Early-onset dysphagia predicts short survival in multiple system atrophy.

BACKGROUND: The prognostic impact of dysphagia in multiple system atrophy (MSA) remains controversial. This study aimed to investigate the relationship between dysphagia severity and survival in MSA and to elucidate whether this impact differs between MSA-cerebellar ataxia (MSA-C) and MSA-parkinsonism (MSA-P). METHODS: This retrospective study included 297 patients with MSA: 251 met criteria for clinically established MSA and 46 for clinically probable MSA. Among them, 171 had MSA-C and 126 had MSA-P. We evaluated symptomatic dysphagia within 3 years of onset and quantified dysphagia severity using the Hyodo score (0 to 12) through fibreoptic endoscopic evaluation of swallowing (FEES) and clinical features, including autonomic dysfunction and vocal cord paralysis. Patients were followed up until death or tracheostomy, and survival factors were analysed using the log-rank test and multivariate Cox proportional hazards model. RESULTS: Ninety patients developed symptomatic dysphagia within 3 years of onset, and 75 were evaluated for dysphagia severity using FEES. Survival from onset was shorter in patients with dysphagia within 3 years compared to those without (median: 4.2 years vs. 7.3 years; p < 0.001). Symptomatic dysphagia within 3 years of onset was an independent predictor of shorter survival in the multivariate Cox analysis. While the Hyodo score was higher in MSA-P than in MSA-C patients (p = 0.048), the Hyodo score was associated with survival in both MSA-C and MSA-P patients (log-rank p < 0.001 and p = 0.046, respectively). CONCLUSION: Symptomatic dysphagia within 3 years of onset predicts shorter survival in MSA-C and MSA-P patients.

Association of dysphagia severity in multiple system atrophy with the specific binding ratio on dopamine transporter SPECT.

OBJECTIVE: Dysphagia in multiple system atrophy (MSA) is life-threatening and is caused by parkinsonism with cerebellar ataxia as a contributing factor. The present study investigated the relationship between dysphagia severity in MSA and the specific binding ratio (SBR) on dopamine transporter (DaT) SPECT using the Hyodo score, a qualitative scale for use with fiberoptic endoscopic evaluation of swallowing (FEES). METHODS: Hyodo score's ability to predict aspiration during a FEES examination of 88 patients with MSA was first tested. Then the clinical characteristics, Hyodo score, and SBR of patients with either predominant parkinsonism (MSA-P; n = 11) or cerebellar ataxia (MSA-C; n = 25) who underwent FEES and DaT SPECT simultaneously were compared. RESULTS: Logistic regression demonstrated that the Hyodo score was a significant predictive factor of aspiration (p = 0.003). The MSA-P group had a significantly higher Hyodo score (p = 0.026) and lower SBR (p = 0.011) than the MSA-C group while neither group demonstrated any significant difference in disease duration at the FEES examination. Linear regression demonstrated a significant, inverse correlation between the Hyodo score and SBR in the MSA-P (p = 0.044; r = -0.616) and MSA-C (p = 0.044; r = -0.406) groups. When the effect of SBR was removed by analysis of covariance, no significant difference in the Hyodo score remained between the groups. CONCLUSIONS: Our results suggested an association between presynaptic changes in nigrostriatal dopaminergic neurons and dysphagia severity in MSA which largely contributes to the difference in dysphagia severity between MSA-P and MSA-C.

Visual fixation suppression of caloric nystagmus in progressive supranuclear palsy - A comparison with Parkinson's disease.

BACKGROUND: Impairment of visual fixation suppression (VS) in progressive supranuclear palsy (PSP) is not well documented. OBJECTIVE: To evaluate the usefulness of impaired VS of caloric nystagmus as an index for differential diagnosis between PSP and Parkinson's disease (PD), which is often difficult, especially in the early stage. METHODS: Subjects comprised 26 PSP patients and 26 PD patients clinically diagnosed at Tokyo Metropolitan Neurological Hospital. We retrospectively investigated VS of caloric nystagmus, horizontal pursuit, saccades, and horizontal optokinetic nystagmus recorded on direct-current-electronystagmography, and neuroradiological findings. RESULTS: The median of the average VS% was 0% and 50.0% in PSP and PD patients, respectively. In PSP, VS was impaired even in the early stage of disease. We found a significant correlation between VS and velocity of saccades or maximum slow phase velocity of optokinetic nystagmus only in PSP patients. PSP patients with atrophy of the subthalamic nucleus or with decreased blood flow in the frontal lobe showed significantly more severe impairment of VS. CONCLUSIONS: VS may be a useful biomarker to differentiate patients with PSP from those with PD. Cerebellar networks that connect with the cerebral cortex and basal ganglia may contribute to impaired VS of caloric nystagmus in PSP.

[Eye movement disturbance in multiple system atrophy: chronological study of 50 patients].

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.

Oral administration of multispecies microbial supplements to sows influences the composition of gut microbiota and fecal organic acids in their post-weaned piglets.

The timings of the administration of microbial supplements to control the populations of gut microbiota of piglets have been poorly understood. Here the effects of temporal administering multispecies microbial supplements to sows on the composition of gut microbiota and on the bacteria-mediated fecal metabolites in their offsprings were investigated. During gestation and lactation, pregnant sows were fed either a normal diet (group A) or a diet with multispecies supplements comprised of nine microbial species such as Lactobacillus delbrueckii subsp. bulgaricus, Bifidobacterium bifidum, Enterococcus faecium, Candida pintolopesii, and Aspergillus oryzae etc. (group B). All of the sows' piglets were temporarily fed with the same supplements around weaning in accordance with the guideline of the farm. This regimen was followed by a normal diet in both groups over one month thereafter. Under such conditions, the concentration of short-chain fatty acids (SCFAs) in fecal samples remarkably increased in group B compared to group A. When 16S rDNA sequences of the fecal bacteria were analyzed, the microbial structure of bacteria was different between both goups. Especially the Clostridium cluster IV and subcluster XIVa were particularly increased in group B, although the administered microbes were undetectable. Thus, temporal administration of multispecies-microbial supplements to pregnant sows changes the composition of SCFAs and gut microbiota in their offsprings.

Kihi-to, a herbal traditional medicine, improves Abeta(25-35)-induced memory impairment and losses of neurites and synapses.

BACKGROUND: We previously hypothesized that achievement of recovery of brain function after the injury requires the reconstruction of neuronal networks, including neurite regeneration and synapse reformation. Kihi-to is composed of twelve crude drugs, some of which have already been shown to possess neurite extension properties in our previous studies. The effect of Kihi-to on memory deficit has not been examined. Thus, the goal of the present study is to determine the in vivo and in vitro effects of Kihi-to on memory, neurite growth and synapse reconstruction. METHODS: Effects of Kihi-to, a traditional Japanese-Chinese traditional medicine, on memory deficits and losses of neurites and synapses were examined using Alzheimer's disease model mice. Improvements of Abeta(25-35)-induced neuritic atrophy by Kihi-to and the mechanism were investigated in cultured cortical neurons. RESULTS: Administration of Kihi-to for consecutive 3 days resulted in marked improvements of Abeta(25-35)-induced impairments in memory acquisition, memory retention, and object recognition memory in mice. Immunohistochemical comparisons suggested that Kihi-to attenuated neuritic, synaptic and myelin losses in the cerebral cortex, hippocampus and striatum. Kihi-to also attenuated the calpain increase in the cerebral cortex and hippocampus. When Kihi-to was added to cells 4 days after Abeta(25-35) treatment, axonal and dendritic outgrowths in cultured cortical neurons were restored as demonstrated by extended lengths of phosphorylated neurofilament-H (P-NF-H) and microtubule-associated protein (MAP)2-positive neurites. Abeta(25-35)-induced cell death in cortical culture was also markedly inhibited by Kihi-to. Since NF-H, MAP2 and myelin basic protein (MBP) are substrates of calpain, and calpain is known to be involved in Abeta-induced axonal atrophy, expression levels of calpain and calpastatin were measured. Treatment with Kihi-to inhibited the Abeta(25-35)-evoked increase in the calpain level and decrease in the calpastatin level. In addition, Kihi-to inhibited Abeta(25-35)-induced calcium entry. CONCLUSION: In conclusion Kihi-to clearly improved the memory impairment and losses of neurites and synapses.

Questionnaire and interview in screening for hearing impairment in adults.

CONCLUSION: Questionnaire and brief interview played an important complementary role in the mass hearing screening. OBJECTIVES: To evaluate the efficacy of mass screening for hearing loss. SUBJECTS AND METHODS: Review of a 9-year prospective screening (n=31 902) in a university. The screening comprised pure tone hearing screening at two frequencies (1000 Hz and 4000 Hz) and a questionnaire. Brief interview was introduced during the later 4-year period. The final diagnosis was made in the university hospital. RESULTS: In hearing screening tests, approximate sensitivity was 89% for 1000 Hz and 91% for 4000 Hz. Approximate specificity was 89% and 88% for 1000 Hz and 4000 Hz, respectively. Brief interview with the subjects on the spot improved the accuracy, especially in specificity. Low tone sensorineural hearing loss, exudative otitis media and chronic otitis media could be overlooked without questionnaires.

Characterization of anti-neurodegenerative effects of Polygala tenuifolia in Abeta(25-35)-treated cortical neurons.

Although Polygala tenuifolia WILLD (PT) was classically mentioned as an anti-dementia drug in Chinese and Japanese traditional medicine, basic research showed only enhancement of the cholinergic function. In Alzheimer's disease, neuritic atrophy and synaptic loss occur prior to neuronal death event, and may be the first trigger of the memory impairment. Therefore, we studied effects of Polygala tenuifolia WILLD (PT) on Abeta(25-35)-induced neuronal damage using rat cortical neurons for characterization of activities of PT under Abeta-induced neuronal damage. Treatment with the water extract of PT enhanced axonal length dose-dependently after Abeta(25-35)-induced axonal atrophy. However, dendritic atrophy and synaptic loss induced by Abeta(25-35) were not recovered by treatment with PT extract. In contrast, Abeta(25-35)-induced cell damage was completely inhibited by PT extract. By characterization of PT effects on neuronal morphological plasticity and cell damage, usefulness as well as an insufficiency of PT as an anti-dementia drug was clarified.

A variant form of nasogastric tube syndrome.

Nasogastric tube syndrome named by Sofferman et al in 1981 is a laryngeal complication presenting with life-threatening vocal cord abductor paralysis derived from peroforation of the NG tube-induced esophageal ulcer. As compared with the previously reported cases of this syndrome, our 4 autopsied patients were so peculiar in the following two points that vocal cord abductor paralysis developed repeatedly and no esophageal ulcer was present in spite of the presence of the laryngeal abductor muscle injury. We hypothesized that the etiology of such a variant form was circulatory injury of the laryngeal abductor muscle which was caused by the compression of the postcricoid blood vessels perfusing this muscle. Nasogastric tube syndrome, which is treatable by decannulation, cannot be ruled out even if no esophageal ulcer is detected by fiberoptic laryngoscopy.

Laryngeal dystonia in a case of severe motor and intellectual disabilities due to Japanese encephalitis sequelae.

Laryngeal dystonia is characterized by stridor due to vocal cord dystonia and is observed in extrapyramidal disorders. Recently, botulinum toxin injection has been used as a primary therapy. Generally, severe motor and intellectual disabilities (SMID) are frequently complicated by various types of respiratory disorders. We report a SMID case with Japanese encephalitis sequelae showing repeated vocal cord abductor disturbance due to laryngeal dystonia, in addition to generalized dystonia, in whom MRI revealed basal ganglia lesions. Tracheostomy was effective for the case, and we believe that botulinum toxin injection may be inappropriate in SMID, both ethically and technically. Also, laryngeal dystonia should be considered as a cause of respiratory disorders in SMID.

Nystagmus-sensation dissociation in spinocerebellar degeneration.

OBJECTIVE: To study nystagmus-sensation dissociation (NSD), i.e. caloric nystagmus without the sensation of vertigo, in patients with spinocerebellar degeneration (SCD). MATERIAL AND METHODS: The neuro-otological and neuro-radiological records of 179 patients clinically diagnosed as having SCD (91 males, 88 females; age range 20-89 years) and 48 patients diagnosed as having peripheral vestibular disorders (15 males, 33 females; age range 21-80 years) were reviewed. Subjects underwent caloric tests using cold water (20 degrees C) in a totally dark room. Immediately after each test session, subjects were asked if they had experienced spinning or moving sensations during the test. Maximum slow phase eye velocities (SPEVs) were measured using electronystagmography. RESULTS: Among patients with peripheral vestibular disorders, all patients with SPEVs > 15 degrees/s experienced spinning or moving sensations during testing. Among the 179 patients with SCD, 21 (39 sides) showed maximum SPEVs > 15 degrees/s without spinning or moving sensations. In particular, 8 patients (10 sides) had maximum SPEVs > 25 degrees/s without spinning or moving sensations. Common lesions in the cerebral cortex could not be detected using either MRI or single-photon emission CT. CONCLUSION: Patients with SCD may also have NSD, which may be attributable to subcortical lesions in the ascending pathways to the vestibular cortex.

Different mechanism of vocal cord paralysis between spinocerebellar ataxia (SCA 1 and SCA 3) and multiple system atrophy.

While multiple system atrophy (MSA) is frequently associated with vocal cord paralysis (VCP) causing severe respiratory failure, it is still unknown whether hereditary types of spinocerebellar degeneration develop similar laryngeal paralysis. We analyzed the laryngeal function from the viewpoints of fiberoptic laryngoscopy and laryngeal myopathology and then attempted to clarify the difference of the mechanism of VCP among the patients with spinocerebellar ataxia type 1 (SCA 1), type 3 (SCA 3), and MSA. Seven patients with SCA 1, nineteen with SCA 3, and eleven with MSA were studied. Vocal cord movement was analyzed by fiberoptic laryngoscopy during wakefulness and diazepam-induced sleep (sleep load test). Paraffin-embedded sections or cryosections of the intrinsic laryngeal muscles from five autopsied cases (one with SCA 1 and four with SCA 3) were histologically examined. VCP was found in two of the seven SCA 1 patients (29%), three of the nineteen SCA 3 patients (16%), and in nine of the eleven MSA patients (82%). VCP observed in SCA 1 and SCA 3 was various in the severity and showed no exacerbation on sleep load test in all of the eight patients but one SCA 3 patient. In this patient, the findings of fiberoptic laryngoscopy were quite similar to those found in MSA. All the intrinsic laryngeal muscles including cricothyroid (CT), interarytenoid (IA), and posterior cricoarytenoid (PCA) muscles showed neurogenic atrophy in one autopsied SCA 1 and four SCA 3 patients. Our conclusion is that VCP in SCA 1 and SCA 3 contrasts with that in MSA in its occurrence, response to the sleep load test, and the distribution of the neurogenic abnormalities among the intrinsic laryngeal muscles.