A 54-year-old man was admitted due to progressive gait disturbance and cognitive impairment. On MRI, a hyperintense region was observed in the periventricular white matter on FLAIR imaging, with Gd-enhancement in the choroid plexus and periventricular wall. Cerebrospinal fluid (CSF) examination showed marked abnormalities including a high white blood cell count (WBC, 360 cells/mm³. 83% lymphocytes), an elevated protein level (1,416 mg/dl), a low glucose level (12 mg/dl), and elevated cryptococcal antigen with positive Indian ink staining. Cryptococcal ventriculitis was diagnosed. The patient was initially treated with liposomal amphotericin B, fluconazole, voriconazole, and flucytosine for 38 weeks, followed by administration of itraconazole and fluconazole with some improvement. The brain MRI after one month showed septum formation in the posterior horn, which was suggestive of ventriculitis. Although ventriculitis is rare, we should pay attention to the presence of ventriculitis due to cryptococcal infection in the central nervous system.

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We report a 70-year-old women with left hemifacial metamorphopsia due to an infarction in the right retrosplenial region. She firstly noticed that the left half of her face reflected in the mirror was distorted. She complained of the same kind of distortion when she looked at the face of humans. Neurological examination on admission showed no other symptoms. Her visual acuity and visual field were normal. Diffusion weighted images of the brain revealed a high intense lesion in the right retrosplenial region, which was considered to account for her symptom. This case contributes to clarify the pathogenesis of hemifacial metamorphopsia.

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We report a patient having classical clinical feature of neurologic muscle weakness, ataxia, and retinitis pigmentosa (NARP) and a novel mutation, m.8729 G>A in mitochondria DNA. The patient was referred to our hospital because of progressive ataxia in her limbs and trunk. She had a history of incapability of running long distances from childhood. Neurological examination revealed cerebellar ataxia, distal dominant muscle weakness in the limbs, hyporeflexia, hypoesthesia, myoclonus, sensorineural deafness, and retinitis pigmentosa. Magnetic resonance imaging (MRI) showed atrophy of brain stem and cerebellum as well as calcification of basal ganglia. In both serum and cerebrospinal fluid, lactate and pyruvate levels were elevated. Histological examination of biopsied muscle revealed chronic neurogenic changes without ragged red fibers. Genetic analysis of mitochondrial DNA (mtDNA) of the muscle revealed a heteroplasmic mutation, m.8729 G>A. Chemical analysis of the respiratory chain complexes in her muscle specimen demonstrated lower activities of complexes I and V. In our case, novel mutation of m.8729 G>A in mtDNA was indicated as the cause of NARP syndrome.

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A 70-year-old man with a 5-month history of progressive bradykinesia of the bilateral lower extremities was admitted to our hospital. At the age of 64, he underwent proximal gastrectomy for gastric cancer. He also had a history of subacute combined degeneration of the spinal cord since the age of 67, which was successfully treated with vitamin B12 therapy. Four weeks before admission to our hospital, he admitted himself to his former hospital complaining of walking difficulty. Two weeks later, however, his symptoms progressed rapidly; he was immobilized for two weeks and did not respond to the vitamin therapy. On admission to our hospital, he showed moderate paralysis of the lower extremities, cog-wheel rigidity of the four extremities, and dystonic posture of his left hand. He also showed orthostatic hypotension and vesicorectal disorders. Blood examination and cerebrospinal fluid analysis revealed no remarkable abnormalities. Electroencephalography showed frontal dominant, high voltage, sharp waves. His brain and spinal MRI revealed no notable abnormalities. We suspected autoimmune disease and commenced one course of intravenous methylprednisolone therapy, resulting in improvement of the parkinsonism and orthostatic hypotension. Based on these results, we investigated possible neural antigens and detected anti-Ma2 antibody. In addition to limbic encephalitis, anti-Ma2 antibody-positive neural disorders are characterized by rapid eye movement sleep behavior disorders or parkinsonism. Here, we report an anti-Ma2 antibody positive patient presenting variable CNS symptoms mimicking multiple system atrophy, who responded to immunotherapy.

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A 66-year-old woman presented with vertigo and deafness. Diffusion-weighted magnetic resonance imaging of the head showed multiple cerebral infarctions involving several blood vessel regions. A diagnosis of cardiogenic embolism was made, and anticoagulation therapy was begun. The woman had no additional symptoms until suddenly developing left hemiparesis one year later. She was again found to have multiple cerebral infarctions. The hemiparesis gradually improved, but ataxic gait and apraxia appeared and progressed over two weeks. Holter ECG, carotid ultrasound, and transthoracic/transesophageal echocardiography revealed no evidence of cardiogenic embolism. However, serum lactate dehydrogenase (LDH) and soluble interleukin-2 receptor (sIL2R) levels were elevated (LDH, 782 IU/l; sIL2R, 1,396 IU/ml), which suggested malignant lymphoma. Contrast chest/abdominal CT scan and gallium-67 scintigraphy revealed no evident lesions; however, random skin biopsy and open brain biopsy showed that blood vessels were infiltrated by CD20-positive atypical lymphocytes. These findings were consistent with intravascular large B-cell lymphoma. This type of lymphoma is known as a rapidly progressive disease with poor prognosis, but this case followed an indolent course, with a one-year interruption in disease progression.

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A 76-year-old female was referred to our department because of diplopia for two months and intermittent claudication for five months. She showed medial longitudinal fasciculus (MLF) syndrome. Brain MRI (T₂WI) showed multiple infarctions in the right pontine tegmentum and left paramedian midbrain. A biopsy of superficial temporal artery showed the characteristic findings of glanulomatous inflammation indicative of giant cell arteritis. We thought the mechanism of this cerebral infarction as artery to artery embolization or intracranial arteritis. Treatment with oral prednisolone (1 mg/kg/day) improved her limb claudication and normalized serum C-reactive protein level.

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A 62-year-old woman with one-year history of type 1 diabetes mellitus was admitted to our hospital with progressive weakness in the lower extremities and urinary dysfunction following high fever. On admission, she had rigidity and myoclonus in the upper extremities with sensory ataxia. Cerebrospinal fluid examination revealed mild pleocytosis and oligoclonal band. Glutamic acid decarboxylase (GAD) antibodies were detected at high titer in serum, but antibodies to glycine receptor (GlyR), thyroid peroxidase, mitochondrial M2, and GM1 were also detected. She was diagnosed with progressive encephalomyelitis with rigidity and myoclonus (PERM), which probably developed on the basis of polyglandular autoimmune syndromes. The clinical symptoms began to improve after initiation of intravenous high-dose methylprednisolone. Muscle weakness might be related to GM1 antibodies. This is the first report of PERM, in which GM1 antibodies were detected with GAD and GlyR antibodies.

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A 64-year old woman was admitted to our hospital with subacute onset paraparesis and sensory disturbance at a level below Th10. Spinal MRI showed a T₂ weighted high-signal intensity lesion at a level from Th5 to Th12, and an abdominal CT showed a mass in the left kidney. Her paraparesis deteriorated rapidly, and administration of high dose methyl prednisolone followed by oral steroid therapy was started before obtaining of a definitive diagnosis. However her symptoms did not improve after the beginning of treatment. At the same time, a bone marrow puncture, and biopsies from kidney and spinal cord were performed. These biopsies demonstrated no clues, diagnostically. Therefore a random skin biopsy was performed at the five sites on the 17th day after the steroid dosage end. From this, pathological evidence of intravascular large B cell lymphoma (IVLBCL) was shown. For rapid diagnosis of acute myelopathy with mass lesion of another organ due to IVLBCL, a biopsy is taken not only from spinal cord or mass lesions, but is also taken of multiple sites in skin randomly. This must be performed without a delay before a sudden deterioration of neurologic symptoms can occur from ischemic events not responsive to steroid therapy.

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A 66-year-old man was admitted to our hospital because of unconsciousness. He was diagnosed with pneumococcal meningitis and treated with a combination of antibiotics (meropenem hydrate), dexamethasone, and intravenous immunoglobulin. Although he gradually regained consciousness, he started showing signs of hearing disturbance. Measurement of auditory brainstem response revealed severe sensorineural hearing loss. The patient then underwent three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging, which revealed increased signals in the cochlea and the vestibuum, and their enhancement after gadolinium administration. This enhancement was still observed on images of the inner ear acquired on the 52nd hospital day. These findings suggested that the change of content in the lymph and the damage to the blood-labyrinth barrier was caused and aggravated by an immune response. Recent studies have shown that an MyD88-dependent immune response contributes to hearing loss in an experimental mouse model of pneumococcal meningitis. The patient was administered steroid pulse and hyperbaric oxygen therapies for improving the hearing deficit, but these therapies were discontinued because of the aggravation of hepatitis B and diabetes mellitus, which he had developed previously.

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Multiple drug hypersensitivity (MDH) is an allergy to two or more chemically unrelated drugs. We present a case of MDH caused by antituberculosis agents during the treatment of tuberculous meningitis (TBM). A 64-year-old man without a history of drug allergy developed fever and severe headache. Examination of cerebrospinal fluid showed lymphocytosis, a low glucose level, and a high ADA activity, suggestive of TBM. The patient was treated with isoniazid, rifampicin, pyrazinamide, and ethambutol, and his symptoms resolved quickly. However, 20 days after the initiation of therapy, he developed remittent fever without mucocutaneous lesions. A drug-induced lymphocyte stimulation test was positive for isoniazid, rifampicin, and pyrazinamide, which was consistent with a diagnosis of MDH. All the antituberculosis drugs were replaced with levofloxacin and ethionamide, both of which have excellent cerebrospinal fluid penetration, and the fever subsided. The patient made a full recovery from TBM. Because standard antituberculosis regimens include three or four antituberculosis drugs, it is difficult to determine the culprit drug when hypersensitivity occurs. Moreover, there can be multiple causative drugs as illustrated by the present case. During a time-consuming desensitization therapy, TBM could flare up, leading to permanent neurological damage. Thus, treatment with suitable alternative drugs should be started immediately.

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[in Japanese]

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[in Japanese]

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