Tomoyoshi Kondo - Academia.edu (original) (raw)
Papers by Tomoyoshi Kondo
Http Dx Doi Org 10 1080 13554794 2012 667118, Jun 14, 2013
We report two patients with avoidance of swallowing saliva despite intact swallowing functions. O... more We report two patients with avoidance of swallowing saliva despite intact swallowing functions. One, with mild, de novo Parkinson's disease, had a fear that his saliva was contaminated and would harm him. The other, with a history of CNS germinoma in remission for 3 years following chemotherapy, expectorated because his saliva was distasteful and disgusting. He had a lesion involving the left pallidum. Both appeared obsessed with the idea of saliva contamination and both expectorated compulsively, presenting obsessive-compulsive disorder (OCD) symptoms. OCD-like behavior may be induced in association with pathological conditions in which aberrant basal ganglia functions are present.
Nō to Shinkei Brain and Nerve, Aug 1, 2003
A 46-year-old man had a 7-year history of dopa-responsive parkinsonism. Four years after starting... more A 46-year-old man had a 7-year history of dopa-responsive parkinsonism. Four years after starting levodopa, he had typical motor complications such as wearing-off and peak dose as well as off-period dystonia of his trunk. Brain MRI showed marked atrophy of the brainstem and cerebellum, and the cross sign was present in the pontine base. There was neither abnormal signal intensity nor atrophy in the basal ganglia. Then, he was suspected as having multiple system atrophy (MSA). It is not easy to differentiate MSA from Parkinson diseases, particularly when the patient shows good response to levodopa and motor complications like those seen in Parkinson's disease. If the striatal pathology was not severe and nigral degeneration was prominent, presynaptic parkinsonism might occur in MSA, and putaminal preservation might account for good response to levodopa therapy. In patients with MSA, disproportionate antecollis is common before levodopa treatment, and levodopa induced off-dystonia of his trunk is very rare.
Neuroreport, 2001
Systemic administration of a dopamine D2 receptor blocker, haloperidol, but not vehicle, signific... more Systemic administration of a dopamine D2 receptor blocker, haloperidol, but not vehicle, significantly increased the number of c-Fos-immunoreactive neurons in the globus pallidus (GP) in rats. Dual immunohistochemistry, a combination of c-Fos immunohistochemistry and retrograde tracing experiments with cholera toxin B (ChB), revealed that a subset of the c-Fos-immunoreactive GP neurons was pallidostriatal feedback neurons. Lesioning of the subthalamic nucleus (STN) by local injection of ibotenic acid inhibited the haloperidol-induced c-Fos expression in the GP neurons, suggesting that the activation of GP neurons is a result of increased excitatory drives from the STN. Therefore, the present findings are evidence of the existence of the subthalamo-pallido-striatal axis as a feedback system in the internal circuits of the basal ganglia.
Nō to Shinkei Brain and Nerve, Feb 1, 2002
Motor fluctuation is the most annoying complication experienced by patients in the advanced stage... more Motor fluctuation is the most annoying complication experienced by patients in the advanced stages of Parkinson's disease. A Combination therapy of a dopamine receptor agonist and levodopa/DCI(DOPA-decarboxylase inhibitor) is commonly used to control the complication. Although administration of levodopa/DCI is useful in minimizing peripheral side effects of levodopa, it increases the incidence of motor complications due to the marked fluctuation of plasma levodopa level. The use of levodopa without DCI might be an option for controlling motor fluctuation, because the extent of plasma levodopa level fluctuation is smaller when levodopa is administered without DCI than with DCI. Six patients with Parkinson's disease who had troublesome motor complications under levodopa/DCI and DA agonist combination therapy were compared in terms of the extent of motor complications and their satisfaction after changing their therapy from levodopa/DCI to levodopa without DCI. The change from levodopa/DCI to levodopa(without DCI) was carried out all at once, and the levodopa/DCI to levodopa dose ratio was started at 1:4. The dose of levodopa(without DCI) was then increased gradually until motor complications improved or side effects were observed in patients. Except two patients who voluntarily quitted levodopa and restarted DOPA/DCI before the dose of levodopa fixed, all cases showed improvement of wearing-off phenomenon. No adverse event was observed. Levodopa-without-DCI-therapy was effective for controlling motor fluctuation in patients of Parkinson's disease in advanced stages.
Brain and Nerve Shinkei Kenkyū No Shinpo, Mar 1, 2011
Parkinson's disease (PD) ... more Parkinson's disease (PD) affects 145,000 people in Japan. Most of these patients are treated with levodopa in combination with other anti-PD therapies. In order to maximize efficacy and patient satisfaction, this survey was conducted to investigate patients' perspective of current PD management in Japan. This survey was conducted in 2008 by questionnaire (3,935) and interview (407). The majority of responders were members of the Japan PD Association. Severity of PD, medication, impact of wearing-off, and patients' attitudes to therapy were assessed. Most patients (95%) were on levodopa, with an average dose of 370 mg/day. Although dose increased with duration of treatment, the majority of patients remained within 300-400 mg/day. Patients with wearing-off were less satisfied with their therapy than those without wearing-off (36 vs 49%). Most patients are less concerned by mild dyskinesias. Hallucination is the most distressing side effect. For patients preferring mobility over dyskinesia, levodopa should be dosed sufficiently, and possibly titrated, to maximize clinical benefit and patient satisfaction.
Journal of Clinical Neuroscience Official Journal of the Neurosurgical Society of Australasia, Jan 12, 2013
Nō to Shinkei Brain and Nerve, Jun 1, 2003
Psychosis characterized by hallucination or delusion, which occurs during drug therapy of parkins... more Psychosis characterized by hallucination or delusion, which occurs during drug therapy of parkinsonian patients, is one of the limiting factors for the control of motor symptoms or complications. In the present study, we encountered three patients with Parkinson's disease (PD) at advanced stages; all three patients had severe psychosis and severe wearing-off phenomenon and one had severe orthostatic hypotension. Their psychotic symptoms were successfully treated by administration of quetiapine, resulting in the favorable control of motor fluctuations and elevation of therapeutic levels unless any aggravation of parkinsonism occurs. Although the measure against drug-induced psychosis is principally a reduction of the doses or withdrawal of causative drugs, the effective use of antipsychotic drugs, such as quetiapine, is helpful to suppress psychosis and allow the patient to adjust to antiparkinsonian drugs for the control of symptoms other than psychosis.
Journal of Pharmacological Sciences, Aug 20, 2006
Selegiline is used an adjunct to L-DOPA therapy. We investigated extracellular striatal dopamine ... more Selegiline is used an adjunct to L-DOPA therapy. We investigated extracellular striatal dopamine (DA) level in awake rats treated with L-DOPA and/or selegiline using a microdialysis method. Rats given 10 mg/kg, i.p. per day selegiline for 7 days were administered with a single dose of 100 mg/kg, i.p. L-DOPA 0 (3 h), 1, 3, 7, 14, 21, or 28 days after the last selegiline treatment. Carbidopa was administered 0.5 h before L-DOPA administration. The significant increase in basal DA level before L-DOPA treatment persisted until 1 day after the last selegiline treatment, and the significant decrease in basal DOPAC level persisted for more than 28 days. Thus, selegiline affected DA catabolism for more than 28 days. Total monoamine oxidase (MAO) and MAO-B activities at day 0 decreased by 22% and 5.7%, respectively. The significant enhancement of L-DOPA-induced increase in DA level was observed until 3 days after the last selegiline treatment. Next, the effects of reducing L-DOPA dose by 25% were examined 3 h after the last selegiline treatment. A dose-dependent decrease in DA level was observed, indicating that DA level in selegiline-treated rats can be controlled by L-DOPA dose.
Brain and Nerve Shinkei Kenkyū No Shinpo, Aug 1, 2012
A 60-year-old woman had frequent relapses of neuromyelitis optica (NMO) for 30 years despite rece... more A 60-year-old woman had frequent relapses of neuromyelitis optica (NMO) for 30 years despite receiving steroid and azathioprine therapy. She developed MGFA Class IIIb type of myasthenia gravis (MG) at the age of 23, and thymectomy resulted in complete remission of MG. The initial symptoms of NMO, including headache, high fever, retrobulbar optic neuritis, and neurogenic bladder, appeared at the age of 30. Two years later, paraplegia also developed. Although she received oral administration of steroids or azathioprine and intravenous steroid pulse therapy for treatment of NMO for over 30 years, she experienced frequent relapses. The examination at the ages of 58 and 60 years showed that anti-aquaporin-4 antibody was absent. Intravenous immunoglobulin therapy administered in January and June 2009 was effective, and she had 2 years of remission of NMO attack. Spinal MRI after frequent NMO attacks for 30 years revealed an extended spinal cord atrophy involving the lower cervical region and the entire thoracic region. We describe and discuss the prognosis of NMO and the effectiveness of therapies in an NMO patient who underwent thymectomy for MG.
Internal Medicine, Feb 1, 2007
There is growing interest in the use of transcranial sonography (TCS) of the substantia nigra (SN... more There is growing interest in the use of transcranial sonography (TCS) of the substantia nigra (SN) in patients with Parkinson's disease (PD), as it has been reported that SN hyperechogenicity may be present in about 90% of PD patients. However, TCS of the SN has not been applied in Japanese patients, and its clinical potential has not been determined. TCS of the SN was performed in patients with PD, progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and essential tremor (ET), and age-matched controls. Ultrasound images of the SN were assessed using semi-qualitative estimation criteria by two investigators unaware of clinical diagnosis. SN hyperechogenicity was observed in approximately 83% of accessible SNs in Japanese PD patients. In comparison, SN hyperechogenicity was less frequently observed in healthy subjects or in patients with PSP, MSA, and ET. However, the rate of successful recording of the SN by TCS decreased prominently with advancing age, particularly in females. The present study confirmed that TCS of the SN is potentially useful in the investigation of Japanese patients, and it provides a better differential diagnosis between PD and atypical parkinsonism. The recording failure of TCS in aged, particularly female subjects, may limit the clinical potential of TCS of the SN in Japanese patients.
Nō to Shinkei Brain and Nerve, Oct 1, 2006
This investigation was conducted to clarify the frequency and characteristics of ALS associated w... more This investigation was conducted to clarify the frequency and characteristics of ALS associated with extrapyramidal symptoms or signs in Wakayama prefecture. The questionnaires to survey ALS cases were mailed to all medical centers in Wakayama prefecture. A total of 252 cases were found to have motor neuron diseases. Among them, 204 cases fulfilled probable or definite according to El Escorial Criteria. In 10 of them, extrapyramidal signs were identified as follows: rigidity 50%, tremor 40% and akinesia 10%. Family history of ALS in these cases (20%) is higher than expected in usual ALS, and all of them are negative for SOD-1 mutation. Dementia and autonomic nervous symptoms were observed in several cases. Incidence of extrapyramidal signs in ALS resulted in 4.8%. The incidence of extrapyramidal signs is more frequent than expected by chance, suggesting that the degeneration of basal ganglia and/or substantia nigra may not be so rare in ALS.
Nō to Shinkei Brain and Nerve, Apr 1, 2003
We report a 56-year-old Japanese man who was admitted because of dysphagia and left side facial d... more We report a 56-year-old Japanese man who was admitted because of dysphagia and left side facial dysesthesia. On admission, his general conditions were unremarkable. Neurological examination revealed that he was alert and well oriented. He exhibited left-side cranial nerve involvement such as the trigeminal(sensory and motor), glossopharyngeal and potential vagal nerve palsy. He exhibited neither long-tract signs, such as motor weakness, sensory disturbance in his exremities and pathological reflex, nor ataxia. By a few days after admission, his symptoms had worsened. Vertigo and diplopia appeared, and his consciousness level became drowsy. Bilateral third and sixth nerves, left fourth, fifth, eighth, ninth and tenth nerves were involved. Results of laboratory tests and CSF studies were within normal. Results of examination of the skull base X-ray and MRIs of the brain were normal. Administration of corticosteroid and intravenous administration of a high dose of gamma-globulin were not effective. His symptoms gradually recovered three months after admission. Based on clinical symptoms and results of physiological examination, i.e., an involvement of his consciousness and abnormal findings in blink reflex test that suggest involvement of the brainstem, he was diagnosed as having brainstem encephalitis. Although the exact pathophysiological mechanisms were unclear, it is clinically important to note that an atypical brainstem encephalitis may present a subacute progressive appearance of unilateral multiple cranial nerve palsies mimicking Garcin syndrome.
Nō to Shinkei Brain and Nerve, Jul 1, 2006
Annals of Clinical and Translational Neurology, 2015
Objective: Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with ... more Objective: Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). To investigate the role of GBA variants in multiple system atrophy (MSA), we analyzed GBA variants in a large case-control series. Methods: We sequenced coding regions and flanking splice sites of GBA in 969 MSA patients (574 Japanese, 223 European, and 172 North American) and 1509 control subjects (900 Japanese, 315 European, and 294 North American). We focused solely on Gaucher-disease-causing GBA variants. Results: In the Japanese series, we found nine carriers among the MSA patients (1.65%) and eight carriers among the control subjects (0.89%). In the European series, we found three carriers among the MSA patients (1.35%) and two carriers among the control subjects (0.63%). In the North American series, we found five carriers among the MSA patients (2.91%) and one carrier among the control subjects (0.34%). Subjecting each series to a Mantel-Haenszel analysis yielded a pooled odds ratio (OR) of 2.44 (95% confidence interval [CI], 1.14-5.21) and a P-value of 0.029 without evidence of significant heterogeneity. Logistic regression analysis yielded similar results, with an adjusted OR of 2.43 (95% CI 1.15-5.37) and a P-value of 0.022. Subtype analysis showed that Gaucher-disease-causing GBA variants are significantly associated with MSA cerebellar subtype (MSA-C) patients (P = 7.3 9 10 À3 ). Interpretation: The findings indicate that, as in PD and DLB, Gaucher-disease-causing GBA variants are associated with MSA.
Journal of neurology, 2014
Rotigotine, a non-ergot dopamine receptor agonist, offers potential for continuous dopaminergic s... more Rotigotine, a non-ergot dopamine receptor agonist, offers potential for continuous dopaminergic stimulation that could avoid the fluctuations observed with traditional treatments. We conducted a randomized, double-blind, placebo-controlled trial in Japanese patients with advanced Parkinson's disease (PD) to investigate the efficacy and safety of rotigotine. Inclusion criteria included the presence of motor complications, such as wearing off, on-off, delayed-on/no-on, any circumstances that could interfere with levodopa dose escalation because of side effects, or declining levodopa efficacy. The enrolled patients received once-daily applications of rotigotine transdermal patches or matched placebo patches. A total of 174 patients were randomly assigned to rotigotine (87 patients) or placebo (87 patients). The full analysis set included 172 patients (86 for the rotigotine group and 86 for the placebo group). The maximum maintenance dose of rotigotine was set at 16 mg/24 h. The cha...
Journal of Parkinson's disease, 2011
The loss of the ability to cycle after disease onset, the so-called "bicycle sign", has... more The loss of the ability to cycle after disease onset, the so-called "bicycle sign", has been proposed as a new red flag for atypical parkinsonism. However, actual environments or situations for bicycling differ from one country to another, raising the question of whether "bicycle sign" could be universally applicable. The present study suggested that "bicycle sign" could contribute to earlier and better differential diagnosis of parkinsonism in a hilly country like Japan.
Brain and nerve = Shinkei kenkyū no shinpo, 2011
Parkinson's disease (PD) affects 145,000 people in Japan. Most of these patients are treated ... more Parkinson's disease (PD) affects 145,000 people in Japan. Most of these patients are treated with levodopa in combination with other anti-PD therapies. In order to maximize efficacy and patient satisfaction, this survey was conducted to investigate patients' perspective of current PD management in Japan. This survey was conducted in 2008 by questionnaire (3,935) and interview (407). The majority of responders were members of the Japan PD Association. Severity of PD, medication, impact of wearing-off, and patients' attitudes to therapy were assessed. Most patients (95%) were on levodopa, with an average dose of 370 mg/day. Although dose increased with duration of treatment, the majority of patients remained within 300-400 mg/day. Patients with wearing-off were less satisfied with their therapy than those without wearing-off (36 vs 49%). Most patients are less concerned by mild dyskinesias. Hallucination is the most distressing side effect. For patients preferring mobility...
Nō to shinkei = Brain and nerve, 2004
A 67-year-old woman was admitted to our hospital, because of wasting of the thigh muscles. Muscul... more A 67-year-old woman was admitted to our hospital, because of wasting of the thigh muscles. Muscular atrophy was confined to the thigh muscles, suggesting that she had quadriceps myopathy. Muscle biopsy from quadriceps muscle revealed characteristic findings, such as invasion of the endomysium and muscle fibers by inflammatory cells, the presence of rimmed vacuoles and ragged red fibers; thereby, she was diagnosed as having inclusion body myositis (IBM). Based on elevated titers of autoantibody as well as biopsy findings from salivary gland and liver, she was also diagnosed as having chronic thyroiditis, Sjögren's syndrome and autoimmune cholangitis. Currently, the pathogenic mechanism underlying IBM is not clarified, however, various factors have been suggested to contribute to it, such as viral infection or mitochondrial insufficiency. Although the pathogenic backgrounds underlying IBM are likely heterogeneous, an autoimmune-mediated mechanism may be related to the pathogenesis...
The International journal of eating disorders, 2004
Reversible cerebral atrophy (pseudoatrophy) is observable in patients with anorexia nervosa. Howe... more Reversible cerebral atrophy (pseudoatrophy) is observable in patients with anorexia nervosa. However, it is extremely rare to see marked cerebellar atrophy. We report on a patient who developed cerebellar atrophy after the severe deterioration of cardiac and respiratory functions resulting from undernutririon. A 30-year-old Japanese woman was admitted to the Wakayama Medical University Hospital (Wakayama, Japan) because of unsteadiness of gait. She had a 7-year history of anorexia nervosa and had been admitted to an emergency hospital because of asthenic shock resulting from severe undernutrition at the age of 28. On admission to our hospital, neurologic examination revealed dysarthria and cerebellar ataxia of the trunk and lower extremities without nystagmus. A brain magnetic resonance imaging scan demonstrated marked atrophy of the cerebellum. Because her cerebellar ataxia appeared during severe deterioration of her general condition, and there has been no subsequent progression, ...
Http Dx Doi Org 10 1080 13554794 2012 667118, Jun 14, 2013
We report two patients with avoidance of swallowing saliva despite intact swallowing functions. O... more We report two patients with avoidance of swallowing saliva despite intact swallowing functions. One, with mild, de novo Parkinson's disease, had a fear that his saliva was contaminated and would harm him. The other, with a history of CNS germinoma in remission for 3 years following chemotherapy, expectorated because his saliva was distasteful and disgusting. He had a lesion involving the left pallidum. Both appeared obsessed with the idea of saliva contamination and both expectorated compulsively, presenting obsessive-compulsive disorder (OCD) symptoms. OCD-like behavior may be induced in association with pathological conditions in which aberrant basal ganglia functions are present.
Nō to Shinkei Brain and Nerve, Aug 1, 2003
A 46-year-old man had a 7-year history of dopa-responsive parkinsonism. Four years after starting... more A 46-year-old man had a 7-year history of dopa-responsive parkinsonism. Four years after starting levodopa, he had typical motor complications such as wearing-off and peak dose as well as off-period dystonia of his trunk. Brain MRI showed marked atrophy of the brainstem and cerebellum, and the cross sign was present in the pontine base. There was neither abnormal signal intensity nor atrophy in the basal ganglia. Then, he was suspected as having multiple system atrophy (MSA). It is not easy to differentiate MSA from Parkinson diseases, particularly when the patient shows good response to levodopa and motor complications like those seen in Parkinson's disease. If the striatal pathology was not severe and nigral degeneration was prominent, presynaptic parkinsonism might occur in MSA, and putaminal preservation might account for good response to levodopa therapy. In patients with MSA, disproportionate antecollis is common before levodopa treatment, and levodopa induced off-dystonia of his trunk is very rare.
Neuroreport, 2001
Systemic administration of a dopamine D2 receptor blocker, haloperidol, but not vehicle, signific... more Systemic administration of a dopamine D2 receptor blocker, haloperidol, but not vehicle, significantly increased the number of c-Fos-immunoreactive neurons in the globus pallidus (GP) in rats. Dual immunohistochemistry, a combination of c-Fos immunohistochemistry and retrograde tracing experiments with cholera toxin B (ChB), revealed that a subset of the c-Fos-immunoreactive GP neurons was pallidostriatal feedback neurons. Lesioning of the subthalamic nucleus (STN) by local injection of ibotenic acid inhibited the haloperidol-induced c-Fos expression in the GP neurons, suggesting that the activation of GP neurons is a result of increased excitatory drives from the STN. Therefore, the present findings are evidence of the existence of the subthalamo-pallido-striatal axis as a feedback system in the internal circuits of the basal ganglia.
Nō to Shinkei Brain and Nerve, Feb 1, 2002
Motor fluctuation is the most annoying complication experienced by patients in the advanced stage... more Motor fluctuation is the most annoying complication experienced by patients in the advanced stages of Parkinson's disease. A Combination therapy of a dopamine receptor agonist and levodopa/DCI(DOPA-decarboxylase inhibitor) is commonly used to control the complication. Although administration of levodopa/DCI is useful in minimizing peripheral side effects of levodopa, it increases the incidence of motor complications due to the marked fluctuation of plasma levodopa level. The use of levodopa without DCI might be an option for controlling motor fluctuation, because the extent of plasma levodopa level fluctuation is smaller when levodopa is administered without DCI than with DCI. Six patients with Parkinson's disease who had troublesome motor complications under levodopa/DCI and DA agonist combination therapy were compared in terms of the extent of motor complications and their satisfaction after changing their therapy from levodopa/DCI to levodopa without DCI. The change from levodopa/DCI to levodopa(without DCI) was carried out all at once, and the levodopa/DCI to levodopa dose ratio was started at 1:4. The dose of levodopa(without DCI) was then increased gradually until motor complications improved or side effects were observed in patients. Except two patients who voluntarily quitted levodopa and restarted DOPA/DCI before the dose of levodopa fixed, all cases showed improvement of wearing-off phenomenon. No adverse event was observed. Levodopa-without-DCI-therapy was effective for controlling motor fluctuation in patients of Parkinson's disease in advanced stages.
Brain and Nerve Shinkei Kenkyū No Shinpo, Mar 1, 2011
Parkinson's disease (PD) ... more Parkinson's disease (PD) affects 145,000 people in Japan. Most of these patients are treated with levodopa in combination with other anti-PD therapies. In order to maximize efficacy and patient satisfaction, this survey was conducted to investigate patients' perspective of current PD management in Japan. This survey was conducted in 2008 by questionnaire (3,935) and interview (407). The majority of responders were members of the Japan PD Association. Severity of PD, medication, impact of wearing-off, and patients' attitudes to therapy were assessed. Most patients (95%) were on levodopa, with an average dose of 370 mg/day. Although dose increased with duration of treatment, the majority of patients remained within 300-400 mg/day. Patients with wearing-off were less satisfied with their therapy than those without wearing-off (36 vs 49%). Most patients are less concerned by mild dyskinesias. Hallucination is the most distressing side effect. For patients preferring mobility over dyskinesia, levodopa should be dosed sufficiently, and possibly titrated, to maximize clinical benefit and patient satisfaction.
Journal of Clinical Neuroscience Official Journal of the Neurosurgical Society of Australasia, Jan 12, 2013
Nō to Shinkei Brain and Nerve, Jun 1, 2003
Psychosis characterized by hallucination or delusion, which occurs during drug therapy of parkins... more Psychosis characterized by hallucination or delusion, which occurs during drug therapy of parkinsonian patients, is one of the limiting factors for the control of motor symptoms or complications. In the present study, we encountered three patients with Parkinson's disease (PD) at advanced stages; all three patients had severe psychosis and severe wearing-off phenomenon and one had severe orthostatic hypotension. Their psychotic symptoms were successfully treated by administration of quetiapine, resulting in the favorable control of motor fluctuations and elevation of therapeutic levels unless any aggravation of parkinsonism occurs. Although the measure against drug-induced psychosis is principally a reduction of the doses or withdrawal of causative drugs, the effective use of antipsychotic drugs, such as quetiapine, is helpful to suppress psychosis and allow the patient to adjust to antiparkinsonian drugs for the control of symptoms other than psychosis.
Journal of Pharmacological Sciences, Aug 20, 2006
Selegiline is used an adjunct to L-DOPA therapy. We investigated extracellular striatal dopamine ... more Selegiline is used an adjunct to L-DOPA therapy. We investigated extracellular striatal dopamine (DA) level in awake rats treated with L-DOPA and/or selegiline using a microdialysis method. Rats given 10 mg/kg, i.p. per day selegiline for 7 days were administered with a single dose of 100 mg/kg, i.p. L-DOPA 0 (3 h), 1, 3, 7, 14, 21, or 28 days after the last selegiline treatment. Carbidopa was administered 0.5 h before L-DOPA administration. The significant increase in basal DA level before L-DOPA treatment persisted until 1 day after the last selegiline treatment, and the significant decrease in basal DOPAC level persisted for more than 28 days. Thus, selegiline affected DA catabolism for more than 28 days. Total monoamine oxidase (MAO) and MAO-B activities at day 0 decreased by 22% and 5.7%, respectively. The significant enhancement of L-DOPA-induced increase in DA level was observed until 3 days after the last selegiline treatment. Next, the effects of reducing L-DOPA dose by 25% were examined 3 h after the last selegiline treatment. A dose-dependent decrease in DA level was observed, indicating that DA level in selegiline-treated rats can be controlled by L-DOPA dose.
Brain and Nerve Shinkei Kenkyū No Shinpo, Aug 1, 2012
A 60-year-old woman had frequent relapses of neuromyelitis optica (NMO) for 30 years despite rece... more A 60-year-old woman had frequent relapses of neuromyelitis optica (NMO) for 30 years despite receiving steroid and azathioprine therapy. She developed MGFA Class IIIb type of myasthenia gravis (MG) at the age of 23, and thymectomy resulted in complete remission of MG. The initial symptoms of NMO, including headache, high fever, retrobulbar optic neuritis, and neurogenic bladder, appeared at the age of 30. Two years later, paraplegia also developed. Although she received oral administration of steroids or azathioprine and intravenous steroid pulse therapy for treatment of NMO for over 30 years, she experienced frequent relapses. The examination at the ages of 58 and 60 years showed that anti-aquaporin-4 antibody was absent. Intravenous immunoglobulin therapy administered in January and June 2009 was effective, and she had 2 years of remission of NMO attack. Spinal MRI after frequent NMO attacks for 30 years revealed an extended spinal cord atrophy involving the lower cervical region and the entire thoracic region. We describe and discuss the prognosis of NMO and the effectiveness of therapies in an NMO patient who underwent thymectomy for MG.
Internal Medicine, Feb 1, 2007
There is growing interest in the use of transcranial sonography (TCS) of the substantia nigra (SN... more There is growing interest in the use of transcranial sonography (TCS) of the substantia nigra (SN) in patients with Parkinson's disease (PD), as it has been reported that SN hyperechogenicity may be present in about 90% of PD patients. However, TCS of the SN has not been applied in Japanese patients, and its clinical potential has not been determined. TCS of the SN was performed in patients with PD, progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and essential tremor (ET), and age-matched controls. Ultrasound images of the SN were assessed using semi-qualitative estimation criteria by two investigators unaware of clinical diagnosis. SN hyperechogenicity was observed in approximately 83% of accessible SNs in Japanese PD patients. In comparison, SN hyperechogenicity was less frequently observed in healthy subjects or in patients with PSP, MSA, and ET. However, the rate of successful recording of the SN by TCS decreased prominently with advancing age, particularly in females. The present study confirmed that TCS of the SN is potentially useful in the investigation of Japanese patients, and it provides a better differential diagnosis between PD and atypical parkinsonism. The recording failure of TCS in aged, particularly female subjects, may limit the clinical potential of TCS of the SN in Japanese patients.
Nō to Shinkei Brain and Nerve, Oct 1, 2006
This investigation was conducted to clarify the frequency and characteristics of ALS associated w... more This investigation was conducted to clarify the frequency and characteristics of ALS associated with extrapyramidal symptoms or signs in Wakayama prefecture. The questionnaires to survey ALS cases were mailed to all medical centers in Wakayama prefecture. A total of 252 cases were found to have motor neuron diseases. Among them, 204 cases fulfilled probable or definite according to El Escorial Criteria. In 10 of them, extrapyramidal signs were identified as follows: rigidity 50%, tremor 40% and akinesia 10%. Family history of ALS in these cases (20%) is higher than expected in usual ALS, and all of them are negative for SOD-1 mutation. Dementia and autonomic nervous symptoms were observed in several cases. Incidence of extrapyramidal signs in ALS resulted in 4.8%. The incidence of extrapyramidal signs is more frequent than expected by chance, suggesting that the degeneration of basal ganglia and/or substantia nigra may not be so rare in ALS.
Nō to Shinkei Brain and Nerve, Apr 1, 2003
We report a 56-year-old Japanese man who was admitted because of dysphagia and left side facial d... more We report a 56-year-old Japanese man who was admitted because of dysphagia and left side facial dysesthesia. On admission, his general conditions were unremarkable. Neurological examination revealed that he was alert and well oriented. He exhibited left-side cranial nerve involvement such as the trigeminal(sensory and motor), glossopharyngeal and potential vagal nerve palsy. He exhibited neither long-tract signs, such as motor weakness, sensory disturbance in his exremities and pathological reflex, nor ataxia. By a few days after admission, his symptoms had worsened. Vertigo and diplopia appeared, and his consciousness level became drowsy. Bilateral third and sixth nerves, left fourth, fifth, eighth, ninth and tenth nerves were involved. Results of laboratory tests and CSF studies were within normal. Results of examination of the skull base X-ray and MRIs of the brain were normal. Administration of corticosteroid and intravenous administration of a high dose of gamma-globulin were not effective. His symptoms gradually recovered three months after admission. Based on clinical symptoms and results of physiological examination, i.e., an involvement of his consciousness and abnormal findings in blink reflex test that suggest involvement of the brainstem, he was diagnosed as having brainstem encephalitis. Although the exact pathophysiological mechanisms were unclear, it is clinically important to note that an atypical brainstem encephalitis may present a subacute progressive appearance of unilateral multiple cranial nerve palsies mimicking Garcin syndrome.
Nō to Shinkei Brain and Nerve, Jul 1, 2006
Annals of Clinical and Translational Neurology, 2015
Objective: Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with ... more Objective: Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). To investigate the role of GBA variants in multiple system atrophy (MSA), we analyzed GBA variants in a large case-control series. Methods: We sequenced coding regions and flanking splice sites of GBA in 969 MSA patients (574 Japanese, 223 European, and 172 North American) and 1509 control subjects (900 Japanese, 315 European, and 294 North American). We focused solely on Gaucher-disease-causing GBA variants. Results: In the Japanese series, we found nine carriers among the MSA patients (1.65%) and eight carriers among the control subjects (0.89%). In the European series, we found three carriers among the MSA patients (1.35%) and two carriers among the control subjects (0.63%). In the North American series, we found five carriers among the MSA patients (2.91%) and one carrier among the control subjects (0.34%). Subjecting each series to a Mantel-Haenszel analysis yielded a pooled odds ratio (OR) of 2.44 (95% confidence interval [CI], 1.14-5.21) and a P-value of 0.029 without evidence of significant heterogeneity. Logistic regression analysis yielded similar results, with an adjusted OR of 2.43 (95% CI 1.15-5.37) and a P-value of 0.022. Subtype analysis showed that Gaucher-disease-causing GBA variants are significantly associated with MSA cerebellar subtype (MSA-C) patients (P = 7.3 9 10 À3 ). Interpretation: The findings indicate that, as in PD and DLB, Gaucher-disease-causing GBA variants are associated with MSA.
Journal of neurology, 2014
Rotigotine, a non-ergot dopamine receptor agonist, offers potential for continuous dopaminergic s... more Rotigotine, a non-ergot dopamine receptor agonist, offers potential for continuous dopaminergic stimulation that could avoid the fluctuations observed with traditional treatments. We conducted a randomized, double-blind, placebo-controlled trial in Japanese patients with advanced Parkinson's disease (PD) to investigate the efficacy and safety of rotigotine. Inclusion criteria included the presence of motor complications, such as wearing off, on-off, delayed-on/no-on, any circumstances that could interfere with levodopa dose escalation because of side effects, or declining levodopa efficacy. The enrolled patients received once-daily applications of rotigotine transdermal patches or matched placebo patches. A total of 174 patients were randomly assigned to rotigotine (87 patients) or placebo (87 patients). The full analysis set included 172 patients (86 for the rotigotine group and 86 for the placebo group). The maximum maintenance dose of rotigotine was set at 16 mg/24 h. The cha...
Journal of Parkinson's disease, 2011
The loss of the ability to cycle after disease onset, the so-called "bicycle sign", has... more The loss of the ability to cycle after disease onset, the so-called "bicycle sign", has been proposed as a new red flag for atypical parkinsonism. However, actual environments or situations for bicycling differ from one country to another, raising the question of whether "bicycle sign" could be universally applicable. The present study suggested that "bicycle sign" could contribute to earlier and better differential diagnosis of parkinsonism in a hilly country like Japan.
Brain and nerve = Shinkei kenkyū no shinpo, 2011
Parkinson's disease (PD) affects 145,000 people in Japan. Most of these patients are treated ... more Parkinson's disease (PD) affects 145,000 people in Japan. Most of these patients are treated with levodopa in combination with other anti-PD therapies. In order to maximize efficacy and patient satisfaction, this survey was conducted to investigate patients' perspective of current PD management in Japan. This survey was conducted in 2008 by questionnaire (3,935) and interview (407). The majority of responders were members of the Japan PD Association. Severity of PD, medication, impact of wearing-off, and patients' attitudes to therapy were assessed. Most patients (95%) were on levodopa, with an average dose of 370 mg/day. Although dose increased with duration of treatment, the majority of patients remained within 300-400 mg/day. Patients with wearing-off were less satisfied with their therapy than those without wearing-off (36 vs 49%). Most patients are less concerned by mild dyskinesias. Hallucination is the most distressing side effect. For patients preferring mobility...
Nō to shinkei = Brain and nerve, 2004
A 67-year-old woman was admitted to our hospital, because of wasting of the thigh muscles. Muscul... more A 67-year-old woman was admitted to our hospital, because of wasting of the thigh muscles. Muscular atrophy was confined to the thigh muscles, suggesting that she had quadriceps myopathy. Muscle biopsy from quadriceps muscle revealed characteristic findings, such as invasion of the endomysium and muscle fibers by inflammatory cells, the presence of rimmed vacuoles and ragged red fibers; thereby, she was diagnosed as having inclusion body myositis (IBM). Based on elevated titers of autoantibody as well as biopsy findings from salivary gland and liver, she was also diagnosed as having chronic thyroiditis, Sjögren's syndrome and autoimmune cholangitis. Currently, the pathogenic mechanism underlying IBM is not clarified, however, various factors have been suggested to contribute to it, such as viral infection or mitochondrial insufficiency. Although the pathogenic backgrounds underlying IBM are likely heterogeneous, an autoimmune-mediated mechanism may be related to the pathogenesis...
The International journal of eating disorders, 2004
Reversible cerebral atrophy (pseudoatrophy) is observable in patients with anorexia nervosa. Howe... more Reversible cerebral atrophy (pseudoatrophy) is observable in patients with anorexia nervosa. However, it is extremely rare to see marked cerebellar atrophy. We report on a patient who developed cerebellar atrophy after the severe deterioration of cardiac and respiratory functions resulting from undernutririon. A 30-year-old Japanese woman was admitted to the Wakayama Medical University Hospital (Wakayama, Japan) because of unsteadiness of gait. She had a 7-year history of anorexia nervosa and had been admitted to an emergency hospital because of asthenic shock resulting from severe undernutrition at the age of 28. On admission to our hospital, neurologic examination revealed dysarthria and cerebellar ataxia of the trunk and lower extremities without nystagmus. A brain magnetic resonance imaging scan demonstrated marked atrophy of the cerebellum. Because her cerebellar ataxia appeared during severe deterioration of her general condition, and there has been no subsequent progression, ...