Ryuichi Osanai

CTG triplet repeat expansion in a laryngeal carcinoma from a patient with myotonic dystrophy

A 66‐year‐old Japanese man with myotonic dystrophy (DM) underwent total laryngectomy for laryngeal carcinoma. The size of the expanded DNA fragment (EF) from the leukocytes and normal laryngeal tissues of this patient was only slightly longer than that in normal subjects. EF, however, was markedly longer in the laryngeal carcinoma. These findings support the hypothesis that elongation of the CTG repeat in the DM kinase gene occurs during acquired cell proliferation.

Neuro-otological and Neuropathological Findings in two Cases with Machado-Joseph Disease

We report chronological changes of neuro-otological findings and associated neuropathological findings in 2 patients. Concerning gaze limitation, upward gaze was primarily disturbed, followed by downward gaze and abduction. Adduction tended to be preserved although convergence was disturbed at the early stage. And, upward gaze limitation was followed by loss of oculocephalic responses (OCRs). Bells phenomenon was preserved until the late stage of the disease. Caloric nystagmus was absent at the early stage. One patient showed dissociation between nystagmus and vestibulo-collic reflex in the caloric test at the early stage of the disease. Neuropathological examination revealed gliosis in the interstitial nucleus of Cajal and the MLF as well as neuronal loss and gliosis in the oculomotor nuclei. The vestibular nuclei also showed gliosis and atrophy of nerve cells.

Olfactory Dysfunction in Parkinson’s Disease

An olfactory function test in 18 patients with Parkinsons disease (PD) and 10 age-matched control subjects was performed. Both detection and recognition thresholds were measured with five kinds of synthesized odorants (T & T olfactometry). Before each test, rhinoscopic inspections were performed to exclude subjects who could have respiratory hyposmia. Both detection and recognition thresholds in patients with PD were significantly elevated in comparison with those of control subjects. Auditory acuity of PD patients, however, was well preserved and there was no significant correlation between auditory and olfactory threshold. On the basis of the present study, the authors conclude that olfactory dysfunction is one of the characteristic symptoms of PD and it may be attributed to lesions in the olfactory neural pathway including olfactory neuroepithelium.

Acute effects of tetrahydrobiopterin on the dynamic characteristics and adaptability of vestibulo-ocular reflex in normal and flocculus lesioned rabbits

The acute effects of (6R)-5,6,7,8-tetrahydro-L-biopterin (R-THBP) on the dynamic characteristics of horizontal vestibulo-ocular reflex (HVOR) were examined in chronically prepared alert pigmented rabbits. The HVOR gain was measured by 10 degrees-0.1 Hz sinusoidal oscillation of the turntable in darkness. In control rabbits, intramuscular injection of R-THBP (10 mg/kg) induced an increase of HVOR gain by 0.1-0.2, which lasted for 1-3 h. Sustained 10 degrees-0.1 Hz sinusoidal oscillation of the turntable and screen in the reversed direction induced an adaptive increase of HVOR gain by 0.2 in 3 h, which was not affected by applications of R-THBP. In flocculus lesioned rabbits, the HVOR gain reduced by 23%, and applications of R-THBP no longer induced a HVOR gain increase. These experimental observations suggested that the R-THBP affected on the HVOR dynamics within the cerebellar flocculus or its related neural areas.

Saccadic slowing in myotonic dystrophy and CTG repeat expansion.

Abstract Recent studies have shown that the severity of the several clinical symptoms of myotonic dystrophy (DM) is closely related to the size of a CTG triplet repeat in the gene encoding myotonin protein kinase. Although neurotological findings, including saccadic slowing in patients with DM, have been reported, the relationship between these neurotological findings and elongation of the CTG triplet repeat has not been discussed to our knowledge. We made a case-control study that compared the saccadic velocity in 13 patients with DM and in 13 controls matched for age and sex. We also examined the correlation between the saccadic velocity in DM patients and the size of the expanded DNA fragment (EF) obtained by Southern blot analysis with EcoRI or BglI.We found: (1) The primary eye position was normal in 9 of 12 patients. Divergent strabismus was present in 3 patients. (2) The range of ocular movement was normal in 2 patients, nearly normal in 5 and minimally limited in the other 5. (3) Only 1 patient had lateral gaze nystagmus, which was fine and transient. (4) The horizontal saccades were essentially normometric in 11 of the 13 patients, slightly hypometric in 1 and obviously hypometric in 1. These last 2 patients had the second longest and longest EF sizes. The vertical saccades were essentially normometric in 8 of 12 patients, hypermetric in 3, and hypometric in the 1 with the longest EF size. (5) The saccadic velocity in the DM patients was significantly lower than that in the controls in the horizontal or vertical direction, the difference being more prominent in the horizontal direction. (6) The correlation coefficients between horizontal saccadic velocity and EF size, 0.801 (EcoRI) and 0.756 (BglI), had a strong negative correlation (P < 0.01 for both EcoRI and BglI). No statistically significant correlation was found between vertical saccadic velocity (upward and downward) and EF sizes.Although it was difficult to determine whether saccadic slowing was caused by central oculomotor system involvement or extraocular muscle atrophy, the absence of gaze-evoked nystagmus in almost all of the patients favours the latter.Our study shows that neurotological examinations that include a saccadic velocity test are very useful for detecting subtle eye movement abnormalities in DM and for quantitatively evaluating the clinical severity of DM.

Stapedial reflex in Parkinson's disease

In 27 patients with Parkinsons disease (PD), stapedial reflexes were measured using impedance audiometry and compared with those of 11 age-matched control subjects. The reflex threshold of PD patients was lower than that of control subjects. A prolongation of contraction time (C50) and relaxation time (D50) was revealed. Between patients with and without L-dopa, there was no significant difference for any reflex parameter. But, the D50 of patients without anticholinergic drugs was longer than that of patients with anticholinergic drugs. The authors could not find any relationship between the severity of PD and the reflex parameters. The authors assume that the prolongation of reflex parameters might be attributed to the hyperactivity of the indirect pathways of the stapedial reflex.

Stapedial reflex in myotonic dystrophy type 1 and CTG repeat expansion

Abstract The severity of clinical symptoms of myotonic dystrophy type 1 (DM1) has been shown to be closely related to the size of a CTG triplet repeat in the gene encoding myotonin protein kinase. Neuro-otological examinations that include eye movement and stapedial reflex (SR) tests can contribute to the quantitative evaluation of muscular involvement in DM1. We previously found that saccadic eye movement velocity in DM1 patients was significantly lower than that in control subjects and that the saccadic velocity and size of the CTG triplet repeat in DM1 patients had a strong inverse correlation. We now report a case-control study that compared the SR wave form (latency: L, contraction time: C50, and relaxation time: D50) measured by the acoustic impedance method in 13 patients with DM1 and in 14 control subjects matched for age and sex. The correlation between the SR wave form and CTG repeat length in DM1 patients obtained by Southern blot analysis with EcoRI was also examined. We found (1) no significant difference between the pure tone audiometric threshold at 500 Hz in the DM1 patients and that in the control subjects; (2) or between the SR thresholds in the patients and controls (500 Hz stimuli); (3) C50 and D50 in DM1 patients to be significantly prolonged, whereas L was not; (4) C50 and D50 in DM1 patients to be significantly correlated with CTG repeat length, whereas L was not. Measurement of SR by the acoustic impedance method is completely non-invasive, causes no discomfort to the subject, and does not depend on the persons effort or cooperation. Our findings show that SR measurement can be used for a quantitative evaluation of muscle involvement in DM1. We believe that the prolongation of D50 in DM1 is caused by myotonia, which has to be confirmed by further clinical and pathological studies.

Eye movement disorders in myotonic dystrophy type 1

Conclusions. No definite sign was found of central oculomotor system disorders being independent of saccadic slowing because (1) diminished maximum slow phase velocity of the optokinetic nystagmus (OKNspv) was closely related to saccadic slowing (p<0.01, r=0.59), (2) maximum frequency of optokinetic nystagmus (OKNfq) was normal, (3) visual suppression (VS) change was mild, and (4) the diminished maximum slow phase velocity of the caloric nystagmus (CNspv) seen in some patients is explained by both peripheral and central vestibular involvement. These findings support the extraocular muscle hypothesis. Objective. To assess whether eye movement disorders seen in patients with myotonic dystrophy type 1 (DM1) are caused by central oculomotor system involvement or extraocular muscle damage. Patients and methods. Oculomotor functions and their correlation with (CTG)n length were studied in 29 DM1 patients and 12 age-matched controls. Results. Values for saccadic velocity (p<0.005), maximum OKNspv (p<0.005), and maximum CNspv (p<0.01) in the patient group were markedly lower than in the control group. VS of caloric nystagmus in the patient group was slightly lower than that in the controls. No significant difference was found between the two groups in the maximum OKNfq. Patients with greater (CTG)n lengths had lower saccadic velocities (p<0.01, r=0.71).

Vocal cord abductor paralysis in multiple system atrophy: a case report

Multiple system atrophy (MSA) is a progressive neurodegenerative disease that is characterized by varying degrees of parkinsonism and cerebellar, corticospinal, and autonomic dysfunction. Vocal cord abductor paralysis (VCAP) is considered a sign of a poor prognosis in MSA, because it is a life-threatening complication that may cause nocturnal sudden death. This case report presents a patient who was treated for Parkinsons disease, and complained of dizziness and sleep apnea. We examined VCAP using fiberoptic laryngoscopy as the possible cause of sleep apnea. VCAP usually occurs in the advanced stages of MSA and is accompanied by a worsening of other symptoms. Optokinetic nystagmus was severely impaired and the caloric test response was bilaterally absent. Objective findings such as VCAP and abnormal neuro-otological results led to the diagnosis of MSA.

Swallowing Disorder in Patients with Myotonic Dystrophy Type I

Abstract Objectives: Swallowing disorder is often seen in patients with myotonic dystrophy type I (DM I) and may cause death from aspiration pneumonia. The purpose of the study was to investigate the incidence and extent of swallowing disorder in DM I. Methods: Twenty-two DM I patients were referred from neurologists for otolaryngologic examination. All the patients were evaluated for vocal cord and pharyngeal movements with laryngeal fiberscopy. Nine patients were additionally evaluated with x-ray fluoroscopy of the hypopharynx and esophagus. The extent of (CTG) expansion of the patients peripheral lymphocytes was determined by Southern blot analysis. Results: Laryngeal fiberscopy showed pooling of saliva in the hypopharynx to some extent in all the 22 patients. X-ray fluoroscopy showed pooling of large amount of contrast media in the hypopharynx of 7 patients after cessation of deglutition. Conclusion: Potential dysphagia and the risk of aspiration pneumonia are frequently seen in DM I patients. The neurologists and even the patients are not aware of this unless notified by otolaryngologists. The otolaryngologist is uniquely qualified to evaluate swallowing function and must continue to play a role in management of swallowing disorder in patients with neurological diseases.