Said R. Beydoun

Randomized Trial of Thymectomy in Myasthenia Gravis

BACKGROUND Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone. METHODS We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period. RESULTS A total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P<0.001); patients in the thymectomy group also had a lower average requirement for alternate-day prednisone (44 mg vs. 60 mg, P<0.001). Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine (17% vs. 48%, P<0.001) or were hospitalized for exacerbations (9% vs. 37%, P<0.001). The number of patients with treatment-associated complications did not differ significantly between groups (P=0.73), but patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications (P<0.001) and lower distress levels related to symptoms (P=0.003). CONCLUSIONS Thymectomy improved clinical outcomes over a 3-year period in patients with nonthymomatous myasthenia gravis. (Funded by the National Institute of Neurological Disorders and Stroke and others; MGTX ClinicalTrials.gov number, NCT00294658.).

Bilateral phrenic neuropathy as a presenting feature of multifocal motor neuropathy with conduction block

Diaphragmatic paralysis has previously been reported as a result of diverse pathologic processes involving the peripheral nervous system. We report the clinical history, physical findings, and antibody profile of an atypical case of multifocal motor neuropathy with conduction block initially presenting with respiratory failure secondary to bilateral phrenic neuropathy.

A controlled trial of intravenous immunoglobulin in multifocal motor neuropathy.

Intravenous immunoglobulin (IVIG) has become the standard treatment for multifocal motor neuropathy (MMN) based on limited data. To critically assess the efficacy, safety, and tolerability of 10% liquid IVIG (IVIG), 44 adults with MMN were randomized 1 : 1 to either double‐blind treatment of IVIG followed by placebo for 12 weeks each or the reverse. Open‐label IVIG was administered for 12 weeks at the beginning and end of the study for clinical stabilization, and between double‐blinded periods to prevent a carry‐over effect. To avoid potential worsening, switching to open‐label IVIG was permitted if deterioration occurred during blinded treatment. Mean maximal grip strength of the more affected hand declined 31.38% during placebo and increased 3.75% during IVIG (p = 0.005). In 35.7% of participants, Guys Neurological Disability scores for upper limbs worsened during placebo and not during IVIG, whereas the converse was true in 11.9% (p = 0.021). Sixty‐nine percent (69.0%) switched prematurely from placebo to open‐label IVIG and 2.4% switched from blinded to open‐label IVIG (p < 0.001). One serious adverse reaction (pulmonary embolism) and 100 non‐serious reactions (69 mild, 20 moderate, and 11 severe) to IVIG occurred. IVIG was effective in improving disability and muscle strength, and was safe and well tolerated in adults with MMN.

Emotional stress as a trigger of myasthenic crisis and concomitant takotsubo cardiomyopathy: a case report

IntroductionMyasthenia gravis is a neuromuscular junction post-synaptic autoimmune disorder. Myasthenic crisis is characterized by respiratory failure requiring mechanical ventilation. Takotsubo cardiomyopathy is a rare clinical syndrome defined as a profound but reversible left ventricular dysfunction in the absence of coronary artery disease.Case presentationWe report a unique case of a 60-year-old Hispanic woman with myasthenia gravis who developed takotsubo cardiomyopathy and concomitant myasthenic crisis that appear to have been triggered by a stressful life event. On admission, she presented with severe mid-sternal chest pain and shortness of breath shortly after a personally significant stressful life event. A pertinent neurological examination showed bilateral facial weakness and right ptosis. The left ventriculogram showed apical ballooning with hyperdynamic proximal segments with sparing of the apex. Her troponin I level was elevated, while cardiac catheterization revealed no significant coronary artery disease. The findings were consistent with takotsubo cardiomyopathy. Shortly after cardiac catheterization, she developed bilateral ophthalmoparesis and significant bulbar and respiratory muscle weakness. Forced vital capacity values were persistently less than 1 L. The patient developed respiratory failure and required endotracheal intubation. After plasmapheresis and corticosteroid treatment, her clinical course improved with successful extubation. A normal left ventricle chamber size and a normal ejection fraction were noted by an echocardiogram repeated 10 months later.ConclusionThis is the first reported case of the simultaneous triggering of both takotsubo cardiomyopathy and myasthenic crisis by the physiologic consequences of a state of severe emotional stress. We hypothesize that the mechanism underlying the rare association of takotsubo cardiomyopathy with myasthenic crisis involves excessive endogenous glucocorticoid release, a high-catecholamine state, or a combination of both. We advocate careful cardiac monitoring of myasthenia gravis patients during acute emotional or physical stress, as there is potential risk of developing takotsubo cardiomyopathy.

Multifocal motor neuropathy with conduction block misdiagnosed as multiple entrapment neuropathies

We describe a 58‐year‐old male with a few years history of multifocal weakness in the upper limbs with minimal to absent sensory complaints. He was diagnosed as having multiple compressive neuropathies, which required repeated decompressive surgeries. Electrodiagnostic studies prior to diagnosis were limited to a few nerves, evaluating only distal segments. Because of delay in making the diagnosis, his condition progressed, and possibly because of the unnecessary surgeries, he developed atrophy in some muscles, which resulted in significant motor disability. He was later diagnosed as having multifocal motor neuropathy with conduction block and has partially responded to intravenous immunoglobulin therapy.

Amyotrophic lateral sclerosis-motor neuron disease, monoclonal gammopathy, hyperparathyroidism, and B12 deficiency: case report and review of the literature

IntroductionAmyotrophic lateral sclerosis (the most common form of motor neuron disease) is a progressive and devastating disease involving both lower and upper motor neurons, typically following a relentless path towards death. Given the gravity of this diagnosis, all efforts must be made by the clinician to exclude alternative and more treatable entities. Frequent serology testing involves searching for treatable disorders, including vitamin B12 deficiency, parathyroid anomalies, and monoclonal gammopathies.Case presentationWe present the case of a 78-year-old Caucasian man with all three of the aforementioned commonly searched for disorders during an investigation for amyotrophic lateral sclerosis.ConclusionsThe clinical utility of these common tests and what they ultimately mean in patients with amyotrophic lateral sclerosis is discussed, along with a review of the literature.

Paraproteinemic neuropathy: a practical review

The term paraproteinemic neuropathy describes a heterogeneous set of neuropathies characterized by the presence of homogeneous immunoglobulin in the serum. An abnormal clonal proliferation of B-lymphocytes or plasma cells, which may or may not occur in the context of a hematologic malignancy, produces the immunoglobulins in excess. If malignancy is identified, treatment should be targeted to the neoplasm. Most cases, however, occur as monoclonal gammopathy of undetermined significance. Few prospective, randomized, placebo-controlled trials are available to inform the management of paraproteinemic neuropathies. Clinical experience combined with data from smaller, uncontrolled studies provide a basis for recommendations, which depend on the specific clinical setting in which the paraprotein occurs. In this review, we provide a clinically practical approach to diagnosis and management of such patients.

Hereditary neuropathy with liability to pressure palsies: description of seven patients without known family history

Objectives –  Hereditary neuropathy with liability to pressure palsies (HNPP) is an inherited disorder resulting in a polyneuropathy with particular involvement at sites of entrapment, and is often underdiagnosed or misdiagnosed. We report findings on seven patients referred for evaluation of focal mononeuropathies or polyneuropathies of undetermined etiology, in whom we established a diagnosis of HNPP.

Chronic immune-mediated demyelinating polyneuropathy in the setting of cetuximab treatment

Cetuximab, a chimeric mouse/human monoclonal antibody directed against the epidermal growth factor receptor, is commonly used in colorectal and head and neck cancer. We describe an acquired neuropathy associated with cetuximab treatment in a patient with squamous cell carcinoma of the tongue. Our patient was treated with cetuximab from May to July 2008. In December 2008, he first noticed numbness in his feet. He progressed over the next 5 months to develop weakness in both legs, a lack of sensation up to his knees, pain in the dorsum of his feet with a burning sensation, and difficulty ambulating to the point of requiring a walker. He also had numbness in his fingertips and was unable to use his hands for fine movements. Electrodiagnostic studies demonstrated prolonged distal latencies, conduction block, and prolonged F-wave latencies, consistent with a diagnosis of definite CIDP according to EFNS/PNS criteria. Low amplitude potentials were noted in nerves of the lower extremities, indicative of secondary axonal loss. Extensive workup for an alternative cause was negative. He improved clinically after IVIG and corticosteroid treatment. We cannot strongly establish a causal relationship in this case, as 5 months elapsed between cetuximab treatment and the onset of neuropathic symptoms. Nonetheless, clinical vigilance is recommended when evaluating patients for neuropathy who have received cetuximab.

Secondary amyloidosis as a life-ending event in multifocal motor neuropathy.

Multifocal motor neuropathy (MMN) is a disorder of peripheral nerve often associated with a high monosialoganglioside (GM1) antibody and multifocal conduction block. It has a chronic, indolent course with involvement of predominantly peripheral motor nerves, usually in an asymmetric fashion. There have been few reported cases of progression to frank quadriplegia. Secondary amyloidosis refers to the deposition of amyloid in various tissues due to an underlying chronic inflammatory state. We report the first case, to our knowledge, of a patient with MMN associated with high titer of GM1 antibody who developed acute paraplegia with both cranial nerve and worsening sensory involvement associated with multiorgan compromise due to a secondary amyloidosis involving the myocardium.