Diagnosis of DOK7 congenital myasthenic syndrome during pregnancy: A case report and literature review.

INTRODUCTION: Pregnancy among patients with congenital myasthenic syndrome (CMS) is a rare occurrence. Since most of the patients with CMS reach adulthood, questions regarding clinical outcome with pregnancy arise. CASE REPORT: We describe a 38-year-old Portuguese female who presented in the second trimester of pregnancy with proximal fluctuating limb-girdle weakness, hyperlordosis, waddling gait, dysphagia, dysphonia and ptosis, with no ophthalmoparesis. Initial diagnosis of seronegative myasthenia, supported by neurophysiology findings, led to unsuccessful treatment with intravenous immunoglobulin, pyridostigmine, prednisolone and plasmapheresis, and the patient slowly progressed to a severe tetraparesis with facial and bulbar involvement. Genetic testing for CMS identified a novel compound heterozygous mutation (c.1124_1127dupTGCC and c.935_936del) in the DOK7 gene. Subsequent treatment with salbutamol resulted in substantial clinical benefit. CONCLUSIONS: This case underlines the importance of considering the diagnosis of CMS in patients with fluctuating weakness during pregnancy. Patients of child-bearing potential diagnosed with CMS, particularly due to DOK7 mutations, should be counseled in advance and closely followed during pregnancy.

Acute-onset chronic inflammatory demyelinating polyneuropathy with anti-neurofascin-155 antibodies and bilateral facial nerve enhancement.

A 26-year-old female presented with acute onset distal paraparesis, upper limb tremor and bilateral facial palsy. Neurophysiology revealed a sensorimotor demyelinating polyneuropathy and lumbar puncture revealed an albuminocytologic dissociation. Neuroaxis MRI revealed bilateral facial nerve and cauda equina enhancement. Initially diagnosed as Guillain-Barré Syndrome, poor response to intravenous immunoglobulin, persistent deterioration, anti-neurofascin-155 antibodies and clinical response to steroid therapy led to diagnosis of acute-onset chronic inflammatory demyelinating polyneuropathy (CIDP). CIDP patients with anti-neurofascin-155 antibodies are younger, with distal predominant weakness, tremor, and poor response to intravenous immunoglobulin. Up to 16% can present acutely, however bilateral facial weakness is rare.

Analysis of riluzole's profile of use in a Central Hospital in Lisbon.

PURPOSE: Riluzole is indicated to prolong life or delay the institution of mechanical ventilation in patients with amyotrophic lateral sclerosis (ALS). Clinical studies have shown that this drug prolongs survival, defined as living patients who are not intubated for mechanical ventilation and without tracheotomy. The purpose of this study is to characterize riluzole's use as well as the user population in order to contribute to a rational and safe use. PATIENTS AND METHODS: Descriptive, observational, retrospective study describing and characterizing the use of riluzole in ALS patients between July 2006 and December 2016 conducted in a Lisbon's Central Hospital. RESULTS: Over the course of the study period, 77 patients with different phenotypes of ALS received riluzole. The majority of patients (63%, n=49) were male. The median survival was 10.1 months, but 12 patients (16%) remained on therapy for more than 3 years; 65% of patients were lost to follow-up. The mean adherence rate was 91.2%, and the median adherence rate was 99.3%. One patient discontinued therapy due to gastrointestinal intolerance. Dyspnea and cough were the most common side effects, with roughly one third of patients experiencing each, followed by asthenia and hepatic effects. CONCLUSION: Despite the extended enrollment period, only 77 patients met the criteria for study inclusion. Nonetheless, statistical data regarding our population is in accordance with reported international data. High adherence rates were observed, but 14% of patients discontinued riluzole. In such cases, assessment by a multidisciplinary team is warranted.

New massive parallel sequencing approach improves the genetic characterization of congenital myopathies.

Congenital myopathies (CMs) are a heterogeneous group of muscle diseases characterized by hypotonia, delayed motor skills and muscle weakness with onset during the first years of life. The diagnostic workup of CM is highly dependent on the interpretation of the muscle histology, where typical pathognomonic findings are suggestive of a CM but are not necessarily gene specific. Over 20 loci have been linked to these myopathies, including three exceptionally large genes (TTN, NEB and RYR1), which are a challenge for molecular diagnosis. We developed a new approach using massive parallel sequencing (MPS) technology to simultaneously analyze 20 genes linked to CMs. Assay design was based on the Ion AmpliSeq strategy and sequencing runs were performed on an Ion PGM system. A total of 12 patients were analyzed in this study. Among the 2534 variants detected, 14 pathogenic mutations were successfully identified in the DNM2, NEB, RYR1, SEPN1 and TTN genes. Most of these had not been documented and/or fully characterized, hereby contributing to expand the CM mutational spectrum. The utility of this approach was demonstrated by the identification of mutations in 70% of the patients included in this study, which is relevant for CMs especially considering its wide phenotypic and genetic heterogeneity.

A sporadic case of late-onset familial amyloid polyneuropathy with a monoclonal gammopathy.

A 77-year-old Portuguese woman reported gradual worsening of burning and numbness in the feet and hands, fatigue, anorexia, weight loss, diarrhoea and decreased visual acuity. She had a medical history of atrial fibrillation and recent episodes of dizziness and blood pressure fluctuations. There was no relevant family history. The diagnostic workup documented a severe axonal sensorimotor peripheral neuropathy, a monoclonal IgG kappa protein on serum, a severe left ventricular hypertrophy on the echocardiogram and probable vitreous deposits of amyloid on ophthalmologic examination. Pain and dysautonomia with an axonal neuropathy and multisystemic involvement raised the possibility of amyloidosis. The presence of a detectable monoclonal protein, older age at disease onset and absence of family history of disease usually suggest immunoglobulin light-chain amyloidosis. However, in this case, both the genetic testing and the biopsy of the salivary glands confirmed transthyretin amyloidosis. In those patients with a monoclonal protein, particularly in sporadic and late-onset cases, the diagnosis of transthyretin amyloidosis can be challenging, mimicking immunoglobulin light-chain amyloidosis.