Combined RNA interference and gene replacement therapy targeting MFN2 as proof of principle for the treatment of Charcot-Marie-Tooth type 2A.

Mitofusin-2 (MFN2) is an outer mitochondrial membrane protein essential for mitochondrial networking in most cells. Autosomal dominant mutations in the MFN2 gene cause Charcot-Marie-Tooth type 2A disease (CMT2A), a severe and disabling sensory-motor neuropathy that impacts the entire nervous system. Here, we propose a novel therapeutic strategy tailored to correcting the root genetic defect of CMT2A.

COVID-19-associated Guillain-Barré syndrome in the early pandemic experience in Lombardia (Italy).

Objective: To estimate the incidence and describe clinical characteristics and outcome of GBS in COVID-19 patients (COVID19-GBS) in one of the most hit regions during the first pandemic wave, Lombardia.

Methods: Adult patients admitted to 20 Neurological Units between 1/3-30/4/2020 with COVID19-GBS were included as part of a multi-center study organized by the Italian society of Hospital Neuroscience (SNO).

Results: Thirty-eight COVID19-GBS patients had a mean age of 60.

Antisense Morpholino-Based In Vitro Correction of a Pseudoexon-Generating Variant in the Gene.

Limb-girdle muscular dystrophies (LGMD) are clinically and genetically heterogenous presentations displaying predominantly proximal muscle weakness due to the loss of skeletal muscle fibers. Beta-sarcoglycanopathy (LGMDR4) results from biallelic molecular defects in SGCB and features pediatric onset with limb-girdle involvement, often complicated by respiratory and heart dysfunction. Here we describe a patient who presented at the age of 12 years reporting high creatine kinase levels and onset of cramps after strenuous exercise.

MicroRNAs as serum biomarkers in Becker muscular dystrophy.

Becker muscular dystrophy (BMD) is an X-linked neuromuscular disorder due to mutation in the DMD gene, encoding dystrophin. Despite a wide clinical variability, BMD is characterized by progressive muscle degeneration and proximal muscle weakness. Interestingly, a dysregulated expression of muscle-specific microRNAs (miRNAs), called myomirs, has been found in patients affected with muscular dystrophies, although few studies have been conducted in BMD.

Cell-penetrating peptide-conjugated Morpholino rescues SMA in a symptomatic preclinical model.

Spinal muscular atrophy (SMA) is a motor neuron disease and the leading genetic cause of infant mortality. Recently approved SMA therapies have transformed a deadly disease into a survivable one, but these compounds show a wide spectrum of clinical response and effective rescue only in the early stages of the disease. Therefore, safe, symptomatic-suitable, non-invasive treatments with high clinical impact across different phenotypes are urgently needed.

Sodium Levels Predict Disability at Discharge in Guillain-Barré Syndrome: A Retrospective Cohort Study.

Guillain-Barré syndrome (GBS) is an inflammatory polyradiculopathy with potentially severe complications. Clinical tools for risk stratification have been developed, but no definitive prognostic biomarker has been reported. Hyponatremia is frequent in GBS patients, but the impact of serum sodium levels on clinical outcomes is still ill-defined.

Clinical, neuroradiological and genetic findings in a cohort of patients with multiple Cerebral Cavernous Malformations.

Cerebral cavernous malformations (CCM) consist of clusters of irregular dilated capillaries and represent the second most common type of vascular malformation affecting the central nervous system. CCM might be asymptomatic or cause cerebral hemorrhage, seizures, recurrent headaches and focal neurologic deficits. Causative mutations underlining CCM have been reported in three genes: KRIT1/CCM1, MGC4607/CCM2 and PDCD10/CCM3.

Impact of COVID-19 on the quality of life of patients with neuromuscular disorders in the Lombardy area, Italy.

Introduction: /AIMS: Patients with neuromuscular disorders (NMDs), including many elderly, immunosuppressed, and disabled individuals, may have been particularly affected during the coronavirus disease 2019 (COVID-19) pandemic in Lombardy, a COVID-19 high-incidence area between February and May 2020. We aimed to evaluate the effects of the COVID-19 pandemic on the quality of life (QoL) and perceived disease burden of this group of patients.

Methods: We conducted a cross-sectional phone-based survey study between June 1 and June 14, 2020, on a sample of 240 NMD patients followed at our clinic in Milan, Italy.

Early Findings in Neonatal Cases of -Related Congenital Myopathies.

Ryanodine receptor type 1-related congenital myopathies are the most represented subgroup among congenital myopathies (CMs), typically presenting a central core or multiminicore muscle histopathology and high clinical heterogeneity. We evaluated a cohort of patients affected with Ryanodine receptor type 1-related congenital myopathy (-RCM), focusing on four patients who showed a severe congenital phenotype and underwent a comprehensive characterization at few months of life. To date there are few reports on precocious instrumental assessment.

Charcot-Marie-Tooth disease type 2F associated with biallelic HSPB1 mutations.

Objective: This work aims to expand knowledge regarding the genetic spectrum of HSPB1-related diseases. HSPB1 is a gene encoding heat shock protein 27, and mutations in HSPB1 have been identified as the cause of axonal Charcot-Marie-Tooth (CMT) disease type 2F and distal hereditary motor neuropathy (dHMN).

Methods: Two patients with axonal sensorimotor neuropathy underwent detailed clinical examinations, neurophysiological studies, and next-generation sequencing with subsequent bioinformatic prioritization of genetic variants and in silico analysis of the likely causal mutation.

Case Report: Efficacy of Rituximab in a Patient With Familial Mediterranean Fever and Multiple Sclerosis.

Familial Mediterranean Fever (FMF) is a genetic autoinflammatory disease characterized by recurrent episodes of fever and serositis caused by mutations in the MEFV gene, while Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the CNS with genetic and environmental etiology. The two diseases rarely occur in association with relevant implications for clinical management and drug choice. In this paper, we present the case of a 53-year-old male with an autosomal dominant FMF since childhood who presented acute paresthesia at the right part of the body.

Clinical features and disease course of patients with acute ischaemic stroke just before the Italian index case: Was COVID-19 already there?

Since the end of February 2020, Italy has suffered one of the most severe outbreaks of coronavirus disease 2019 (COVID-19). However, what happened just before the Italian index case has not yet been investigated. To answer this question, we evaluated the potential impact of COVID-19 on the clinical features of a cohort of neurological inpatients admitted right before the Italian index case, as compared to the same period of the previous year.

Posterior reversible encephalopathy syndrome and COVID-19: A series of 6 cases from Lombardy, Italy.

Posterior reversible encephalopathy cases are increasingly being reported in patients affected by COVID-19, but the largest series so far only includes 4 patients. We present a series of 6 patients diagnosed with PRES during COVID-19 hospitalized in 5 Centers in Lombardia, Italy. 5 out of the 6 patients required intensive care assistence and seizures developed at weaning from assisted ventilation.

Unravelling Genetic Factors Underlying Corticobasal Syndrome: A Systematic Review.

Corticobasal syndrome (CBS) is an atypical parkinsonian presentation characterized by heterogeneous clinical features and different underlying neuropathology. Most CBS cases are sporadic; nevertheless, reports of families and isolated individuals with genetically determined CBS have been reported. In this systematic review, we analyze the demographical, clinical, radiological, and anatomopathological features of genetically confirmed cases of CBS.

A Novel Homozygous VPS11 Variant May Cause Generalized Dystonia.

In this work, we describe the association of a novel homozygous VPS11 variant with adult-onset generalized dystonia, providing a detailed clinical report and biological evidence of disease mechanism. Vps11 is a subunit of the homotypic fusion and protein sorting (HOPS) complex, which promotes the fusion of late endosomes and autophagosomes with the lysosome. Functional studies on mutated fibroblasts showed marked lysosomal and autophagic abnormalities, which improved after overexpression of the wild type Vps11 protein.

A case report of late-onset cerebellar ataxia associated with a rare p.R342W TGM6 (SCA35) mutation.

Background: Mutations in TGM6 gene, encoding for transglutaminase 6 (TG6), have been implicated in the pathogenesis of spinocerebellar ataxia type 35 (SCA35), a rare autosomal dominant disease marked by cerebellar degeneration and characterized by postural instability, incoordination of gait, features of cerebellar dysfunction and pyramidal signs.

Case Presentation: Here we report the case of an Italian patient with late-onset, slowly progressive cerebellar features, including gait ataxia, scanning speech and ocular dysmetria and pyramidal tract signs. Whole exome sequencing revealed the rare heterozygous c.

Hyperacute extensive spinal cord infarction and negative spine magnetic resonance imaging: a case report and review of the literature.

Rationale: Spinal cord infarction (SCI) accounts for only 1% to 2% of all ischemic strokes and 5% to 8% of acute myelopathies. Magnetic resonance imaging (MRI) holds a role in ruling out non-ischemic etiologies, but the diagnostic accuracy of this procedure may be low in confirming the diagnosis, even when extensive cord lesions are present. Indeed, T2 changes on MRI can develop over hours to days, thus accounting for the low sensitivity in the hyperacute setting (ie, within 6 hours from symptom onset).