Nobuatsu Nomoto

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.

Anti-TNF therapy using etanercept suppresses degenerative and inflammatory changes in skeletal muscle of older SJL/J mice.

Limb-girdle muscular dystrophy 2B and Miyoshi myopathy are characterized by muscle fiber necrosis caused by a defect in dysferlin and inflammatory changes. SJL/J mice are deficient in dysferlin and display severe inflammatory changes, most notably the presence of cytokines, which may be related to destruction of the sarcolemma. We tested the hypothesis that tumor necrosis factor (TNF) contributes to myofibril necrosis. Administration of etanercept, an agent that blocks TNF, resulted in dose-dependent reductions in inflammatory change, necrosis, and fatty/fibrous change. These findings indicate that TNF does indeed play a role in the damage to muscle in SJL/J mice and that etanercept has the potential to reduce such damage.

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.

Extrathymic tumors in patients with myasthenia gravis: a 35-year retrospective study.

Objective:Autoimmune diseases are frequently associated with malignant tumor. In addition, prolonged immunosuppression may favor the development of malignancy. While the coincidence of myasthenia gravis and extrathymic tumor has been reported, the risk and features of these tumors are not well understood. Review Summary:We treated 305 patients with myasthenia gravis from 1968–2003, including 48 thymoma cases. Two hundred twenty-nine patients had undergone thymectomy and 76 had not. We examined cancer risk, tumor characteristics, and associations to medications. We encountered 9 cases of extrathymic tumor. Cancer risk in the thymoma cases was 6.3% and 2.3% in the nonthymoma cases, a statistically insignificant difference. Azathioprine was administered to only 14 in this series of patients; however, 2 patients developed cancer. Conclusions:Cancer risk in patients with myasthenia gravis is 2.6%, similar to that of the general population in Japan. We neurologists need to be aware that prolonged immunosuppression may favor the development of malignancy.

Guillain-Barré syndrome with optic neuritis and cytomegalovirus infection.

Dear Editor, Although the cranial nerves are often involved in Guillain-Barré syndrome (GBS), the optic nerves are usually spared presumably because they are part of the central nervous system (CNS). Here, we report a case of GBS with concurrent optic neuritis (ON) with antecedent cytomegalovirus (CMV) infection. This combination suggests that some epitope shared with both the CNS and peripheral nervous system (PNS) was targeted by an autoimmune process triggered by CMV infection. A previously healthy 68-year-old man noticed visual loss in the right eye when he woke up and had cough and low-grade fever 4 days prior. Examination the next day revealed no light perception on either eye with normal optic discs, fundi and ocular movements. The peripheral facial nerve and the right hypoglossal nerve palsies in the right side were present. Three days after disease onset, he developed bilateral ophthalmoplegia and bulbar palsy. On day 4, he developed muscle weakness in the upper extremities and respiratory failure. On day 5, quadriplegia, loss of deep tendon reflexes, and sensory disturbance in all modalities were noted. The nerve conduction studies were consistent with primary demyelination. The visual evoked potential could not be obtained. The cerebrospinal fluid protein was elevated to 209 mg/dL with normal cell count (4/mL, M : P 1⁄4 1 : 3). Myelin basic protein and oligoclonal immunoglobulin G (IgG) bands were negative. MRI of the brain and optic nerves was normal. The serum titers of IgG anti-GQ1b, anti-GT1a antibodies increased on days 4, 11, and 41, normalized on day 74. The antibody titers against CMV were significantly high during the clinical course (Table 1). He was diagnosed as having atypical GBS. High-dose intravenous immunoglobulin (0.4 mg/kg/ day for 5 days) alleviated his symptoms except for ON. A course of intravenous methylprednisolon pulse therapy (1 g/day for 3 days) was employed on day 31 and resulted in gradual recovery of visual acuity. After 6 months, he could walk more than one kilometer without support and could count fingers with either eye. The unique point of this case is that descending paralysis with multiple cranial nerve involvement started from the optic nerves. On admission, the diagnosis of GBS was unclear because his neurological signs were restricted to the cranial nerves including bilateral optic nerves recognized as part of the CNS. Within a few days, however, bulbar palsy with respiratory failure and motor-sensory peripheral neuropathy became evident. GBS, an acute generalized inflammatory demyelinating peripheral nerve disorder, rarely complicates CNS involvements including, if any, lesions in the cerebral white matter, the brain stem, the spinal cord, or the optic nerves. In most reported GBS cases with ON, the temporal profile of GBS is different from that of ON (Nikoskelainen and Riekkinen, 1972; Behan et al., 1976; Nadkarni and Lisak, 1993). This biphasic clinical profile suggests that an autoantigen, not pathogenic for the first lesion, was liberated from the nervous system during the first attack and subsequently sensitized the host to cause the second insult (Behan et al., 1976). In the present case, however, GBS and ON developed synchronously. This indicates that an epitope shared in both the CNS and PNS was targeted. The mechanism is still unknown, but the involvement of CMV infection, serologically confirmed in the present case, is speculated. Some cases with concurrent GBS and ON have the evidence of direct infection of mumps virus (Bajaj et al., 2001) or Mycoplasma pneumoniae (Henderson et al., 1998). CMV, a potent neurotropic virus, is a common antecedent infectious agent of GBS as well (Visser et al., 1996; Hadden et al., 2001). Whether there is a linkage of GBS with ON and anti-ganglioside antibody (GQ1b or GT1a) and CMV infection remains unclear, however, the fact that Address correspondence to: Dr. Toshiki Fujioka, Department of Neurology, Toho University Medical Centre Omori Hospital, 6-11-1 Omori-nishi Ota-ku, Tokyo 143–8541, Japan. Tel: þ81-3-3762-4151; Fax: þ81-3-3768-2566; E-mail: fujioka@med.toho-u.ac.jp Journal of the Peripherl Nervous System 10:340–341 (2005)

Anhedonia and its correlation with clinical aspects in Parkinson's disease

Anhedonia is one of the non-motor symptoms observed in the Parkinsons disease (PD). However, there is no clear relationship between anhedonia and its correlation with other symptoms of PD. The aim of this study is to evaluate the characteristics of anhedonia and its correlation with clinical aspects of PD in a relatively large cohort. We enrolled 318 patients with PD and 62 control subjects for this study. Patients and subjects were tested using the Snaith-Hamilton Pleasure Scale Japanese version and the Beck Depression Inventory 2nd edition for the assessment of anhedonia and depression. We also investigated the correlation among clinical aspects of PD, anhedonia, and depression in patients with PD. The Snaith-Hamilton Pleasure Scale Japanese version and the Beck Depression Inventory 2nd edition scores were significantly higher in patients with PD than in control subjects (p=0.03 and p=0.0006, respectively). All PD patients with anhedonia had a significantly higher score on the unified Parkinsons disease rating scale (UPDRS) parts I and II compared to PD patients without anhedonia. Additionally, all PD patients with depression scored significantly higher on UPDRS part I-IV than PD patients without depression. The patients with anhedonia and without depression had mild motor severity and their treatment was relatively low dosage. These results suggest that anhedonia and depression are slightly linked, but not the same. PD patients with only anhedonia may be closely linked apathy found in untreated early stages of PD.

Triphasic waves in a patient with tuberculous meningitis

We report on the case of a 32-year-old woman with tuberculous meningitis (TBM) with electroencephalogram (EEG) output displaying triphasic waves (TWs). The EEG on day 8 revealed generalized slowing, frontal bilateral TWs, a background of 2Hz delta waves, and no epileptiform activity. The patients condition improved slowly with antituberculosis chemotherapy treatment. A follow-up EEG on day 34 showed marked improvement, with no TWs, background activity improved to a 12Hz symmetric alpha wave pattern, and no epileptiform activity, as before. To our knowledge, this is the first report of TWs observed in a TBM case.

Rhinorrhea in Parkinson's disease: A consecutive multicenter study in Japan

Recent reports suggest that rhinorrhea, defined as the presence of a runny nose unrelated to respiratory infections, allergies, or sinus problems, occurs more frequently among patients with Parkinsons disease (PD) than among healthy controls. We conducted a questionnaire survey in a multicenter study throughout Japan and compared the frequency of rhinorrhea between 231 PD and 187 normal control (NC) subjects. After excluding patients with rhinitis or paranasal sinusitis, a total of 159 PD and 59 NC subjects were included in our analysis. Rhinorrhea occurred more frequently in PD patients than NC subjects (33.3% vs. 11.9%; P=0.01). Among PD patients, rhinorrhea was more common in men than women (P=0.005). Rhinorrhea was not correlated with disease duration, modified Hoehn and Yahr score, disease type (akinesia rigidity vs. tremor dominant), or cardiac sympathetic function (evaluated by (123)I-metaiodobenzylguanidine uptake). To our knowledge, this is the first multicenter study on the frequency of PD-related rhinorrhea in Asian countries.

Legionellosis presenting as singultus and external ophthalmoplegia

We report a 71-year-old man with legionellosis, who presented with abducens nerve palsy, singultus, confusion, memory impairment, ataxia, and hyporeflexia. Legionella pneumonia was diagnosed on the basis of detection of Legionella pneumophila antigen in the urine. The cerebrospinal fluid was negative for the antigen and antibody, but an oligoclonal band was detected, and the IgG index was elevated. It was speculated that an undetermined immune-mediated mechanism had contributed to the development of the neurological manifestations.

Autoimmune polyglandular syndrome type 2 with myasthenia gravis crisis.

We describe a rare case of autoimmune polyglandular syndrome type 2 initially presenting as Addison disease and autoimmune thyroid disease, with subsequent development of autoimmune hepatitis and myasthenia gravis (MG) crisis in a Japanese woman. MG improved with oral prednisolone followed by plasmapheresis for immunoadsorption; thymectomy was not performed. Conventional treatment for MG was effective and safe in this case, in which there was positivity for human leukocyte antigen A23, B52, B62, DR11, and DR15.