AChR-seropositive myasthenia gravis in muscular dystrophy: diagnostic pitfalls and clinical management challenges.

The co-occurrence of genetic myopathies with myasthenia gravis (MG) is extremely rare, however a few studies have been reported. We aim to explore the link between genetically inherited muscle disorders and immune-mediated neuromuscular junction conditions, taking into account the diagnostic and therapeutic implications posed by these combined conditions. We searched all English medical papers registered in Web of Knowledge, PubMed, Google Scholar, and Science Direct between January 1987 concerning the association between muscular dystrophies (MD) and MG, also adding three new cases to the series reported so far. Three new clinical cases in which MG concurs with oculopharyngeal muscular dystrophy (OPMD) or facioscapulohumeral muscular dystrophy (FSHD) or myotonic dystrophy type 2 (DM2) were reported. A comprehensive literature review showed that FSHD is the dystrophy most frequently associated with generalized MG. The AChR antibody titer is high and neurophysiologic tests prove to be an essential tool for the diagnosis. The association between MG and MD is rare but should not be underestimated. The presence of unusual clinical features suggest investigating additional overlapping condition, especially when a treatable disease like MG is suspected.

The spectrum of anti-GQ1B antibody syndrome: beyond Miller Fisher syndrome and Bickerstaff brainstem encephalitis.

INTRODUCTION: Since the initial identification of Miller Fisher syndrome (MFS) and Bickerstaff brainstem encephalitis (BBE),significant milestones have been achieved in understanding these diseases.Discoveries of common serum antibodies (IgG anti-GQ1b), antecedent infections, neurophysiological data, andneuroimaging suggested a shared autoimmune pathogenetic mechanism rather than distinct pathogenesis, leadingto the hypothesis that both diseases are part of a unified syndrome, termed "Fisher-Bickerstaff syndrome". The subsequent identification of atypical anti-GQ1b-positive forms expanded the classification to a broader condition known as "Anti-GQ1b-Antibody syndrome". METHODS: An exhaustive literature review was conducted, analyzing a substantial body of research spanning from the initialdescriptions of the syndrome's components to recent developments in diagnostic classification and researchperspectives. RESULTS: Anti-GQ1b syndrome encompasses a continuous spectrum of conditions defined by a common serological profilewith varying degrees of peripheral (PNS) and central nervous system (CNS) involvement. MFS and BBE represent theopposite ends of this spectrum, with MFS primarily affecting the PNS and BBE predominantly involving the CNS.Recently identified atypical forms, such as acute ophthalmoparesis, acute ataxic neuropathy withoutophthalmoparesis, Guillain-Barré syndrome (GBS) with ophthalmoparesis, MFS-GBS and BBE-GBS overlap syndromes,have broadened this spectrum. CONCLUSION: This work aims to provide an extensive, detailed, and updated overview of all aspects of the anti-GQ1b syndromewith the intention of serving as a stepping stone for further shaping thereof. Special attention was given to therecently identified atypical forms, underscoring their significance in redefining the boundaries of the syndrome.

Anti-pan-neurofascin nodopathy: cause of fulminant neuropathy.

Autoimmune nodopathies are inflammatory diseases of the peripheral nervous system with clinical and neurophysiological peculiar characteristics. In this nosological category, we find patients with autoantibodies against Neurofascin 140/186 and 155, Contactin1, and Caspr1 directed precisely towards nodal and paranodal structures. These antibodies are extremely rare and cause severe clinical symptoms. We describe the clinical case of a patient with autoimmune nodopathy caused by the coexistence of anti-neurofascin (NF) 186/140 and 155, characterized by progressive weakness in all limbs leading to tetraplegia, involving cranial nerves, and respiratory insufficiency. Response to first-line treatments was good followed by rapid dramatic clinical relapse. There are few reported cases of anti-pan NF neuropathy in the literature, and they present a clinical phenotype similar to our patient. In these cases, early recognition of clinical red flags of nodopathies and serial neurophysiological studies can facilitate the diagnosis. However, the severe clinical relapse suggests a possible early use of immunosuppressive therapies for this rare category of patients.

The Growing Role of Telerehabilitation and Teleassessment in the Management of Movement Disorders in Rare Neurological Diseases: A Scoping Review.

Background: People with rare neurological diseases (RNDs) often experience symptoms related to movement disorders, requiring a multidisciplinary approach, including rehabilitation. Telemedicine applied to rehabilitation and symptom monitoring may be suitable to ensure treatment consistency and personalized intervention. The objective of this scoping review aimed to emphasize the potential role of telerehabilitation and teleassessment in managing movement disorders within RNDs. By providing a systematic overview of the available literature, we sought to highlight potential interventions, outcomes, and critical issues. Methods: A literature search was conducted on PubMed, Google Scholar, IEEE, and Scopus up to March 2024. Two inclusion criteria were followed: (1) papers focusing on telerehabilitation and teleassessment and (2) papers dealing with movement disorders in RNDs. Results: Eighteen papers fulfilled the inclusion criteria. The main interventions were home-based software and training programs, exergames, wearable sensors, smartphone applications, virtual reality and digital music players for telerehabilitation; wearable sensors, mobile applications, and patient home video for teleassessment. Key findings revealed positive outcomes in gait, balance, limb disability, and in remote monitoring. Limitations include small sample sizes, short intervention durations, and the lack of standardized protocols. Conclusion: This review highlighted the potential of telerehabilitation and teleassessment in addressing movement disorders within RNDs. Data indicate that these modalities may play a major role in supporting conventional programs. Addressing limitations through multicenter studies, longer-term follow-ups, and standardized protocols is essential. These measures are essential for improving remote rehabilitation and assessment, contributing to an improved quality of life for people with RNDs.

Anterior lumbosacral polyradiculoneuropathy following intrathecal methotrexate administration: a case report and literature update.

INTRODUCTION: We describe a case of intrathecal methotrexate toxicity and perform a literature review of existing cases. CASE PRESENTATION: A 23-year-old man who received diagnosis of acute lymphoblastic leukemia and started chemotherapy according to the LAL1913 protocol underwent CNS prophylaxis with intrathecal methotrexate. About 1 month after, he developed a flaccid paraparesis. CSF analysis showed albumin/cytological dissociation. Spinal MRI showed thickening of the ventral roots of the cauda equina with contrast enhancement. Nerve conduction studies showed severe lower limb motor axonal neuropathy. Needle examination showed acute denervation involving L3-S1 roots. Methotrexate was stopped, and the patient was treated with intravenous immunoglobulins, followed by high-dose intravenous methylprednisolone, with a gradual improvement. Three months later, the spine MRI was normal. Electrophysiological and imaging findings were indicative of pure motor L3-S1 polyradiculopathy. DISCUSSION: Literature review of existing cases confirm the relatively selective involvement of lumbosacral ventral roots in intrathecal methotrexate toxicity. Pathophysiologic mechanisms suggest either a direct toxicity with localized folate deficiency or an immune-mediated mechanism, the latter consistent, in our patient, with the albumin/cytological dissociation and response to immunomodulatory treatments. Pure motor polyradiculopathy of the lower limbs is rare but predictable complication of intrathecal methotrexate, which can benefit from early withdrawal and immunomodulatory treatments.

Starting eculizumab as rescue therapy in refractory myasthenic crisis.

INTRODUCTION: Myasthenia gravis is a long-lasting autoimmune neuromuscular disease caused by antibodies attacking the neuromuscular junction, which can result in muscle weakness, fatigue, and respiratory failure in severe cases. Myasthenic crisis is a life-threatening event that requires hospitalization and treatments with intravenous immunoglobulin or plasma exchange. We reported the case of an AChR-Ab-positive myasthenia gravis patient with refractory myasthenic crisis, in which starting eculizumab as rescue therapy led to a complete resolution of the acute neuromuscular condition. CASE PRESENTATION: A 74-year-old man diagnosed with myasthenia gravis. ACh-receptor antibodies positivity comes to our observation for a recrudescence of symptoms, unresponsive to conventional rescue therapies. Due to the clinical worsening over the following weeks, the patient was admitted to intensive care unit, where he underwent therapy with eculizumab. About 5 days after the treatment, there was a significant and complete recovery of clinical condition with weaning-off from invasive ventilation and discharge to outpatient regimen, with reduction of steroid intake and biweekly maintenance with eculizumab. DISCUSSION: Eculizumab, a humanized monoclonal antibody that inhibits complement activation, is now approved as treatment for refractory generalized myasthenia gravis with anti-AChR antibodies. The use of eculizumab in myasthenic crisis is still investigational, but this case report suggests that it may be a promising treatment option for patients with severe clinical condition. Ongoing clinical trials will be needed to further evaluate the safety and efficacy of eculizumab in myasthenic crisis.

The role of brain radiotherapy for EGFR- and ALK-positive non-small-cell lung cancer with brain metastases: a review.

Non-small cell lung cancer (NSCLC) is frequently complicated by central nervous system (CNS) metastases affecting patients' life expectancy and quality. At the present clinical trials including neurosurgery, radiotherapy (RT) and systemic treatments alone or in combination have provided controversial results. CNS involvement is even more frequent in NSCLC patients with EGFR activating mutations or ALK rearrangement suggesting a role of target therapy in the upfront treatment in place of loco-regionals treatments (i.e. RT and/or surgery). So far clinical research has not explored the potential role of accurate brain imaging (i.e. MRI instead of the routine total-body contrast CT and/or PET/CT staging) to identify patients that could benefit of local therapies. Moreover, for patients who require concomitant RT there are no clear guidelines on the timing of intervention with respect to innovative precision medicine approaches with Tyrosine Kinase Inhibitors, ALK-inhibitors and/or immuno-oncological therapies. On this basis the present review describes the therapeutic strategies integrating medical and radiation oncology in patients with metastatic NSCLC (mNSCLC) adenocarcinoma with CNS involvement and EGFR activating mutations or ALK rearrangement.

Neurological music therapy during the COVID-19 outbreak: updates and future challenges.

BACKGROUND: In the last few years, several studies confirmed the effectiveness of music therapy (MT) for the rehabilitative management of patients with neurological disorders. AIM: Here we discuss the feasibility and disadvantages of tele-neurological MT (tele-NMT) compared to the traditional MT programmes. METHODS: We selected all the articles registered in the Web of Knowledge, PubMed, Google Scholar and ScienceDirect from March 2020 to November 2021 concerning tele-NMT during the COVID-19 outbreak, collecting same examples and experiences. RESULTS: With the advent of the COVID-19, several music-based interventions (MBIs) have been adapted from "in person" to a "remote and virtual" mode (through the telemedicine). DISCUSSION: Tele-NMT could represent a promising option to provide constant care and support to people with neurological diseases during the pandemic.

Risk factors of asymptomatic reduction of motor conduction velocity of the ulnar nerve across the elbow.

INTRODUCTION: The aim of the study was to check the risk factors for subjects with motor conduction velocity (MCV) reduction of the ulnar nerve across the elbow without symptoms/signs of ulnar neuropathy at the elbow (UNE) using a database of a previous multicenter case-control study on UNE patients. METHODS: From the previous database, we extracted all asymptomatic UNE (A-UNE) and matched for age and sex with a control and UNE groups with a ratio of 1:2. Anthropometric factors were measured and all participants filled in a questionnaire on demographic, lifestyle factors, and medical history. One-sample proportion test and univariate and multivariate logistic regression analyses were performed. RESULTS: We enrolled 64 A-UNE, 124 UNE, and 124 controls (mean age 53 years). There were more males with A-UNE than females (74.2%). The predominantly or exclusively concerned side of A-UNE was the right. Logistic regression showed that A-UNE was associated with diabetes (OR = 2.99, 95% CI = 1.21-7.39) and width of cubital groove (CGW) (OR = 0.89, 95%  CI = 0.81-0.97). DISCUSSION: Risk factors for A-UNE are different from UNE. The prevalence of right side in A-UNE was not due to particular elbow postures. Diabetes is a risk factor, probably because MCV reduction of the ulnar nerve across the elbow was an early manifestation of asymptomatic polyneuropathy in diabetes. A-UNE is associated with narrow CGW as already demonstrated in UNE, even if the OR was higher in UNE than in A-UNE. Only future longitudinal studies will be able to check whether the A-UNE subjects develop symptoms and signs of true mononeuropathy with time.

Gray matter atrophy cannot be fully explained by white matter damage in patients with MS.

BACKGROUND: Source-based morphometry (SBM) was recently used for non-random "patterns" of gray matter (GM) atrophy or white matter (WM) microstructural damage. OBJECTIVE: To assess whether and to what extent such patterns may be inter-related in MS. METHODS: SBM was applied to images of GM concentration and fractional anisotropy (FA) in MS patients (n = 41, median EDSS = 1) and normal controls (NC, n = 28). The same procedure was repeated on an independent and similar data set (39 MS patients and 13 NC). RESULTS: We found in MS patterns of GM atrophy and reduced FA (p < 0.05, corrected). Deep GM atrophy was mostly (70%) explained by lesion load in projection tracts and lower FA in posterior corona radiata and thalamic radiation. By contrast, sensorimotor and posterior cortex atrophy was less (50%) dependent from WM damage. All patterns correlated with EDSS (r from -0.33 to -0.56, p < 0.03) while the only cognition-related correlation was between posterior GM atrophy pattern and processing speed (r = 0.45, p = 0.014). Reliability analysis showed similar results. CONCLUSION: In relatively early MS, we found a close link between deep GM atrophy pattern and WM damage while sensorimotor and posterior cortex patterns were partially independent from WM damage and perhaps related to primary mechanisms. Patterns were clinically relevant.

Comorbidities, anthropometric, demographic, and lifestyle risk factors for ulnar neuropathy at the elbow: A case control study.

We performed a prospective multicenter case-control study to explore the association between ulnar neuropathy at elbow (UNE) and body and elbow anthropometric measures, demographic and lifestyle factors, and comorbidities. Cases and controls were consecutively enrolled among subjects admitted to four electromyography labs. UNE diagnosis was made on clinical and neurographic findings. The control group included all other subjects without signs/symptoms of ulnar neuropathy and with normal ulnar nerve neurography. Anthropometric measurements included weight, height, waist, hip circumferences, and external measures of elbow using a caliper. The participants filled in a self-administered questionnaire on personal characteristics, lifestyle factors, and medical history. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) by fitting unconditional logistic regression models adjusted by center and education level. We enrolled 220 cases (males 61.8%; mean age 51.7 years) and 460 controls (47.4% males; mean age 47.8 years). At multivariable analysis, UNE was associated to male gender (OR = 2.4, 95%CI = 1.6-3.7), smoking habits (>25 pack-years (OR = 2.3, 95%CI = 1.3-4.1), body mass index (OR = 1.05, 95%CI 1.01-1.10), polyneuropathies (OR = 4.1, 95%CI 1.5-11.5), and leaning with flexed elbow on a table/desk (OR = 1.5, 95%CI 1.0-2.2). Cubital groove width (CGW) turned out to be negatively associated with UNE (OR = 0.80, 95%CI = 0.74-0.85). Our study suggests that some personal factors especially anthropometric measures of the elbow may play a role in UNE pathogenesis as the measures of wrist in CTS. We demonstrated that for each millimeter of smaller CGW the risk of idiopathic UNE increases of 25%.

The external elbow measure as surrogate of the anatomical width of cubital groove and possible risk factor of ulnar neuropathy at the elbow.

Introduction: There are no studies on elbow anthropometry in ulnar neuropathy at the elbow (UNE). We aimed to test the interrater agreement of external elbow measurements with caliper, the matching of external width of cubital groove (WCG) measures with those obtained through conventional radiography (XR) and ultrasonography (US). The final aim was to evaluate the differences of anthropometric elbow and body measures between UNE cases and controls with multicenter prospective study.Materials and methods: After common training of five observers for external elbow and body anthropometric measurements, we assessed the interrater agreement of measures in a single blind measurement session in 16 healthy volunteers. Then we verified if external WCG measures in eight and four of the above 16 subjects matched with those obtained with US and XR. Finally, we enrolled 40 consecutive idiopathic UNE cases in four electromyographic labs matched for sex and age with 40 controls to evaluate the differences of anthropometric measures.Results: There was high interrater agreement of all anthropometric body and elbow measures (Kendal's and interclass correlation coefficients between 0.84 and >0.9). We found high relations between WCG caliper measures and those obtained with US and XR (r > 0.9). WCG was smaller in cases than in controls (13.2 vs.15.7 mm, p < 0.001). There were no differences in body anthropometric measures (BMI and waist-to-hip ratio).Conclusion: The external measurement of WCG is reliable and reproducible and may be risk factor of UNE. Future studies should be performed in lager samples evaluating the relations with lifestyle and occupational factors.

Role of perilesional edema and tumor volume in the prognosis of non-small cell lung cancer (NSCLC) undergoing radiosurgery (SRS) for brain metastases.

AIM: To assess the role of perilesional edema (PE) in non-small cell lung carcinoma (NSCLC) brain metastases (BM) undergoing radiosurgery (SRS). METHODS: This series includes 46 patients with 1-2 BM treated with SRS, selected out of all patients referred for radiotherapy (RT) for BMs over 5 years (2013 to 2017). Both the PE and gross tumor volume (GTV) were contoured on MRI images, and the PE/GTV ratio and PE + GTV value (TV, total volume) were calculated. Our clinical endpoints were brain recurrence free-survival, divided into local brain control (in field, LBC) and distant brain control (out of field, DBC) and overall survival (OS). We analyzed the role of the previously described volumetric parameters and of known clinical prognosticators (disease specific GPA, DS-GPA; chemotherapy, CHT) with Cox regression analyses. RESULTS: Only four patients (9%) developed in-field progression, whereas 10 patients (22%) showed new out-of-field BM and thirty-eight patients died in the follow up (83%). In univariate analysis, both volumetric parameters and clinical parameters were correlated with DBC and OS, whereas we did not find any correlation with LBC. In the multivariate analysis of DBC, the significant parameters were PE/GTV ratio (HR 0.302), sex (HR 0.131), and DS-GPA (HR 0.261). The OS multivariate analysis showed that the only significant parameters were DS-GPA (HR 0.478) and TV (HR: 1.038). CONCLUSION: Our study, although with the limitations of a monocentric retrospective study analyzing a small cohort of patients, suggests the role of PE/GTV ratio for the development of new BMs. TV also seems to be correlated with OS, together with known clinical prognosticators. These findings, if validated in a larger prospective dataset, could help in selecting patients for the most suitable RT modality (or systemic therapy approach).

Exploring the role of music therapy in multiple sclerosis: brief updates from research to clinical practice.

BACKGROUND: Physical, cognitive and mood-behavioral disturbances are very common in people with multiple sclerosis (MS) representing a relevant disease burden. Recently, in this field, several studies investigated the role of music therapy (MT) as a complementary therapeutic approach especially in terms of rehabilitation strategy. OBJECTIVES: The aim of this review is to report and discuss the effectiveness of various music-based interventions (MBIs) for clinical outcomes in MS patients. DATA SOURCES: All English medical papers registered in the Web of Knowledge, PubMed, Google Scholar, and ScienceDirect from March 1999 to March 2019. INCLUSION AND EXCLUSION CRITERIA: We selected all the articles concerning MBIs in MS including papers that dealt with human samples and excluding non-human samples, reviews and case reports. RESULTS: Out of 46 articles, we selected 24 papers of which 13 completely following the inclusion criteria were evaluated for the present analysis. DISCUSSION: We explored the efficacy of several MT programs, taking into account the different aspects of application feasibility in the clinical management of MS patients and the future challenges.

Perilesional edema in brain metastasis from non-small cell lung cancer (NSCLC) as predictor of response to radiosurgery (SRS).

Radiosurgery (SRS) is widely used in the treatment of brain oligo-metastases from NSCLC. The aim of present study is to evaluate the extent of perilesional edema in brain metastases as predictive factor of treatment response. This single center retrospective study included 42 consecutive patients (January 2011-December 2014) with 1-2 brain metastasis from NSCLC treated with Radiosurgery (SRS). Extent of perilesional edema was measured as maximal extension from the edge of lesion and classified as minor (<10 mm) or major (≥10 mm). We analyzed Modality of Brain Recurrence (MBR), classified as in-field or out-of- field, and Brain Progression Free-Survival (BPFS) after treatment stratified according to extent of perilesional edema. Analyzing modality of brain recurrence and BPFS, after a median follow-up of 6 months, we found that patients with minor edema had a better radiological response to SRS with none in-field recurrences and a lower risk of the onset of new brain lesions (out-of-field recurrence). Instead, patients group with major edema had a worse response rate of lesions treated, further, a higher risk of out-of-field brain relapse. Extent of perilesional edema in brain metastasis from NSCLC could be a predictive factor of response and brain progression after SRS treatment alone.

Spatial ranking strategy and enhanced peripheral vision discrimination optimize performance and efficiency of visual sequential search.

Visual sequential search might use a peripheral spatial ranking of the scene to put the next target of the sequence in the correct order. This strategy, indeed, might enhance the discriminative capacity of the human peripheral vision and spare neural resources associated with foveation. However, it is not known how exactly the peripheral vision sustains sequential search and whether the sparing of neural resources has a cost in terms of performance. To elucidate these issues, we compared strategy and performance during an alpha-numeric sequential task where peripheral vision was modulated in three different conditions: normal, blurred, or obscured. If spatial ranking is applied to increase the peripheral discrimination, its use as a strategy in visual sequencing should differ according to the degree of discriminative information that can be obtained from the periphery. Moreover, if this strategy spares neural resources without impairing the performance, its use should be associated with better performance. We found that spatial ranking was applied when peripheral vision was fully available, reducing the number and time of explorative fixations. When the periphery was obscured, explorative fixations were numerous and sparse; when the periphery was blurred, explorative fixations were longer and often located close to the items. Performance was significantly improved by this strategy. Our results demonstrated that spatial ranking is an efficient strategy adopted by the brain in visual sequencing to highlight peripheral detection and discrimination; it reduces the neural cost by avoiding unnecessary foveations, and promotes sequential search by facilitating the onset of a new saccade.

Homozygosity and severity of phenotypic presentation in a CADASIL family.

Most of causative mutations of the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are missense point mutations either creating or deleting one cysteine residue, inherited in a heterozygous state. Only few homozygous patients are reported to date and some of them showed phenotypic peculiarities. We here describe a CADASIL family in which a member showed homozygous mutation and compare its clinical profile with five subjects throughout three generation of the pedigree, carrying the same mutation in heterozygosity. The index patient was a 44-year-old Italian man, born from consanguineous parents (first cousins). Symptoms started at 23 years and progressing with recurrent ischemic stroke episode. Diffuse leukoencephalopathy and a severe cognitive impairment were evident, GOMs were detected in skin specimens and a homozygous p.Cys183Ser mutation of the NOTCH3 gene was found. Among the other five heterozygous relatives for the same mutation, both parents developed stroke in advanced age and all the others were clinically asymptomatic. We discuss these findings in relationship to previous data from the literature in CADASIL and in other dominant neurological disorders.

Towards personalized management of myasthenia gravis phenotypes: From the role of multi-omics to the emerging biomarkers and therapeutic targets.

Predicting the onset, progression, and outcome of rare and chronic neurological diseases, i.e. neuromuscular diseases, is an important goal for both clinicians and researchers and should guide clinical decision-making and personalized treatment plans. A prime example is myasthenia gravis (MG), an antibody-mediated disease that affects multiple components of the postsynaptic membrane, impairing neuromuscular transmission and producing fatigable muscle weakness. MG is characterized by several clinical phenotypes, defined by a broad spectrum of factors, which have contributed to the current lack of consensus on the optimal management and treatments of this disease and its related phenotypes (subtypes). This represents a crucial challenge in MG and encourages a revolutionary change in diagnostic, prognostic and therapeutic guidelines. Emerging factors, such as demographic, clinical and pathophysiological factors, must also be considered. Consequently, the different MG phenotypes are characterized by precise biological signatures, which could represent appropriate biomarkers and targets. Here we describe and discuss these new concepts, highlighting that, thanks to multi-omics technologies, the identification of emerging diagnostic/prognostic biomarkers, such as miRNAs, and the subsequent development of new diagnostic/therapeutic algorithms could be facilitated. The latter, in turn, could facilitate the management of different MG phenotypes also in a personalized manner. Limitations and advantages are also reported.