Journal of Clinical Neuromuscular Disease最新文献

Objectives: Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is a rare, yet treatable, disorder of fatty acid β-oxidation with clinical presentations ranging from neonatal to very-late-onset forms. Very-late-onset MADD often has no identifiable genetic mutations and has been linked to sertraline exposure.

Methods: We report a case of very late-onset MADD with negative genetic testing, potentially associated with sertraline use.

Results: A 75-year-old woman presented with 3-year history of progressive, proximal-predominant weakness, dysphagia, and dysarthria. Examination revealed severe axial and proximal-predominant limb weakness. Laboratory studies showed elevation of multiple acylcarnitines. Muscle biopsy demonstrated a lipid storage myopathy. Comprehensive genetic testing was negative. Sertraline use was identified as a potential trigger. Treatment with riboflavin, coenzyme Q10, and levocarnitine, along with discontinuation of sertraline, led to rapid clinical improvement within weeks.

Discussion: This case supports the recent findings that sertraline can be associated with very-late-onset MADD. Neurologists should maintain a high index of suspicion for MADD in sertraline-treated patients with unexplained weakness because prompt initiation of riboflavin is crucial for strength recovery.

Abstract: A 19-year-old woman presented with acute progressive generalized limb weakness and inability to ambulate, after a recent upper respiratory tract infection. Given the flaccid quadriparesis and preceding infection, Guillain-Barré syndrome (GBS) was initially considered. This case aims to illustrate the diagnostic challenges and the critical role of backward reasoning in differentiating GBS mimickers. Neurologic examination, electrodiagnostic studies, brain MRI, and hematologic testing were performed. Motor nerve conduction and late responses were normal, whereas sensory studies indicated pure distal sensory polyneuropathy. MRI revealed cervical spinal cord hyperintensities, and blood tests showed macrocytic anemia and low serum vitamin B12. The diagnosis of severe vitamin B12 deficiency was established. The patient received cobalamin replacement therapy, and significant clinical improvement was observed for a 3-month follow-up period. Vitamin B12 deficiency can mimic GBS, particularly in acute settings. Accurate clinical reasoning, including the application of backward reasoning when atypical findings emerge, is essential to avoid misdiagnosis and ensure timely treatment in patients with acute neurologic presentations.

Objectives: X-linked Charcot-Marie-Tooth disease Type 1 (CMTX1), caused by gap junction beta-1 (GJB1) mutations, is the second most common form of CMT. Patients present with length-dependent sensorimotor polyneuropathy and split hand syndrome. Males are more severely affected; females show variable symptoms because of skewed X-inactivation. This study reclassifies a GJB1 variant of uncertain significance as pathogenic using American College of Medical Genetics criteria.

Methods: A family with neurologic symptoms underwent clinical evaluation, electrodiagnostic studies, genetic testing, and imaging.

Results: Affected individuals exhibited a sensorimotor polyneuropathy in an X-linked inheritance pattern with males having earlier, more severe symptoms. Characteristic findings included split hand syndrome and the suggestion of stroke-like episodes. Genetic testing revealed a GJB1 c.841T>C p.(Ser281Pro) variant. Analysis met American College of Medical Genetics criteria (1 strong, 3 moderate, 1 supporting) for pathogenicity.

Conclusions: The Ser281Pro GJB1 variant meets pathogenic criteria for CMTX1, extending known pathogenic regions beyond the C-terminal Arg220 codon.

Background: Clinical evaluation of distal symmetric polyneuropathy (DSP), which can include small fiber neuropathy (SFN), differs among neurologists, neuromuscular specialists, and internists. The American Academy of Neurology (AAN) 2009 Practice Parameter guides evaluation of DSP, but there are no guidelines or AAN practice parameters for the evaluation of SFN.

Objective: Determine how neurologists evaluate and test for SFN in their clinical practice and compare responses between neuromuscular (NM) and non-neuromuscular specialists (non-NM).

Design/methods: Eight hundred randomly selected AAN members, which included 400 members who indicated NM medicine to be a primary or secondary specialty, were selected to answer a survey about SFN. Respondents answered a survey instrument with a list of 44 serum tests and procedures for different neuropathy clinical scenarios.

Results: The survey response rate was 29.3% (234/798), with 48.8% (N = 114) indicating that their primary specialty was neuromuscular. For an initial evaluation of distal symmetric SFN, respondents ordered a mean of 12 tests (SD 5.8) with a range of 0-26 tests. There was no statistically significant difference between the mean number of tests ordered by neuromuscular versus non-neuromuscular specialists. The 5 most common overall responses were complete blood count (87%), vitamin B12 (86%), basic metabolic panel (84%), thyroid stimulating hormone (78%), and hemoglobin A1c (77%). For a secondary evaluation of etiologies of distal symmetric SFN, 52% of non-neuromuscular specialists (95% CI, 42%-61%) versus 35% of neuromuscular specialists (95% CI, 26%-45%) would order a paraneoplastic panel. There was significant disparity in ordering a skin biopsy for intraepidermal nerve fiber density, with 65% of neuromuscular specialists (95% CI, 55%-74%) indicating that they would order this test compared with 38% of non-neuromuscular specialists (95% CI, 29%-48%).

Conclusions: The recommended studies with the highest yield for finding a cause of DSP were not universally ordered. There is variability in approaches to diagnosing SFN and searching for a possible etiology. The development of an AAN practice parameter for SFN may help promote consistent practice among neurologists of all subspecialties.

Abstract: This issue of What Is in the Literature focuses on articles over the past year on clinical aspects of motor neuron disease, including amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). Disease-modifying treatment for ALS remains a challenge as 2 formal drug trials did not hold up to retesting. There are new thoughts based on a multistep model to partially explain why ALS develops relatively late in life. New information on fluid biomarkers, sex differences, efficacy of medical marijuana for common symptoms, and cognitive dysfunction are discussed. For the clinic, there are updated guidelines for multidisciplinary management. Other articles address how frequently the topic of sexual health is brought up in the clinic, and insights into how patients view end-of-life issues and quality of life when using tracheal ventilation. PLS has diagnostic challenges and practical aspects, which are reviewed.

Objectives: Anti-myelin-associated glycoprotein (MAG) polyneuropathy has been described as a progressive distal, sensorimotor, demyelinating polyneuropathy associated with immunoglobulin M paraprotein and low terminal latency index (TLI) on electrodiagnostic testing. We describe the features of patients with MAG antibody polyneuropathy at a single academic center.

Methods: A retrospective search of the electronic medical record identified patients with high titer anti-MAG antibody polyneuropathy. Demographic characteristics, clinical features, and nerve conduction studies were reviewed. TLI was calculated for tested nerves.

Results: Sixteen patients were identified. Mean age was 75 years. Sixty-nine percent were male. Twenty-five percent of patients had Waldenstrom macroglobulinemia. Half of patients had demyelinating features on nerve conduction studies. Mean TLI for the median, ulnar, fibular, and tibial nerves was 0.36, 0.41, 0.37, and 0.39 respectively. Average TLI for all nerves was 0.38. All but 1 patient received treatment-most often rituximab or intravenous immunoglobulin. Clinical improvement was noted in 56% of treated patients.

Conclusions: This cohort of MAG antibody neuropathy patients had greater clinical variability than typically described.

Objectives: Myofibrillar myopathy (MFM) is a group of hereditary neuromuscular disorders with heterogenous manifestations in skeletal and cardiac muscles. Little is known about phenotype-genotype spectrum of MFM in Indian population. This study aims to characterize the clinico-genetic spectrum of 12 MFM ptients from India.

Methods: A detailed description of the clinical, radiological and mutation spectrum of genetically confirmed MFM patients were done.

Results: The M:F ratio was 3:1. Median age of onset, presentation and illness duration were 20 (range: birth - 57 years), 31.5 (range: 6-59 years) and 9 (range: 1 - 28 years) years, respectively. Consanguinity was noted in n = 3 (25%) and motor developmental delay in n = 2 (16.7%). Clinical features noted include ptosis (n = 5, 41.7%) and ophthalmoparesis (n = 3, 25%), bifacial weakness (n = 3, 25%), flaccid dysarthria (n = 3, 41.7%), neck weakness (n = 5, 41.7%), limb-girdle weakness (n = 5, 41.7%), foot drop (n = 1, 8.3%), distal upper limb weakness (n = 2, 16.7%), proximo-distal weakness (n = 5, 41.7%), exertional dyspnoea (n = 4, 33.3%) and joint contractures (n = 8, 66.7%). Cardiac involvement (n = 4, 33.3%) including restrictive, dilated, hypertrophic cardiomyopathy. Median creatine kinase level was 884U/L (range: 347 - 3070 U/L). Muscle biopsy revealed reduced/absent sarcoplasmic desmin expression. Muscle MRI in three patients with predominant fatty infiltration in gluteus maximus and minimus, sartorius, gracilus and semitendinosus in DES; anterior and posterior compartments of distal legs in CRYAB; glutei, hamstrings, adductors of hip and legs with relative sparing of quadriceps, adductor magnus, medial gastrocnemius and peroneal muscles in TTN. Next generation sequencing (NGS) showed the most common gene involved is DES (n = 7, 58.3%) followed by other genes such as HSPB8 (n = 1), FLNC (n = 1), CRYAB (n = 1), LDB3 (n = 1) and TTN (n = 1).

Conclusions: This is the first study on clinic-genetic features of MFM from India. The various novel phenotypes noted in our cohort include: CRYAB with late symptom onset without cardiac or bulbar involvement, LDB3 with early onset limb girdle syndrome, ptosis and FLNC with distal myopathy and cardiomyopathy and HSPB8 with limb girdle syndrome and ptosis, further expanding the phenotypic spectrum of MFM.