[A case of neuroleptic malignant syndrome caused by discontinuation of psychotropic drugs].

A 71-year-old woman with schizophrenia and diabetes discontinued psychotropic drugs due to right purulent knee bursitis. Five days after discontinuation, she presented with a fever of >40°C, severe disturbance of consciousness, lead-pipe muscle rigidity, tachypnea, and hypertension. She was diagnosed with neuroleptic malignant syndrome (NMS) induced by the discontinuation of psychotropic drugs. The patient's symptoms improved after dantrolene administration and systemic management. We investigated the clinical characteristics of cases with NMS induced by the discontinuation of psychotropic drugs reported in Japan, including the present case. When psychotropic drugs are discontinued, patients should be monitored for signs of NMS. Strict management of early onset NMS is needed to prevent the condition from worsening.

[A case of Wernicke's encephalopathy with detrusor-sphincter dyssynergia].

We report a case of a 54-year-old man with alcoholic Wernicke's encephalopathy. Neurological examination showed unconsciousness, absence of the oculocephalic reflex, generalized hyporeflexia, and urinary retention. The patient immediately regained consciousness after the administration of thiamine, but amnesia and cerebellar ataxia became apparent. The urinary retention persisted, and an urodynamic study showed detrusor-sphincter dyssynergia. Three months after the treatment, the urinary retention resolved, and a second urodynamic study showed disappearance of the detrusor-sphincter dyssynergia. Wernicke's encephalopathy involves the periaqueductal gray matter and the floor of the fourth ventricle. For the voiding reflex, the periaqueductal gray matter neurons project to the pontine micturition center, which seems to be located adjacent to the locus coeruleus. We concluded that lesions of the periaqueductal gray matter and/or the dorsolateral portion of the pons were responsible for the micturitional disturbance in the patient.

[A case of asymptomatic takotsubo cardiomyopathy with intraventricular thrombus associated with epileptic seizure].

A 69-year-old woman was admitted to our department for consciousness disturbance with generalized clonic seizure. She had a history of complex partial seizure with automatism 3 years previously, but had not received any antiepileptic drug therapy. On admission, she was unconscious with a Japan Coma Scale of 200. Physical examination demonstrated a blood pressure of 162/90 mm Hg and pulse of 126 beats/min. Neurological examination did not detect any focal findings. Four hours later, she was conscious and antiepileptic drug therapy was initiated. Twenty-six hours post admission, ECG monitoring showed giant T-wave inversion, but cardiac symptoms were absent. Echocardiography showed apical ballooning of the left ventricle. Echocardiography on day 6 demonstrated a thrombus at the apex of the left ventricle. Anticoagulant therapy was started immediately. Echocardiography on day 14 showed that the left ventricular apical asynergy had completely resolved, and the thrombus had disappeared. Takotsubo cardiomyopathy could be a complication of epilepsy. It occurs most often soon after epileptic seizure, rarely occurs with a time lag and is asymptomatic as in the present case. ECG monitoring after epileptic seizure is useful for prompt detection and treatment of takotsubo cardiomyopathy.

[A case of theophylline-associated seizures with postictal fever and postictal pleocytosis].

We report a 70-year-old man who developed theophylline-associated seizure with postictal fever and postictal pleocytosis. He was admitted to our hospital for a left hemiconvulsion lasting for two hours. The concentration of theophylline was high (21.6ng/ml), and electroencephalogram demonstrated periodic lateralized epileptiform discharges. Diffusion-weighted magnetic resonance imaging showed high signal intensity lesions in the right cingulated gyrus, insula and thalamus. Temperature above 38.0° was detected 5.5 hours after seizure and lasted for 60 hours. Cerebrospinal fluid (CSF) analysis on day 2 demonstrated pleocytosis (62/uL) with a predominance of polymorphonuclear leukocytes (90%). Temperature and CSF pleocytosis subsided after sedation. Intracranial inflammatory or infectious disease is the first consideration in epilepsy with fever and CSF pleocytosis, and then diagnosis of postictal fever and postictal pleocytosis should be made only by rigorous exclusion of that possibility.

[A case of hypokalemic myopathy mimicking hemiparesis].

We report the case of an 86-year-old female with licorice-induced hypokalemic myopathy. For four years, she had been taking two kinds of Chinese medicines containing licorice. The patient presented with difficulty in holding her head up and proximal-dominant tetraparesis with significant laterality. In manual muscle tests, the right extremities showed grade 2/5 and the left extremities, grade 4/5. The general reflexes were decreased, and the bilateral Chaddock's reflexes were repeatedly positive. The sensory, cerebellar and autonomic systems were normal and discrete movements of all extremities were well preserved. Laboratory tests showed elevated levels of CK (559 IU/1), hypokalemia (1.6 mEq/1), and metabolic alkalosis (pH 7.51, base excess 10.9 mmol/1). Magnetic resonance imaging showed mild compression of the spinal cord due to cervical spondylosis. Electromyography revealed myopathic patterns in the deltoid muscle. Steady clinical recovery was noted following treatment including cessation of licorice intake and administration of potassium supplementation. Neck weakness, tetraparesis with laterality and Chaddock's reflexes were diminished. We conclude that the pathologic reflex was caused by the aggravation of cervical spondylotic myelopathy due to neck weakness and that tetraparesis with laterality was caused by hypokalemic myopathy.

[A case of pure agraphia due to left parietal lobe infarction].

We reported a case of an 86-year old woman with pure agraphia due to the left parietal lobe infarction. The characteristics of agraphia were as follows. Most errors in Kana and Kanji writing to dictation and copying were no response. She was able to write only numerals from 1 to 12 precisely. Most errors in numerals were substitution. One unrecognizable numeral was found. She succeeded in pointing to nine among ten single Kana letter named by the examiner with the systematic table of the Japanese syllabary, but missed in pointing to Kana words. It took more time for the patient to point to single Kana letter than the control. Magnetic resonance imaging showed a cerebral infarction in the left parietal lobe which included a part of superior parietal lobule and supramarginal gyrus. We classified pure agraphia with parietal lobe infarction into two types in our previous report. In one type (type 1), letters in writing are poorly formed, but the ability to make words with the methods other than writing are reserved. The only deficit of graphic motor pattern could cause Type 1 agraphia. In another type (type 2), letters in writing were well-formed, but spelling with anagram or typing was disturbed. The deficits of writing process other than graphic motor pattern could cause Type 2 agraphia. This typing seems to be effective not only in Kana but also in Kanji. In this report, we investigated the differences of lesion between two types out of some references. Type1 agraphia seems related to lesion of left superior parietal lobule, while Type 2 agraphia seems related to lesion of left supramarginal gyrus. This case had the features of type 2 agraphia at least, and the compatible lesions.

Encephalopathy with isolated reversible splenial lesion of the corpus callosum.

We report a 51-year-old Japanese man with chronic alcoholism who complained of mental confusion following respiratory and intestinal infections. The splenium of the corpus callosum showed hyperintensity on both diffusion-weighted MR images and fluid-attenuated inversion recovery images and hypointensity on T1-weighted images. These findings were resolved on MR images obtained 3 days later. He showed complete neurological recovery within 2 months. We suspected that he had mild encephalopathy with a reversible splenial lesion after systemic viral or bacterial infection.

Morphological differences of intraneuronal ubiquitin-positive inclusions in the dentate gyrus and parahippocampal gyrus of motor neuron disease with dementia.

Semiquantitative morphological analysis of cerebral intraneuronal ubiquitin-positive tau-negative inclusions, a pathologic marker for motor neuron disease with dementia (MND-D), was performed in the dentate gyrus and parahippocampal gyrus of 20 clinicopathologically confirmed patients with MND-D. The forms of the inclusions were tentatively classified into three types: (i) C-type, consisting of relatively large and intensely stained crescent or circular structures; (ii) L-type, showing fine linear structures around the nuclei; and (iii) G-type, showing faintly stained granular structures. The frequencies of the C-type, L-type and G-type was 0.5-9.3%,0.2-6.5% and 0-6.6% of dentate granule cells, respectively. In contrast to the dentate gyrus, almost all inclusions showed either the C-type or L-type form in the parahippocampal gyrus. A positive correlation was noted only between incidences of C-type inclusion of the dentate gyrus and that of the parahippocampal gyrus (r = 0.69, P < 0.05). The morphological differences of the inclusions probably reflect different stages of their formation.

Gliomatosis cerebri involving the lumbosacral spinal cord.

We report a 35-year-old man with gliomatosis cerebri, of which fluid-attenuated inversion-recovery (FLAIR) and T2-weighted magnetic resonance (MR) images revealed diffuse and high signal intensity areas in the bilateral cerebral hemispheres, bilateral middle cerebellar peduncles, cerebellum and lumbosacral spinal cord. Malignant features were not detected by 123 I-IMP SPECT, 201TI SPECT, 18F-fluorodeoxyglucose PET or MR spectroscopy. Histopathological examination of biopsy specimens from the right frontal lobe demonstrated diffuse infiltration of neoplastic cells with relative preservation of the underlying cytoarchitecture. Gliomatosis cerebri demonstrating a lumbosacral spinal cord lesion on MR images is rare and thus this case is important from the aspect of the differential diagnosis of spinal cord lesions.

[A case of postural and kinetic tremor caused by diffuse axonal injury].

We reported a 25-year-old woman with postural and kinetic tremor caused by diffuse axonal injury. The patient demonstrated consciousness disturbance, left oculomotor palsy and tetraparesis because of an automobile accident. T2-weighted and FLAIR MRI showed features of diffuse axonal injury. Hyperintense lesions appeared in the corpus callosum, fornix, dorsal portion of midbrain, right cerebral peduncle, and bilateral internal capsules. About 3 weeks later, head tremor and left hemiparesis appeared with improvement of consciousness. Administration of trihexyphenidyl decreased the tremor. Ten weeks after the accident, a coarse tremor in the head and right upper extremity developed after withdrawal of trihexyphenidyl. Tremor in the right upper limb predominantly occurred while maintaining an upright posture and with intended movements. Re-administration of trihexyphenidyl decreased the tremors. The dentatothalamic pathway is one of the lesions responsible for posttraumatic tremor. Our patient demonstrated lesions of diffuse axonal injury involving the dentatothalamic pathway. We considered that these lesions were associated with postural and kinetic tremor in our case. The tremor occurred at least 3 weeks after the accident. This finding suggested that the tremor was caused by transsynaptic alternations of thalamus or the extrapyramidal system secondary to involvement of the dentatothalamic pathway.

Reduction of the size of the Golgi apparatus of spinal anterior horn cells in patients with X-linked spinal and bulbar muscular atrophy.

The Golgi apparatus (GA) of spinal anterior horn cells was examined immunohistochemically in five patients with X-linked spinal and bulbar muscular atrophy (SBMA), in five patients with sporadic amyotrophic lateral sclerosis (ALS) and in five patients without neurodegenerative diseases. In SBMA cases, reduction of the size of the GA was observed in numerous anterior horn cells; however, fragmentation of the GA, previously described in sporadic and familial ALS with SOD1 mutations, was observed only in a few neurons. In addition, motor neurons bearing an intranuclear inclusion showed a normal network of elements of the GA. The frequencies of fragmented GA in counted motor neurons were 0-2.4 % in SBMA cases, 0-3.0 % in normal control cases and 15.7-55.3 % in ALS cases. The different frequency of fragmented GA between SBMA and ALS adds another finding of pathogenetic difference of neurodegeneration in these two motor neuron diseases.

Neuropathological study of C57BL/6Akita mouse, type 2 diabetic model: enhanced expression of alphaB-crystallin in oligodendrocytes.

The structure of the central and peripheral nervous systems was studied. in the C57BL/6Akita (Akita) mouse, a non-obese type 2 diabetes model characterized by early onset, autosomal dominant inheritance and a mutation of the insulin 2 gene. Usual neuropathological examinations showed no remarkable abnormalities in the brain, spinal cord or sciatic nerve of Akita mice up to 48 weeks of age. However, immunohistochemical examination revealed that expression of alphaB-crystallin was enhanced in oligodendrocytes in the cerebral white matter, especially in the corpus callosum, after 32 weeks of age. The oligodendrocytes were not positive for ubiquitin and HSP25. It is suggested that long-standing hyperglycemia might stress the CNS and thus enhance the expression of alphaB-crystallin in oligodendrocytes.

Frontotemporal dementia with cerebral intraneuronal ubiquitin-positive inclusions but lacking lower motor neuron involvement.

A case of frontotemporal dementia with cerebral intraneuronal ubiquitin-positive, tau- and alpha-synuclein-negative inclusions is reported. A 50-year-old female patient exhibited mental changes; however, no clinical evidence of motor neuron disease was detected in her 11-year history. Neuronal loss and spongiform changes were mainly found in the frontotemporal cortices. Degeneration of the pyramidal tract was observed. Depletion of Betz cells was observed, whereas motor neurons of the hypoglossal nuclei and spinal anterior horn were well preserved. Immunohistochemically, intraneuronal ubiquitin-positive, tau and alpha-synuclein -negative inclusions were present in the small neurons of the dentate gyrus, frontal cortices and putamen. Neither Betz cells nor the anterior horn cells contained any inclusions. Fragmentation of the Golgi apparatus was visible only in 2.2% of anterior horn cells. A large number of tau-positive glial structures lacking argyrophilia were seen in the area of the frontopontine tract in the cerebral peduncle. The pyramidal tract lesions of the present case may be based on frontal lobe degeneration with spread of lesions to the motor cortex. Except for the pyramidal tract lesions, our case is similar to cases of motor neuron disease-inclusion dementia.

Pathology of the inferior olivary nucleus in patients with multiple system atrophy.

The inferior olivary nucleus (ION) from nine patients with multiple system atrophy was examined with antibodies against alpha-synuclein, ubiquitin, synaptophysin, glial fibrillary acidic protein, the Golgi apparatus (GA)-trans-Golgi network (TGN), and microglia/macrophages. As previously reported, there were neuronal loss, gliosis, and alpha-synuclein-positive cytoplasmic inclusions in neurons and glia. In addition, all neurons with alpha-synuclein-positive cytoplasmic inclusions contained abnormal profiles of the GA and TGN, which were reduced in size and numbers. This finding suggests a relationship between the pathogenetic mechanisms causing inclusion body formation and abnormalities of the GA-TGN. This study is also consistent with the conclusion that lesions of the ION may not always reflect changes of transsynaptic degeneration secondary to Purkinje cell loss.