Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a 65-year-old man with rigid-bradykinetic parkinsonism, vertical gaze palsy, difficulty in eye-lid opening, and marked pseudo-bulbar palsy. He felt difficulty of it, hand movement at 59 years old. When he was 60 years old, monotonous speech and slowness of movement appeared. He visited a neurologist who noted vertical gaze palsy, neck rigidity, and bradykinesia. He was diagnosed as progressive supranuclear palsy (PSP) and given 300 mg L-Dopa/Benserazide by the neurologist. This medication improved his rigidity and bradykinesia. At 62 years of the age, his eye-lids closed involuntary and it was difficult to open. In addition, he began to complain of wearing-off, autonomic symptoms, and dysphagia. Anti-parkinsonian drugs were increased, but his bradykinesia progressed. At 64 years of the age, he was admitted to the Neurology Service of Juntendo Hospital. On admission, he was alert and not demented. No aphasia, apraxia, or agnosia was noted. In the cranial nerves, upward and downward gaze were markedly restricted. His face was hypomimic and seborrhoic. It was difficult to swallow liquid or solid for him. No weakness was noted, but he walked in small steps with freezing and falling tendency to backward. Rigidity was noted on his extremities and stronger on his left side than right. Tremor was absent. Bradykinesia of his body and extremities was marked. No cerebellar ataxia was noted. Deep tendon reflexes were within normal range. Planter response was flexor bilaterally. Myerson's sign was noted. Sensory and autonomic function were normal. He was treated with L-Dopa, Pergolide, and Bromocriptine. However, these medications improved his bradykinesia and gait disturbance only slightly, dysphagia became progressively worse. He developed aspiration pneumonia when he was 65 years old and admitted to Juntendo Hospital. A large amount of sputum was aspirated from his trachea. Two days after from admission, he was found dead on his bed. He was discussed in a neurological CPC and the chief discussant arrived at a conclusion that the patient had progressive supranuclear palsy (PSP). Other differential diagnoses included Parkinson's disease, pallido-nigroluysian atrophy (PNLA), multiple system atrophy (MSA), and corticobasal degeneration(CBD). Many participants considered that PSP or PNLA was most likely. Post-mortem exmination revealed marked nigral neuronal loss and gliosis. The globus pallidus and the luysian body changed mildly. However, the frontal cortex was relatively spared, there were many ballooned neurons in the cortical layer. Other parts were spared. With sliver (Bodian and Gallyas-Braak) and anti-phsphorylated tau stain, abundant astrocytic plaques, neurofibrillary tangles, and argyrophilic threads on the frontal cortex, striatum, and substantia nigra were seen. There was no tufted astrocyte which was hallmark of diagnosis of PSP. In addition, several Lewy bodies were seen in the brainstem. Because astrocyte plaque was considered specific for pathology of CBD, the pathologist revealed that the pathological diagnosis of this patient was CBD. Nevertheless, discussion was focused on the relatively mild degeneration of the frontal cortex for CBD.
 ...
PMID:[A 65-year-old man with rigid-bradykinetic parkinsonism, vertical gaze palsy, difficulty of eye-lid opening, and marked pseudo-bulbar palsy]. 1578 4

Assessment of nonspeech tongue function is common in speech-language pathology. This paper reviews techniques used to determine tongue strength and endurance, and describes a constant-effort task. These techniques are intended to reveal and quantify the presence of weakness or fatigue of the tongue. The consequences of performing these tasks with and without a bite block, used to fix jaw position, are considered. Whether nonspeech tongue impairment is associated with speech dysfunction in Parkinson's disease is another topic of interest. Past studies indicated reduced tongue strength and endurance in Parkinson's disease, but these measures did not correlate with speech measures. It was hypothesized that weakness and fatigue need to be impaired to a "critical" level before speech is perceptibly affected. To examine whether experimentally induced tongue fatigue affects speech, normal speakers performed prolonged strenuous tongue exercise. Speech deteriorated following these exercises. A new investigation examines whether 1 hour of speech-like tongue exercise (rapid syllable repetitions) affects dysarthric speech. Preliminary data from 6 participants with Parkinson's disease, 1 person with bulbar ALS, and 6 neurologically normal control subjects indicate that sentences sound more precise but less natural after the exercises. Surprisingly, results did not differ significantly between the groups. Continued collection of data and refinement of tasks will contribute to our understanding of the potential relationships between weakness, fatigue, and speech.
 ...
PMID:Assessment of tongue weakness and fatigue. 1583 58

We report a 73-year-old woman who had depression, dementia, and parkinsonism. She had postural tremor since her fortics. She was losing her weight since age 66 years. She noted difficulty in walk at age 72 (2001). She could not stand without assistance on July 2001, and she became hypobulic. On admission to our hospital on November 2001, she had dementia and revised Hasegawa dementia scale (HDS-R) was 8/30. She had mild limitation of the upward gaze, and rigidity in the neck, but not in the limbs. Postural tremor was seen. No muscle weakness was noted and tendon reflexes were normal. She was treated with levodopa/carvidopa, but she did not improve. She did not eat much. She was transferred to another hospital and she suddenly died on January 2002. The patient was discussed in a neurological CPC, and a chief discussant arrived at a conclusion that the patient had Parkinson disease with dementia. Some participants thought the diagnosis was progressive supranuclear palsy or diffuse Lewy body disease. The examination at autopsy revealed mild neuronal loss and Lewy bodies in the substantia nigra. Many Lewy bodies were observed in the cerebral cortex which corresponded to the neocortical type of DLB, and Lewy neurites were seen in the CA2 of the hippocampus by immunohistochemistry for alpha-synuclein. Spongy change was seen in the parahippocampus. Pathological diagnosis was diffuse Lewy body disease.
 ...
PMID:[A 73-year-old woman with depression, dementia, and parkinsonism]. 1627 38

Respiratory symptoms are recognized as sequelae of motor dysfunction in idiopathic Parkinson's disease (IPD) and these symptoms have the potential to cause problems with swallow, cough, voice and speech. Specifically, maneuvers that require rapid activation and coordination of upper airway and chest wall musculature become progressively impaired as motor dysfunction progresses during the natural course of the disease. This study reports on the maximum inspiratory and expiratory pressures produced by 28 participants (average age 64) diagnosed with moderate to severe IPD (average stage 2.5 with a range of 2.0-3.0). All measures were collected during the "medication on" state. Outcomes of a specific respiratory muscle strength training technique for improving maximum expiratory pressure are reported for three of the patients in this study. Techniques that focus on strengthening the respiratory muscles in patients with IPD (other than with low load breathing exercises), have not been previously reported. The results of this pilot study demonstrate that respiratory muscle weakness may be an important factor in the respiratory complications in IPD and that respiratory muscle strength training has the potential to improve expiratory muscle strength for this population. This improvement has the potential to positively impact high forced respiratory activities, such as forced breathing maneuvers, swallow, cough and speech functions that require greater magnitude and duration of expiration.
 ...
PMID:Tutorial on maximum inspiratory and expiratory mouth pressures in individuals with idiopathic Parkinson disease (IPD) and the preliminary results of an expiratory muscle strength training program. 1672 Sep 40

Abnormal accumulation of disease-causing protein is a commonly observed characteristic in chronic neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and polyglutamine (polyQ) diseases. A therapeutic approach that could selectively eliminate would be a promising remedy for neurodegenerative disorders. Spinal and bulbar muscular atrophy (SBMA), one of the polyQ diseases, is a late-onset motor neuron disease characterized by proximal muscle atrophy, weakness, contraction fasciculations, and bulbar involvement. The pathogenic gene product is polyQ-expanded androgen receptor (AR), which belongs to the heat shock protein (Hsp) 90 client protein family. 17-Allylamino-17-demethoxygeldanamycin (17-AAG), a novel Hsp90 inhibitor, is a new derivative of geldanamycin that shares its important biological activities but shows less toxicity. 17-AAG is now in phase II clinical trials as a potential anti-cancer agent because of its ability to selectively degrade several oncoproteins. We have recently demonstrated the efficacy and safety of 17-AAG in a mouse model of SBMA. The administration of 17-AAG significantly ameliorated polyQ-mediated motor neuron degeneration by reducing the total amount of mutant AR. 17-AAG accomplished the preferential reduction of mutant AR mainly through Hsp90 chaperone complex formation and subsequent proteasome-dependent degradation. 17-AAG induced Hsp70 and Hsp40 in vivo as previously reported; however, its ability to induce HSPs was limited, suggesting that the HSP induction might support the degradation of mutant protein. The ability of 17-AAG to preferentially degrade mutant protein would be directly applicable to SBMA and other neurodegenerative diseases in which the disease-causing proteins also belong to the Hsp90 client protein family. Our proposed therapeutic approach, modulation of Hsp90 function by 17-AAG treatment, has emerged as a candidate for molecular-targeted therapies for neurodegenerative diseases. This review will consider our research findings and discuss the possibility of a clinical application of 17-AAG to SBMA and other neurodegenerative diseases.
 ...
PMID:Modulation of Hsp90 function in neurodegenerative disorders: a molecular-targeted therapy against disease-causing protein. 1674 51

We investigated the risk of Parkinson's disease (PD) associated with calcium channel blockers (CCBs) and beta-blockers in a population-based case-control study of 206 men and women between ages 35 and 89 with a new diagnosis of idiopathic PD between 1992 and 2002, and 383 controls without PD or other neurodegenerative disorders who were frequency matched on age, sex, duration of GHC enrollment and clinic. The adjusted odds ratio associated with ever use was 0.85 (95% confidence interval [CI]: 0.43, 1.66) for CCBs, and 1.20 (95% CI: 0.71, 2.03) for beta-blockers. We observed no association with PD risk for either class of medication in terms of duration, dose, number of prescriptions or pattern of use. The weakness of these associations and the absence of additional influence of dose or duration of use argue against any causal interpretation.
 ...
PMID:Calcium channel blockers and beta-blockers in relation to Parkinson's disease. 1705 23

Clinical symptoms of the idiopathic Parkinson's syndrome (IPS) are numerous. Clinical experience as well as pharmacological research identified symptoms not responsive to dopaminergic stimulation. These symptoms in particular were the target of rehabilitative therapy approaches. Several of these approaches have been evaluated in prospective studies. In the present paper, these studies and the respective therapeutic interventions were categorized and rated concerning their clinical relevance and their study design supporting a differential therapeutic approach. Symptoms were arranged relating to their clinical relevance and specific therapeutic approaches were described and rated. The rating was based on a novel developed approach to check for clinical relevance. In addition, areas in need of further and more intensive scientific research, as depression, cognitive deficits, and tremor, were identified. On the contrary, conclusive therapeutic approaches were available for the treatment of symptoms like gait and postural disturbances and dysarthria. Some advice for the therapy of muscular weakness, dexterity problems and dysphagia was given, but further studies are warranted in these fields.
 ...
PMID:Clinical relevance of rehabilitation programs for patients with idiopathic Parkinson syndrome. II: Symptom-specific therapeutic approaches. 1705 66

Charcot-Marie-Tooth disease, the most common hereditary motor and sensory neuropathy, is a slowly progressive disorder characterized by diffuse muscle weakness and prominent distal atrophy that predominantly involves the intrinsic muscles of the feet and the peroneal muscles. It results in marked reduction in functional aerobic capacity during exercise and fatigue is commonly reported. To date, no pharmacologic treatment has been shown to be effective for treating fatigue in Charcot-Marie-Tooth. Modafinil is used to treat the symptoms of fatigue and excessive daytime sleepiness in narcolepsy. However, fatigue and subsequent excessive daytime sleepiness secondary to fatigue are common symptoms in many neurologic disorders. Prior reports on patients with myotonic muscular dystrophy, multiple sclerosis, Parkinson's disease, and amyotrophic lateral sclerosis, have shown beneficial effects of modafinil in treating fatigue. We report 4 patients with genetically confirmed Charcot-Marie-Tooth disease who had significant fatigue that was almost completely relieved by modafinil.
 ...
PMID:Modafinil reduces fatigue in Charcot-Marie-Tooth disease type 1A: a case series. 1706 Mar 10

"A propensity to bend the trunk forward" and "the chin is now almost immovably bent down upon the sternum" were described by James Parkinson in patients with Parkinson's disease (PD). The term "dropped head" was first reported in "Gerlier disease" in Switzerland and 'kubisagari' in Japan and since then also reported in myositis, myopathy, myasthenia gravis, amyotrophic lateral sclerosis, neuropathy, and hypothyroidism. Disproportionate antecollis occurs in about half cases of multiple system atrophy (MSA) and is considered dystonic in nature. Dropped head is considered rare in PD, both in advanced and early stages of PD. However, it is known to progress subacutely over a period of several days. In my experience, dropped head is relatively common in PD. The mechanism of dropped head in PD is either dystonia of flexor neck muscles or weakness of extensor neck muscles. The response of dropped head to various anti-parkinsonian medications is rather inconsistent. Levodopa is reported to induce amelioration in some patients while dopamine agonists can cause deterioration. Muscle afferent block with lidocaine and ethanol is reported to be effective, while the effect of botulinum toxin injection into the affected muscles is limited. The effect of stereotaxic neurosurgery on dropped head is controversial. Early diagnosis and prompt treatment is necessary to prevent muscle damage associated with longterm overstretch of extensor neck muscles.
 ...
PMID:Dropped head in Parkinson's disease. 1713 Dec 24

Ethylene glycol and methanol are toxic alcohols commonly found in a variety of commercial products. We report two cases, one associated with ethylene glycol and one with methanol poisoning, which both led to acute hemorrhagic necrosis of the basal ganglia and resulted in acute Parkinson's syndrome. It is unlikely that oxalate crystal deposition is the only mechanism for such basal ganglia necrosis, because similar findings were seen following methanol intoxication. We discuss other possible mechanisms that may contribute towards this unusual neurotoxicity. Both of our patients survived their toxic ingestions, but then developed acute Parkinson's syndrome within 10 days of the ingestion. However, the patient who ingested methanol developed respiratory muscle stiffness/weakness, which responded poorly to anti-Parkinsonian drug therapy. Treatment with carbidopa/levodopa improved cogwheel rigidity and bradykinesia in both patients. We conclude that acute Parkinsonism is one of the lesser-recognized devastating complications of both ethylene glycol and methanol poisoning.
 ...
PMID:Two cases of rapid onset Parkinson's syndrome following toxic ingestion of ethylene glycol and methanol. 1718 9


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>