Electrophysiological Changes After Human Muscle Tear: A Potential Confounder.

The goal of this prospective electrophysiologic study is to describe the chronological electromyographic findings observed in a human gastrocnemius muscle after a traumatic tear. A 30-yr-old man sustained a tear of the medial gastrocnemius. Needle electromyography was performed serially at 5, 15, and 26 wks after injury, with the contralateral gastrocnemius muscle serving as a control. Audiovisual recordings of the studies were analyzed in a blinded manner. Five weeks after injury, the affected gastrocnemius displayed increased insertional activity on electromyography. By 15-wk postinjury, insertional activity had diminished. However, motor unit action potentials showed chronic neurogenic morphological changes not previously observed. These changes persisted 26 wks after injury. The study findings reveal a chronological trajectory of increased insertional activity followed by reinnervation changes in a human muscle after local trauma, paralleling a course previously observed in a rat model. Electrodiagnosticians unaware of this phenomenon are at risk for making erroneous interpretations when examining patients with a history of muscle trauma.

Maintenance plasma exchange treatment for muscle specific kinase antibody positive myasthenia gravis patients.

BACKGROUND: Anti-muscle specific kinase antibody positive myasthenia gravis (MuSK MG) is often characterized by a relatively severe and progressive course, refractoriness to standard myasthenia gravis (MG) medications, and an increased risk of myasthenic crisis. We report here successful management of three MuSK MG patients using maintenance therapeutic plasma exchange (TPE) treatment for up to 4.5 years. MATERIALS: The study was a 5-year retrospective review of all MG patients treated with TPE between 2008 and 2013 at University of Michigan. Inclusion criteria of MuSK MG were positive for anti-MuSK antibodies and a diagnosis of MuSK MG by staff neurologists. Patient data included age, gender, diagnostic testing results, medications, and the dates and response to TPE treatments. RESULTS: A total of 153 MG patients underwent at least one course of TPE between 2008 and 2013. A total of 12 patients (7.8%) were positive for anti-MuSK antibodies. Patients were predominantly female (83.3%) and a median age of onset was 46-years old. Three MuSK MG patients were successfully managed with maintenance TPE. CONCLUSION: Maintenance TPE may be an effective option for MuSK MG patients. The key of successful maintenance treatment at our institution has been to tailor the TPE frequency for each individual, and to modify the treatment interval in conjunction with medical management.

Amyotrophic lateral sclerosis in a patient with a family history of huntington disease: genetic counseling challenges.

Amyotrophic lateral sclerosis (ALS) and Huntington disease (HD) are generally considered to be distinct and easily differentiated neurologic conditions. However, there are case reports of the co-occurrence of ALS with HD. We present a 57-year-old male with a clinical diagnosis of sporadic ALS in the context of a family history of HD. This case adds to the limited literature regarding individuals with a family history of HD who present with features of ALS. There were several genetic counseling challenges in counseling this patient including the diagnostic consideration of two fatal conditions, complex risk information, the personal and familial implications, and the patient's inability to communicate verbally or through writing due to disease progression. DNA banking effectively preserved the right of our patient and his wife not to learn his HD genetic status during a stressful time of disease progression while providing the option for family members to learn this information in the future if desired. We present lessons learned and considerations for other clinical genetics professionals who are presented with similar challenging issues.

A novel mutation expands the genetic and clinical spectrum of MYH7-related myopathies.

MYH7 mutations are an established cause of Laing distal myopathy, myosin storage myopathy, and cardiomyopathy, as well as additional myopathy subtypes. We report a novel MYH7 mutation (p.Leu1597Arg) that arose de novo in two unrelated probands. Proband 1 has a myopathy characterized by distal weakness and prominent contractures and histopathology typical of multi-minicore disease. Proband 2 has an axial myopathy and histopathology consistent with congenital fiber type disproportion. These cases highlight the broad spectrum of clinical and histological patterns associated with MYH7 mutations, and provide further evidence that MYH7 is likely responsible for a greater proportion of congenital myopathies than currently appreciated.

Inflammatory and toxic myopathy.

Although muscle diseases are relatively rare, several treatable myopathies must be recognized by the clinician to maximize the possibility of restoring strength in affected patients. The inflammatory myopathies, including polymyositis, dermatomyositis, inflammatory necrotizing myopathy, and myositis in association with mixed connective tissue disease, typically respond well to immunosuppressive treatment. Inclusion body myositis, a myopathy that has features of both inflammation and primary degeneration, may not be treatable at this time, but treatments are actively being sought. Muscle dysfunction caused by toxins must also be recognized because removal of the offending toxin usually results in restoration of normal muscle function. Important muscle toxins include cholesterol-lowering medications, colchicine, zidovudine, corticosteroids, emetine, and ethanol.

Multifocal motor neuropathy.

Multifocal motor neuropathy is an acquired disorder in which demyelination of motor axons, presumably due to autoimmune attack, results in progressive painless weakness without sensory loss. Motor axonal damage also occurs. It is a frequent mimic of motor neuron disease. Recognition of multifocal motor neuropathy is critical because it tends to be very responsive to treatment. Infusion of intravenous immunoglobulin is the initial treatment of choice, but other immunosuppressive treatments may also be effective. It appears that corticosteroids produce minimal benefit.

Miller Fisher's syndrome.

Miller Fisher's syndrome is a rare variant of Guillain-Barré's syndrome characterized by the acute development of ataxia, ophthalmoparesis, and areflexia. Most patients have a measureable antibody in serum directed against the GQ1b ganglioside. This antibody is also present in the serum of patients with other forms of Guillain-Barré's syndrome who have prominent ataxia or ophthalmoplegia as part of their clinical presentation. Miller Fisher's syndrome generally is self-limited and has an excellent prognosis.

Late-onset Pompe's disease.

Glycogen storage disease type II, also known as Pompe's disease or acid maltase deficiency, is caused by a deficiency in acid α-glucosidase. Severe enzyme deficiency results in infantile Pompe's disease with multiorgan involvement; a partial deficiency produces a less severe phenotype mainly consisting of a myopathy, with a later age of onset. Treatment is now available with intravenous infusion of recombinant acid α-glucosidase. Such treatment results in marked improvement in patients with infantile Pompe's disease, and modest improvement or stabilization in patients with late-onset Pompe's disease.

Stiff Person syndrome and other anti-GAD-associated neurologic disorders.

Antibodies directed against glutamic acid decarboxylase (GAD) are present in many patients with stiff person syndrome and increasingly found in patients with other symptoms indicative of central nervous system (CNS) dysfunction, such as ataxia. The classic clinical features of stiff person syndrome include muscular stiffness with superimposed painful muscular spasms. Gait is often impaired. Other CNS disorders associated with GAD antibodies include progressive encephalomyelitis with rigidity and myoclonus (PERM), limbic encephalitis, and even epilepsy. Glutamic acid decarboxylase is the rate-limiting enzyme in the production of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter. Presumably, antibodies directed against GAD impair GABA production, but the precise pathogenic mechanism of GAD-antibody-related neurologic disorders is uncertain. Many patients respond to treatment with immunomodulating therapy. Symptomatic treatment with agents that enhance GABA activity, such as benzodiazepines and baclofen, is also helpful for many patients.

Noninvasive model of sciatic nerve conduction in healthy and septic mice: reliability and normative data.

Neuromuscular disorders frequently complicate sepsis and other critical illnesses in patients. Mice are the major species used as a model for sepsis. Nerve conduction studies (NCS), the primary tool for noninvasive assessment of nerve and muscle function, is challenging to perform in small animals. A reliable method for noninvasive, repeated NCS testing has not been reported in mice. We developed and validated a method for the repeated measurement of mouse sciatic nerve conduction in normal and septic mice. Our sedated and awake NCS system enabled minimally invasive long-term repeated measurements. The mean compound muscle action potential (CMAP) amplitude and latency were 17.4 mV and 1.11 ms, respectively (n = 59). There was an excellent intertester reproducibility by linear regression in both normal (r = 0.95) and septic (r = 0.98) mice. We also showed significant, time-dependent isoflurane-induced CMAP suppression in all animals, which was further exacerbated in septic mice. This study provides a new tool for the assessment of peripheral nerve/muscle function in mouse neuromuscular disease models that require repeated, long-term, and minimally invasive monitoring.

Dysregulation of sodium channel gating in critical illness myopathy.

Critical illness myopathy (CIM) is the most common caused of acquired weakness in critically ill patients. While atrophy of muscle fibers causes weakness, the primary cause of acute weakness is loss of muscle excitability. Studies in an animal model of CIM suggest that both depolarization of the resting potential and a hyperpolarized shift in the voltage dependence of sodium channel gating combine to cause inexcitability. In active adult skeletal muscle the only sodium channel isoform expressed is Nav1.4. In the animal model of CIM the Nav1.5 sodium channel isoform is upregulated, but the majority of sodium current is still carried by Nav1.4 sodium channels. Experiments using toxins to selectively bock the Nav1.4 isoform demonstrated that the cause of the hyperpolarized shift in sodium channel inactivation is a hyperpolarized shift in inactivation of the Nav1.4 isoform. These data suggest that CIM represents a new type of ion channel disease in which altered gating of sodium channels is due to improper regulation of the channels rather than mutation of channels or changes in isoform expression. The hypothesis that dysregulation of sodium channel gating underlies inexcitability of skeletal muscle in CIM raises the possibility that there maybe dysregulation of sodium channel gating in other tissues in critically ill patients. We propose that there is a syndrome of reduced electrical excitability in critically ill patients that affects skeletal muscle, peripheral nerve, the heart and central nervous system. This syndrome manifests as CIM, critical illness polyneuropathy, reduced cardiac contractility and septic encephalopathy.

ECG changes during septic shock.

We have previously found that skeletal muscle becomes electrically inexcitable in septic patients. Work in an animal model suggests that a decrease in the available sodium current underlies the loss of electrical excitability. We examined ECGs from patients during periods of septic shock to determine whether there were any ECG abnormalities that might suggest a similar loss of excitability in cardiac tissue during sepsis. Fourteen out of 17 patients had low or significantly decreased QRS amplitudes during septic shock; 8 of 17 had long or increased QRS duration with or without bundle branch block. The mean decrease in QRS amplitude in septic patients was 41%, significantly higher than in controls where no consistent decrease in QRS amplitude was found (p < 0.01). In patients who recovered from septic shock, the QRS amplitude and the increased QRS duration both returned to normal. We conclude that there is a loss of QRS amplitude during septic shock that may be due to altered cardiac excitability.