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[Background] Supranuclear extraorbital muscle palsy is the core feature of progressive supranuclear palsy (PSP), and ordinarily presents as spontaneous vertical gaze constriction. However, higher visual function associated with visuospatial cognition in PSP patients was not previously considered. [Case presentation] We present a 72-year old right-handed man with PSP- Richardson syndrome (PSP-RS) and abnormal higher visual function. His symptoms began 2 years previously and included the use of small steps while walking, forgetfulness, and postural instability. Neurological examination revealed supranuclear vertical gaze limitation, akinesia, and lead-pipe rigidity without laterality. Neuro-ophthalmological examination showed abnormal ocular movement consistent with PSP, and no visual abnormality was observed. General cognitive functions, including attention and prominent visuospatial orientation and visual attention disturbances, were assessed using neuropsychological tests and concomitant spatial agraphia and impaired configuration using figure copying. Although he presented with mildly decreased and monotonous speech with palilalia, he showed no apparent aphasia, apraxia, visual object agnosia, or Bálint's 'optische Ataxie' i.e. visual ataxia under fixation. Brain MRI revealed atrophy of the mesencephalic tegmentum, bilateral frontal lobe, and bilateral hippocampus. N-isopropyl-p-(iodine-123)-iodoamphetamine single photon emission computed tomography revealed decreased cerebral blood flow in the bilateral frontal lobe, lateral temporal lobe, and basal ganglia. Dopamine transporter single photon emission CT revealed uptake attenuation in the bilateral striatum. 123 I-metaiodobenzyl-guanidine myocardium scintigraphy results were normal. [Discussion] The patient's symptoms indicated classical PSP-RS accompanied with a combination of disturbances in spatial orientation and visual attention as noted by Holmes and Horrax and 'ataxie optique' by Garcin. Thus, as observed in this patient, many clinically diagnosed PSP patients with undiagnosed higher visual dysfunction, masked by limited eye movement may exist. These symptoms may further our understanding about posterior cortical atrophy and tauopathy including not only PSP but also corticobasal syndrome and Alzheimer disease.

We report an autopsy case of dementia associated with amyotrophic lateral sclerosis (ALS) in a 73-year-old female. She developed memory impairment at the age of 68 years. Atrophy of her hand muscles was noted at the age of 71 years. She was not aware of her memory impairment or muscle weakness, and was loquacious and euphoric. She was clinically diagnosed as having Alzheimer disease (AD) complicated by ALS with dementia/frontotemporal lobar degeneration with motor neuron disease (ALS-D/FTLD-MND). A neuropathological study confirmed the presence of features of sporadic ALS. Furthermore, severe neuronal loss involving the subiculum and the rostral portion of the medial side of the temporal pole cortex was detected, and TAR DNA-binding protein-43-positive-neuronal cytoplasmic inclusions were identified in the granule cells of the dentate gyrus. These findings were compatible with the pathological features of ALS-D/FTLD-MND. Although many pretangles, neuropil threads and senile plaques were revealed in the degenerated areas, there were few neurofibrillary tangles and typical plaques (Braak stage III, C). Further discussion is required to determine whether AD with ALS-D/FTLD-MND is different from typical AD. This case might be helpful for diagnosing similar cases in the future.

To clarify the features of the eye movement disturbance in the patients with multiple system atrophy (MSA), we retrospectively examined chronological changes of 9 oculomotor parameters as described below in 50 MSA patients including 12 autopsied cases. Patients with MSA were consisted of 35 patients with cerebellar ataxia-preceding type and 15 patients with parkinsonism-preceding type. Nine parameters include saccade test, eye tracking test, positioning/positional/gaze/caloric nystagmus tests, and visual suppression test. Each parameter was evaluated by three categories; normal and the two abnormal findings according to their characteristic features. In all of the 9 parameters, no significant differences were found between the cerebellar ataxia- and the parkinsonism-preceding types of MSA both in the early (disease duration less than 3 years) and in the advanced stages (duration between 8 to 11 years). From the chronological analysis, 9 oculomotor parameters could be divided into three groups: the first group with the higher frequency of the abnormality from the early stage, the second with gradual increase of the frequency, and the third with less increased frequency even in the advanced stage. We here focused on the three representatives corresponding with the above-described each group; positioning nystagmus test mainly showing downbeat nystagmus as a first group, visual suppression test showing a qualitative change from depressed into increased response as the second, and the caloric nystagmus test showing decreased response as the third. Based on these chronological changes of the oculomotor parameters, we supposed that in MSA the dorsal vermis is involved at first, followed by the flocculus in the cerebellum, and then the degenerative lesions might expand to the vestibular nucleus, and the cerebral cortex including the vestibular cortex.

Non-invasive positive pressure ventilation (NPPV) has recently been applied to the patients with multiple system atrophy (MSA) with various respiratory complications including vocal cord abduction impairment and respiratory disturbance by the central origin. Any consensus guidelines on setting up the inspiratory positive airway pressure (IPAP) and expiratory one (EPAP), however, have not been raised yet. To investigate this problem, we made the upper airway tract model with moderately and severely narrow glottis using a training/test lung and the artificial vocal cord which was developed for a humanoid talking robot in Waseda University. The artificial vocal cord was molded out of a high performance thermoplastic rubber in imitation of the human larynx. Previous studies using with a high-speed camera and a sound analyzer showed that the artificial vocal cord resembled human larynx closely both morphologically and functionally. The opening and closing movements of the artificial vocal cord were observed fiberscopically under various conditions of IPAP (4-20 cmH2O) and EPAP (4-10 cmH2O). The maximal glottic width during inspiration and expiration were measured by a pair of calipers on the video-monitored display. Both of the moderately and the severely narrow artificial vocal cords without non-paralytic factors showed typical paradoxical movement showing adduction in inspiration and abduction in expiration, which is characteristic to vocal cord abductor impairment seen in MSA. In the model with moderately severe narrow glottis, this paradoxical movement was released under any positive pressures of continuous (CPAP) and bilevel (Bilevel PAP) modes. In the model with severely narrow glottis, however, there existed a threshold in setting up the optimal EPAP to release the paradoxical movement. In conclusion, EPAP-leading procedure seems to be preferable to IPAP-leading procedure to dilate the narrow glottis as a pneumatic splint in the managements of the patients with MSA presenting with a paralytic type of vocal cord abductor impairment.

A 71-year-old man had recurrent spells of transient diplopia for about four years. Vertical diplopia were induced by downward gaze, mostly to the lower-left, and lasted for about ten seconds. During the spells, limitation in elevation of the left eye was observed. Other neurological examinations were normal except for a minor paresis of the left trochlear nerve revealed only by detailed neuroophthalmological examination. The patient was treated with carbamazepine 200 mg daily, which abolished the spells. He was diagnosed to have idiopathic ocular neuromyotonia of the left third or fourth nerve. Ocular neuromyotonia is a rare disturbance of ocular motility, characterized by paroxysmal monocular involuntary spasms of one or more extraocular muscles supplied by the third, fourth or sixth cranial nerves. Past studies showed that most patients had radiation therapy to the parasellar or sellar regions. Slight injury to the peripheral nerves such as one caused by radiation may have an important role in the development of ocular neuromyotonia. Furthermore, patients with ocular neuromyotonia often benefit from the use of carbamazepine, a membrane-stabilizing agent. We report a case of idiopathic ocular neuromyotonia without history of damage to the cranial nerves. It is the first report in Japan.

Human parvovirus B19 (HPV-B19) infection is recently known to produce variable clinical manifestations, but neurological disorder associated with this infection is uncommon. We reported a case of GBS associated with transient lupus-like status following HPV-B19 infection. This is the first report describing an adult case of GBS following HPV-B19 infection. A healthy female, aged 33, developed erythema infectiosum simultaneously with her 5-year-old daughter. On the same day, she noticed leg fatigue, which worsened in the following days. On the day 11th, she became unable to walk. Mild pancytopenia, liver injury, proteinuria, hypocomplementemia, and increased anti-nuclear antibody (ANA) were revealed at a hospital. Polymerase chain reaction detected HPV-B19 DNA in the serum. On the day 17th, she was admitted to our hospital because of moderate generalized weakness and mild sensory disturbance, which were symmetrical and distal-dominant. The deep tendon reflexes were absent. Analysis of cerebrospinal fluid showed albuminocytologic dissociation. Other laboratory data were normal except positive ANA. Enzyme-linked immunosorbent assay (ELISA) showed high titer of the serum IgM antibody to GM1 and GD1b. Serum anti HPV-B19 IgM and IgG tested by ELISA were also positive. She improved gradually after 2 courses of double filtrated plasma pheresis.

To investigate the mechanism of the vocal cord abductor paralysis (VCAP) in the neurodegenerative diseases, the intrinsic laryngeal muscles (the crycothyroid, the interarytenoid, and the posterior crycoarytenoid muscles) from 41 autopsied cases were histologically examined: 10 cases of amyotrophic lateral sclerosis (ALS), 10 of Parkinson's disease (PD), 9 of multiple system atrophy (MSA), 4 of Machado-Joseph disease (MJD), 4 of progressive supranuclear palsy (PSP), 1 of familial amyloidotic polyneuropathy (FAP), and 3 of cerebrovascular diseases as a control. According to the distribution of the neurogenic changes among above-described three intrinsic laryngeal muscles, three forms were raised: 1. The totally paralytic form showing that all the three muscles developed neurogenic atrophy. This form includes ALS, MJD, and FAP. 2. The posterior muscle-paralytic form showing that only the posterior crycoarytenoid muscle was selectively involved. This form includes MSA. 3. The nonparalytic form showing no morphological abnormalities in any of the intrinsic laryngeal muscles. This type includes PD and PSP. In this nonparalytic form, supranuclear mechanism such as pyramidal or extrapyramidal tract involvement may cause VCAP through the increased laryngeal muscles tone. Considering that VCAP can be seen in any of the above-described forms, our results indicate that the mechanism of VCAP is different among the neurological disorders.

We described a 41-year-old man with chorea-acanthocytosis, who presented severe choreoathetosis in all the limbs, neck, face and tongue. Especially, the oral area was affected most strikingly. He had difficulty in eating, because he pushed foods out of the mouth with the tongue. He received left posteroventral pallidotomy (PVP). His involuntary movements became much less enough for the patient to eat with a spoon in a sitting position by himself. Six months after the first operation, although involuntary movement on the right hand remained reduced, choreoballistic movement appeared on the left side. He received PVP on the right side. The choreoballistic movement was remarkably improved after the right PVP. No neurological aggravation has been found for 7 months after the second PVP. Bilateral PVP was fully effective as for the improvement of the activity of daily life. The output from the internal globus pallidus (GPi) is well-known to be inhibitory. Therefore, it is understandable that the coagulation of GPi results in improvement of hypokinesia and rigidity in patients with Parkinson's disease. However, some clinical reports, including ours, have described the significant reduction of hyperkinetic choreoballistic movement after PVP. The exact mechanism of these surgical effects has not been elucidated yet, and further clinical and basic studies are needed to answer this question.

Here we report 2 cases of opsoclonus-polymyoclonus syndrome (OPS) associated with viral encephalitis. They had sleep disturbance, and visual hallucination. Case 1 had auditory hallucination in addition, and case 2 had dreamlike behavior. Those hallucination, which were colorful and vivid, usually appeared at the bed time. Their hallucinations were similar to peduncular hallucinations and you may also call hypnagogic hallucinations, which are often seen in patients with narcolepsy. Dreamlike behavior is observed during REM sleep in patients with brainstem damage or sometimes in the healthy elderly people. The presence of sleep disturbance, hypnagogic hallucination, and dreamlike behavior suggests that there may be some relationship between OPS and REM sleep. Considering that REM sleep is suppressed by serotonergic projection of the dorsal raphe nucleus in addition to several reports about brainstem lesion with serotonergic abnormalities in this disorder, we considered that dysfunction of serotonergic neurons of the dorsal raphe nucleus might be related in the development of OPS.

We described a 34-year-old man who developed opsoclonus-polymyoclonus syndrome (OPS) associated with benign encephalitis. His older sister also suffered from the same syndrome 12 years ago. We examined HLA types in 6 patients with OPS who were admitted to our hospital, including these sibling cases. All 6 patients have type A2 antigen and statistical analysis suggested that there is a positive relationship between OPS and HLA A2 antigen. Considering the two facts that the existence of the sibling cases in this relatively rare disorder and sharing of HLA A2 antigen in our 6 cases, some genetic factors might be involved in the development of OPS.

Rigid spine syndrome (RSS) is thought to be a group of heterogeneous muscle disorders. We reviewed the clinical and myopathologic findings of 55 patients with RSS including 49 previously reported and our own 6 patients. The results were as follows: the first, 80% showed restrictive ventilatory failure and 40% atrophy of the sternocleidomastoid muscle (SCM), which became manifest in the early stage of the illness, namely in less than 5 years from the onset. The second, paraspinal muscles usually began to be involved from the cervical semispinal muscle extending to other paraspinal muscles such as the more laterally located splenium muscle. The third, muscle biopsy demonstrated rimmed vacuoles (RV) in 41% of the 55 patients. RV were more frequently seen in the paraspinal muscles than the limb muscles, where marked myopathic changes of endomysial fibrosis and increased variation of the muscle fiber size were recognized. Based on the anatomical analysis of the paraspinal muscles, alligator sign, a radiological finding of the posterior opening between the cervical spine C1 and C2, seemed to result from the shortening of the cervical semispinal muscle due to its degeneration. This sign may, however, disappear as the whole paraspinal muscles including the semispinal muscles are affected. The RV seen in RSS seems to be a secondary, nonspecific structure related to the muscle degeneration. On the other hand, the above findings, namely the atrophy of SCM, restrictive ventilatory failure, and RV, have not been reported in Emery-Dreifuss muscular dystrophy (EDMD) so far. Accordingly, those findings and the absence of cardiac conduction abnormality are valuable for differential diagnosis of RSS from EDMD.

Bilateral vocal cord abductor paralysis (VCAP) is frequently associated with multiple system atrophy (MSA) and the early clinical manifestation of VCAP is nocturnal inspiratory stridor simulating heavy snoring observed in patients with obstructive sleep apnea syndrome. We examined six MSA patients with nocturnal stridor and four disease controls including sleep apnea syndrome. Vocal cord movements were analyzed by laryngofiberscopy during both wakefulness and sleep induced by intravenous administration of diazepam. The results were as follows: First, the stenotic portion in the upper airway tract was the larynx (the vocal cords) in MSA patients with stridor, while the soft palate or the pharynx in the disease controls. Second, in the MSA patients, while awake-laryngofiberscopy showed abduction restriction suggestive of VCAP in only one of the six patients, sleep-laryngofiberscopy showed obvious paradoxical movement of the vocal cord in all the rests, where the vocal cords abducted in expiration and adducted in inspiration. In addition, there were two patterns in the inspiratory vocal cord position during sleep: one pattern where vocal glottis was still opening at the posterior one-third area and the other pattern where vocal glottis was almost completely closed through total length of the cords. Tracheostomy should be considered in the latter stage of VCAP.

The authors analyzed rhythmical involuntary movements at rest, which appeared as complications in 12 (sporadic 11, hereditary 1) out of a total of 139 cases (sporadic 99, hereditary 40) of olivo-ponto-cerebellar atrophy. These movements tended to be seen in patients with sporadic OPCA of longer illness duration and at more advanced stages. They were distributed over the face, neck and extremities. Palatal myoclonus was observed in only one case. The movements were exacerbated by maintenance of a fixed posture, motion and mental stress, and stopped during sleep. In some cases, clonazepam, trihexyphenidyl or 1-Dopa was effective. In the surface electromyogram, rhythmical grouped discharges of 2-4 Hz were recorded only on agonist muscles or on both agonist and antagonist muscles synchronously, which is characteristic of skeletal myoclonus. However, pathological study of 3 cases with involuntary movements revealed marked putaminal degenerations as compared with 3 uncomplicated cases. This suggests that these rhythmical movements might be related to parkinsonian tremor.

A 72-year-old man developed supranuclear ophthalmoplegia, bradykinesia, rigidity, unsteady gait, dementia, dysphagia, retrocollis, grasp reflex and apraxia of eyelid opening. These findings were compatible with progressive supranuclear palsy (PSP). At the age of 66, he presented a peculiar phenomenon characterized by simultaneous tonic contraction of the orbicularis oris muscle (OOM) and the palatal muscles elicited by pronouncing "pa", which resulted in difficulty of voluntary opening of the mouth and the rhinopharynx. Therefore, the respiration air reciprocated between the lung and the closed mouth. The expiratory pressure puffed out the cheeks, while the lips remained tightly closed. While the respiratory movements and the pressure increased by degree, the OOM contracted more strongly in proportion to the pressure. Sixty to ninety seconds after the elicitation, the pressure overcame the contraction of the OOM and the course of the phenomenon was completed. The electromyograms showed that the OOM activity was prolonged after initial voluntary contraction, remaining thus after a tracheostomy for pneumonia at the age of 72, and that it increased in response to the pressure. Apraxia of eyelid opening, one of the other symptoms, resembled this phenomenon in terms of the aspect of difficulty of voluntary mouth opening. The "holding" phase of grasp reflex, yet another symptom, resembled it in the recruitment of the OOM activity. The phenomenon is not common in patients with PSP. However, we concluded that it may be included among the symptoms of PSP because it has similar characteristics to apraxia of eyelid opening and grasp reflex, which are not uncommon in patients with PSP.

We have reported a 50-year-old woman with HTLV-I associated myelopathy (HAM) who had bilateral abductor vocal cord paralysis. The symptoms and signs were slowly progressive spastic paraplegia, dysuria, inspiratory stridor, and snoring during sleep. She had no hoarseness. Titers of anti-HTLV-I antibody were elevated in both the serum and cerebrospinal fluid. FEV1.0% on the spirogram was reduced to 66%. The fiberscopic examination demonstrated the abductor limitation of the vocal cords during the inspiratory phase. During induced sleep after the intravenous administration of thiopental sodium, this abductor paralysis was worsened, producing a high pitched inspiratory stridor. The adduction was not disturbed at all. Needle electromyogram of the posterior crico-arytenoid muscle which is a sole abductor muscle revealed the high amplitude up to approximately 1.0 mV (normal less than 0.8 mV) with poor interference pattern, indicating neurogenic changes. After 2 months course of prednisolone (60 mg/alternative day), FEV1.0% was recovered to be 92% with the improvement of the gait disturbance, which suggests the abductor vocal cord paralysis is related to HAM. The abductor vocal cord paralysis in HAM would require a careful follow-up observation to protect the respiratory failure in the advanced stage.

In order to elucidate the clinical features and the prognosis for life in the patients with multiple system atrophy (MSA) presenting with vocal cord paralysis (VCP), we studied the correlation between VCP and other neurological findings including cerebellar, pyramidal, extrapyramidal and autonomic nervous signs. Subjects were 48 MSA patients: 23 with VCP and age- and illness duration-matched 25 without VCP. MSA in this paper comprised clinically Shy-Drager syndrome, olivopontocerebellar atrophy, and striatonigral degeneration. MSA patients with VCP had in general more severe neurological findings, compared with those without VCP. Urinary incontinence developed in the relatively early stage of illness and preceded VCP in all patients. VCP developed not only in far-advanced stage but at any time in the course of illness. As to swallowing function when a diagnosis of VCP was established, about half of the patients with VCP needed nasogastric tube feeding and the remaining half tolerated oral feeding. VCP correlated strongly with urinary incontinence but not always with the severity of orthostatic hypotension or extrapyramidal tract sign such as parkinsonism. Five of the eight patients without tracheostomy came to sudden death. The mean duration from making a diagnosis of VCP to death was 1.1 years. In contrast, nine of the 11 patients with tracheostomy were alive and the survival periods after tracheostomy reached a maximum, five years. These facts suggest that the prognosis for life in the patients with VCP depends in part upon whether tracheostomy was carried out or not.(ABSTRACT TRUNCATED AT 250 WORDS)

We have already described that ragged red fiber (RRF), core/targetoid fiber and type 1 fiber predominance were found at autopsy in the diaphragm taken from patients with chronic obstructive pulmonary diseases. The purpose of the present study is to investigate morphological and histochemical changes in the diaphragm in denervating neurologic disorders. The diaphragm in the costal portion was taken from 22 autopsy cases including 4 with amyotrophic lateral sclerosis (ALS), 4 cerebrovascular diseases, 3 Parkinson disease, 2 olivopontocerebellar atrophy. In addition, 4 diaphragm muscles were biopsied at the time of surgery for lung cancer. In the diaphragm we observed not only RRF and core/targetoid fiber but also cytoplasmic body and ring fiber in many cases. These findings were, however, not specific for neurologic disorders. Focal cytochrome c oxidase deficiency was found in muscles with RRF. It should be emphasized that RRF was absent in 3 of 4 cases with ALS and in a case with elevated hemidiaphragm from phrenic nerve paralysis. In the previous report, we suggested that RRF was formed under the relative ischemic state in overworking diaphragm. The relative ischemia means a condition that oxygen (energy) demand for respiratory work exceeds over oxygen supply from the blood in the overworking diaphragm. The reason why no RRF was found in the denervated muscle is that the ischemic state in the denervated muscles is relieved by immobilization after denervation. Karpati et al conformed that denervation prevented ischemic state in the muscle. Other histochemical features in the diaphragm included cytoplasmic body and ring fiber.(ABSTRACT TRUNCATED AT 250 WORDS)