•A rare case of a monophasic cranial nerve multineuropathy after SARS-CoV2 vaccine.•Clinical manifestations were ophtalmoparesis and ptosis occurred after vaccination.•Single-fiber electromyography ...has showed a subclinical facial nerve impairment.•We have successfully treated the patient with steroid therapy.
Neuromuscular manifestations of SARS-CoV-2 vaccinations have been reported increasingly over the last years. Specifically, cranial multineuropathies are extremely rare entities and few cases have been reported related to COVID-19, whereas, todate, no case has been observed after vaccine against SARS-CoV-2. Herein we describe a patient who presented ptosis, ophthalmoparesis and a subclinical facial nerve impairment after two weeks from the second dose of AZD1222 (ChAdOx1-S recombinant) vaccine.
Objective:
The aim of our study was to evaluate the long-term efficacy and safety of mexiletine in 112 patients affected by genetically confirmed non-dystrophic myotonias. The study was performed at ...the Neurophysiologic Division of Fondazione Policlinico Universitario A. Gemelli Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Rome and the Children's Hospital Bambino Gesù, Rome.
Methods:
The treatment was accepted by 59 patients according to clinical severity, individual needs, and concerns about a chronic medication. Forty-three patients were affected by recessive congenita myotonia, 11 by sodium channel myotonia, and five by dominant congenital myotonia. They underwent clinical examination before and after starting therapy, and Electromyography (EMG). A number of recessive myotonia patients underwent a protocol of repetitive nerve stimulations, for detecting and quantifying the transitory weakness, and a modified version of the Timed Up and Go test, to document and quantify the gait impairment.
Results:
Treatment duration ranged from 1 month to 20 years and the daily dosages in adults ranged between 200 and 600 mg. No patient developed cardiac arrhythmias causing drug discontinuation. Mexiletine was suspended in 13 cases (22%); in three patients, affected by Sodium Channel myotonia, because flecainide showed better efficacy; in one patient because of a gastric cancer antecedent treatment; in four patients because of untreatable dyspepsia; and five patients considered the treatment not necessary.
Conclusions:
In our experience, mexiletine is very useful and not expensive. We did not observe any hazarding cardiac arrhythmias. Dyspepsia was the most frequent dose-limiting side effect.
Genome-wide gene expression profiling of skeletal muscle from Duchenne muscular dystrophy (DMD) patients has been used to describe muscle tissue alterations in DMD children older than 5 years. By ...studying the expression profile of 19 patients younger than 2 years, we describe with high resolution the gene expression signature that characterizes DMD muscle during the initial or "presymptomatic" phase of the disease. We show that in the first 2 years of the disease, DMD muscle is already set to express a distinctive gene expression pattern considerably different from the one expressed by normal, age-matched muscle. This "dystrophic" molecular signature is characterized by a coordinate induction of genes involved in the inflammatory response, extracellular matrix (ECM) remodeling and muscle regeneration, and the reduced transcription of those involved in energy metabolism. Despite the lower degree of muscle dysfunction experienced, our younger patients showed abnormal expression of most of the genes reported as differentially expressed in more advanced stages of the disease. By analyzing our patients as a time series, we provide evidence that some genes, including members of three pathways involved in morphogenetic signaling--Wnt, Notch, and BMP--are progressively induced or repressed in the natural history of DMD.--Pescatori, M., Broccolini, A., Minetti, C., Bertini, E., Bruno, C., D'amico, A., Bernardini, C., Mirabella, M., Silvestri, G., Giglio, V., Modoni, A., Pedemonte, M., Tasca, G., Galluzzi, G., Mercuri, E., Tonali, P. A., Ricci, E. Gene expression profiling in the early phases of DMD: a constant molecular signature characterizes DMD muscle from early postnatal life throughout disease progression.
Myotonic dystrophy type 1 (DM1, MIM #160900), the most common muscular dystrophy among adults, is a multisystem disorder, which affects, besides the skeletal muscle, several other tissues and/or ...organs, including the gastrointestinal apparatus, with manifestations that frequently affect the quality of life of DM1 patients. So far, only few, mainly retrospective studies evaluated this specific topic in DM1, so we performed a perspective study, enrolling 61 DM1 patients who underwent an extensive diagnostic protocol, including administration of the Gastrointestinal Symptom Rating Scale (GSRS), a validated patient-reported questionnaire about GI symptoms, laboratory tests, liver US scan, and an intestinal permeability assay, in order to characterize frequency and assess correlations regarding specific gastrointestinal manifestations with demographic or other DM1-related features. Our results in our DM1 cohort confirm the high frequency of various gastrointestinal manifestations, with the most frequent being constipation (45.9%). γGT levels were pathologically increased in 65% of DM1 patients and GPT in 29.82%; liver ultrasound studies showed steatosis in 34.4% of patients. Significantly, 91.22% of DM1 patients showed signs of altered intestinal permeability at the specific assay. We documented a gender-related prevalence and severity of gastrointestinal manifestations in DM1 females compared to DM1 males, while males showed higher serum GPT and γGT levels than females. Correlation studies documented a direct correlation between severity of muscle weakness estimated by MIRS score and γGT and alkaline phosphatase levels, suggesting their potential use as biomarkers of muscle disease severity in DM1.
Neurological manifestations of Sars-CoV-2 infection have been described since March 2020 and include both central and peripheral nervous system manifestations. Neurological symptoms, such as headache ...or persistent loss of smell and taste, have also been documented in COVID-19 long-haulers. Moreover, long lasting fatigue, mild cognitive impairment and sleep disorders appear to be frequent long term neurological manifestations after hospitalization due to COVID-19. Less is known in relation to peripheral nerve injury related to Sars-CoV-2 infection.
We report the case of a 47-year-old female presenting with a unilateral chest pain radiating to the left arm lasting for more than two months after recovery from Sars-CoV-2 infection. After referral to our post-acute outpatient service for COVID-19 long haulers, she was diagnosed with a unilateral, atypical, pure sensory brachial plexus neuritis potentially related to COVID-19, which occurred during the acute phase of a mild Sars-CoV-2 infection and persisted for months after resolution of the infection.
We presented a case of atypical Parsonage-Turner syndrome potentially triggered by Sars-CoV-2 infection, with symptoms and repercussion lasting after viral clearance. A direct involvement of the virus remains uncertain, and the physiopathology is unclear. The treatment of COVID-19 and its long-term consequences represents a relatively new challenge for clinicians and health care providers. A multidisciplinary approach to following-up COVID-19 survivors is strongly advised.
Channelopathy mutations prove informative on disease causing mechanisms and channel gating dynamics. We have identified a novel heterozygous mutation in the KCNA1 gene of a young proband displaying ...typical signs and symptoms of Episodic Ataxia type 1 (EA1). This mutation is in the S4 helix of the voltage-sensing domain and results in the substitution of the highly conserved phenylalanine 303 by valine (p.F303V). The contributions of F303 towards K
channel voltage gating are unclear and here have been assessed biophysically and by performing structural analysis using rat Kv1.2 coordinates. We observed significant positive shifts of voltage-dependence, changes in the activation, deactivation and slow inactivation kinetics, reduced window currents, and decreased current amplitudes of both Kv1.1 and Kv1.1/1.2 channels. Structural analysis revealed altered interactions between F303V and L339 and I335 of the S5 helix of a neighboring subunit. The substitution of an aromatic phenylalanine with an aliphatic valine within the voltage-sensor destabilizes the open state of the channel. Thus, F303 fine-tunes the Kv1.1 gating properties and contributes to the interactions between the S4 segment and neighboring alpha helices. The resulting channel's loss of function validates the clinical relevance of the mutation for EA1 pathogenesis.
Intensive Care Unit (ICU)-Acquired Weakness (ICU-AW) is a generalized muscle weakness that is clinically detected in critical patients and has no plausible etiology other than critical illness. ...ICU-AW is uncommon in patients undergoing orthotopic liver transplantation (OLT). Our report sheds light on the highest number of ICU-AW cases observed in a single center on OLT patients with early allograft dysfunction. Out of 282 patients who underwent OLT from January 2015 to June 2023, 7 (2.5%) developed generalized muscle weakness in the ICU and underwent neurophysiological investigations. The neurologic examination showed preserved extraocular, flaccid quadriplegia with the absence of deep tendon reflexes in all patients. Neurophysiological studies, including electromyography and nerve conduction studies, showed abnormalities with fibrillation potentials and the rapid recruitment of small polyphasic motor units in the examined muscles, as well as a reduced amplitude of the compound muscle action potential and sensory nerve action potential, with an absence of demyelinating features. Pre-transplant clinical status was critical in all patients. During ICU stay, early allograft dysfunction, acute kidney injury, prolonged mechanical ventilation, sepsis, hyperglycemia, and high blood transfusions were observed in all patients. Two patients were retransplanted. Five patients were alive at 90 days; two patients died. In non-cooperative OLT patients, neurophysiological investigations are essential for the diagnosis of ICU-AW. In this setting, the high number of red blood cell transfusions is a potential risk factor for ICU-AW.
Friedreich’s ataxia (FRDA) is usually due to a homozygous GAA expansion in intron 1 of the frataxin (
FXN
) gene. Rarely, uncommon molecular rearrangements at the
FXN
locus can cause pitfalls in the ...molecular diagnosis of FRDA. Here we describe a family whose proband was affected by late-onset Friedreich’s ataxia (LOFA); long-range PCR (LR-PCR) documented two small expanded GAA alleles both in the proband and in her unaffected younger sister, who therefore received a diagnosis of pre-symptomatic LOFA. Later studies, however, revealed that the proband’s unaffected sister, as well as their healthy mother, were both carriers of an expanded GAA allele and an uncommon (GAAGGA)
66–67
repeat mimicking a GAA expansion at the LR-PCR that was the cause of the wrong initial diagnosis of pre-symptomatic LOFA. Extensive studies in tissues from all the family members, including LR-PCR, assessment of methylation status of
FXN
locus,
MboII
restriction analysis and direct sequencing of LR-PCR products, analysis of
FXN
mRNA, and frataxin protein expression, support the virtual lack of pathogenicity of the rare (GAAGGA)
66–67
repeat, also providing significant data about the modulation of epigenetic modifications at the
FXN
locus. Overall, this report highlights a rare but possible pitfall in FRDA molecular diagnosis, emphasizing the need of further analysis in case of discrepancy between clinical and molecular data.
Prevalence estimates for the 2 forms of myotonic dystrophy types 1 and 2 (DM1 and DM2) are not exhaustive or non-available. Our aim was to estimate the minimum prevalence of DM1 and DM2 in Italy in ...the Rome province, applying standards of descriptive epidemiology.
All patients with a molecular diagnosis of DM1/DM2 and residents in the Rome province in 2013 have been enrolled, and the age-standardized prevalence has been calculated, assuming a Poisson distribution and adjusting for age.
We identified 395 DM1 patients: the age-standardized prevalence for total, females and males was 9.65, 8.35 and 11.07/100,000, respectively. The mean age of subjects differed considerably according to CTG repeat length (p = 0.001). Forty DM2 patients were identified. The age-standardized prevalence for total, females and males was 0.99, 1.07 and 0.90/100,000, respectively. The mean age was 57.05.
We estimated for the first time the age-standardized prevalence and the sex and age distribution of DM1 and DM2 in a general population. A higher prevalence of males in DM1 and females in DM2 and a higher mean age of DM2 patients (+8 years) were ascertained. Prevalence of DM2 was 10% that of DM1. These prevalence values are probably lower than mutational rates due to the incomplete penetrance of DM1 mutations and to the clinical elusiveness of DM2. Our findings will be useful in designing cohort studies and for developing a disease registry.
Myotonic dystrophy type 1 (DM1) is a spliceopathy related to the mis-splicing of several genes caused by sequestration of nuclear transcriptional RNA-binding factors from non-coding CUG repeats of ...DMPK pre-mRNAs. Dysregulation of ryanodine receptor 1 (RYR1), sarcoplasmatic/endoplasmatic Ca2+-ATPase (SERCA) and α1S subunit of voltage-gated Ca2+ channels (Cav1.1) is related to Ca2+ homeostasis and excitation-contraction coupling impairment. Though no pharmacological treatment for DM1 exists, aberrant splicing correction represents one major therapeutic target for this disease. Resveratrol (RES, 3,5,4′-trihydroxy-trans-stilbene) is a promising pharmacological tools for DM1 treatment for its ability to directly bind the DNA and RNA influencing gene expression and alternative splicing. Herein, we analyzed the therapeutic effects of RES in DM1 myotubes in a pilot study including cultured myotubes from two DM1 patients and two healthy controls. Our results indicated that RES treatment corrected the aberrant splicing of RYR1, and this event appeared associated with restoring of depolarization-induced Ca2+ release from RYR1 dependent on the electro-mechanical coupling between RYR1 and Cav1.1. Interestingly, immunoblotting studies showed that RES treatment was associated with a reduction in the levels of CUGBP Elav-like family member 1, while RYR1, Cav1.1 and SERCA1 protein levels were unchanged. Finally, RES treatment did not induce any major changes either in the amount of ribonuclear foci or sequestration of muscleblind-like splicing regulator 1. Overall, the results of this pilot study would support RES as an attractive compound for future clinical trials in DM1. Ethical approval was obtained from the Ethical Committee of IRCCS Fondazione Policlinico Universitario A. Gemelli, Rome, Italy (rs9879/14) on May 20, 2014.
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