Myasthenia gravis with inflammatory myopathy without elevation of creatine kinase

Cases of myasthenia gravis with inflammatory myopathy usually show elevated creatine kinase (CK) levels. There are few case reports of myasthenia gravis with inflammatory myopathy without elevated CK levels, and clinical features and useful diagnostic methods for these patients are little known. We describe the case of a 79-year-old man with myasthenia gravis that was complicated with inflammatory myopathy without elevated CK levels and successfully treated with immunological treatment. Initially, he was diagnosed with ocular myasthenia gravis and treated with pyridostigmine, but dysphagia and weakness in the neck and bilateral upper limb without fatigability gradually developed. Needle electromyography revealed myopathic changes, and the results of muscle biopsy were consistent with inflammatory myopathy. Blood tests showed normal CK levels throughout the clinical course and elevated myoglobin levels alone. The possibility of developing inflammatory myopathy in patients with myasthenia gravis cannot be excluded, even if CK levels are normal.     

EMG evidence of myopathy and the occurrence of titin autoantibodies in patients with myasthenia gravis

We studied 65 patients with myasthenia gravis (MG). Clinical, neurophysiological, immunological, and histological findings suggested the coexistence of a presumed autoimmune myopathy. The clinical features were persistent pyridostigmine-resistant weakness and atrophy of striated muscles. The myopathy was found more often in patients with late-onset MG than in those with early-onset (37% vs 13%). Patients with myopathy were also prone to have other immune disorders (47% vs 13%). Elevated titres of antibodies against titin were detected more often in patients with electromyography (EMG) evidence of myopathy than in the sera of those without, and only in late-onset MG cases. Copyright Lippincott Williams & Wilkins     

Mitochondrial myopathy associated with myasthenia gravis in a young man

An 18-year-old man presented with progressive weakness of proximal muscles with prominent diurnal variation for 3 months. He had bilateral ptosis since his childhood without diurnal variation or double vision. Neurological examination showed involvement of levator palpebrae superioris and lateral rectus muscles bilaterally. The plasma glucose after 75 gm glucose load was 302 mg/dL. The electrophysiological study revealed myopathic pattern and a decremental response in repetitive nerve stimulation. The plasma lactate was elevated and the muscle biopsy showed numerous ragged-red fibers. Serum acetylcholine receptor antibody assay was positive. We diagnosed myasthenia gravis with mitochondrial myopathy.     

Myasthenia gravis presenting with unusual neurogenic muscle atrophy

We report a patient with myasthenia gravis who had neurogenic muscle atrophy in association with external ophthalmoplegia and weakness of the upper limbs. Neurogenic changes in the limb muscles were found on needle electromyography and histological studies. Symptoms improved and atrophy of the limbs diminished after intravenous immunoglobulin and oral corticosteroid therapy. We concluded that functional interruption of the neuromuscular junction caused the neurogenic muscle atrophy and that this was relieved by appropriate therapy.     

Diagnostic outcome of muscle biopsy

Introduction: We reviewed the diagnostic yield of muscle biopsy according to the presence or absence of muscle weakness, hyperCKemia, and electromyogaphic (EMG) abnormalities. Methods: In a retrospective study, 698 muscle biopsy reports were analyzed. Logistic regression models for myopathy and specific myopathy were fit, and receiver‐operating characteristic (ROC) curves were generated to assess prediction accuracy. The probability of finding specific myopathy was considered the main indication of a positive muscle biopsy. Results: Isolated hyperCKemia was poorly predictive of either myopathy or specific myopathy. Combined myopathic EMG, proximal weakness, and hyperCKemia were predictive. The predictability increased proportionally to the creatine kinase (CK) level in patients with proximal weakness and myopathic EMG. Cross validation showed accuracy around 70% for a probability threshold of 50%. Conclusions: The presence of hyperCKemia, proximal weakness, and myopathic EMG together were associated with highly positive diagnostic outcome of muscle biopsy. Isolated hyperCKemia had a poor diagnostic yield. Muscle Nerve 51 :662–668, 2015     

Familial limb-girdle myasthenia with tubular aggregates

Two sisters developed slowly progressive limb-girdle weakness in their childhood. The weakness responded to acetylcholinesterase inhibitors. Repetitive nerve stimulation showed decremental responses and single-fiber electromyography demonstrated increased jitter and blocking. Needle electromyography revealed myopathic changes. Antiacetylcholine receptor antibodies were negative. Histologic examinations demonstrated myopathy with tubular aggregates in the muscle fibers while the neuromuscular junctions appeared normal. They were diagnosed with familial limb-girdle myasthenia. This is the first report of this syndrome with morphologic studies of neuromuscular junctions. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 599–603, 1997.     

A novel case of inclusion body myositis and myasthenia gravis

The co-existence of myasthenia gravis and other inflammatory myopathies has been reported in the literature before, but no clinical cases involving inclusion body myositis have been reported. We report a case of a 67-year-old patient who presented with dysphagia, exhibiting the typical electrophysiological features of postsynaptic neuromuscular junction defect with positive muscle acetylcholine receptor antibodies, consistent with the diagnosis of myasthenia gravis. Nevertheless, response to acetylcholinesterase inhibitors and immunomodulatory treatment was unexpectedly poor. As the disease progressed, the patient developed asymmetric muscle weakness, initially affecting mainly the quadriceps and the finger flexors. Muscle MRI imaging supported the presence of an inflammatory myopathy and muscle biopsy confirmed the diagnosis of inclusion body myositis. Thus, our patient represents the first reported overlap case of myasthenia gravis and inclusion body myositis.     

Association between musk antibody concentrations and the myasthenia gravis composite score in 3 patients: A marker of relapse?

Introduction: Muscle-specific tyrosine kinase (MuSK) autoantibody related myasthenia gravis is characterized by bulbar and respiratory manifestations, a poor response to anticholinergics, and a generally good response to plasma exchange and rituximab. It is not known if MuSK-antibody (Ab) levels could be used to predict the clinical course Methods: Three patients for whom frequent long-term monitoring of MuSK-Ab levels and the Myasthenia Gravis Composite (MGC) scores were performed are described. Results: A close relationship existed between the MuSK-Ab concentrations and the MGC score. Furthermore, a rise in Ab concentration preceded a more serious clinical relapse in all patients Conclusions: These findings suggest that MuSK-Ab concentrations may be a useful biomarker for the long-term monitoring of MuSK myasthenia gravis, particularly while in clinical remission. This may allow preemptive escalation of therapy to prevent clinical relapse, and conversely permitting greater weaning of unnecessary immunosuppression. Muscle Nerve, 2019     

Diagnostic difficulties in myasthenia gravis

Four patients with myasthenia gravis presented with severe, largely isolated, bulbar and respiratory muscles weakness. Tensilon tests were positive and antiacetylcholine receptor (anti-AChR) antibody titers were negative in all patients. Only 1 patient had a greater than 10% decremental response during the period of respiratory failure. Although routine nerve conduction studies were normal, all had very low-amplitude diaphragmatic compound muscle action potentials. Three patients had abundant fibrillation potentials and positive sharp waves largely restricted to respiratory muscles. Clinical and electrophysiological findings improved with corticosteroids, and surprisingly, decremental responses became positive in all patients. The assessment of patients with largely isolated bulbar and respiratory muscle weakness due to myasthenia gravis may be difficult and misleading, as anti-AChR antibody titers may be negative, decremental responses may be absent, and electrophysiological assessment atypical. Due consideration of clinical symptomatology, a Tensilon test, and a trial of immunosuppression may be necessary to establish the diagnosis. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:577–583, 1998.     

Ocular myasthenia: evaluation of Tensilon tonography and electronystagmography as diagnostic tests

The value of electronystagmography (ENG) and of tonography in monitoring the beneficial effect of edrophonium chloride (Tensilon) on the extraocular muscles in myasthenia gravis has been assessed. Studies were performed on 17 patients with myasthenia gravis and on 18 control subjects, of whom nine had extraocular muscle weakness due to myopathic or neurogenic lesions.     

Trouble at the junction: When myopathy and myasthenia overlap

Although myopathies and neuromuscular junction disorders are typically distinct, their coexistence has been reported in several inherited and acquired conditions. Affected individuals have variable clinical phenotypes but typically display both a decrement on repetitive nerve stimulation and myopathic findings on muscle biopsy. Inherited causes include myopathies related to mutations in BIN1, DES, DNM2, GMPPB, MTM1, or PLEC and congenital myasthenic syndromes due to mutations in ALG2, ALG14, COL13A1, DOK7, DPAGT1, or GFPT1. Additionally, a decrement due to muscle fiber inexcitability is observed in certain myotonic disorders. The identification of a defect of neuromuscular transmission in an inherited myopathy may assist in establishing a molecular diagnosis and in selecting patients who would benefit from pharmacological correction of this defect. Acquired cases meanwhile stem from the co-occurrence of myasthenia gravis or Lambert-Eaton myasthenic syndrome with an immune-mediated myopathy, which may be due to paraneoplastic disorders or exposure to immune checkpoint inhibitors.     

Musk-antibody positive myasthenia gravis presenting with isolated neck extensor weakness

Dropped head sign is characterized by the gradual forward sagging of the head due to weakness of neck extensor muscles. This may be a prominent sign of several neuromuscular disorders and may be an isolated feature of myasthenia gravis (MG). We describe a patient with isolated neck extensor weakness, eletrophysiological findings suggesting myasthenia gravis and positive MuSK antibodies. This case supports that finding anti-MuSK antibodies may be extremely helpful in dropped head patients and negative acetylcholine receptor antibodies especially if needle EMG does not reveal myopathic or neurogenic patterns.     

Seronegative myasthenia gravis

Six to 20 p.cent of patients with generalized myasthenia gravis and 30 to 50 p.cent of those with ocular myasthenia gravis do not have anti AchR antibodies. Strict clinical, pharmacological and electrophysiological criteria are needed for the diagnosis of sero-negative myasthenia gravis. Sero-negative myasthenia gravis is an autoimmune disorder. But thymic hyperplasia is generally absent. Antibodies directed against the muscle receptor of tyrosine kinase (anti MuSK antibodies) were recently demonstrated in 40 to 70 p.cent of patients with sero-negative myasthenia gravis. Sero-negative and sero-positive myasthenia gravis may be clinically very similar. But sero-negative myasthenia gravis may express predominantly severe oculobulbar weakness or mainly neck, shoulder and respiratory muscle weakness. Sero-negative myasthenia gravis is never associated with thymoma. Sero-negative myasthenia gravis responds to immunodulation but perhaps less well than sero-positive myasthenia gravis.     

Paradoxical lid elevation with sustained upgaze: a sign of Lambert-Eaton syndrome

Myasthenia gravis and Lambert-Eaton myasthenic syndrome are causes of acquired extraocular muscle weakness and ptosis. Exacerbation of ptosis after sustained upgaze is a clinically useful sign in the diagnosis of myasthenia gravis. A 54-year-old woman with established Lambert-Eaton myasthenic syndrome exhibited transient improvement of her ptosis after sustained upgaze. We suggest that paradoxical lid elevation after sustained upgaze may be a clinically useful sign in distinguishing Lambert-Eaton myasthenic syndrome from myasthenia gravis.     

Parkinsonism and dropped head: Dystonia,myopathy or both?

BackgroundDropped head syndrome (DHS) occurring with parkinsonism is often suggested to be a clue to multiple system atrophy (MSA), but it may occur in other parkinsonian conditions. The substrate for DHS is controversial, with some concluding that the cause is myopathic and others, exclusively dystonic. We report our clinical series of DHS arising in the setting of parkinsonism.MethodsPatients with DHS were initially identified by a retrospective computer search of the Mayo Clinic (Rochester, MN) medical record database from January 1997 to July 2010. Subsequent record review confirmed DHS and documented those with parkinsonism.ResultsWe identified 21 patients with DHS and parkinsonism, 12 male, 9, female. The median age of DHS onset was 69 years (interquartile range: 63.6–77.5 years). This included 10 patients with Parkinson‘s disease (PD), 10 with MSA, and 1 with drug-induced parkinsonism. The DHS component of their disorder segregated into three different subgroups: dystonia-alone (12 patients); myopathy-alone (4 patients; focal cervical myopathy in 3 and generalized myopathy in one); coexisting dystonia and myopathy (5 patients; 3 generalized, 2 focal cervical myopathy).ConclusionsDHS may be seen in either MSA or PD. It may be due to myopathy, dystonia or both. In some cases, the myopathy was focal, confined to the neck musculature. Whether dystonic antecollis predisposes to local muscle pathology is open to speculation.     

Distal myasthenia gravis: case report

We report the case of a 30-year-old woman with a 7-year history of distal lower limbs weakness that evolved to upper limbs weakness. On neurological examination, she presented normal cranial nerves, bilateral quadriceps and feet interosseous atrophy, normal muscular tonus, muscular weakness more severe in dorsal feet interosseous and anterior tibial, and decreased deep tendon reflexes. Repetitive nerve stimulation of the ulnar and fibular nerves showed a decrement greater than 10% of the compound muscle action potential. Antibody against acetylcholine receptor titer was positive. Computed tomography scan of the thorax was normal. Thyroid function tests showed evidence of hyperthyroidism. Distal muscular weakness is a rare onset presentation of myasthenia gravis. However, myasthenia gravis must be considered in the differential diagnosis of distal limb weakness.     

Myasthenia gravis Lambert‐Eaton overlap syndrome

Introduction: To assess whether a myasthenia gravis (MG) Lambert‐Eaton overlap syndrome (MLOS) exists. Methods: Case reports that met the universally accepted diagnostic criteria for MG and Lambert‐Eaton myasthenic syndrome (LEMS) were sought through a PubMed search. Fifty‐five possible cases of MLOS were identified. Results: Thirty‐nine cases met the diagnostic criteria for MG and LEMS. Analysis of clinical features showed that these patients have common MG and LEMS symptoms: oculo‐bulbar paresis and good response to anti‐cholinesterase for MG and limb weakness and decreased or absent reflexes for LEMS. All had the classical LEMS pattern in the repetitive nerve stimulation test: low compound muscle action potential amplitude and incremental response > 60% with brief exercise or at high rate of stimulation. Eight patients had combined positive acetylcholine receptor antibody (AChR‐ab) or muscle‐specific kinase‐ab and voltage‐gated calcium channel‐ ab tests. Conclusions: A myasthenia gravis Lambert‐Eaton overlap syndrome (MLOS) does exist. Muscle Nerve 53 : 20–26, 2016     

Unusual neurophysiological and immunological findings in myasthenia gravis: a case report

We describe the case of a male patient with ocular myasthenia gravis who developed a diabetic neuropathy similar to chronic inflammatory demyelinating polyradiculoneuropathy associated with transient generalized 'myokymic' discharges and distal weakness. He had antibodies against acetylcholine receptor and GQ1b ganglioside, but not anti-voltage-gated K(+) channel antibodies. Serial electrophysiological and immunological findings showed that diabetes was involved in the immune-mediated mechanism of peripheral neuropathy. We hypothesize that the concomitant appearance of distal motor weakness and decreased compound muscle action potentials upon repetitive nerve stimulation, together with increased distal motor latency and generalized peripheral nerve hyperexcitability, were all related to transient serum positivity to anti-GQ1b antibodies.     

Endocrine myopathies

The atrophy produced by endocrine disorders is primarily due to alterations in protein and carbohydrate metabolism. Type II muscle fibers are more severely affected than are Type I fibers. Steroid myopathy and the myopathy associated with excess ACTH have a typical pattern of proximal weakness affecting the legs more than the arms. Steroid myopathy is usually not apparent until other signs of glucocorticoid excess are present. Treatments of steroid myopathy are as follows: Lower the dose of steroid, use a nonfluorinated glucocorticoid, and exercise or physical therapy. Adrenal insufficiency produces generalized weakness, muscle cramping, and fatigue in 50 per cent of patients. Some patients also develop hyperkalemic paralysis. The treatment is hormone replacement. Thyrotoxicosis produces myopathy caused by net protein catabolism, accelerated basal metabolic rate and impaired carbohydrate metabolism. Shortening of contraction time may result from accelerated myosin ATPase activity and enhanced calcium uptake by the sarcoplasmic reticulum. Depolarization of the muscle fiber and impaired Na-K activity in muscle may predispose to thyrotoxic periodic paralysis. Neuromuscular presynaptic impairment may account for the worsening of myasthenia gravis by thyrotoxicosis. In hypothyroidism, impaired energy metabolism may limit force generation. Slow contraction and relaxation reflect reduction in myosin ATPase activity and impaired calcium uptake by the sarcoplasmic reticulum. Treatment for thyroid-associated muscle disorders is restoration of a euthyroid state. Muscle weakness associated with hypopituitarism is due to loss of thyroid and adrenal cortical hormones. Children require growth hormone for muscle development. T3 and growth hormone synergize to maintain normal protein synthesis. Primary and secondary hyperparathyroidism and osteomalacia are often associated with proximal weakness and fatigability. The myopathy improves with restoration of normal PTH levels and vitamin D replacement. Hypoparathyroidism and pseudohypothyroidism are associated with tetany. Tetany is worsened by alkalosis and is treated by calcium and magnesium replacement.     

Fiberoptic endoscopic evaluation of swallowing with simultaneous tensilon application in diagnosis and therapy of myasthenia gravis

Background Dysphagia is a common symptom in myasthenia gravis (MG). Clinical examination alone fails to detect and grade myasthenic dysphagia sufficiently. For a more precise examination of swallowing function in myasthenia gravis additional technical tools are necessary. Objective To investigate the diagnostic and therapeutic impact of fiberoptic endoscopic evaluation of swallowing with simultaneous Tensilon application (FEES-Tensilon Test) in myasthenia gravis. Methods FEES-Tensilon Test was performed following a standardized protocol. Four severely affected patients with dysphagia as their leading symptom were examined. Dysphagia was characterized by five salient endoscopic findings: leakage, delayed swallowing reflex, penetration, aspiration and residues. If a normalisation or at least an improvement of swallowing function occurred shortly after Tensilon administration the FEES-Tensilon Test was rated as being positive. Results In three patients the FEES-Tensilon Test successfully detected MG-related dysphagia. In one patient with dysphagia caused by oculopharyngeal muscular dystrophy the FEES-Tensilon Test was truly negative. Beside an early diagnosis of MG-related dysphagia, the FEES-Tensilon Test was useful in the differentiation between myasthenic and cholinergic crisis and in guiding treatment decisions. In all patients the FEES-Tensilon Test was superior to clinical evaluation of dysphagia. No severe side effect occurred while performing the FEES-Tensilon Test. Conclusion The FEES-Tensilon Test is a suitable tool in the diagnosis and therapy of myasthenia gravis with pharyngeal muscles weakness.