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Magnesium (Mg) competes with calcium in normal synaptic transmission, inhibiting neurotransmitter release. As a drug, it is usually given as a treatment for eclampsia and preeclampsia. Two eclamptic pregnant women treated with Mg developed a pseudocoma state immediately after emergency Caesarian section. The clinical presentation was flaccid quadriparesis, areflexia, absent respiratory effort and vestibular-ocular reflexes, but with preserved pupillary responses. Decremental responses on repetitive nerve stimulation were found in both women. Recovery was obtained after cessation of Mg. The persistence of pupillary reflexes in the absence of reflexes involving striated muscles was an important clinical clue, indicating neuromuscular junction dysfunction., (© 2022 American Academy of Neurology.)

Objective: To characterize the pattern and extent of muscle weakness and impact on physical functioning in adults with GNEM., Methods: Strength and function were assessed in GNEM subjects (n = 47) using hand-held dynamometry, manual muscle testing, upper and lower extremity functional capacity tests, and the GNEM-Functional Activity Scale (GNEM-FAS)., Results: Profound upper and lower muscle weakness was measured using hand-held dynamometry in a characteristic pattern, previously described. Functional tests and clinician-reported outcomes demonstrated the consequence of muscle weakness on physical functioning., Conclusions: The characteristic pattern of upper and lower muscle weakness associated with GNEM and the resulting functional limitations can be reliably measured using these clinical outcome assessments of muscle strength and function.

Purpose of Review: To review some management issues in myasthenic disorders that are not part of the immune interventions. These are mainly related to pharmacotherapy of these conditions and side effects of various medications, but also referred to acute management of respiration in myasthenic crises., Recent Findings: Antisense compound inhibiting acetylcholine esterase has positive therapeutic effects during short-term administration, but further studies are needed to confirm its chronic effects. Pyridostigmine seems not to have an additional effect to 3-4 diaminopyridine in Lambert Eaton myasthenic syndrome. Bilevel positive airway pressure and other external respiratory supportive systems may prevent in some myasthenic crises the need for intubation or at least shorten it. Statins can aggravate myasthenia gravis but the risk is not well quantified, and these compounds are not completely contraindicated in myasthenia., Summary: Further research of the above findings is still necessary to make them a solid conclusion for the management of the myasthenias.

Mutations in GNE encoding UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) cause hereditary inclusion body myopathy (HIBM). To define the role of GNE mutations in HIBM pathogenesis, GNE protein expression was analyzed. GNE protein is expressed at equal levels in HIBM patients and normal control subjects. Immunofluorescence detection of GNE did not reveal any mislocalization of GNE in skeletal muscle. We conclude that impaired GNE function, not lack of expression, may be the key pathogenic factor in HIBM. For diagnostic purposes, direct genetic analysis of the GNE gene in patients with IBM will remain the mainstay and is not aided by immunohistochemistry or immunoblotting using antibodies against the GNE protein.

Background: Recessively inherited hereditary inclusion body myopathy (HIBM) with quadriceps sparing was initially described only in Jews originating from the region of Persia. The recent identification of the gene responsible for this myopathy and the common "Persian Jewish mutation" (M712T) enabled the re-evaluation of atypical phenotypes and the epidemiology of HIBM in various communities in the Middle East., Objective: To test for the M712T mutation in the DNA from HIBM patients in the Middle East., Methods: DNA from all suspected HIBM patients was tested for the M712T mutation. Unaffected members of families with genetically proven HIBM were studied too. In the majority of families, haplotype construction with markers spanning the 700-kb region of the HIBM gene was performed., Results: One hundred twenty-nine HIBM patients of 55 families (Middle Eastern Jews, Karaites, and Arab Muslims of Palestinian and Bedouin origin) were homozygous for the M712T mutation, and all carried the same haplotype. Five clinically unaffected subjects were also homozygous for the common mutation and haplotype, including two older adults (ages 50 and 68 years). Atypical features with this same mutation were marked quadriceps weakness in five patients, proximal weakness only in two patients, facial weakness in three patients, and a muscle biopsy showing perivascular inflammation in one patient., Conclusions: The phenotypic spectrum of recessive HIBM is wider than previously described, and the diagnostic criteria for this myopathy must be changed. The Middle Eastern cluster is the result of a founder mutation, with incomplete penetrance, that is approximately 1,300 years old and is not limited to Jews.

Two major entities continue to be controversial in the field of clinical myotoxicity: the various myopathies that are induced by the cholesterol-lowering agents and the acute quadriplegic myopathy of intensive care. Both conditions are relatively common, but their pathogenesis is unclear. The problematic issues related to these disorders are presented, with suggested topics for future research.

We studied the physiologic adaptation of patients with mitochondrial myopathies to aerobic training. Ten patients underwent individually supervised, moderate-intensity aerobic training on a treadmill for 8 weeks. Biochemical and functional measures improved with training. Estimated aerobic capacity increased by 30%. Blood lactate concentrations at rest and after exercise decreased by 30%. Muscle phosphorus magnetic resonance spectroscopy measurements of adenosine diphosphate recovery after exercise improved by more than 60%. Fatigue and tolerance to daily activities also improved. Although the improvement in exercise tolerance may be due in part to reversal of the effects of secondary deconditioning, this uncontrolled clinical trial suggests that aerobic training can benefit patients with mitochondrial myopathies.

We report a new neurocutaneous syndrome of apparent autosomal recessive inheritance consisting of early-childhood-onset palmoplantar keratoderma followed in adulthood by progressive tetrapyramidal syndrome and cognitive impairment. Of the four affected siblings, two were available for evaluation. Investigation disclosed cerebral white-matter involvement on MRI and arylsulfatase A pseudodeficiency carrier state, which was also identified in clinically unaffected family members. Since skin biopsies showed dermal connective tissue abnormalities, we studied collagens I, III, and VI biosynthesis. Northern blotting of RNA extracted from cultured skin fibroblasts revealed an increased steady-state messenger RNA (mRNA) level of alpha 1(VI) collagen, whereas no differences were detected for pro alpha 1(I), pro alpha 1(III), and tropoelastin mRNAs. The skin content of collagen and total protein was higher in the patients than in controls. We suggest that an extracellular matrix abnormality may be involved in the pathogenesis of this disorder.

Late-onset muscle weakness is rare in glycolytic disorders. There are two reports in the literature of phosphofructokinase (PFK)-deficient Ashkenazi Jews with severe vacuolar myopathy manifesting in late adulthood. The genetic abnormality in these patients is unknown. We report a third patient with a similar syndrome: early-onset exercise intolerance in young childhood and progressive weakness in a limb-girdle distribution appearing at 57 years of age, leading to severe incapacity. Muscle histology showed diffuse vacuolar changes, and muscle fibers contained excess glycogen-like material. Muscle biochemistry was diagnostic for PFK deficiency. DNA analysis from the patient and his family showed that he was homozygous for a recently identified point mutation at the exon 5/intron 5 junction (a G-to-A change); two other family members were heterozygous for this mutation. It is not clear whether late-onset weakness is the natural course for all PFK-deficient patients or whether the exon 5 mutation carries increased risk for this severe myopathy.

After observing a 72-year-old myasthenic patient develop an acute myasthenic exacerbation following the administration of routine diagnostic IV contrast material, an observation rarely described in the literature, we used the experimental autoimmune myasthenia gravis model in rabbits injected with a contrast agent to simulate the situation. There was significant worsening of the decremental response to 3 Hz repetitive nerve stimulation from 40 +/- 29% to 55 +/- 27% following the IV administration of contrast agent at doses similar to those used in humans. IV calcium partially reversed this aggravation. Caution is merited when myasthenic patients are administered contrast media.

Twelve adults with mitochondrial myopathies were studied by phosphorus magnetic resonance spectroscopy of muscle. All 12 had abnormal 31P-NMR findings; recovery from exercise was abnormal in 11 patients. At rest, the ratio of phosphocreatine to inorganic phosphate was reduced in 10. Exercise transfer characteristics were abnormal in all five patients who could exercise. Exercise-induced intracellular acidosis was subnormal in nine patients. The range of abnormalities indicates biochemical heterogeneity, with two possible groups: primary defects of energy metabolism with marked 31P-NMR abnormalities, and secondary, less specific 31P-NMR abnormalities.

Guillain-Barré syndrome (GBS) appeared in four patients 1 to 2 weeks after epidural anesthesia. In all patients, clinical diagnosis was confirmed by CSF findings and nerve conduction velocity studies. Although epidural anesthesia has not been listed as an antecedent event in GBS, evidence for the relationship has been previously reported. Interaction between the anesthetic agents and peripheral nervous system myelin or local trauma to roots may initiate a cascade of immunologic events that result in the demyelinating neuropathy.

Five patients with McArdle's syndrome were examined by phosphorus magnetic resonance spectroscopy (31P-NMR). Adenosine triphosphate (ATP) levels at rest were reduced by 22%, but did not fall further during exercise or contracture. The slope of work rate versus inorganic phosphate/phosphocreatine (Pi/PCr) was 42 +/- 8 joules/min/Pi/PCr in three patients without muscle wasting, compared with 13 and 16 in patients with atrophy (normal, 30 to 50 joules/min/Pi/PCr). Recovery from exercise showed similar rates in patients (postischemic exercise 1.03 +/- 0.17, post-aerobic 1.63 +/- 0.17 PCr/Pi units per minute) and controls (1.0 +/- 0.2 and 1.8 +/- 0.2, respectively) independent of intracellular pH. Infusion of glucose improved exercise kinetics by 163 to 190%, but an oral load of protein had no effect. We conclude that (1) muscle mitochondria operate normally in vivo in this glycogenolytic disorder, suggesting a sufficient alternate fuel supply. (2) Blood-borne glucose may serve as one alternate fuel for the "second wind" phenomenon. (3) ATP control mechanisms are altered only at rest. (4) Recovery from exercise is relatively pH-independent.

Chronic idiopathic intestinal pseudo-obstruction (CIIP) is characterized by recurrent episodes of bowel obstruction without mechanical cause. In five members of two Jewish-Iranian families, CIIP was associated with progressive neuronal disease, starting before age 30, with ophthalmoplegia, sensorimotor peripheral neuropathy, and hearing loss. There was no evidence of CNS involvement. The pattern suggested autosomal recessive inheritance.

Using in vivo 31P NMR spectroscopy, the authors compared the NMR spectra of the flexor muscles of the forearm from 13 humans characterized as MH susceptible on the basis of in vitro caffeine/halothane contracture tests with those from 25 normal controls. The levels of phosphocreatine (PCr), inorganic phosphate (Pi), and ATP during rest, graded exercise, and post-exercise recovery were measured in their forearms. MH susceptible subjects had significantly (P less than 0.001) higher Pi/PCr values (0.222 +/- 0.009) at rest than did normal controls (0.140 +/- 0.004). In addition, a significantly (P less than 0.01) slower post-exercise recovery rate was found in the MH-susceptible group. There was no significant difference between the two groups in the relationship of work rate to Pi/PCr. These data suggest that unchallenged MH susceptible patients can be distinguished from normals using 31P NMR spectroscopy. The potential use of this technique as a non-invasive tool in determining MH susceptibility is discussed, as well as the possible mechanisms underlying the observed 31P NMR abnormalities.