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Posterior cortical atrophy (PCA) is a neurodegenerative disorder characterized by an early prominent deficit of visual functions associated with signs and symptoms that are the expression of dysfunction of posterior brain regions. Although PCA is commonly associated with Alzheimer’s disease (AD), in recent years new pathological substrates have emerged. Among them, frontotemporal lobar degeneration (FTLD) is the most commonly reported but, to date, little is known about the clinical features of PCA due to FTLD. We conducted a systematic search in the main biomedical database MEDLINE. We searched for all clinical PCA reports that assessed the pathological basis of such syndrome with at least one of the following: (1) neuropathological examination, (2) cerebrospinal fluid biomarkers, (3) amyloid-PET imaging and (4) genetic testing. Of 369 potentially eligible studies, 40 fulfilled the inclusion criteria with an overall number of 144 patients (127 PCA-AD vs. 17 PCA-FTD/non-AD). We found that hallucinations/illusions were present in none of the probable PCA-FTD/non-AD subjects while were reported in 15 out of 97 PCA-AD individuals. Optic ataxia and Parkinsonism showed a significantly greater prevalence in probable PCA FTD/non-AD than in PCA-AD whereas myoclonus and disorientation in time and space were significantly more frequent in PCA-AD than in probable PCA FTD/non-AD. We also found a predominance of a left-side pattern of atrophy/hypometabolism in the probable PCA FTD/non-AD. Clinical features such as optic ataxia, Parkinsonism, myoclonus, hallucinations and disorientation in time and space suggest the underlying pathological basis of PCA and help in leading the diagnostic protocol consequently.

Few studies evaluated coping strategies in people with multiple sclerosis (pwMS) in relation to annualized relapse rate (ARR) and lesion load (LL). Overall, results might have been influenced by the inclusion of depressed patients. To investigate the coping strategies and their association to disease activity, we studied relapsing–remitting pwMS accurately selected to avoid the confounding effect of depression. Sixty-seven relapsing–remitting pwMS and 67 healthy subjects (HS) underwent to Coping Orientation to Problems Experienced (I-COPE) and Coping Inventory for Stressful Situation (CISS) and Beck Depression Inventory-II. Cognitive performances, ARR, physical disability and magnetic resonance imaging T2-LL were assessed for correlation with coping and depression scores. pwMS showed lower scores than HSs on social support and turning to religion subscales of I-COPE and on emotion dimension of CISS. In pwMS, higher ARR was related to higher positive attitude and lower score on the turning to religion subscale of I-COPE. The present study revealed a less employment of emotion-based coping strategies in pwMS. A scarce use of faith for support and a frequent adoption of a positive attitude were associated with an increase of MS activity in terms of ARR.

•SDQ assesses the frequency of dysphagic symptoms.•SDQ also evaluates dysphagia for saliva and different food textures.•SDQ may be used to investigate dysphagia in multiple sclerosis.

Introduction: Migraine shows a significantly higher prevalence in women, especially during reproductive age when menstrual-related hormonal fluctuations represent the most common migraine trigger. Indeed, over 50% of patients report a higher occurrence of migraine attacks during the perimenstrual window. Menstrual migraine attacks are consistently referred to as more disabling, less responsive to symptomatic treatments, longer in duration, and more prone to relapse than non-menstrual migraine attacks. Evidence strongly suggests that estrogen fluctuations are involved in migraine attacks worsening during the perimenstrual window through several mechanisms directly or indirectly involving the CGRP pathway. We aimed to evaluate whether mAbs blocking CGRP-ligand or receptor (CGRP-mAbs) could represent an effective and safe preventive treatment for menstrual migraine attacks in patients with menstrual-related migraine (MRM) with previous treatment failures. Methods: Forty patients with MRM with at least three previous treatment failures received monthly CGRP-mAbs. At the baseline and after six CGRP-mAbs administrations, patients underwent to extensive interviews to assess frequency, duration, intensity, and responsiveness to painkiller intake of migraine attacks occurring during the perimenstrual window. Results: After six administrations of CGRP-mAbs we observed a reduction of median menstrual migraine frequency (from 5 to 2 days per month), pain intensity (from 8/10 to 6/10), and attacks duration (from 24 to 8 h) (p< 0.001). Nevertheless, a significant increase in the percentage of responding to migraine painkillers was observed from 42.5% at baseline to 95% at T1 (p< 0.001). Conclusions: CGRP-mAbs could represent a safe and effective preventive therapeutic strategy able to reduce the disabling burden of menstrual migraine attack frequency, duration, intensity, and significantly improve the response to painkillers. These findings could be related to and further indirectly prove the greater influence of CGRP-mediated mechanisms in the pathophysiology of menstrual migraine attacks.

Aim:The present study aims at investigating the possible correlation between peripheral markers of inflammation and brain networks.Introduction:Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease dominated by progressive motor impairment. Among the complex mechanisms contributing to the pathogenesis of the disease, neuroinflammation, which is associated with altered circulating cytokine levels, is suggested to play a prominent role.Methods:Based on magnetoencephalography data, we estimated topological properties of the brain networks in ALS patients and healthy controls. Subsequently, the blood levels of a subset of cytokines were assayed. Finally, we modeled the brain topological features in the function of the cytokine levels.Results:Significant differences were found in the levels of the cytokines interleukin (IL)-4, IL-1β, and interferon-gamma (IFN-γ) between patients and controls. In particular, IL-4 and IL-1β levels increased in ALS patients, while the IFN-γ level was higher in healthy controls. We also detected modifications in brain global topological parameters in terms of hyperconnectedness. Despite both blood cytokines and brain topology being altered in ALS patients, such changes do not appear to be in a direct relationship.Conclusion:Our results would be in line with the idea that topological changes relate to neurodegenerative processes. However, the absence of correlation between blood cytokines and topological parameters of brain networks does not preclude that inflammatory processes contribute to the alterations of the brain networks.Impact statementThe progression of amyotrophic lateral sclerosis entails both neurodegenerative and inflammatory processes. Furthermore, disease progression induces global modifications of the brain networks, with advanced stages showing a more compact, hyperconnected network topology. The pathophysiological processes underlying topological changes are unknown. In this article, we hypothesized that the global inflammatory profile would relate to the topological alterations. Our results showed that this is not the case, as modeling the topological properties as a function of the inflammatory state did not yield good predictions. Hence, our results suggest that topological changes might directly relate to neurodegenerative processes instead.

IntroductionNatalizumab (NTZ) is one of the most effective treatment options for multiple sclerosis (MS) treatment. Our study aimed to evaluate the effectiveness of NTZ when administered according to the extended dosing strategy compared with standard 4-weekly administration in a large Italian MS population.Materials and methodsThis retrospective multicentre study included patients with relapsing-remitting MS (RR-MS) who received NTZ administrations between the 1 June 2012 and the 15 May 2018 and were followed by the ‘Italian MS Register’. All patients with MS were stratified into two groups based on NTZ administration schedule: standard interval dosing (SID) patients who received infusions on average from 28 to 32 days (median 30) and extended interval dosing (EID) including patients who have been infused with interval between 33 and 49 days (median 43). Clinical data were assessed at baseline (before starting NTZ), after 12 (T1) and 24 months (T2) of treatment.ResultsOut of 5231 patients with RR-MS screened, 2092 (mean age 43.2±12.0, 60.6% women) were enrolled. A total of 1254 (59.9%) received NTZ according to SID, and 838 (40.1%) according to EID. At 12 and 24 months, no differences in terms of annualised relapse rate and disability status were found between the two groups. Progression index and confirmed disability worsening were similar between the two groups.DiscussionThe use of NTZ with an extended interval schedule showed similar effectiveness compared with SID. Unchanged clinical efficacy of EID schedule may raise the question of a possible advantage in terms of tolerability and safety.

Phrenic nerve palsy (PNP) is a well-known complication of cardiac surgery or jugular/subclavian vein catheterization, presenting with cough, hiccups, dyspnoea/shortness of breath and, in some cases, ventilatory failure. Rarely, PNP is a complication of transcatheter radiofrequency ablation for atrial fibrillation. This report describes the case of a 72-year-old woman with a 2-year history of recurrent paroxysmal atrial fibrillation associated with occasional palpitations and shortness of breath who underwent routine transcatheter radiofrequency ablation. Three days after the procedure, the patient developed shortness of breath and progressive dyspnoea. Motor nerve conduction showed the absence of the right phrenic nerve compound motor action potential compared with the normal left side confirming the diagnosis of a right phrenic nerve palsy. This current case demonstrated the importance of undertaking an electrophysiological evaluation of phrenic nerve conduction after transcatheter radiofrequency ablation in patients presenting with palpitations and shortness of breath even if present a few days after the procedure.

•Gait analysis is able to detect preclinical motion impairment in MS.•The cognitive dual task condition worsened the gait parameters.•No significant correlation was found between gait abnormalities and cognitive status.•MRI measurements did not correlated with altered gait parameters.

•The improvement of the diagnostic process allowed the anticipation of MS diagnosis.•Earlier diagnoses of MS have really impacted on therapeutic management of the disease.•Web services may keep several aspects of patients’ clinical history in an easy-to-use and easily connectable approach.

•The BICAMS is the most widely used screening tool for cognitive impairment in MS•We developed a tablet version of the BICAMS (iBICAMS)•The iBICAMS showed a high reliability over the paper version•iBICAMS could become a standard in clinical practice for cognitive assessment of MS

Multiple sclerosis (MS) is a multifactorial, inflammatory, and neurodegenerative disease of the central nervous system, where environmental factors interact with genetic susceptibility. The role of diet on MS has not been comprehensively elucidated; therefore, through an extensive search of relevant literature, this review reports the most significant evidence regarding nutrition as a possible co-factor influencing the inflammatory cascade by acting on both its molecular pathways and gut microbiota. Since nutritional status and dietary habits in MS patients have not been extensively reported, the lack of a scientific-based consensus on dietary recommendation in MS could encourage many patients to experiment alternative dietetic regimens, increasing the risk of malnutrition. This work investigates the health implications of an unbalanced diet in MS, and collects recent findings on nutrients of great interest among MS patients and physicians. The aim of this review is to elucidate the role of an accurate nutritional counseling in MS to move toward a multidisciplinary management of the disease and to encourage future studies demonstrating the role of a healthy diet on the onset and course of MS.

•PDDS is a useful self-administered scale to quickly assess disability in MS.•PDDS is validated in English language.•PDDS/IT is a valid and reproducible disability scale in italian people with MS.

Lesbian, gay, bisexual and transgender (LGBT) patients might experience unique difficulties and barriers to treatment of chronic diseases related to their sexual orientation. Thus, we investigated concerns experienced by LGBT patients with multiple sclerosis (MS). We conducted a web-based survey using a multi-choice questionnaire published in an Italian social-network (www.smsocialnetwork.com) for MS patients. The survey investigated: socio-demographic factors, lifestyle habits, MS-related health status and LGBT specific issues (e.g. friendliness to their sexual orientation and eventual homophobic behaviors in the MS Center). Among MS patients willing to use psychological services, LGBT patients were associated with a smaller number of psychological consultations, compared to heterosexuals (Coeff.=−0.449; p<0.001; 95%CI=−0.682 to −0.217). LGBT patients were more likely to change MS Center, compared to heterosexuals (OR=2.064; p=0.046; 95%CI=1.011–4.212). The number of MS Center changes was associated with MS Center friendliness (p=0.037; rho=−0.229) and with the occurrence of homophobic behaviors (p=0.036; rho=0.234). LGBT MS patients more frequently changed MS Center and had a reduced use of psychological services, compared to heterosexuals. The attitude towards LGBT MS patients might affect resource utilizations and LGBTs health status.

•The diagnosis of the progression phase of Multiple Sclerosis is still retrospective.•Identifying the progression as early as possible is crucial to maximize novel drug efficacy.•PROM scores could be useful for catching progressive disease onset early.•SF36 Physical Functioning was revealed to be an independent predictor of disease progression.

•Vitamin D has immunomodulatory effects.•Vitamin D deficiency is associated with a higher likelihood of disease activity in MS.•Low vitamin D serum levels might be associated to early B cell repopulation.

The Dress picture recently has become a hot topic on the Internet, prompting a debate whether it was black and blue, or white and gold.

•The pandemic's negative aspects were associated with worse disability.•Greater endorsed post-traumatic growth was associated with lesser disability.•Greater self-protection against COVID-19 was associated more disability in the US.

•Lymphopenia is reported in 20.7% of RRMS patients taking Ocrelizumab.•Among T cells, the treatment predominantly impacts CD8 cells.•CD8 T cell decrease is more pronounced in patients with lymphopenia.

•Chronic immunosuppression is crucial in preventing NMSOD relapses.•CD27+ B cells might be a useful biomarker to guide RTX retreatment in AQP4-IgG positive patients.•Relapses in anti-MOG NMSOD occurred regardless of B cell depletion.

To investigate functional connectivity of the visual resting-state network (V-RSN) in normal-sighted relapsing-remitting multiple sclerosis (RRMS) patients with and without previous optic neuritis (ON).

Two brothers with a leukodystrophy, progressive spastic diplegia, and peripheral neuropathy were found to have proteinaceous aggregates in the peripheral nerve myelin sheath. The patients' mother had only subclinical peripheral neuropathy, but the maternal grandmother had adult‐onset leukodystrophy. Sequencing of the proteolipid protein (PLP) gene showed a point mutation IVS4 + 1 G→A within the donor splice site of intron 4. We identified one transcript with a deletion of exon 4 (Δex4, 169bp) encoding for PLP and DM20 proteins and lacking two transmembrane domains, and a second transcript with exon 4 + 10bp encoding three transmembrane domains. Immunohistochemistry showed abnormal aggregation in the myelin sheath of MBP and P0. Myelin‐associated glycoprotein was present in the Schmidt–Lanterman clefts but significantly reduced in the periaxonal region. Using immunogold electron microscopy, we demonstrated the presence of mutated PLP/DM20 and the absence of the intact protein in the patient peripheral myelin sheath. We conclude that insertion of mutant PLP/DM20 with resulting aberrant distribution of other myelin proteins in peripheral nerve may constitute an important mechanism of dysmyelination in disorders associated with PLP mutations. Ann Neurol 2003;54:769–780

Two brothers with a leukodystrophy, progressive spastic diplegia, and peripheral neuropathy were found to have proteinaceous aggregates in the peripheral nerve myelin sheath. The patients' mother had only subclinical peripheral neuropathy, but the maternal grandmother had adult-onset leukodystrophy. Sequencing of the proteolipid protein (PLP) gene showed a point mutation IVS4 + 1 G→A within the donor splice site of intron 4. We identified one transcript with a deletion of exon 4 (Δex4, 169bp) encoding for PLP and DM20 proteins and lacking two transmembrane domains, and a second transcript with exon 4 + 10bp encoding three transmembrane domains. Immunohistochemistry showed abnormal aggregation in the myelin sheath of MBP and P0. Myelin-associated glycoprotein was present in the Schmidt–Lanterman clefts but significantly reduced in the periaxonal region. Using immunogold electron microscopy, we demonstrated the presence of mutated PLP/DM20 and the absence of the intact protein in the patient peripheral myelin sheath. We conclude that insertion of mutant PLP/DM20 with resulting aberrant distribution of other myelin proteins in peripheral nerve may constitute an important mechanism of dysmyelination in disorders associated with PLP mutations. Ann Neurol 2003;54:769–780

Background: Digital health, including telemedicine, is increasingly recommended for the management of chronic neurological disorders, and it has changed the roles of patients and clinicians.Methods: In this cross-sectional study we aimed to investigate the digital work engagement of Italian neurologists through a survey collected between September 2020 and January 2021. Questionnaires were anonymous and collected demographic characteristics, attitudes towards digital devices and social media, and details about the clinician–patient relationship. We used logistic-regression models to identify characteristics associated with the propensity to communicate with patients using social media.Results: Among the 553 neurologists who participated to the study, smartphones and computers were widely preferred compared with tablets; wearable devices were not common, although some neurologists desired them. A total of 48% of participants reported communicating with patients using social media but only a few were in favor of social friendship with patients; WhatsApp was the social media most popular for professional (86%) and personal (98%) purposes. Propensity to communicate with social media was significantly higher among those who were older (p< 0.001) and lived in regions outside northern Italy (center: p= 0.006; south and the islands: p< 0.001). For 58% of responders, social media improved their relationship with patients, but 72% usually warned patients about unreliable websites.Conclusions: The preferred social media were those which were rapid and which safeguard privacy more effectively; neurologists made many efforts to disprove fake news circulating online, providing help to patients in various ways. This analysis can help direct future interventions for the management of chronic neurological disorders.

The impact of image segmentation on 0.84-ml nominal voxel volume proton spectroscopic imaging in normal brain and in age-related cortical atrophy was investigated. Segmentation improved the gray matter-white matter (GM-WM) contrast for N-acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr in normal brain, and for NAA/Cho and NAA/Cr in atrophic brain. NAAGM/WM (~0.7), ChoGM/WM (~0.8), and CrGM/WM (~1.3) in normal brain obtained with segmentation agreed with values obtained with quantitative magnetic resonance spectroscopy. Age-related cortical atrophy led to decreased cortical GM NAA/Cho and NAA/Cr; no changes were evident in WM or in NAAGM/WM, ChoGM/WM, or CrGM/WM. GM/WM metabolite analysis may be of limited use in conditions in which parallel metabolite changes occur in WM and GM. Magn Reson Med 41:841–845, 1999. Published 1999 Wiley-Liss, Inc.

The impact of image segmentation on 0.84‐ml nominal voxel volume proton spectroscopic imaging in normal brain and in age‐related cortical atrophy was investigated. Segmentation improved the gray matter‐white matter (GM‐WM) contrast for N‐acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr in normal brain, and for NAA/Cho and NAA/Cr in atrophic brain. NAAGM/WM (∼0.7), ChoGM/WM (∼0.8), and CrGM/WM (∼1.3) in normal brain obtained with segmentation agreed with values obtained with quantitative magnetic resonance spectroscopy. Age‐related cortical atrophy led to decreased cortical GM NAA/Cho and NAA/Cr; no changes were evident in WM or in NAAGM/WM, ChoGM/WM, or CrGM/WM. GM/WM metabolite analysis may be of limited use in conditions in which parallel metabolite changes occur in WM and GM. Magn Reson Med 41:841–845, 1999. Published 1999 Wiley‐Liss, Inc.

An assessment of the detectability of white matter lesions and of concordance between observers with different levels of MRI reading experience was performed with comparative evaluation of spin-echo MRI images and of corresponding “multispectral”maps in 16 patients with definite multiple sclerosis (MS). Multispectral maps were obtained by means of a recently described post-processing technique based on the simultaneous display of MRI parameters and a standardized colour scale with red, green and blue coding for relaxation rates R1 and R2 and proton density, respectively. Spin-echo images on films and multispectral maps displayed on a personal computer were randomly rated at 2-month intervals. Interobserver concordance (k-test) was assessed among three readers with different levels of MRI experience (an experienced neuroradiologist, a radiology resident and a neurologist). For multispectral maps we found increased interobserver concordance with the experienced neuroradiologist (multispectral vs conventional images: k = 0.77 vs 0.66 for the radiology resident and 0.66 vs 0.56 for the neurologist), an increased number of detected lesions and decreased reading time. Multispectral maps permit easy detection of MS lesions and may improve interobserver concordance compared with conventional spin-echo studies.

•Relapsing-Remitting MS (RR-MS) patients will slowly convert to secondary progressive (SP-MS) phenotype throughout the disease course.•Clinicians still struggle to define the turning-point between the two phenotypes leaving space for a transition phase delaying appropriate treatment strategies.•We aimed at defining clinical markers predicting confirmed transition to SP-MS in patients presumptively converting from RR-MS to SP-MS.•At their first confirmed disability worsening (CDW), RR-MS patients with higher EDSS, experiencing CDW without relapse and developing a further CDW within 2 years are at higher risk of SP-MS clinical diagnosis.•Our study will provide proxies for conversion to SP-MS since first episode of CDW, reducing SP-MS clinical diagnosis delay.

•Patient's age is the most important factor in DMTs choice•Choice of oral drugs vs self-injectables ones is driven by unfavorable prognostic factors•Natalizumab preferred in early stage of severe disease and in younger patients

•RTX is effective in preventing attacks in patients with NMOSD.•No concerning safety issues occurred in our real-life cohort.•Use of specific induction and maintenance regimen might boost RTX efficacy.•RTX could be less effective in MOG-ab positive patients.