Use of the Intermittent Abdominal Pressure Ventilation to guarantee speech in a tracheostomized Amyotrophic Lateral Sclerosis patient

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Review of the Diagnosis and Treatment of Periodic Paralysis

Periodic paralyses (PPs) are rare neuromuscular disorders caused by mutations in skeletal muscle sodium, calcium, and potassium channel genes. PPs include hypokalemic paralysis, hyperkalemic paralysis, and Andersen-Tawil syndrome. Common features of PP include autosomal dominant inheritance, onset typically in the first or second decades, episodic attacks of flaccid weakness, which are often triggered by diet or rest after exercise. Diagnosis is based on the characteristic clinic presentation then confirmed by genetic testing. In the absence of an identified genetic mutation, documented low or high potassium levels during attacks or a decrement on long exercise testing support diagnosis. The treatment approach should include both management of acute attacks and prevention of attacks. Treatments include behavioral interventions directed at avoidance of triggers, modification of potassium levels, diuretics, and carbonic anhydrase inhibitors

“Be an ambassador for change that you would like to see”: a call to action to all stakeholders for co-creation in healthcare and medical research to improve quality of life of people with a neuromuscular disease

Merit, Expertise and Measuremen

Being Yourself and Thinking About the Future in People With Motor Neuron Disease : a Grounded Theory of Self-care Processes

INTRODUCTION: Self-care is a crucial aspect in the management of people with motor neuron disease (MND). Nurses and healthcare professionals must know the processes used by patients in performing self-care to identify problems and help them. Decision-making processes, self-understanding, and political and social support influence the self-care process in chronic diseases. Little is known about the self-care process in MND. OBJECTIVE: The aim of this study was to gain insight on the self-care processes in people with MND. METHOD: A grounded theory method was chosen for this study. Data from interviews were gathered, and a simultaneous comparative analysis was conducted to identify categories and codes. RESULTS: Twenty-one people with spinal muscular atrophy and amyotrophic lateral sclerosis participated in the study. Five categories were identified as grounded in the data. The process starts from "being yourself in the care," and it develops thanks to "growing and changing" and with a "thinking about the future" approach. "Family role" and "you and who helps you" categories affect the process itself. CONCLUSION: The self-care process in people with MND is not seen in a daily perspective but changes with the evolution of the disease. For the growing patients with MND, changing, accepting and controlling the disease while deciding autonomously are the foundations of the process

Asymptomatic myotonia congenita unmasked by severe hypothyroidism

Myotonia congenita is an inherited muscle disorder sustained by mutations in the skeletal muscle chloride channel gene CLCN1. Symptoms vary from mild to severe and generalized myotonia and worsen with cold, stressful events and hormonal fluctuations. Here we report the case of a young woman who sought medical attention because of subacute onset of diffuse and severe limb myotonia. CLCN1 gene sequencing showed a heterozygous transversion (T550M), two polymorphisms and one silent mutation. Thyroid function screening revealed severe hypothyroidism. She was placed on l-thyroxine replacement therapy which dramatically improved myotonia. We conclude that hypothyroidism unmasked a genetically determined, clinically asymptomatic chloride channelopathy. Diagnostic work-up in patients with clinically isolated myotonia should not be limited to genetic screening of non-dystrophic or dystrophic myotonias. Considering the high prevalence of hypothyroidism in females, systematic thyroid function screening by looking for additional hypothyroid symptoms and serum TSH levels measurement is mandatory in these patients

Amyotrophic Lateral Sclerosis Survival Score (ALS-SS) : a simple scoring system for early prediction of patient survival

Our objectives were: (1) to identify independent prognostic factors to determine a survival score for amyotrophic lateral sclerosis (ALS) in a cohort of patients followed in the NEMO Centre (NEuroMuscular Omnicentre); (2) to replicate results in an independent cohort obtained from the Pooled Resource Open Access ALS Clinical Trial Consortium (PRO-ACT) database. Samples were collected from 428 ALS patients from the NEMO database and 2481 patients from the PRO-ACT database. Study design was a retrospective analysis with clinical and biochemical variables, using univariable and multivariable Cox models of analysis. Results showed that, in multivariable analysis, age at diagnosis, diagnostic delay, ALSFRS-R total score, Body Mass Index, aspartate aminotransferase and creatinine level were independently related to survival. These factors were recoded as categorical variables assigning a score from 5 to 15, and the sums of these scores were used to obtain the ALS-Survival Score (ALS-SS). This then allowed to identify three groups having different survival curves. The ALS-SS results were also replicated using data from the PRO-ACT database. In conclusion, considering independent prognostic factors, we were able to give an estimate of survival in our cohort of ALS patients. Whether this ALS-SS may be useful in clinical practice, and potentially in clinical trials, will have to be determined prospectively

In vitro analysis of splice site mutations in the CLCN1 gene using the minigene assay

Mutations in the chloride channel gene CLCN1 cause the allelic disorders Thomsen (dominant) and Becker (recessive) myotonia congenita (MC). The encoded protein, ClC-1, is the primary channel that mediates chloride (Cl-) conductance in skeletal muscle. Mutations in CLCN1 lower the channel's threshold voltage, leading to spontaneous action potentials that are not coupled to neuromuscular transmission and resulting in myotonia. Over 120 mutations in CLCN1 have been described, 10\ua0% of which are splicing defects. Biological specimens suitable for RNA extraction are not always available, but obtaining genomic DNA for analysis is easy and non-invasive. This is the first study to evaluate the pathogenic potential of novel splicing mutations using the minigene approach, which is based on genomic DNA analysis. Splicing mutations accounted for 23\ua0% of all pathogenic variants in our cohort of MC patients. Four were heterozygous mutations in four unrelated individuals, belonging to this cohort: c.563G>T in exon 5; c.1169-5T>G in intron 10; c.1251+1G>A in intron 11, and c.1931-2A>G in intron 16. These variants were expressed in HEK 293 cells, and aberrant splicing was verified by in vitro transcription and sequencing of the cDNA. Our findings confirm the need to further investigate the nature of rearrangements associated with this class of mutations and their effects on mature transcripts. In particular, splicing mutations predicted to generate in-frame transcripts may generate out-of-frame mRNA transcripts that do not produce functional ClC-1. Clinically, incomplete molecular evaluation could lead to delayed or faulty diagnosis. \ua9 2014 Springer Science+Business Media Dordrecht

Amyotrophic lateral sclerosis in pregnancy is associated with a vascular endothelial growth factor promoter genotype

Background and purpose: The occurrence of amyotrophic lateral sclerosis (ALS) during pregnancy is uncommon and the effect of one on the other is not well described. Methods: The clinical and genetic features of five cases of ALS are reported with an onset during pregnancy or within 1 month from delivery. Charts from 239 women with a diagnosis of ALS attending the neuromuscular clinics at the Neuromuscular Omnicentre (NEMO) and at IRCCS Policlinico San Donato from 2008 to 2011 were reviewed. Results: Of these, 12.8% of the women in child-bearing age had a diagnosis of ALS during pregnancy or immediately after delivery. Genetic screening of the major causative genes revealed two mutations in superoxide dismutase 1 (SOD1) gene the analysis of vascular endothelial growth factor (VEGF) promoter variation showed a segregation of the haplotype CA/AG (-2578C/A; -1190A/G) in patients developing ALS related to pregnancy. No effects on foetal development or neonatal course were observed. Conclusions: Pregnancy may unmask ALS but whether this is coincidental is unclear. Hormonal and inflammatory modifications might trigger ALS in subjects with increased susceptibility to oxidative stress related to the toxic function of SOD1 or in subjects with a reduction of neuroprotective molecules such as VEGF