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A 52-year-old man had developed hearing loss since childhood, as well as recurrent foot ulcers and osteomyelitis since his forties. He presented with gait disturbance and dysarthria that had worsened over four years and a month, respectively. Neurological exams revealed cognitive impairment, proximal weakness of the lower extremities, generalized hyperrflexia, ataxia, sensory disturbances predominant in deep sensation, urinary retention, and gait instability. On nerve conduction study, no sensory nerve action potentials were evoked in the upper and lower limbs. Since his grandmother suffered from similar symptoms, we investigated genetic analysis, which revealed a missense mutation (c.1483T>C, p.Y495H) in DNA methyltransferase 1 gene. He was subsequently diagnosed with hereditary sensory and autonomic neuropathy 1E (HSAN1E). It is important to recognize that increased deep tendon reflex can be observed in HSAN1E.

We report a 72-year-old man with eosinophilic myositis (EM). At age 71 he noticed a painful nodule in his left calf. A biopsy (first biopsy) showed marked infiltration of mononucleated cells and necrotic muscle fibers. Several phagocytosed fibers were also seen. He was diagnosed as having myositis. The painful nodule disappeared spontaneously. At age 72, he again had a painful nodule, but this time in his right calf; again, this disappeared spontaneously on the first admission. Just after discharge, he noted painful nodules in the left thigh and right anterior tibial muscles and was again admitted (second admission). Neurological examination revealed mild proximal-dominant weakness in all four extremities but no other abnormalities. Laboratory studies showed elevated creatine kinase (CK) level (38,803 U/l; normal 62-287) and positive Jo-1 antibody, but no eosinophilia. Needle electromyography of the limb muscles showed myogenic patterns. Magnetic resonance imaging of the lower limbs demonstrated several T2-high and gadolinium (Gd)-enhanced lesions. Muscle biopsy (second biopsy) from the left quadriceps femoris showed marked infiltration of eosinophils; he was diagnosed as having EM. Administration of prednisolone was initiated at 60 mg/day and then gradually tapered. After starting treatment with steroids, his muscle weakness gradually ameliorated, CK level dramatically decreased, and the nodules disappeared. Clinically, the patient had developed localized nodular myositis (LNM), but pathologically it was EM without peripheral blood eosinophilia and positive Jo-1 antibody that is occasionally found in polymyositis (PM). Thus, this patient demonstrated overlapping characteristics of EM, LNM, and possibly PM, suggesting that a common mechanism underlay these conditions. As discussed, the involvement of eosinophils in three inflammatory myopathies was indicated.

A 29-year-old woman with benign congenital nemaline myopathy is reported. She did not walk until the age of one year and seven months. Although she acquired the ability to run, she ran very slowly. She first noticed the progression of weakness of the limbs at age 21, and it worsened gradually. On admission, she showed moderate weakness in the face, neck, and four limbs. Serum creatine kinase was elevated to 218 U/l. Needle electromyography showed giant and polyphasic motor unit potentials with a reduced reference pattern in the four limbs diffusely. In muscle biopsy, about 10% of fibers had many small vacuoles, and half of them were rimmed. Modified Gomori trichrome stain revealed nemaline rods in about 20% of both type I and type II fibers. Fibers with large diameter and atrophic ones showed increased acid phosphatase activity. Type I fibers were small, and type II fibers numbered only 2%. We diagnosed her illness as a congenital nemaline myopathy that began in infancy and progressed in adulthood. The increased autophagic activity probably caused the progression of muscle weakness. Moreover, the presence of both nemaline rods and rimmed vacuoles may have contributed to the development of diffuse neurogenic changes seen in electromyography.

We report a 23-year-old man with mitochondrial encephalomyopathy. At 21 years of age, he noted speech distubance. Since his dysarthria did not improve thereafter, he was admitted to our hospital. On admission, he showed mild gynecomastia. Neurological examination revealed mild decrease in performance IQ in WAIS-R, mild scanning speech, mild left hearing disturbance, mild to moderate muscle weakness in proximal four extremities, mild bilateral limb ataxia, and mild to moderate truncal ataxia. While, no brisk deep tendon reflex, pathological reflex, aberrant muscle tonus, sensory disturbance, retinopathy, myoclonus or autonomic disorder was found. Serum levels of lactate (23.2 mg/dl, normal<18.7) and pyruvate (1.23 mg/dl, normal<0.94) were elevated, and serum lactate levels were markedly elevated (118.1 mg/dl) after 15-minute exercise (15 Watts/minute). CSF levels of lactate (31.2 mg/dl, normal<12.5) and pyruvate (1.48 mg/dl, normal<0.75) were also elevated. Head MRI showed mild cerebral and cerebellar atrophy, but 1H-MRS showed no lactate peak. Moreover, muscle biopsy from left biceps muscle showed lots of ragged-red fibers, and he was thus diagnosed as having mitochondrial encephalomyopathy. However, nt3243 mutation of mitochondria DNA was not present. Next, we confirmed gynecomastia by mammography, and checked serum levels of estrogens. Mildly decreased estradiol (19.9 pg/ml, normal, 20-59), normal estrone (24.0 pg/ml, normal<30.0) and mildly increased estriol (6.03 pg/ml, normal<5.0) were found. While, the serum levels of cortisol, dehydroepiandrosterone-sulfate (DHEA-S), androstenedione, testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were all within normal limits. Since the steroid hormone synthesis system and hypothalamus-pituitary system seem to be normal, 16alpha-hydroxylase that converts estradiol to estriol may be upregulated. While, aromatase (P-450arom) is well known to convert androgens to estrogens. In addition, 16alpha-hydroxylase and P-450arom convert DHEA-S to estriol. Since it is recently reported that P-450arom is considerably expressed in muscle tissues as well as fat tissues and that muscle tissue may be a major organ to produce estrogens in men and postmenopausal women, estriol production may be increased in the present patient's muscle. Although hypogonadism due to hypothalamus-pituitary disorders was sometimes reported, there have been no reports that suggest an increased estrogen production in skeletal muscles in mitochondrial encephalomyopathies. Recently, estrogen has been known to protect muscle fibers from oxidative damages due to exercise. Thus, it is of potential that estrogens increased locally in muscle tissues of the patients with mitochondrial encephalomyopathies protect muscle fibers from oxidative damage due to mitochondrial dysfunction.

A 58-year-old woman suffered from stiffness, swelling, rubor and muscle pain in the extremities one month after she climbed a mountain in Kyushu, an island in southern Japan. On admission, mild proximal weakness was present in the extremities. Her range of motion in the extremities was limited due to firm skin and subcutaneous stiffness which was similar to scleroderma. She showed peripheral blood eosinophilia and hypergammaglobulinemia as well as a high erythrocyte sedimentation rate. An IgM antibody against Borrelia afzelii was positive. MRI of the skeletal muscles demonstrated enhancing fascia around the biceps brachii muscle, and a biopsy specimen revealed perivascular infiltration of mononuclear cells within the hypertrophic fascia. Eosinophilic infiltration was absent. We treated the patient with prednisolone, doxycycline and amoxicillin, which alleviated the symptoms. This is the first report to show that Borrelia afzelii was involved in eosinophilic fasciitis.

We report a 20-year-old man with temporal lobe epilepsy (TLE) accompanied by hereditary motor and sensory neuropathy (HMSN). He had experienced complex partial seizures (CPS), which started with a nausea-like feeling, followed by loss of consciousness and automatism, since he was 6 years old. The frequency of attacks was at first decreased by phenytoin. However, attacks increased again when he was 18 years old. On admission, neurological examination showed mild weakness of the toes, pes cavus, hammer toe and mildly impaired vibratory sensation in his legs. Ten people in four generations of his family showed a history of epilepsy in the autosomal dominant inheritance form. His younger sister and mother had a history of epilepsy accompanied with pes cavus, hammer toe, weakness of toe and finger extension and mildly impaired vibratory sensation as well. Direct sequencing of the glioma-inactivated leucine-rich gene (LGI1), in which several mutations were reported in patients with familial lateral temporal lobe epilepsy, showed no specific mutation in this family. On consecutive video-EEG monitoring, paroxysmal rhythmic activity was confirmed in his left fronto-temporal region when he showed automatism, and then a generalized slow burst activity was detected when he lost consciousness. For his seizures, TLE with secondary generalization was diagnosed. In the nerve conduction study, delayed nerve conduction, distal motor latency and decreased amplitudes of the compound muscle action potentials (CMAP) of bilateral peroneal nerves were observed, indicating the existence of mild axonal degeneration. Based on these data, we consider that this family to be a new phenotype of autosomal dominant TLE accompanied by motor and sensory neuropathy.

We report a 60-year-old man with myelodysplastic syndrome (MDS) who developed polymyositis and cutaneous vasculitis. He noticed difficulty in climbing up stairs 4 months before admission. On admission, he showed brownish skin pigmentation in the distal positions of the four extremities. Neurological examination revealed muscle weakness of the neck flexor and proximal muscles of four extremities. Serum myogenic enzymes including creatine kinase increased, and electromyography showed denervation potentials and MUPs were myogenic, which was compatible with polymyositis. Muscle biopsy indicated perivascular mononuclear cell infiltration and muscle fiber necrosis with cytoplasmic bodies and rimmed vacuoles in the muscle fibers. Complete blood cell counts revealed macrocytic normochromic anemia and bone marrow puncture disclosed marked hyperplasia of megakaryocytes, erythroblasts and myeloblasts, suggesting a refractory anemia type of MDS. In addition, skin biopsy showed chronic cutaneous vasculitis. Serum protein electrophoresis and immunoelectrophoresis revealed the presence of IgM gamma type monoclonal gammopathy. With immunosuppressive therapy, serum creatine kinase level was decreased. Since immunological abnormalities and the presence of autoimmune diseases have been reported in patients with MDS, both polymyositis and chronic cutaneous vasculitis in the present patient may be caused by the similar autoimmune mechanisms related to MDS.

Central alveolar hypoventilation syndrome (CAH), or Ondine's curse, is a very rare disease characterized by dysfunction of respiratory center in the brain stem. Here, we report a case of CAH associated with cerebral infarction. A 59-year-old man developed right facial sensory deficit at age 56. Then, the facial sensory deficit spread to the left side and dysarthria and dysphagia also developed. Since age 58, he often developed respiratory failure and consciousness disturbance. Arterial blood gas analysis revealed alveolar hypoventilation and respiratory acidosis. Disorders of peripheral organs such as lung, airway, thorax and neuromuscular diseases were ruled out. Brain MRI showed cerebral infarction in the brain stem. We diagnosed him as CAH associated with brain stem infarction.

A 14-year-old girl, whose birth and developmental history were normal till the age of 7, was admitted to our hospital because of slowly progressive difficulties in walking, speaking and hearing. She also complained of absence of menstruation. She showed poor school records since the age of 7. On neurological examination, she showed limb and truncal ataxia. There was no nystagmus but slurred speech was found. Muscular power was good and her sensory system was normal. Tendon reflexes were equally present, and plantar reflexes were flexor. Bilateral moderate nerve deafness was also present. Mental deficiency was diagnosed on an intelligence test. Brain CT and MRI showed cerebellar atrophy. Gynecological examination revealed scanty pubic hair and small uterus. Karyotype was 46XX. Endocrinological studies demonstrated high level of FSH, low level of E2, and the normal response to pituitary stimulation with LHRH, indicating the existence of primary hypogonadism. Although the etiology of this multisystem disorder is unknown, it is possible that both nervous and endocrine disorders were genetically determined.