Concurrence of non-myasthenic symptoms with myasthenia gravis.

Myasthenia gravis (MG) is a disease that is known to be accompanied by various complications. But the relationship between these complications and MG and the treatment for these complications still partly remain unknown. We report two cases of MG with unusual complications. The first one is a case of a 72-year-old woman with lingual dyskinesia, and the second is a 28-year-old man with dysgeusia. Both symptoms improved in parallel after the treatment of MG. Here we report these cases and review similar cases in the literature.

Long-term effect of bone marrow transplantation in adult-onset adrenoleukodystrophy.

We report a long-term outcome of motor function in a patient with adult-onset adrenoleukodystrophy after bone marrow transplantation (BMT). Clinically motor function gradually improved and became almost normal in 2 years after BMT. Serial transcranial magnetic stimulation showed gradual improvement of central motor conduction until 1 year after BMT, and then it became stable. Central motor conduction time and motor threshold were useful for monitoring the central motor function in this patient.

Improvement of central motor conduction after bone marrow transplantation in adrenoleukodystrophy.

The case is described of a 20-year-old man with adrenoleukodystrophy who showed right spastic hemiparesis and gait disturbance. Brain magnetic resonance imaging disclosed predominant involvement of the left corticospinal pathway. The clinical symptoms improved after bone marrow transplantation. Transcranial magnetic stimulation disclosed significant improvement in various parameters of central motor conduction.

[Significance of soluble thrombomodulin in the coronary circulation of patients with coronary artery disease].

OBJECTIVES: The relationship between plasma levels of soluble thrombomodulin, a probable marker for endothelial damage, and the severity of coronary atherosclerosis was investigated. METHODS: Plasma soluble thrombomodulin levels were evaluated in 160 patients(mean age 62 +/- 11 years) who underwent coronary angiography. Blood samples were obtained from the peripheral vein, ostium of the left coronary artery and coronary sinus. The levels of plasma thrombomodulin were measured by enzyme-linked immunosorbent assay. The change of thrombomodulin level in the coronary circulation (delta TM) was calculated as the coronary sino-arterial difference. Patients were classified into four groups according to the number of diseased vessels, and the severity of coronary atherosclerosis was evaluated with the modified Gensini score. RESULTS: Coronary sinus levels of thrombomodulin were significantly higher in the two or more vessel disease(VD) groups than in the no or one VD groups(p < 0.05). delta TM were significantly higher in the 2VD than in the 0VD groups(p < 0.05), and higher in the 3VD than in the 0VD or 1VD groups(p < 0.05). delta TM showed positive correlation with Gensini score for left coronary arteries(r = 0.347, p < 0.0001). CONCLUSIONS: The increment of thrombomodulin across the coronary circulation was significantly correlated with the severity of coronary atherosclerosis, suggesting a close association between the progression of coronary atherosclerotic stenosis and damage to the endothelial surface.

Discrepancy between inducibility of ventricular tachycardia and activity of cardiac sarcoidosis. Requirement of defibrillator implantation for the inactive stage of cardiac sarcoidosis.

Monomorphic ventricular tachycardia (VT) developed in two patients with cardiac sarcoidosis. Before treatment with prednisolone, technetium or gallium scintigram revealed abnormal accumulation in the heart and bilateral hilar lymph nodes, but programmed electrical stimulation failed to induce VT in either case. Prednisolone was administered and the abnormal accumulation of the scintigra ms disappeared. However, VT became reproducibly inducible, and in one of the patients, transient entrainment was demonstrated in clinical VT morphology. Defibrillators were implanted in both patients. Some VTs associated with cardiac sarcoidosis are due to reentry, and inducibility of VT is not associated with the activity of cardiac sarcoidosis. Even though steroid therapy suppresses the activity of cardiac sarcoidosis, defibrillator implantation is necessary to prevent a possible arrhythmic event during the follow-up.

[Relationship between endothelial dysfunction and nitric oxide production in young male smokers].

OBJECTIVES: Endothelial function in the brachial arteries is impaired in smokers. However, little is known about this condition in young adult men. The relationship between nitric oxide(NO) production and the endothelial function was investigated in young smokers and compared with non-smokers. METHODS: Flow-mediated vasodilation of the brachial artery during reactive hyperemia was examined in 10 young smokers(mean age 31 years) and 12 control subjects(mean age 28 years). The vasodilator response in the brachial artery was measured by ultrasonography, and blood samples were obtained from the right cephalic vein. Blood samples were taken at baseline, 30 sec after cuff deflation, and before and 5 min after 0.3 mg of nitroglycerin administration. Blood flow was calculated by multiplying mean flow velocity and vessel cross-sectional area. Plasma NOx(nitrate + nitrite) levels were measured, and the percentage change of NOx production(delta NOx) was calculated as follows: delta NOx(%) = [(NOx concentration at peak flow-mediated vasodilation or after 0.3 mg nitroglycerin administration) - baseline NOx concentration)] x 100/baseline NOx concentration. RESULTS: Percentage changes in diameter of the brachial artery, NOx production and delta NOx in response to nitroglycerin were not statistically different between the two groups(smokers: 27.6 +/- 8.0 mumol/l, control subjects: 34.0 +/- 8.7 mumol/l). However, percentage change of flow-mediated vasodilation during reactive hyperemia in the young smokers was significantly smaller than that in the control subjects(4.8 +/- 2.7%, 9.1 +/- 5.3%, respectively, p < 0.05). Moreover, delta NOx during reactive hyperemia in the smokers was significantly smaller than that in the control subjects(388.8 +/- 90.2%, 738.0 +/- 284.5%, respectively, p < 0.05). CONCLUSIONS: The impaired response to reactive hyperemia in young smokers might be associated with decreases in flow-dependent NO production.

[Effect of percutaneous transvenous mitral commissurotomy for the preservation of sinus rhythm in patients with mitral stenosis].

OBJECTIVES: Atrial fibrillation is frequently associated with mitral stenosis and is considered to be an unfavorable factor for the long-term prognosis. The efficacy of percutaneous transvenous mitral commissurotomy(PTMC) was examined for the preservation of sinus rhythm in patients with mitral stenosis after PTMC. METHODS: Long-term clinical data after PTMC were obtained from 71 patients who had undergone PTMC from March 1989 to September 1999. Eighteen patients in sinus rhythm before PTMC were divided into two groups: the SR group(n = 5) who remained in sinus rhythm, and the Af group(n = 13) who showed change from sinus rhythm to persistent or paroxysmal atrial fibrillation after PTMC. RESULTS: Age, sex, mitral valve area(1.4 +/- 0.3 vs 1.2 +/- 0.3 cm2), mean mitral pressure gradient(14.3 +/- 5.5 vs 12.6 +/- 5.9 mmHg), mean left atrial pressure(15.9 +/- 7.6 vs 19.0 +/- 7.7 mmHg), left ventricular end-diastolic pressure(7.5 +/- 2.8 vs 9.3 +/- 3.9 mmHg), left ventricular end-diastolic volume index(77 +/- 13 vs 82 +/- 14 ml/m2), left ventricular ejection fraction(60 +/- 6% vs 55 +/- 4%) and cardiac output(5.1 +/- 0.4 vs 4.9 +/- 0.8 l/m2) before PTMC were not different between the two groups. Changes in mean mitral pressure gradient, mean left atrial pressure and cardiac output immediately after PTMC were not different statistically. Mitral valve area immediately after PTMC was significantly greater in the SR group compared to the Af group(2.3 +/- 0.3 vs 1.8 +/- 0.3 cm2, p < 0.05). The change in mitral valve area was also greater in the SR group(1.0 +/- 0.2 vs 0.6 +/- 0.4 cm2, p < 0.05), but there was no statistical difference in the percentage change of mitral valve area between before and immediately after PTMC(SR group 78 +/- 35% vs Af group 50 +/- 35%). End-diastolic pressure, end-diastolic volume index and ejection fraction immediately after PTMC were not statistically different. CONCLUSIONS: The final mitral valve area immediately after PTMC in the patients with mitral stenosis in sinus rhythm, but not the changes of mean mitral pressure gradient, mean left atrial pressure or cardiac output, is important for the maintenance of sinus rhythm.

Sensorimotor demyelinating neuropathy with IgM antibody against gangliosides GD1a, GT1b and GM3.

We report a patient with sensorimotor demyelinating neuropathy with high-titer IgM antibody against gangliosides GD1a, GT1b and GM3. The patient was a 65-year-old male who was hospitalized with chief complaints of muscular weakness of all limbs and numbness of the hands and feet. Nerve-conduction studies revealed reduced conduction velocities of the motor nerves with increased temporal dispersion and loss of sensory nerve action potentials. Treatment with steroids was ineffective. IgM antibody against GD1a, GT1b and GM3, which are known to be the ligands for myelin-associated glycoprotein (MAG), might have played a role in the demyelination in this patient by inhibiting adhesion between myelin and axonal membrane.

[Relationship of Chlamydia pneumoniae infection to severity of coronary atherosclerosis in patients with chronic coronary artery disease and with normal coronary arteries].

OBJECTIVES: Recent studies have demonstrated an association between infection with Chlamydia (C.) pneumoniae and coronary artery disease. However, the association is less clear in the Japanese population. The relationship of C. pneumoniae infection to severity of coronary atherosclerosis was investigated in patients with chronic coronary artery disease and with normal coronary arteries. METHODS: Serum levels of IgA and IgG antibodies to C. pneumoniae outer membrane complex were measured by enzyme-linked immunosorbent assay and C-reactive protein (CRP) analyses in 130 patients who underwent coronary angiography. Patients with unstable angina and recent myocardial infarction were excluded. Results were divided into three groups according to Gensini coronary score (GCS): normal (n = 19, GCS = 0); mild atherosclerosis (n = 56, GCS = 1-19); and severe atherosclerosis (n = 55, GCS > or = 20). RESULTS: Cut off indices of IgA and IgG in the atherosclerosis groups (severe: 1.53 +/- 0.72 and 1.67 +/- 0.97, mild: 1.58 +/- 0.92 and 1.42 +/- 0.86, respectively) were higher than in the normal group (1.22 +/- 0.59 and 1.28 +/- 0.82), but there were no significant differences. There were no correlations between indices of IgA and IgG, and GCS. The normal CRP group (n = 118, < 0.3 mg/dl) and the high CRP group (n = 12, > or = 0.3 mg/dl) showed no differences in IgA and IgG indices and GCS. CONCLUSIONS: Serum antibody indices against C. pneumoniae are not associated with the severity of coronary atherosclerosis in chronic stable coronary artery disease.

von Recklinghausen disease complicated by pulmonary hypertension.

Two patients with von Recklinghausen disease (neurofibromatosis type 1) were admitted to the hospital because of progressive heart failure. Both patients had prominent pulmonary hypertension revealed on cardiac catheterization. A lung perfusion scan did not show any gross defect. There were no underlying causes of pulmonary hypertension in either patient, such as chronic lung disease, congenital or acquired heart disease, deep vein thrombosis, or systemic hypercoagulable states. There may be an unrecognized association between von Recklinghausen disease and pulmonary hypertension.

DYT1 mutation in Japanese patients with primary torsion dystonia.

A GAG deletion at position 946 in the DYT1 gene has been identified as one of the gene mutations responsible for autosomal dominant primary torsion dystonia. We examined 178 Japanese patients with various forms of dystonia, and found the mutation in six patients (3.4%) from three families. Five of them had early clinical onset (before age 12) with initial involvement of a limb. To our knowledge, this is the first report of the frequency and the clinical features of DYT1 mutation in oriental patients, and the clinical presentation of the mutation in these patients was similar to that of Jewish or non-Jewish Caucasian patients.

Demonstration of transient entrainment in monomorphic sustained ventricular tachycardia associated with cardiac sarcoidosis.

A 49-year-old man was referred for further treatment of sustained monomorphic ventricular tachycardia (VT) associated with cardiac sarcoidosis. During an electrophysiologic study (EP), dl-sotalol suppressed the spontaneous VT and prevented induction of VT. However, when predonisolone treatment was started, monomorphic VT recurred frequently. To terminate the VT, a temporal pacing lead was placed at the apex of the right ventricle, and programmed electrical stimulation was attempted from the lead. During the EP study, 2 different monomorphic VTs were repetitively induced and both types were able to be terminated by rapid ventricular pacing; in one of the VT morphologies, constant and progressive fusion was obvious during the ventricular pacing. Some monomorphic VTs associated with cardiac sarcoidosis are due to reentry with an excitable gap, but the clinical efficacy of EP-guided antiarrhythmic drug treatment seems to be less certain during steroid therapy. In the present case, a defibrillator device was implanted to prevent a possible arrhythmic event.

[Cervical echomyography in cervical dystonia and its application to the monitoring for muscle afferent block (MAB)].

Muscle afferent block (MAB) is an intramuscular injection of 0.5% lidocaine and pure ethanol with a volume ratio of 10:1, introduced as an alternative to botulinum toxin injection for focal dystonia and spasticity. As in the case of botulinum toxin injection, the precise localization of target muscles is crucial to obtain the maximal effect from MAB. For this purpose, we performed ultrasonography of cervical muscles (echomyography) in 20 patients with cervical dystonia (11 men, 9 women; mean age 46.1), with ultrasonograph SSD-5500 (Aloca Co. Ltd., Japan) and a 7.5 MHz linear probe. In untreated subjects, the boundaries of muscles could be easily identified, while they tended to become ambiguous after repeated MAB sessions. At rest, there were involuntary worm-like movements of a specific muscle group observed in all patients. Contrary to our expectation, in all but one patient abnormal contraction was limited only in a part of synergists responsible for the abnormal posture. In normal subjects there was no abnormal contraction at rest, and all the synergists were simultaneously activated by the voluntary neck deviation. Normal subjects could not mimick the pattern of muscle activity in dystonic patients. The echo-guided MAB was performed in 16 patients. We could easily observe the diffusion of lidocaine and ethanol into the targeted muscle, and injected portions of the muscle stopped their activities just after MAB. The effect persisted for 3-4 days in at least 5 out of 10 patients who had follow-up examination. On the other hand, the movement stopped only temporarily after the injection of saline or lidocaine only. In 3 out of 16 patients, some of the uninjected synergists were activated as if to substitute for the treated muscle just after the injection. We conclude that cervical echomyography is useful to investigate the pattern of muscle activity in cervical dystonia and to accurately localize the contracting muscles during MAB.

[Treatment of chronic inflammatory demyelinating polyradiculoneuropathy(CIDP)--a review].

This is a review article about the recent progress and the general consensus of the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Although the first line treatment is believed to be adrenocorticosteroid prescribed orally or intravenously, some insist that plasmapheresis or intravenous immunoglobulin is better. The latter two are expensive but the effects are comparable to that of steroid, and in some patients complete remission might be induced. On the other hand, about 30% of patients do not respond to any of these conventional procedures, and for these the combination of two or three of them might be effective. As another choice, immunosuppressant or interferon (alfa-2 a or beta-1 a) has been applied although its usefulness is still inconclusive. For any of these here mentioned, the clinical response greatly varies among patients, and the elucidation of predictive factors of effectiveness is eagerly awaited from the standpoint of reasonable treatment selection and cost-effectiveness.

[Changes of autonomic functions by endoscopic upper thoracic sympathectomy on idiopathic hyperhidrosis].

Changes of autonomic functions before and after bilateral endoscopic upper thoracic sympathectomy (EUTS) were evaluated in 13 patients with idiopathic hyperhidrosis, with the sympathetic skin response, coefficient of variation of R-R intervals, mean heart rate, thermography, and non-invasive Valsalva test of the tonometry method. EUTS electronically destructs the upper thoracic sympathetic ganglions which innervate the upper extremities, and partially the heart. The decrement of mean heart rate, and persistent inhibition of the vascular contraction and hidrosis of the hands appeared after EUTS. These manifestations were effect produced by the abortion of sympathetic activity by EUTS. In 10 of the 12 cases, the baroreceptor sensitivity index II of Valsalva test which reflects the sympathetic autonomic nervous function of the heart showed normal pattern after EUTS. Four cases revealed reincrement of both the blood pressure and heart rate at the latter half phase of the second stage of the Valsalva test. The sympathetic dysfunction of the heart was limited to the decrement of mean heart rate although EUTS partially destroys sympathetic fibers innervating the heart. A long-term study is necessary to evaluate the effect of EUTS on the cardiac function.

Combined use of type A and F botulinum toxins for blepharospasm: a double-blind controlled trial.

Type A botulinum toxin has widened its clinical range of applications, but the risk of developing antibodies limits the repeated use of high-dose injection. To minimize the risk, mixing different types of toxin might reduce the antigenic presentation of a specific toxin and associated proteins. At the same time, inhibition of the neuromuscular release process at the multiple sites might potentiate the clinical response or the duration of action. We compared the effectiveness of a mixture of type A and type F botulinum toxins with that of type A or type F toxin alone for treating patients with blepharospasm in a double-blind study. Fifty-four patients had 10 units of toxin injection, a mixture of type A and F toxins (including 5 units of each) on one side and either type A or F toxin on the other side of the orbicularis oculi muscle. Clinical evaluation at 4 and 10 weeks after the injection revealed that the peak clinical effect at 4 weeks was similar among the three preparations. The duration of action of the mixture was intermediate between type A and type F alone, as assessed at 10 weeks, when there was a tendency of conserving the beneficial effect on one eye at the expense of that on the other. Although there was no apparent potentiation of the clinical efficacy, the combination of these different types of toxin might be used for decreasing the risk of antibody development.