Nobuo Wakata

Polymyositis and dermatomyositis associated with malignancy: a 30‐year retrospective study

Background Polymyositis and dermatomyositis in association with malignancy are paraneoplastic syndromes, but the incidence, treatment and factors that predict associated cancer and its prognosis all remain unclear.

Bupivacaine Hydrochloride Induces Muscle Fiber Necrosis and Hydroxyl Radical Formation-Dimethyl Sulphoxide Reduces Hydroxyl Radical Formation

We induced acute skeletal muscle necrosis in rats using bupivacaine hydrochloride and found that both 2,5- and 2,3-dihydroxybenzoic acid significantly increased in skeletal muscle. A single administration of dimethyl sulphoxide, a free radical scavenger, significantly lowered concentrations of 2,5- and 2,3-dihydroxybenzoic acid. These results suggest that dimethyl sulphoxide is an effective hydroxyl radical scavenger and may be useful in the treatment of myopathy.

Parkinsonism induced by pyridostigmine

In February 1987, a 62-year-old Japanese woman developed bilateral ptosis and diplopia. These signs and symptoms were dramatically improved by an IV injection of edrophonium chloride. Electrophysiological tests demonstrated decremental responses at 1-5 Hz in abductor the digiti minimi. Acetylcholine receptor (Ach R) antibody titers was 0.02 n mol/l (normal < 0.05). The patient was diagnosed as having myasthenia gravis (MG) and pyridostigmine was given in a dosage of 360 mg daily with dramatic improvement of the ptosis and diplopia. Two months later, the patient developed finger tremor, bradykinesia, and loss of facial expression. After continuing daily dosage of 360 mg of Pyridostigmine for a further month, her symptoms worsened and she was referred to our department. Neurological examination showed typical parkinsonian features of resting tremor, bradykinesia, rigidity, and loss of postural reflexes. There was no ptosis, ophthalmoparesis, dysphagia or facial weakness. C T brain scan was normal and a C T chest scan revealed no evidence of thymoma. Routine laboratory tests were normal. The ratio of peripheral lymphocyte subsets was normal. Electrophysiological examination showed neither incremental nor decremental responses in the abductor digiti minimi. The patient was free of myasthenic symptoms and she was suffering from diarrhea. Withdrawal of pyridostigmine was followed by improvement of the parkinsonism. The patients is now treatment free, and has no symptoms of either parkinsonism or myasthenia. We were unable to rechallenge with pyridostigmine because the patient was reluctant to re-start the drug. It is well known that antidopaminergic drugs can induce parkinsonism in patients with no evidence of pre-existing striatal dopamine deficiency. In this case, pyridostigmine appears to have adversely effected the nigrostriatal function. The dopamine-Ach inbalance hypothesis can explain some aspects of the pharmacology of parkinsonism. Pyridostigmine, a cholinesterase inhibitor, might be expected, by increasing Ach levels, to induce or worsen parkinsonism. However, experimental studies in the rat suggest pyridostigmine can not pass the BBB (1). In our patient, disruption or alteration of the BBB would have been necessary to explain a CNS effect causing parkinsonism.

Tacrolimus hydrate (FK506): therapeutic effects and selection of responders in the treatment of myasthenia gravis

Tacrolimus hydrate (FK506) reduces myasthenic symptoms due to its immunosuppressive properties. We studied the therapeutic effects of FK506 and noted improvement in 7 of 13 myasthenic patients on the clinical muscle test (myasthenia gravis, MG score). Two other patients with relapsing ocular symptoms improved. We also examined patient sensitivity to FK506, but could not predict such sensitivity before FK506 treatment in the present study.

Ulcerative colitis presenting as sensorineural deafness, brainstem encephalopathy, and white matter lesions.

Background:Several rare neurologic complications of ulcerative colitis have been reported. Review Summary:We report a 69-year-old Japanese woman who developed bilateral sensorineural deafness, 2 attacks of bilateral ophthalmoplegia, and bilateral facial nerve palsy in association with ulcerative colitis. Laboratory data showed elevated cerebrospinal fluid (CSF) protein without pleocytosis, abnormal auditory brainstem evoked potentials, and multiple high signal lesions on magnetic resonance imaging of the brainstem and cerebral deep white matter. Her symptoms improved with corticosteroid therapy except for sensorineural deafness and an exacerbation of cerebral deep white matter lesions without any new clinical signs. Conclusion:Immunologic mechanisms may have led to her central and peripheral nervous system findings in addition to her colon disorder.

Bone density in myasthenia gravis patients receiving long-term prednisolone therapy

Osteoporosis is an adverse effect of prednisolone therapy, although no study has been conducted on myasthenia gravis patients receiving high-dose prednisolone. We measured bone density in 36 patients (26 females and 10 males) who had undergone long-term prednisolone administration, and found a decrease in bone density in 31% of female patients and osteoporosis in only 11.5% (three cases). This frequency is lower than the presumptive rate of the general population in Japan (22.6%). No osteoporosis was detected in male patients. In conclusion, prednisolone-treated patients with myasthenia gravis have an acceptable risk of bone loss if prophylactic medication is administered.

A case of Guillain-Barré syndrome associated with cerebellar ataxia and positive serum anti-GD1b IgG antibody

Sirs: It is well known that the antibody against ganglioside is detectable in the Guillain-Barré syndrome (GBS) [2, 5, 9]. AntiGD1b IgG antibody has been found in a case of ataxia with disturbance of deep sensation [7]. We encountered a case of GBS associated with cerebellar type ataxia and positive serum anti-GD1b IgG antibody. A 21-year-old woman presented on 9 May 1999, suffering from diarrhoea. On 20 May, she felt weakness in the lower extremities and later developed paraesthesia in the distal part of both extremities and diplopia. On 26 May, she had difficulty in walking. On 3 June, she was admitted to our hospital. On admission, neurological examination revealed normal consciousness. In the cranial nerves, a left abducens paralysis was found. The muscle strength was 3/5 in all extremities. Grip strength was 2 kg on the right side and 3 kg on the left side. All deep tendon reflexes were diminished and pathological reflexes were not observed. Objective sensations were all normal. Rectal sphincter and bladder dysfunction and cerebellar signs were not observed. Laboratory studies disclosed that Campylobacter jejuni was not detected in her faeces. Serum antiGD1b IgG antibody titre was 1:200 (normal < 100). Anti-GM1, GM2, GD1a,GD1b, GT1b and GQ1b antibody titres were all within normal ranges. Cerebero-spinal fluid examination revealed that the cell count was 2/μl, total protein was 217 mg/dl, and sugar was 54 mg/dl (blood sugar 88 mg/dl). Electrophysiological examination revealed that the motor nerve conduction velocity was 37.1 m/s (normal > 43.0) in the right peroneal nerve and 36.6 m/s (normal > 41.0) in the right tibial nerve. Sensory nerve conduction velocity was not detected in the right peroneal nerve and was 39.9 m/s (normal > 46.0) in the right tibial nerve. After admission, she was immediately treated with immuno-absorption therapy (tryptophan calumn; TR-250). After beginning the 1st immuno-absorption therapy, cerebellar speech appeared. Subsequently, disturbance of finger-nose and heel-knee tests, intention tremor, dysmetria and dysdiadochokinesis were observed; however, Romberg’s sign and disturbance of deep sensation were not detected. After 4 courses of immuno-absorption therapy, muscle weakness, paraesthesia and disturbance of eye movement gradually improved, but did not completely disappear. The delayed cerebellar signs also improved by the end of June, and she discharged herself. At this point, serum anti-GD1b IgG antibody titre was still elevated at 1:200. However, following discharge, exacerbation occurred after a few days, including muscle weakness mostly in the upper extremities and paraesthesia. After re-admission another 4 courses of immuno-absorption therapy were administered. At the end of August, her symptoms all subsided, with normal serum anti-GD1b IgG antibody titre (< 1:100). Head MRI was performed twice during her admission, but no abnormal signs were detected in the cerebrum, cerebellum or brain stem. The clinical course is shown in Figure. In the present case, muscle weakness, paraesthesia and diminished deep tendon reflexes occurred, followed by diarrhoea, and LETTER TO THE EDITORS

A case of voluntary palatal myoclonus with ear click: relationship between palatal myoclonus and click.

Introduction Anatomy and pathology of palatal myoclonus are well established and commonly involve hypertrophic degeneration of the inferior olivary nucleus including the Guillain-Mollaret triangle (dentate nucleus, red nucleus, and inferior olivary nucleus and central tegmental tract). Deuschl et al. [1], after a survey of the literature, reported that cerebrovascular disease was present in 55% of the patients having symptomatic palatal myoclonus. Other conditions present included multiple sclerosis, meningoencephalitis, infectious diseases, head trauma, vertebral artery aneurysms, neoplasms, psychosis, and heredofamilial tremor. We encountered a patient with essential palatal myoclonus who was able to voluntarily induce the disturbance. His condition was associated with clicking, and to clarify the mechanism responsible for this, we conducted an otorhinolaryngological study.

Relapse of ocular symptoms after remission of myasthenia gravis—a comparison of relapsed and complete remission cases

Extended thymectomy and high-dose alternate-day prednisolone administration may increase the chance of remission in myasthenia gravis (MG) patients. In cases of remission, ocular symptoms sometimes reappear after a gradual decrease or discontinuation of prednisolone administration. We compared relapsed patients with those who experienced complete remission. We found that the period from onset of MG to thymectomy and initiation of prednisolone administration was longer in the relapsed cases, which suggests that early thymectomy and administration of prednisolone can lead to a superior outcome in MG patients.

A case of myasthenia gravis accompanied by erythema elevatum diutinum and rheumatoid arthritis

Sirs: Myasthenia gravis can occasionally be accompanied by many autoimmune diseases, such as rheumatoid arthritis [9, 12], systemic lupus erythematosus [9, 12], Sjogrens syndrome [2, 3], ulcerative colitis [10], Hashi toxicosis [9, 12], alopecia areata [10, 11], lichen planus [10], vitiligo [10] and lympoma [6]. We have never experienced a case of myasthenia gravis associated with erythema elevatum diutinum (EED). The aetiology of EED is still unknown; however, immunological causes have been postulated. A 56-year-old woman first experienced a nasal voice in December 1993, a symptom which worsened in the afternoon, though she could speak comfortably after resting. In May 1994, she experienced dysphagia and subsequently visited an otolaryngologist, where weak palatal movement was discovered. In June, she visited a neurologist. She was diagnosed with myasthenia gravis because of facial weakness, dysarthria and weakness of palatal movement, though her symptoms disappeared with an edrohoneum chloride test. Subsequently, she was treated with 180 mg/day pyridostigumine bromide. In June, she was admitted to an university hospital. Serum antiACh-receptor antibody was 65 nmol/ml. Median nerve repetitive stimulation test revealed waning (50~60 % decrease). She was administered prednisolone (PSL) on alternate days, and the dose was gradually increased to 100 mg on alternate days. Her symptoms gradually improved. Thymectomy was performed on August 8, and pathology of thymus revealed hyperplasia. The dose of PSL was gradually decreased and finally discontinued on 15 March, 1997. In May 1997, she suffered polyarthralgia, and an orthopaedist diagnosed rheumatoid arthritis. In January 1999, multiple skin lesions appeared in the limbs. On May 5, 1999 she visited our hospital, and her myasthenic symptoms were almost recovered except for slight weakness of the upper limbs. Rheumatoid factor was 107 IU/ml. Symmetrical multiple red-purple erythematous, nodular lesions were observed on the extensor surface of the hands, especially the extensor surface of joints (Fig. 1-a,b,c). Dermatologists diagnosed this condiLETTER TO THE EDITORS