Ice test as a simple diagnostic aid for myasthenia gravis

It is known that myasthenia gravis is improved by cold. In two previously reported studies performed on a limited number of myasthenic patients and controls, local cold application to the eyelid was suggested for use as a diagnostic test for ocular myasthenia gravis. In this study, ice test to the eyelid was evaluated as a diagnostic test on 12 myasthenic patients and 15 controls with blepharoptosis and the results were compared with those of edrophonium test.     

The regional curare test in myasthenia gravis

Summary 30 subjects without disturbance of neuromuscular transmission and 18 patients with myasthenia gravis were used in conducting the regional curare test. The adductor pollicis and the hypothenar muscles were studied with the 3/sec stimulation test. With three different dosages of curare one could find no reliable border between normal and pathological. In the patients with myasthenia no definite relation could be found between the findings with the regional curare test and the clinical picture.The curare concentration reaching the muscle is probably quite variable from case to case as regards diffusion and volume in the tissue. The 3/sec stimulation test with registration from the deltoid muscle, and in certain cases the systemic curare test, appear more suitable than the regional curare test for routine diagnosis as well as indication for thymectomy. But for cases of ocular myasthenia showing no further weaknesses by the systemic curare test, the regional curare test can be put to use. The advantage lies in the higher concentration of curare which can thereby be brought to the muscle. The precautionary measures should be similar to those taken with the systemic curare test.

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Zusammenfassung Bei 30 Kontrollpersonen und 18 Myastheniepatienten wurde der lokale Curaretest durchgefÜhrt. Mit der 3/sec-Stimulation wurde der Adduktor pollicis und der Hypothenar untersucht. Bei drei verschiedenen Curaredosierungen ließ sich keine eindeutige Grenze zwischen normal und pathologisch finden. Bei den Myastheniepatienten bestand keine zuverlässige Beziehung zwischen dem Ergebnis des lokalen Curaretests und dem klinischen Bild.Wahrscheinlich ist die den Muskel erreichende Curarekonzentration je nach Diffusion und Gewebsvolumen von Fall zu Fall recht unterschiedlich. Für die Routinediagnostik, aber auch für die Indikation zur Thymektomie, scheinen die 3/sec-Stimulation mit Registrierung vom Deltoideus und in besonderen Fällen der systemische Curaretest geeigneter als der lokale Curaretest zu sein. Bei den Fällen von okulärer Myasthenie, die auch im systemischen Curaretest keine weitere Schwäche zeigen, kann aber der lokale Curaretest zur Anwendung kommen. Der Vorteil liegt dann in der höheren Curarekonzentration, die an den Muskel herangebracht werden kann. Die Vorsichtsmaßnahmen sollten die gleichen sein wie beim systemischen Curaretest.

     

Neuropsychological test performance and affect in myasthenia gravis

Neuropsychological test performance, including memory, and affect were investigated in 16 patients with myasthenia gravis (MG) and in a matched control group. Clinical electroencephalograms (EEGs) were recorded from MG patients. Cognitive measures included the Randt Memory Test and a number of tests from the computerized Neurobehavioral Evaluation Battery which included a test of motor speed. Affect was assessed by means of an anxiety questionnaire (IPAT) and a computer based questionnaire similar to the Profile of Mood States (POMS). There were no significant intergroup differences in memory performance and only an isolated significant finding in a timed measure in symbol-digit comparison. The MG group revealed significantly reduced finger tapping. Significantly higher levels of anxiety, tension, anger, fatigue and confusion were associated with the MG group. Abnormal EEGs occurred in 35% of the MG patients, mostly mild-moderate diffuse slowing, but in one case epileptogenic activity was present. The failure to confirm memory deficits in this study appeared not to be related to age or whether patients had generalized or ocular MG. Medication was suggested as a possible factor. These, and other variables, need to be evaluated in further studies.     

眼肌型重症肌无力进展为全身型重症肌无力的临床相关因素分析

目的 :探讨眼肌型重症肌无力进展为全身型重症肌无力的临床相关预测因素。方法 :33例初诊为眼肌型重症肌无力的患者经过3年随访,根据疾病进展结局分为眼肌型重症肌无力组(13例)和进展为全身型重症肌无力组(20例)。对与疾病进展可能相关的临床因素进行分析。结果 :进展为全身型重症肌无力组患者初诊时的定量重症肌无力评分、乙酰胆碱受体抗体阳性率、抗核抗体阳性率、合并胸腺瘤的比例以及合并糖尿病的比例均高于眼肌型重症肌无力组(P值均0.05)。结论 :定量重症肌无力评分高、乙酰胆碱受体抗体阳性、抗核抗体阳性以及合并胸腺瘤和糖尿病可能是眼肌型重症肌无力进展为全身型重症肌无力的预测指标。     

Stapedius reflexometry: A diagnostic test of myasthenia gravis

Contraction of the stapedius muscle can be measured by electroacoustic impedance bridge. Muscle weakness and easy fatiguability which are cardinal features of myasthenia gravis (MG) are manifested by increased threshold and early decay of the stapedius reflex. This can be used as an objective test in the diagnosis of myasthenia gravis. Stapedius reflex was measured using Madsen Zo72 electroacoustic impedance bridge in 10 patients with myasthenia gravis and in an equal number of controls. The test was done before and 30 min after intramuscular injection of neostigmin.All patients with myasthenia gravis showed an elevated reflex threshold and 5 patients showed reflex decay. These findings reverted to normal after neostigmin injection. Stapedius reflexometry is a simple objective test for the diagnosis of myasthenia gravis.     

Nerve stimulation test in murine experimental autoimmune myasthenia gravis

Use of the mouse model of myasthenia gravis (murine EAMG), ideally suited for immunological study, has been hampered by the relatively mild character of the disease and by the extended time and effort required for inducing severe disease. Electromyographic measurement of the compound action potential after repetitive stimuli, the nerve stimulation test, was evaluated for its ability to diagnose neuromuscular transmission defects in mice immunized with Torpedo acetylcholine receptor. With the combination of provocative maneuvers and raising of the body temperature, EAMG could be diagnosed in nearly all immunized animals a few weeks after immunization, whereas clinical evaluation of muscle weakness was positive in less than half of immunized mice months after the first immunization. Thus, EMG provides a means of objective evaluation of the disease and attempts at its experimental modification.     

Juvenile myasthenia gravis

Juvenile myasthenia gravis shares a similar pathophysiologic origin with adult myasthenia gravis, but there are important differences, mostly relating to epidemiology, presentation, and therapeutic decision making. Gender ratios and the proportion of seropositive patients differ in the pre‐ and postpubertal age groups. The diagnostic evaluation is similar to that in adults, although special techniques are sometimes necessary to perform single‐fiber electromyography in younger patients. Therapeutic decisions in affected children and adolescents are complicated by the greater long‐term consequences of using steroids, and thus other interventions, such as intravenous immunoglobulin (IVIg) and plasmapheresis, may play a greater therapeutic role in this population than in adults. Steroid‐sparing agents may contribute to the management of refractory cases, but they should be used with caution due to the risk of malignancy. Muscle Nerve, 2008     

Seronegative myasthenia gravis

Of 221 patients with myasthenia gravis, 18.5% had no detectable antibodies to acetylcholine receptor. Seven of 14 patients (50%) with only ocular symptoms for more than 2 years were seronegative, and 25 of 145 (17%) patients with generalized myasthenia were seronegative. The clinical characteristics of seronegative patients did not differ from patients with high antibody titers. No seronegative patient had a thymoma, but that difference did not reach statistical significance. Lack of serum antibodies did not preclude favorable response to thymectomy or plasmapheresis.     

Penicillamine-associated myasthenia gravis

Electroneuromyographic studies have been reported as abnormal in only 9 of 23 cases of penicillamine-associated myasthenia gravis (MG). We report a patient with rheumatoid arthritis who developed clinical and electrodiagnostic evidence of myasthenia 7 months after beginning penicillamine therapy. Six months after discontinuing penicillamine, it was possible to discontinue anticholinesterase medications. With clinical improvement, electrodiagnostic studies (including single-fiber electrmyography) improved, serum antibody titers to human muscle acetylcholine receptor fell, and lymphocytes became more responsive to the nonspecific mitogen phytohemagglutinin. Evidence suggests that penicillamine-associated myasthenia is a distinct syndrome rather than the chance occurrence of two diseases. This syndrome is clinically and electrophysiologically distinguishable from idiopathic myasthenia only by the high remission rate after penicillamine is discontinued.     

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.     

Distal myasthenia gravis

Myasthenia gravis (MG) characteristically involves ocular, bulbar, and proximal extremity muscles. Distal extremity muscles are typically spared or less prominently involved. The authors performed a retrospective chart review of MG patients treated at two university-based neuromuscular clinics. From a total population of 236, nine patients (3%) had distal extremity weakness exceeding proximal weakness by at least one Medical Research Council grade during their illness. Hand muscles, particularly finger extensors, were involved more frequently than were distal leg and foot muscles.     

Clinical and CN-SFEMG evaluation of neostigmine test in myasthenia gravis

Neostigmine test (NT) is a pharmacological test, demonstrating a clinical improvement in patients affected by myasthenia gravis (MG). We aim to compare clinical evaluation and neurophysiological recordings by concentric-needle single-fiber electromyography (CN-SFEMG) in response to acute administration of neostigmine in ocular and generalized MG patients. Twenty-three MG patients (10 with ocular MG and 13 with generalized MG) were evaluated before and after 90 min neostigmine 0.5-mg administration. Clinical responsiveness was assessed by MG composite (MGC) scale. Neurophysiological evaluation by CN-SFEMG considered analysis of mean value of consecutive differences (MCD), single-pair jitter, and blocks. MGC scores significantly improved after NT in generalized MG patients (MGC 11.1?±?7.6 vs 9.1?±?6.7, p?=?0.02), whereas the improvement was not significant in the ocular group. CN-SFEMG recordings significantly improved after NT in generalized MG patients (MCD 58.9?±?18.8 vs 45.9?±?23.2 μs, p?=?0.003; single-pair jitter 49.8?±?26.9 vs 24.1?±?26.7%, p?=?0.0001; blocks 6.2?±?9.5 vs 2.6?±?7.4%, p?=?0.03) as well as in ocular MG patients (MCD 50.8?±?22.7 vs 40.1?±?22.9 μs, p?=?0.01; single-pair jitter 35.9?±?23.7 vs 20.0?±?25.1%, p?=?0.001). CN-SFEMG is a reliable tool to evaluate responsiveness to acute administration of neostigmine in MG. Moreover, neurophysiological modifications to NT could show subclinical improvement in ocular MG better than that of the clinical scale.     

Seronegative myasthenia gravis

Some myasthenia gravis (MG) patients do not have detectable acetylcholine receptor (AChR) antibodies and have been termed "seronegative" (SNMG) in many previous studies. A high proportion of patients with purely ocular symptoms, ocular MG, are seronegative; this may be because the sensitivity of the assay is insufficient to detect low levels of circulating AChR antibodies and because of intrinsic differences in the ocular muscles that make them more susceptible to circulating factors. Seronegative generalized myasthenia is proving to be heterogeneous both clinically and immunologically. Plasma from SNMG patients often contains a factor, probably an immunoglobulin M antibody, that alters AChR function in in vitro assays, but its target is not yet clear. A variable proportion of SNMG patients have antibodies to the muscle-specific tyrosine kinase (MuSK). These antibodies are directed against the extracellular domain of MuSK and inhibit agrin-induced AChR clustering in muscle myotubes. Although the role of these antibodies in causing myasthenic symptoms in vivo has not been elucidated, MuSK antibodies appear to define a group of patients who are often female with bulbar weakness, contrasting with MuSK antibody-negative SNMG patients who are more likely to have generalized weakness. MuSK antibody-positive patients may also differ in the distribution of their electrophysiological abnormalities and their responses to treatments.