allele (TT), as well as the VDR-1 TaqI, ApaI, FokI: TCC haplotype could be associated with a better rehabilitation outcome in RRMS patients.

Watch brain circulation in unexplained progressive myelopathy: a review of Cognard type V arterio-venous fistulas.

BACKGROUND: Intracranial dural arterio-venous fistulas are pathological anastomoses between arteries and veins located within dural sheets and whose clinical manifestations depend on location and hemodynamic features. They can sometimes display perimedullary venous drainage (Cognard type V fistulas-CVFs) and present as a progressive myelopathy. Our review aims at describing CVFs' variety of clinical presentation, investigating a possible association between diagnostic delay and outcome and assessing whether there is a correlation between clinical and/or radiological signs and clinical outcomes. METHODS: We conducted a systematic search on Pubmed, looking for articles describing patients with CVFs complicated with myelopathy. RESULTS: A total of 72 articles for an overall of 100 patients were selected. The mean age was 56.20 ± 14.07, 72% of patients were man, and 58% received an initial misdiagnosis. CVFs showed a progressive onset in 65% of cases, beginning with motor symptoms in 79% of cases. As for the MRI, 81% presented spinal flow voids. The median time from symptoms' onset to diagnosis was 5 months with longer delays for patients experiencing worse outcomes. Finally, 67.1% of patients showed poor outcomes while the remaining 32.9% obtained a partial-to-full recovery. CONCLUSIONS: We confirmed CVFs' broad clinical spectrum of presentation and found that the outcome is not associated with the severity of the clinical picture at onset, but it has a negative correlation with the length of diagnostic delay. We furthermore underlined the importance of cervico-dorsal perimedullary T1/T2 flow voids as a reliable MRI parameter to orient the diagnosis and distinguish CVFs from most of their mimics.

Factors Associated With Treatment-Related Changes in Voice Volume in People With Multiple Sclerosis.

BACKGROUND: Vocal disorders are frequent in people with multiple sclerosis (MS). Cognitive impairment, fatigue, depression, and other clinical characteristics can be associated with treatment effectiveness in rehabilitation. Finding baseline characteristics that identify those who are responding to treatment can help the clinical decision-making process, which can then help improve the effectiveness of voice treatment. We developed a model to identify factors associated with treatment-related improvement on voice intensity in people with MS. METHODS: Data are from a randomized controlled trial of the effects of voice therapy. Forty-four people with MS were enrolled and randomized to receive Lee Silverman Voice Treatment LOUD, specifically addressing voice intensity, or conventional speech-therapy group. Voice intensity (dB) was measured during monologue before and after treatment and was used to differentiate those who responded (posttreatment voice intensity > 60 dB) from those who did not. Possible associated factors were cognitive impairment, fatigue, depression, disability, and disease duration. Associations were assessed by univariate logistic regression and univariate and multivariate linear regressions. RESULTS: Mean ± SD monologue voice intensity is improved in the whole sample (before rehabilitation: 51.8 ± 4.2 dB; and after rehabilitation 57.0 ± 6.5 dB; P < .001), and 11 people with MS (27.5%) responded to treatment. Specificity of treatment was associated with the return to normal voice intensity (OR, 14.28; 95% CI, 12.17-309.56) and we found a linear association between voice improvement and the specificity of treatment (6.65 [SE = 1.54] dB; P < .05). Moreover, the analysis revealed a nonlinear association between improvement and fatigue, suggesting increased benefits for people with MS with moderate fatigue. Other factors were not significantly associated with treatment effectiveness. CONCLUSIONS: Moderate fatigue and the specificity of the intervention seem to be key factors associated with clinically relevant improvement in voice intensity even in people with MS with a high level of disability and long disease duration.

Brain positron emission tomography (PET) and cognitive abnormalities one year after COVID-19.

Emerging evidence indicates that the etiologic agent responsible for coronavirus disease 2019 (COVID-19), can cause neurological complications. COVID-19 may induce cognitive impairment through multiple mechanisms. The aim of the present study was to describe the possible neuropsychological and metabolic neuroimaging consequences of COVID-19 12 months after patients' hospital discharge. We retrospectively recruited 7 patients (age [mean ± SD] = 56 years ± 12.39, 4 men) who had been hospitalized for COVID-19 with persistent neuropsychological deficits 12 months after hospital discharge. All patients underwent cognitive assessment and brain (18F-FDG) PET/CT, and one also underwent 18F-amyloid PET/CT. Of the seven patients studied, four had normal glucose metabolism in the brain. Three patients showed various brain hypometabolism patterns: (1) unilateral left temporal mesial area hypometabolism; (2) pontine involvement; and (3) bilateral prefrontal area abnormalities with asymmetric parietal impairment. The patient who showed the most widespread glucose hypometabolism in the brain underwent an 18F-amyloid PET/CT to assess the presence of Aß plaques. This examination showed significant Aß deposition in the superior and middle frontal cortex, and in the posterior cingulate cortex extending mildly in the rostral and caudal anterior cingulate areas. Although some other reports have already suggested that brain hypometabolism may be associated with cognitive impairment at shorter intervals from SarsCov-2 infection, our study is the first to assess cognitive functions, brain metabolic activity and in a patient also amyloid PET one year after COVID-19, demonstrating that cerebral effects of COVID-19 can largely outlast the acute phase of the disease and even be followed by amyloid deposition.

SORL1 gene mutation and octapeptide repeat insertion in PRNP gene in a case presenting with rapidly progressive dementia and cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) has been associated with a variety of neurodegenerative disorders, included prion diseases and Alzheimer's disease; its pathophysiology is still largely unknown. We report the case of an 80-year-old man with rapidly progressive dementia and neuroimaging features consistent with CAA carrying two genetic defects in the PRNP and SORL1 genes. METHODS: Neurological examination, brain magnetic resonance imaging (MRI), electroencephalographic-electromyographic (EEG-EMG) polygraphy, and analysis of 14-3-3 and tau proteins, Aß40, and Aß42 in the cerebrospinal fluid (CSF) were performed. The patient underwent a detailed genetic study by next generation sequencing analysis. RESULTS: The patient presented with progressive cognitive dysfunction, generalized myoclonus, and ataxia. Approximately 9 months after symptom onset, he was bed-bound, almost mute, and akinetic. Brain MRI was consistent with CAA. CSF analysis showed high levels of t-tau and p-tau, decreased Aß42, decreased Aß42/Aß40 ratio, and absence of 14.3.3 protein. EEG-EMG polygraphy demonstrated diffuse slowing, frontal theta activity, and generalized spike-waves related to upper limb myoclonus induced by intermittent photic stimulation. Genetic tests revealed the presence of the E270K variant in the SORL1 gene and the presence of a single octapeptide repeat insertion in the coding region of the PRNP gene. CONCLUSIONS: The specific pathogenic contribution of the two DNA variations is difficult to determine without neuropathology; among the possible explanations, we discuss the possibility of their link with CAA. Vascular and degenerative pathways actually interact in a synergistic way, and genetic studies may lead to more insight into pathophysiological mechanisms.

One-year cognitive follow-up of COVID-19 hospitalized patients.

BACKGROUND AND PURPOSE: Cognitive dysfunction has been observed following recovery from COVID-19. To the best of our knowledge, however, no study has assessed the progression of cognitive impairment after 1 year. The aim was to assess cognitive functioning at 1 year from hospital discharge, and eventual associations with specific clinical variables. METHODS: Seventy-six patients (aged 22-74 years) who had been hospitalized for COVID-19 were recruited. Patients received neuropsychological assessments at 5 (n = 76) and 12 months (n = 53) from hospital discharge. RESULTS: Over half (63.2%) of the patients had deficits in at least one test at 5 months. Compared to the assessment at 5 months, verbal memory, attention and processing speed improved significantly after 1 year (all p < 0.05), whereas visuospatial memory did not (all p > 0.500). The most affected domains after 1 year were processing speed (28.3%) and long-term visuospatial (18.1%) and verbal (15.1%) memory. Lower PaO2 /FiO2 ratios in the acute phase were associated with worse verbal long-term memory (p = 0.029) and visuospatial learning (p = 0.041) at 5 months. Worse visuospatial long-term memory at 5 months was associated with hyposmia (p = 0.020) and dysgeusia (p = 0.037). CONCLUSION: Our study expands the results from previous studies showing that cognitive impairment can still be observed after 1 year. Patients with severe COVID-19 should receive periodic cognitive follow-up evaluations, as cognitive deficits in recovered patients could have social and occupational implications.

Identification of modified dynamic gait index cutoff scores for assessing fall risk in people with Parkinson disease, stroke and multiple sclerosis.

BACKGROUND: Balance and gait impairments increase fall rate and injury in people with neurological disorders(PwND). The modified Dynamic Gait Index(mDGI) is a scale assessing dynamic balance during walking, however its ability in identifying Fallers and Recurrent Fallers has not been studied. RESEARCH QUESTION: To evaluate mDGI's ability in identifying retrospective Fallers and Recurrent Fallers establishing cut-off scores for its use in clinical practice. METHOD: In this cross-sectional study, the number of retrospective falls and mDGI scores were collected. PwND were categorised as Non-Fallers or Fallers (falls≥1) and as Recurrent Fallers(falls≥2) or Non-Recurrent/Non-Fallers(falls<2) according to their number of retrospective falls over two months. Two generalised linear logistic models were developed using a machine learning method to detect Fallers (Model 1) and Recurrent Fallers (Model 2) based on mDGI scores. ROC curves were used to identify mDGI cut-off scores to distinguish between different fall categories. RESULTS: 58 PwND (mean ± standard deviation age: 63.4 ± 12 years) including 28 people with Multiple Sclerosis, 15 people with Parkinson's disease and 15 people with Stroke were analysed. The mDGI score(median (IQR)) for Non-Fallers, Fallers, Recurrent Fallers and Non-Recurrent/Non-Fallers was respectively 50(22), 37(22), 26.5(20.25) and 46.5(20.5)points. The cut-off to identify Fallers from Non-Fallers was 49 points(sensitivity:100 %, specificity:50 %, post-test probability with mDGI ≤ cut-off: 53.2 %, post-test probability with mDGI > cut-off: 0%, AUC:0.68), while 29 points(sensitivity:60 %, specificity:79 %, post-test probability with mDGI ≤ cut-off:52.1 %, post-test probability with mDGI > cut-off:16.1 %, AUC:0.70) was the best cut-off to identify Recurrent Fallers. SIGNIFICANCE: People with mDGI score>49 points have low or minimal fall risk, while people with mDGI score≤49 points should be further investigated with other scales before starting a balance-focused rehabilitation intervention. People scoring ≤29 points on the mDGI scale may need a fall prevention intervention, regardless of the results of other balance clinical measures.

Effects of Intensive Voice Treatment (The Lee Silverman Voice Treatment [LSVT LOUD]) in Subjects With Multiple Sclerosis: A Pilot Study.

AIM: The rehabilitation of voice disorders is an unmet need in multiple sclerosis (MS). The Lee Silverman Voice Treatment (LSVT LOUD) is a well-documented and effective speech treatment, developed to treat voice disorders in Parkinson Disease. The purpose of the present study was to examine the viability of applying the LSVT LOUD to individuals with MS and verify short- and long-term improvements in acoustic and perceptual voice parameters. METHODS: A single subject design was performed in a consecutive sample of 8 subjects with MS. The subjects' voice was recorded with PRAAT software for 5 days at baseline during the 16  treatment sessions, and at follow-up (FU) 6/12 months later. PRAAT provided data on sustained /a/ (SPL/a/) voice intensity and maximum phonation time (MPT/a/) of sustained /a/, and on functional sentences voice intensity. In addition, self-assessment questionnaire Voice Handicap Index, the perceptual GIRBAS scale and intensity of monologue were collected at first day of baseline, post-treatment and at FU. In the treatment phase each subject received treatment according to LSVT LOUD protocol. Visual analysis calculated for daily acoustic variables was used to determine baseline stability and analyse changes following treatment. The Wilcoxon test was used to assess statistically significant differences between baseline and post treatment. RESULTS: All participants completed the LSVT LOUD programme; one participant dropped out at FU. Improvements in acoustic analysis were found: SPL/a/ improved on average (± standard deviation) 11.64 ± 4.19 dB with 7 subjects showing statistically significant improvement (P < 0.05); MPT/a/ improved on average 1.2 ± 1.53seconds, while intensity of functional sentences improved on average 8.11 ± 3.46  dB with 4 and 5 subjects showed statistically significant improvement, respectively. Intensity of monologue improved 14.90 ± 3.33 dB. Acoustic values are maintained or increased at FU respect to baseline. All subjects improved perceptual ratings at Voice Handicap Index and results were maintained at FU. These changes were associated with improvements on five parameters on the GIRBAS scale at post-treatment, however no further improvement were observed at FU. CONCLUSION: Intensive LSVT LOUD treatment is a viable approach to treat hypophonia in MS. LSVT LOUD improved both quantitative-instrumental and perceptive-subjective assessments. Randomised controlled trials are needed to provide a firm support on the effectiveness of LSVT LOUD in MS.

Prevalence and patterns of subclinical motor and cognitive impairments in non-disabled individuals with early multiple sclerosis: A multicenter cross-sectional study.

BACKGROUND: Motor and cognitive disorders appear early in the course of multiple sclerosis (MS) and develop gradually over time. OBJECTIVE: To study the frequency and pattern of subtle functional disorders in people with MS (PwMS) with no overt signs of disability in an early phase of the disease and their association with walking impairments in daily activities. METHODS: In this cross-sectional study, we recruited PwMS with an Expanded Disability Status Scale (EDSS) score≤2.5 and disease duration≤5years. Participants were assessed with functional scales rating walking endurance (6-Min Walk Test), perceived walking ability (Twelve-item Multiple Sclerosis Walking Scale), balance (Fullerton Advanced Balance scale_short), manual dexterity (Nine Hole Peg Test), fatigue (Fatigue Severity Scale), and cognitive impairments (Brief International Cognitive Assessment). RESULTS: About 90% of the 82 PwMS (mean [SD] EDSS score 1.5 [0.7] and disease duration 2.2 [1.7] years) showed endurance values below the expected score; almost 30% showed impairment, and for 57%, perceived walking ability score was abnormal. Balance was impaired in 48% of participants, as was manual dexterity (29%) and fatigue (24%), but only a few showed cognitive impairments. Only 11% of PwMS had no abnormal score on the scales used in the assessment. As compared with EDSS score 0 to 1.5, with EDSS score 2 to 2.5, performance was worse for endurance (difference±61.0m, P=0.016), perceived walking ability (-11 points, P=0.002), balance (+1.9 points, P=0.005), manual dexterity (-2.8 s, P=0.004), and fatigue (-1.3 points, P=0.013). Factors that predicted perceived walking ability were balance (B=-1.37, P<0.001) and fatigue (B=5.11, P<0.001) rather than endurance (B=-0.01, P=048). CONCLUSION: Even PwMS with no clinical disability and classified as having "no problem walking" present walking and other functional deficits when assessed with specific functional tests. The addition of specific tools could better identify subtle motor and cognitive deficits. Finally, the assessment of balance disorders and fatigue is important to understand individuals' perceived walking impairments in daily activities.

Effects of voice rehabilitation in people with MS: A double-blinded long-term randomized controlled trial.

BACKGROUND: Hypophonia is a prevailing problem in people with multiple sclerosis (PwMS). However, evidence supporting the effectiveness of voice rehabilitation is lacking. OBJECTIVE: The aim of this study was to identify the most effective method to reduce hypophonia. METHODS: In this randomized controlled trial, 44 PwMS were randomized to intensive and high-effort voice treatment groups, the LSVT-LOUD®, and conventional treatment group. Subjects received 16 treatments (4 sessions/week) lasting 45 minutes. The primary outcome was voice intensity (dB) in monologue, vocalization, and sentences while voice handicap index (VHI) measured voice self-perception. Outcomes were assessed by a blinded observer at baseline, post-treatment, and 15-month follow-up (FU). RESULTS: Linear models revealed a significant post-intervention between-group mean difference in favor of LSVT-LOUD for monologue: +6.3 dB (95% CI: 2.5 to 10.1); vocalization: +7.4 dB (95% CI: 2.3 to 12.5); and sentences: +9.5 dB (95% CI: 4.7 to 14.3). However, 43.7% PwMS in the LSVT-LOUD and 10% in the conventional treatment group obtained a full recovery of voice intensity (>60 dB) post-treatment, Fisher's test = 13.3, p < 0.01. However, these improvements were not maintained at FU. Between-group differences at VHI were -10.8 (95% CI: -21.2 to -0.4) and -11.3 (95% CI: -24.3 to -1.7) in favor of LSVT-LOUD at post and FU. CONCLUSION: LSVT-LOUD can be a valid treatment to increase voice intensity in PwMS. However, results suggest the need for FU interventions targeting maintenance.

Critical illness neuropathy in severe COVID-19: a case series.

INTRODUCTION: Neurological complications of SARS-CoV-2 disease have received growing attention, but only few studies have described to date clinical and neurophysiological findings in COVID patients during their stay in intensive care units (ICUs). Here, we neurophysiologically assessed the presence of either critical illness neuropathy (CIP) or myopathy (CIM) in ICU patients. MATERIALS AND METHODS: Patients underwent a neurophysiological assessment, including bilateral examination of the median, ulnar, deep peroneal and tibial motor nerves and of the median, ulnar, radial and sural sensory nerves. Needle electromyography (EMG) was performed for both distal and proximal muscles of the lower and upper limbs. In order to differentiate CIP from CIM, Direct Muscle Stimulation (DMS) was applied either to the deltoid or tibialis anterior muscles. Peak to peak amplitudes and onset latencies of the responses evoked by DMS (DMSamp, DMSlat) or by motor nerve stimulation (MNSamp, MNSlat) were compared. The ratio MNSamp to DMSamp (NMR) and the MNSlat to DMSlat difference (NMD: MNSlat - DMSlat) were also evaluated. RESULTS: Nerve conduction studies showed a sensory-motor polyneuropathy with axonal neurogenic pattern, as confirmed by needle EMG. Both MNSamp and NMR were significantly reduced when compared to controls (p < 0.0001), whereas MNSlat and NMD were markedly increased (p = 0.0049). CONCLUSIONS: We have described COVID patients in the ICU with critical illness neuropathy (CIP). COVID-related CIP could have implications for the functional recovery and rehabilitation strategies.

Minimal clinically important difference of modified dynamic gait index in people with neurological disorders.

BACKGROUND: The minimal clinically important difference (MCID) of modified Dynamic Gait Index (mDGI) has not yet been determined for People with Neurological Disorders (PwND). RESEARCH QUESTION: To establish the MCID of the mDGI to determine clinically meaningful improvement in balance and gait in PwND. METHODS: In this longitudinal study from a randomised clinical trial, 55 participants both in and outpatients with neurological disorders, received fifteen 40-minute rehabilitation sessions. Inpatients received daily treatments over a period of three weeks while outpatients received three treatments/week over a period of five weeks. An anchor-based method using percentage rating of improvement in balance (Activities Balance Confidence scale, ABC) was used to determine the MCID of mDGI. The MCID was defined as the minimum change in mDGI total score (post - pre intervention) that was needed to perceive at least a 10 % improvement on the ABC scale. A Receiver Operating Characteristic curve was used to define the cut-off for the optimal MCID of the mDGI discriminating between improved and not improved participants. RESULTS: The MCID of the mDGI total score was 6 points and Area under the Curve was 0.64. For the mDGI time sub-scores the MCID was 2 points and Area under the Curve was 0.6. SIGNIFICANCE: The MCID of balance and gait improvement measured by mDGI was prudently establish at ≥7 points, meaning that this is the minimum improvement score PwND need to get to perceive a clinically relevant change in their balance and gait confidence. These reference values can be a tool incorporated into clinicians daily practice to interpret mDGI change scores helping to determine whether the intervention is effective; to develop clinical tailored intervention goals and to establish meaningful perceived change in PwND.

Long-Lasting Cognitive Abnormalities after COVID-19.

Considering the mechanisms capable of causing brain alterations in COVID-19, we aimed to study the occurrence of cognitive abnormalities in the months following hospital discharge. We recruited 38 (aged 22-74 years; 27 males) patients hospitalized for complications of SARS-CoV-2 infection in nonintensive COVID units. Participants underwent neuropsychological testing about 5 months after hospital discharge. Of all patients, 42.1% had processing speed deficits, while 26.3% showed delayed verbal recall deficits. Twenty-one percent presented with deficits in both processing speed and verbal memory. Bivariate analysis revealed a positive correlation between the lowest arterial oxygen partial pressure (PaO2) to fractional inspired oxygen (FiO2) (P/F) ratio during hospitalization and verbal memory consolidation performance (SRT-LTS score, r = 0.404, p = 0.027), as well as a positive correlation between SpO2 levels upon hospital arrival and delayed verbal recall performance (SRT-D score, rs = 0.373, p = 0.042). Acute respiratory distress syndrome (ARDS) during hospitalization was associated with worse verbal memory performance (ARDS vs. no ARDS: SRT-LTS mean score = 30.63 ± 13.33 vs. 44.50 ± 13.16, p = 0.007; SRT-D mean score = 5.95 ± 2.56 vs. 8.10 ± 2.62, p = 0.029). Cognitive abnormalities can frequently be found in COVID-19 patients 5 months after hospital discharge. Increased fatigability, deficits of concentration and memory, and overall decreased cognitive speed months after hospital discharge can interfere with work and daily activities.

Longitudinal changes in cerebral white matter microstructure in newly diagnosed systemic lupus erythematosus patients.

OBJECTIVES: To evaluate longitudinal variations in diffusion tensor imaging (DTI) metrics of different white matter (WM) tracts of newly diagnosed SLE patients, and to assess whether DTI changes relate to changes in clinical characteristics over time. METHODS: A total of 17 newly diagnosed SLE patients (19-55 years) were assessed within 24 months from diagnosis with brain MRI (1.5 T Philips Achieva) at baseline, and after at least 12 months. Fractional anisotropy, mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity values were calculated in several normal-appearing WM tracts. Longitudinal variations in DTI metrics were analysed by repeated measures analysis of variance. DTI changes were separately assessed for 21 WM tracts. Associations between longitudinal alterations of DTI metrics and clinical variables (SLEDAI-2K, complement levels, glucocorticoid dosage) were evaluated using adjusted Spearman correlation analysis. RESULTS: Mean MD and RD values from the normal-appearing WM significantly increased over time (P = 0.019 and P = 0.021, respectively). A significant increase in RD (P = 0.005) and MD (P = 0.012) was found in the left posterior limb of the internal capsule; RD significantly increased in the left retro-lenticular part of the internal capsule (P = 0.013), and fractional anisotropy significantly decreased in the left corticospinal tract (P = 0.029). No significant correlation was found between the longitudinal change in DTI metrics and the change in clinical measures. CONCLUSION: Increase in diffusivity, reflecting a compromised WM tissue microstructure, starts in initial phases of the SLE disease course, even in the absence of overt neuropsychiatric (NP) symptoms. These results indicate the importance of monitoring NP involvement in SLE, even shortly after diagnosis.

Botulinum toxin for the management of spasticity in multiple sclerosis: the Italian botulinum toxin network study.

BACKGROUND: Botulinum toxin (BT) is an effective and safe treatment for spasticity, with limited evidence in multiple sclerosis (MS). We aim to describe the use of BT for the management of MS spasticity in the clinical practice, its combination with other anti-spastic treatments in MS and possible MS clinical correlates. METHODS: This is a multicentre cross-sectional observational study including 386 MS patients, receiving BT for spasticity in 19 Italian centres (age 53.6 ± 10.9 years; female 228 (59.1%); disease duration 18.7 ± 9.2 years; baseline Expanded Disability Status Scale (EDSS) 6.5 (2.0-9.0)). RESULTS: BT was used for improving mobility (n = 170), functioning in activities of daily living (n = 56), pain (n = 56), posturing-hygiene (n = 63) and daily assistance (n = 41). BT formulations were AbobotulinumtoxinA (n = 138), OnabotulinumtoxinA (n = 133) and IncobotulinumtoxinA (n = 115). After conversion to unified dose units, higher BT dose was associated with higher EDSS (Coeff = 0.591; p < 0.001), higher modified Ashworth scale (Coeff = 0.796; p < 0.001) and non-ambulatory patients (Coeff = 209.382; p = 0.006). Lower BT dose was used in younger patients (Coeff = - 1.746; p = 0.009), with relapsing-remitting MS (Coeff = - 60.371; p = 0.012). BT dose was higher in patients with previous BT injections (Coeff = 5.167; p = 0.001), and with concomitant treatments (Coeff = 43.576; p = 0.022). Three patients (0.7%) reported on post-injection temporary asthenia/weakness (n = 2) and hypophonia (n = 1). CONCLUSION: BT was used for spasticity and its consequences from the early stages of MS, without significant adverse effects. MS-specific goals and injection characteristics can be used to refer MS patients to BT treatment, to decide for the strategy of BT injections and to guide the design of future clinical trials and observational studies.

Factors influencing balance improvement in multiple sclerosis rehabilitation: A pragmatic multicentric trial.

OBJECTIVES: Treatment for progressive multiple sclerosis (pMS) is a key area of research. To date, whether MS type and the rehabilitation setting are associated with worse or better response to rehabilitation is unclear. We aimed to understand the association between balance and MS type, in/outpatient treatment and specificity of the intervention. METHODS: We assessed 150 people with MS before and after in/outpatient rehabilitation. The Berg Balance Scale (BBS) was used to discriminate between responders (≥+3-point improvement in BBS score; a clinically meaningful improvement) and non-responders to specific or non-specific balance rehabilitation. Factors associated with balance were analyzed by univariate and multivariable logistic regression analyses, estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Balance improved after rehabilitation: median (quartile 1 [Q1]-Q3) BBS score pre- and post-rehabilitation of 49 (45-53) and 52 (47-55) (P<0.001). Univariate logistic analysis revealed a clinically meaningful improvement in balance associated with pMS (OR 2.21 [95% CI 1.09-4.05]), inpatient therapy (0.41 [0.19-0.84]), using a walking aid (1.68 [1.06-2.69]), and low baseline BBS score (0.86 [0.81-0.92]). On multivariable analysis, probability of improvement was similar for participants with pMS and the relapsing-remitting form but was associated with low baseline BBS score and specific treatment (OR 0.81 [95% CI 0.74-0.89] and 5.66 [1.79-21.5]). CONCLUSION: A clinically meaningful improvement in balance was more likely when MS individuals with moderate to high disability had specific exercises targeting balance, but MS type did not influence the outcome.

Predictors of hospital-based multidisciplinary rehabilitation effects in persons with multiple sclerosis: a large-scale, single-centre study.

BACKGROUND: Persons with multiple sclerosis may benefit from hospital-based multidisciplinary rehabilitation. OBJECTIVES: To investigate the effects of hospital-based multidisciplinary rehabilitation and to identify their potential predictors in a large sample of persons with multiple sclerosis. METHODS: From the charts of 655 persons with multiple sclerosis consecutively admitted to our unit, disease profiles, modified Barthel index, Expanded Disability Status Scale (EDSS), pain numerical rating score and type of interventions were retrospectively collected. We defined an improvement at discharge as follows: modified Barthel index increase of at least 5 points, EDSS decrease of 1.0 if baseline score was 5.5 or less and of 0.5 if baseline score was greater than 5.5; any numerical rating score decrease. RESULTS: After a median admission period of 36 days, at discharge 65%, 22% and 89% of persons with multiple sclerosis improved for modified Barthel index, EDSS and numerical rating score, respectively. The modified Barthel index improvement was associated with shorter disease duration, lower EDSS at baseline and with access to psychological counselling. EDSS improvement was associated with shorter disease duration, relapsing-remitting course, female gender and longer duration of the admission period. CONCLUSIONS: Inpatient multidisciplinary rehabilitation was associated with improved autonomy in activities of daily living in a relevant proportion of persons with multiple sclerosis. The effect seems to be more evident in individuals with shorter multiple sclerosis duration and relapsing-remitting disease course.

Social Mind and Long-Lasting Disease: Focus on Affective and Cognitive Theory of Mind in Multiple Sclerosis.

The role of social cognition, including theory of mind (ToM), in affecting quality of life (QoL) along the course of diseases has been reported. This is a considerable aspect in chronic pathologies, such as multiple sclerosis (MS), in which supporting and maintaining QoL is of crucial importance. We aimed to investigate the relation between ToM, clinical variables and neuropsychological profile in a cohort of adults with long lasting disease, such as different clinical MS phenotypes (Relapsing Remitting -RR- versus Progressive -Pr). In particular, our study focuses on (1) how (affective and cognitive) ToM impairment occurs in different phenotypes, (2) whether MS ToM impairment is secondary to or independent from cognitive deficit and (3) whether ToM deficit impacts QoL. 42 adults with MS (18 M: 24 F, 52.38 ± 10.31 mean age, 21.24 ± 10.94 mean disease duration, 26 RR and 16 Pr) and 26 matched healthy controls (HC) (7 M: 19 F, 51.35 ± 12.42 mean age) were screened with a neuropsychological and ToM battery, assessing both affective and cognitive components. We found statistically significant groups differences in cognitive but not affective ToM, with a lower performance in PrMS than those with a RRMS disease course. Also, significant predictive effects of neuropsychological tests on ToM were identified in MS group. Finally, MS people with different level of affective ToM differed significantly in QoL. ToM deficit in moderately disabled people with MS involves cognitive but not affective ToM components with implications on QoL. It also appears to be related to cognitive performance. As neurological and neurocognitive profiles influence mentalizing in MS, ToM evaluation should be considered for inclusion in clinical screening.

Is Peripheral Oxygen Saturation a Reliable Predictor of Upper Airways Air-Flow Limitation?

BACKGROUND: Dyspnea secondary to acute upper airways airflow limitation (UAAFL) represents a clinical emergency that can be difficult to recognize without a suitable history; even when etiology is known, parameters to assess the severity are unclear and often improperly used. OBJECTIVES: The aim of this study was to assess the role of peripheral oxygen saturation (SpO2) as a predictor of severity of upper airway obstruction. METHODS: The authors propose an experimental model of upper airway obstruction by a progressive increase of UAAFL. Ten healthy volunteers randomly underwent ventilation for 6 min with different degrees of UAAFL. SpO2, heart rate, respiratory rate (RR), tidal volume, accessory respiratory muscle activation, and subjective dyspnea indexes were measured. RESULTS: In this model, SpO2 was not reliable as the untimely gravity index of UAAFL. Respiratory rate, visual analogue scale (VAS), and Borg dyspnea scale were statistically correlated with UAAFL (p < 0.0001 for RR and p < 0.05 for VAS and Borg scale). No significant changes were observed on heart rate (p > 0.05) and tidal volume (p > 0.05); a RR ≤ 7 breaths/min; VAS and Borg scale showed statistically significant parameters changes (p < 0.05). CONCLUSIONS: RR, VAS, and Borg dyspnea scales are sensitive parameters to detect and stage, easily and quickly, the gravity of an upper airways impairment, and should be used in emergency settings for an early diagnosis of a UAAFL. SpO2 is a poorer predictor of the degree of upper airways flow limitation.

Multiple Sclerosis in Italy: A 40-Year Follow-Up of the Prevalence in Ferrara.

BACKGROUND: To assess a longitudinal follow-up of the prevalence of multiple sclerosis (MS) through 4 decades in the province of Ferrara, northern Italy, and reappraise the current rates on December 31, 2016. METHODS: We conducted a community-based intensive prevalence study, by adopting a complete enumeration approach. MS cases were identified from administrative health data and medical records from the Units of Neurology and Motor Rehabilitation, Ferrara University Hospital, from other provincial neurological structures and from archives of the National Pension Institute and National Health Insurance scheme of the study area. Case ascertainment method and case definition are analogous to those adopted in previous surveys in the same area of study. RESULTS: On December 31, 2016, 685 patients (478 women and 207 men) affected by definite or probable MS (Poser's criteria) were living in the province of Ferrara (population 386,896), yielding a crude prevalence ratio of 194.91 (95% CI 180.4-209.6) per 100,000, 260.8 (95% CI 238.10-285.82) for women and 123.1 (95% CI 106.98-141.21) for men The prevalence ratio was 26.9 per 100,000 in 1978, increased to a value of 46.1 per 100,000 in 1981, 69.4 per 100,000 in 1993, 120.9 per 100,000 in 2004. Female to male ratio was 2.31 (1.2 on December 31, 1978). The mean duration of the disease at prevalence day was 17.5 ± 11.9 years (13.9 ± 10.8 years in 1978). The mean age at prevalence day was 52.04 ± 10.8 years (13.8 ± 10.8 years in 1978). CONCLUSION: Our study has confirmed the province of Ferrara is an area at high risk for MS, in line with epidemiological data from the regions of continental and insular Italy. The sharp increase in MS prevalence over time in this population can be imputed in part to a greater exposition to risk factors in genetically susceptible subjects but also to an increased survival and improved ascertainment. So, the results suggest that both methodologic and environmental factors are essential in determining the real distribution of MS. The need to get reliable estimates of MS prevalence must be highlighted as a public health and research priority, essential to support planning and prioritization of care services and to reduce the overall burden of chronic disease.