Drug discarding: a problematic therapeutic event in Parkinson's disease.
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Aged↗
Biomedical subjects
Hideto Miwa
Publications and source records attributed to Hideto Miwa.
Effects of subchronic treatment with selegiline on L-DOPA-induced increase in extracellular dopamine level in rat striatum.
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.
3,4-Dihydroxyphenylacetic Acid↗
Intragastric proteasome inhibition induces alpha-synuclein-immunopositive aggregations in neurons in the dorsal motor nucleus of the vagus in rats.
The neuropathological hallmark of idiopathic Parkinson's disease (PD) is dopaminergic neuron degeneration in the substantia nigra. However, it has been suggested that the neurodegenerative process initially may occur in the dorsal motor nucleus of the vagus (DMV). This implies that unidentified environmental toxins or neurotropic pathogens that is capable of passing the mucosal barrier of the gastrointestinal tract might affect the enteric nerve endings of the vagal neurons, possibly resulting in retrograde degeneration of the DMV. The present study aimed to evaluate the effects of proteasome inhibition of the intragastric nerve terminals of the DMV in rats. Following multiple injections of PSI, a selective proteasome inhibitor, or vehicle into the ventral wall of the stomach, the medulla oblongata was studied immunohistologically. In the DMV neurons of rats treated with PSI but not vehicle, alpha-synuclein-immunopositive intracytoplasmic inclusions and activated microglia were observed, predominantly in the left DMV. However, there was no significant loss of neurons. These results suggest that intragastric proteasome inhibition has a retrograde effect on DMV neurons but is insufficient to induce cell death, suggesting no causal linkage between inclusion body formation with proteasome inhibition and neuron death in the DMV. This might also implicate that Lewy body formation in the DMV in PD is possibly related to peroral invasion of environmental toxins that inhibit ubiquitin-proteasome system function.
Animals↗
A species-specific difference in the effects of harmaline on the rodent olivocerebellar system.
The rodent model of harmaline-induced tremor has been widely used for experimental analysis of tremor. Activation of the olivocerebellar system plays a key role in tremor-generating mechanisms. One undetermined problem is whether there are species-specific differences in effects of harmaline. The present study investigated effects of harmaline on olivocerebellar systems of mice and rats. Systemic administration of harmaline, but not vehicle, produced generalized, high-frequency tremors in both types of rodents. Immunohistochemical studies revealed significant degeneration of Purkinje cells that was associated with activated microgliosis in the cerebellar cortex, following administration of harmaline in rats but not in mice. However, in mice but not rats, microgliosis was induced following administration of harmaline in the inferior olivary nucleus (ION), particularly in its caudal and medial subdivisions. Numbers of neurons in the mouse ION did not decrease, suggesting the possibility that microgliosis in ION might not be a simple neurotoxic effect. Presumably, differences in sensitivity of Purkinje cells between rats and mice may be related to differences in functional alterations in their respective olivocerebellar systems induced by harmaline. Recognition of these species-specific differences in the response of the olivocerebellar system to harmaline is an important consideration for experimental analysis of the rodent model of tremors.
Animals↗
[Echogenicity of the substantia nigra in Parkinson's disease: its relation to clinical findings].
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Early Diagnosis↗
[Chronic inflammatory demyelinating polyneuropathy followed by systemic lupus erythematosus and Sjögren syndrome: a case report].
We report a 60-year-old man with chronic inflammatory demyelinating polyneuropathy (CIDP) accompanying systemic lupus erythematosus (SLE) and Sjögren syndrome (SS). He was admitted to our hospital because of progressive weakness and dysesthesia in the distal parts of the bilateral upper and lower extremities. We diagnosed the illness as CIDP and treated him with steroids, plasma filtration and high-dose intravenous immunoglobulin therapy (IvIg). Consequently, his symptoms improved gradually and he was discharged. However, 2 years after the first admission, he experienced dyspnea on effort and chest X-ray demonstrated right pleural effusion. Consequently, he gradually developed gait disturbance, loss of taste, and severe dysesthesia in his lower limbs. Therefore, he was admitted again. On neurological examination, mild weakness was detected in all limbs distally. Deep tendon reflexes were absent. The sensation of position and vibration was diminished in the fingers and toes. He could not walk by himself and demonstrated an ataxic gait with a wide base. Examination of cranial nerves demonstrated no abnormalities, except for loss of taste. Serological examination demonstrated positive auto-antibodies including antinuclear, anti-DNA, and anti-SS-A antibodies. Urinalyses showed albuminuria and microscopic hematuria. Cerebrospinal fluid (CSF) was clear and colorless, containing 3 mononuclear cells per cubic mm, with a protein of 275 mg/dl. Magnetic resonance images (MRIs) of the brain and entire spine were normal. Neurophysiological studies demonstrated an absence of sensory nerve action potentials in the right arm and markedly slow conduction velocities, conduction block in the ulnar forearm segment and absence of F waves in all limbs. The renal biopsy revealed lupus nephritis. The lip biopsy demonstrated chronic sialoadenitis consistent with SS, altough patient did not show symptoms of arthritis or vasculitis. It is well known that mononeuritis multiplex and acute demyelinating polyneuropathy accompany SLE. However there are few reports that describe the occurrence of CIDP in patients with SLE, and the association of "CIDP-like" neuropathy in patients with SS. Our case suggests that the autoimmune disease associated with SLE and SS may induce "CIDP-like" inflammatory demyelinating polyneuropathy.
Antibodies, Antinuclear↗
[Pure dysarthria caused by a small cortical infarction].
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Aged, 80 and over↗
[Amyotrophic lateral sclerosis associated with extrapyramidal symptoms or signs].
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.
Aged↗
Retrograde dopaminergic neuron degeneration following intrastriatal proteasome inhibition.
Recent studies have suggested that defects in the ubiquitin-proteasome system (UPS) contribute to the etiopathogenetic mechanisms underlying dopaminergic neuronal degeneration in Parkinson's disease. The present study aims to study the effects of proteasome inhibition in the nerve terminals of nigrostriatal dopaminergic neurons in the substantia nigra pars compacta (SNpc). Following a unilaterally intrastriatal injection of lactacystin, a selective proteasome inhibitor, dopaminergic neurons in the ipsilateral SNpc progressively degenerated with alpha-synuclein-immunopositive intracytoplasmic inclusions. When lactacystin was administered at a high concentration, the striatum was simultaneously involved, and alpha-synuclein-immunopositive extracytoplasmic granules appeared extensively within the SN pars reticulata (SNpr). In addition, during the retrograde neuron degeneration in SN, the level of heme oxygenase-1 immunopositivity, an oxidative stress marker, was markedly increased in SNpc neurons. These results reveal that intrastriatal proteasome inhibition sufficiently induces retrograde dopaminergic neuronal degeneration with abundant accumulation of alpha-synuclein in the SN.
Acetylcysteine↗
Myoclonic tremulous movements in multiple system atrophy are a form of cortical myoclonus.
We prospectively studied the clinical and electrophysiological features of myoclonic tremulous movements in patients with multiple system atrophy (MSA). Among 42 consecutive patients, 12 MSA-p (parkinsonian type) and 3 MSA-c (cerebellar type) patients showed small-amplitude myoclonic movements. These movements occurred in the distal part of the arms and fingers, particularly in posture or during voluntary movements. We conducted detailed electrophysiological studies in 11 patients. Electromyographic recordings showed irregular bursts of brief duration often synchronously involving the antagonistic muscles. Somatosensory evoked responses were slightly enlarged in some patients. Long-latency reflexes were enhanced in 7 patients. A jerk-locked averaging technique revealed premyoclonic cortical potentials in 9 patients. These findings suggest that small-amplitude myoclonic movements in MSA are a form of cortical myoclonus.
Aged↗
Effect of zonisamide on essential tremor: a pilot crossover study in comparison with arotinolol.
We performed a pilot, crossover trial of zonisamide (ZNS) on essential tremor patients. Patients were randomly selected to start either ZNS or arotinolol treatment for 2 weeks. After a washout period, the patients were switched to an alternative drug. The assessment of tremor was carried out using the Fahn-Tolosa-Marin's clinical rating scale for tremor at baseline and 2 weeks after administration of each drug. There was a significant improvement after ZNS and arotinolol administration compared with the baseline. There was no significant difference in the antitremor effect between ZNS and arotinolol; however, ZNS was more effective for tremors of cranial nerve areas. Although the number of enrolled patients was limited in the present study, this open-label pilot study suggests that ZNS may have a therapeutic potential for essential tremor. A controlled trial of this drug in the future would be valuable.
Adrenergic alpha-Antagonists↗
Increased writing activity in Parkinson's disease: a punding-like behavior?
We report a 32-year-old male patient with early-onset Parkinson's disease who exhibited abnormally increased writing activity. The patient displayed a disabling and pronounced increased writing activity, filling up to 10 pages or more per day in a notebook, and spending more than 12 h writing. In general, there was not much meaning in most of the writing, though there was a particular preference in tabulating the names of various sport and TV personalities. The writing activity gradually diminished following treatment with quetiapine hydrochloride, an anti-psychotic agent, at 25 mg/day. Although the pathophysiological mechanism underlying the increased writing is unclear, we believe it should be regarded as a form of punding or stereotyped behavior that has been suggested to be associated with dopaminergic therapy in Parkinson's disease.
Adult↗
Changes in the incidence of amyotrophic lateral sclerosis in Wakayama, Japan.
In the 1960s, the incidence of amyotrophic lateral sclerosis (ALS) in the Kozagawa and Koza areas in Wakayama prefecture was much higher than that in other areas of the world. However, between 1980 and 1993, a gradual decrease in the incidence of the disease in these areas was reported. To ascertain whether the decreased incidence has persisted, we conducted a retrospective epidemiological study, and determined the average annual incidence of ALS in Wakayama prefecture from 1998 to 2002. The number of ALS cases encountered during the period was 134 (male 79, female 55). The crude average annual incidence in Wakayama prefecture in total was 2.50 (male 3.08, female 1.99) per 100,000. In the Kozagawa and Koza areas in Wakayama prefecture, where the senility rate rapidly increased in recent years, the average annual incidence of ALS in the present research was 10.56 (male 14.14, female 7.66). When the crude rate was standardized for both age and sex to the Japanese population in 1990, the expected value was 5.24 (male 7.34, female 3.18), which was lower than that of our previous survey. The prevalence in Wakayama prefecture at 31 December 2002 was 11.31 (male 14.40, female 8.53). In Kozagawa and Koza areas, the crude prevalence was 52.81 (male 70.70, female 38.28). These results indicated that the incidence of ALS in Wakayama prefecture, especially for females, steadily decreased compared to that in previous reports. However, a high incidence of ALS persisted among males in Wakayama prefecture, especially in the Kozagawa and Koza areas. Some environmental factors and gender specificity may be related to the decreased incidence of ALS in focus areas.
Amyotrophic Lateral Sclerosis↗
Oxidative stress and microglial activation in substantia nigra following striatal MPP+.
The present study aims to study sequential alterations occurring in both dopaminergic neurons and microglia in substantia nigra (SN) following intrastriatal injection of 1-methyl-4-phenylpridium ion (MPP+) in rats. Heme oxygenase-1 (HO-1), a marker of oxidative stress, first appeared in dopaminergic neurons in SN at 1 day post-lesion. Subsequently, microglia in SN exhibited morphological changes indicative of activation. At 7 days post-lesion, those findings increased severity and 7a significant reduction in the number of dopaminergic neurons was observed. The present finding suggests that extensive oxidative stress and secondary-induced neuroinflammation play a relevant role in MPP(+)-induced retrograde dopaminergic neuron degeneration. We hope that this model will be useful in developing a disease modifying therapy of Parkinson's disease.
1-Methyl-4-phenylpyridinium↗
Sensorimotor hemiparesis with secondary cervical dystonia following lateral caudal medullary infarction without signs and symptoms of Wallenberg syndrome.
We report the case of an 84-year-old woman who suddenly developed motor and both superficial and deep sensory hemiparesis on the left side, and cervical dystonia with a head tilt to the right side. A brain MRI showed an infarct in the left lateral caudal medulla. It is clinically important to recognize that the lateral caudal medullary infarction appears without signs and symptoms of lower cranial nerve palsies commonly involved in Wallenberg syndrome.
Aged↗
Cerebellar atrophy in a patient with anorexia nervosa.
UNLABELLED: Reversible cerebral atrophy (pseudoatrophy) is observable in patients with anorexia nervosa. However, it is extremely rare to see marked cerebellar atrophy. OBJECTIVES: We report on a patient who developed cerebellar atrophy after the severe deterioration of cardiac and respiratory functions resulting from undernutririon. RESULTS: 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. DISCUSSION: Because her cerebellar ataxia appeared during severe deterioration of her general condition, and there has been no subsequent progression, it is possible that her cerebellar atrophy was induced by undernutrition.
Adult↗
Stereotyped behaviors or punding after quetiapine administration in Parkinson's disease.
Quetiapine has been suggested to be useful for the treatment of psychosis in patients with Parkinson's disease without prominent deterioration of motor functions. We present two patients with Parkinson's disease in whom administration of quetiapine for drug-induced psychosis caused characteristic stereotyped behaviors or punding. Since stereotyped behaviors are usually associated with excessive dopaminergic activity, it is clinically important to note that stereotyped behaviors or punding may be induced by an atypical antipsychotic drug for the treatment of psychosis in patients with Parkinson's disease.
Aged↗
[A case of spinocerebellar ataxia 6 accompanied with schizophrenia].
An abnormally expanded CAG repeats (25, normal; 4-20) was identified in the alpha 1A voltage-dependent calcium channel (CACNA1A) gene of a 50-year-old Japanese man with 25 years history of schizophrenia. At age 45, he first noted unsteadiness of standing and gait, which gradually worsened subsequently. In addition to the psychiatric symptoms of schizophrenia, neurological examination revealed marked truncal ataxia and mild limb ataxia. Brain magnetic resonance imaging showed atrophy of the cerebellar vermis. Gene analysis confirmed the diagnosis of spinocerebellar ataxia type 6 (SCA 6). No family members showed similar neuropsychiatric symptoms except that the patient's father had been suffering from an unknown dementing disease. Occurrence of both schizophrenia and SCA 6 in the identical patient may be coincidental. However, growing evidence has shown that various mutations in the CACNA1A gene are associated with phenotypic variability, such as progressive ataxia, episodic ataxia, migraine, coma, epilepsy and mental retardation. Therefore, the schizophrenic symptoms, association of which with SCA 6 has previously reported in a few cases, may represent rare clinical features of the channelopathy associated with the mutation in the CACNA1A gene.
Brain↗