Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026837 (muscle rigidity)
 1,077 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to determine the relationship between the presence of extrapyramidal signs and the severity of cognitive and functional impairment in patients with Alzheimer's disease (AD). Eleven university medical centers in the United States and France participated in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) study of extrapyramidal signs in AD. Forty-seven patients with probable AD who had extrapyramidal signs were matched by sex, race, education, and age with 132 probable AD patients without extrapyramidal signs. The main outcome measures were the Clinical Dementia Rating, Blessed Dementia Scale, and the CERAD Neuropsychology Battery (verbal fluency, naming, Mini-Mental State Examination, word list learning, word list recall, savings ratio, word list recognition, and constructional praxis). AD patients with extrapyramidal signs performed more poorly than AD patients without parkinsonism on various neuropsychological tests, even after controlling for the Clinical Dementia Rating and reported duration of cognitive impairment. The severity of the extrapyramidal manifestations was related to the degree of cognitive and functional impairment. Muscular rigidity and bradykinesia were the most frequent extrapyramidal signs associated with AD. Patients with AD associated with extrapyramidal signs have greater cognitive and functional impairment than AD patients without clinical evidence of parkinsonism.
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PMID:The relationship between extrapyramidal signs and cognitive performance in patients with Alzheimer's disease enrolled in the CERAD Study. Consortium to Establish a Registry for Alzheimer's Disease. 922 72

GAIT ARRESTS: They affect the evolution of the disease. This freezing phenomenon which induces falls sometimes constitutes an initial sign. Like the gait initiation failure, freezing can be controlled by sensory stimulation, notably visual inputs, but also by more sustained attention. FALLS ARE MAINLY CONNECTED WITH BOTH POSTURAL INSTABILITY AND RIGIDITY: They are poorly influenced by dopaminergic therapies. The progressive decrease of step width represents a main factor in their occurrence. PRECOCITY OF GAIT DISORDERS IS UNUSUAL IN PARKINSON'S DISEASE: Other parkinsonian syndromes such as progressive supranuclear palsy, multiple system atrophy and vascular parkinsonian syndrome must then be evoked. Their association with a cognitive impairment and abnormal sphincter behaviour infers a diagnosis of normal pressure hydrocephalus. GAIT IMPROVES WITH L-DOPA THERAPY: Speed, step length and duration of the swing phase are increased without change of cadence. Progressive loss of L-dopa efficiency on gait and postural stability contrasts with the persistent effect on tremor, rigidity and bradykinesia; a functional abnormality of nondopaminergic systems can explain these symptoms. In the following stages, gait troubles increased by motor fluctuations and abnormal involuntary movements are less controlled by L-dopa therapy. PHYSICAL THERAPY PLAYS A MAJOR ROLE IN THERAPEUTIC MANAGEMENT: An individual or collective rehabilitation project must be established according to the stage of evolution; the exercises aim to protect postural control and coordination. Visual or sound rhythmic inputs can be employed in the case of gait initiation failure. THE EFFECTS OF FUNCTIONAL NEUROSURGERY ARE IN THE COURSE OF EVALUATION: Thermolesion and chronic electrical stimulation of deep brain structures have opposite effects on gait troubles. Bilateral thalamotomy or pallidotomy are sometimes a source of disequilibrium. Chronic thalamic stimulation does not induce either benefits or adverse effects. On the other hand, stimulation of the internal pallidum improves gait kinematic parameters; improved postural adjustments have also been reported. The effect of subthalamic nucleus stimulation is comparable to that of L-dopa, however the long-term effect remains to be evaluated.
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PMID:[Gait disorders in Parkinson disease. Gait freezing and falls: therapeutic management]. 1128 86

We reported a 74-year-old male case of progressive supranuclear palsy (PSP) who responded to tandospirone citrate, a serotonin receptor (5-HT1A) agonist. The patient manifested postural instability and gait disturbance at 71 years. Additionally, he showed vertical gaze paresis, regidity of the neck, extremities and trunk, bradykinesia and mild cognitive impairment. A brain MRI revealed moderate atrophy of bilateral frontal/temporal lobes and of midbrain tegmentum one year after the onset. The patient had been diagnosed as PSP and treated with L-DOPA. However, L-DOPA therapy showed only transient response for a few months. His symptoms deteriorated gradually, and he became unable to sit, stand up or walk by himself. Tandospirone citrate was additionally administered at 30 mg/day. Rigidity and bradykinesia were remarkably improved in two weeks after the start of tandospirone treatment. He became able to stand up and walk a short distance with supports in four weeks. Cognitive disturbance was also slightly improved. Tandospirone citrate was effective on our case of PSP, especially on rigidity. Our findings suggest that combination of levodopa and tandospirone citrate is a useful therapy for PSP.
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PMID:[A case of progressive supranuclear palsy improved with tandospirone citrate]. 1148 61

The motor and neuropsychological abnormalities in eight Greek patients with Parkinson's disease (PD) carrying the alpha-synuclein gene mutation (G209A) were studied. These patients (five men, three women) belonged to six different families. Their symptoms started between 32-50 years of age (mean +/- SD, 39.7 +/- 7.6 years) and they had a mean disease duration of 5.4 +/- 2.1 years (range, 2-9 years) at the time of examination. Rigidity and bradykinesia predominated both at disease onset as well as in the later stages and rest tremor was relatively uncommon. Neuropsychological assessment showed that one patient was mildly demented while another had impairment in memory, visuoconstructive abilities, and executive function. Depression was present in only one patient. Our findings indicate that genetic forms of parkinsonism share common motor and cognitive characteristics with sporadic PD but raise the possibility that greater cognitive impairment and the relative rarity of tremor may be distinctive features worthy of further investigation.
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PMID:Clinical features of parkinsonian patients with the alpha-synuclein (G209A) mutation. 1221 Aug 94

A 69-year-old woman was admitted to our hospital due to an interval form of carbon monoxide (CO) poisoning one month after acute CO poisoning. On admission, she had disorientation, memory disturbance, apathy, masked face, muscle rigidity, bradykinesia and parkisonian gait. An MRI (FLAIR image) revealed high signal intensity lesions in the bilateral globus pallidus and the white matter of the frontal lobe. Hyperbaric oxygen (HBO) therapy at 2 atmospheres for 60 min was given every day, in addition to citicoline, levodopa/DCI and selegiline hydrochloride. Cognitive disturbance and parkinsonism gradually decreased, and abnormal signals in the bilateral globus pallidus and the cerebral white matter were attenuated after the treatment. Neuropsychiatric abnormalities except for a slight gait disturbance disappeared one and a half month after starting the treatment. In addition to HBO therapy, administration of citicoline, lovodopa and selegiline may be useful in the case of the interval form of CO poisoning.
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PMID:[A case of interval form of carbon monoxide poisoning with a remarkable recovery]. 1598 66

We report the first case of early-onset Parkinson's disease (EOP) with the PTEN-induced kinase 1 (PINK1) gene deletion in 62 years old Japanese female. The symptoms were started with unstable gait at the age 38. Parkinsonian symptoms became apparent in 45 years old. L-Dopa was markedly effective on her parkinsonian symptoms. However, equinovarus foot induced by L-Dopa intake appeared three months prior to the admission. On admission, she presented with mild cognitive impairment, severe depression, marked retropulsion, resting tremor in the left upper limb and mild hyperreflexia in the four limbs. Rigidity was not present. Mutational analysis revealed homozygous deletion from exon 6 to 8 in the PINK1 gene. An ethnic diversity in PINK1 mutation is suggested.
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PMID:[A 62-year-old woman with early-onset Parkinson's disease associated with the PINKi gene deletion]. 1664 30

Parkinson's disease, the most common neurological disorder in the elderly, is characterized by progressive extrapyramidal motor dysfunction including resting tremors, muscle rigidity, hypolocomotion (bradykinesia and akinesia) and postural instability. Various non-motor features are also seen such as cognitive impairments (deficits in learning and memory) and mood disorders (depression and anxiety). While the 5-HT(1A) receptor has long been implicated in the pathogenesis and treatment of anxiety and depression, recent research has revealed new therapeutic roles for 5-HT(1A) receptors in the treatment of Parkinson's disease. These include the modulation of parkinsonian motor symptoms, L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia, cognitive impairments and emesis. Thus, 5-HT(1A) agonists improve the various motor disorders associated with dopaminergic deficits, dyskinesia induced by chronic L-DOPA treatment, mood disturbances (anxiety and depression) and dopamine agonist-induced emesis. In addition, partial 5-HT(1A) agonists are expected to improve cognitive impairment in Parkinson's patients. These findings encourage research into new 5-HT(1A) receptor ligands, which will improve efficacy and/or ameliorate adverse reactions in the treatment of Parkinson's disease.
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PMID:Improving the Treatment of Parkinson's Disease: A Novel Approach by Modulating 5-HT(1A) Receptors. 2342 44

Fibromyalgia syndrome (FM), the most common central sensitivity syndrome (CSS) affecting over 5% of the population, is a disorder of chronic widespread pain accompanied by numerous other symptoms that causes significant functional impairment. The core FM symptom domains can be recalled using the FIBRO mnemonic and include Fatigue and Fog (cognitive dysfunction), Insomnia (difficulties with all aspects of sleep including initiation, maintenance and restorative), Blues (depression and anxiety), Rigidity (stiffness in muscles and joints) and Ow! (widespread pain and tenderness). While typically presenting in middle-aged women, FM can affect both sexes at any age. FM is a syndrome of abnormal central pain processing and increased central sensitivity caused by neurobiological changes that cause dysregulation of mechanisms that normally regulate pain sensation. There are currently three different methods for diagnosing FM; the 1990, 2010 and modified 2010 American College of Rheumatology (ACR) criteria. While disabling, FM symptoms can be managed with a regimen of pharmacologic and nonpharmacologic treatments. Medication types with benefit in treating FM include anticonvulsants, antidepressants, anti-inflammatories, muscle relaxers, tramadol, and stimulants. Beneficial nonpharmacologic therapies include aerobic and resistance exercise, stretching, cognitive behavioral therapy, and education. Effective management requires formulation of an individualized regimen since patients differ widely in symptoms and treatments they find beneficial. Such an individualized regimen should be based on a systematic assessment of problematic symptoms conducted at baseline and each follow-up with treatments modified over time. While challenging, FM symptoms can be effectively managed and patients can lead full, productive lives.
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PMID:Fibromyalgia: the prototypical central sensitivity syndrome. 2608 13

Parkinson's disease (PD) is a common, late-onset neurodegenerative disorder that shows progressive extrapyramidal motor disorders (e.g., bradykinesia, resting tremors, muscle rigidity and postural instability) and various non-motor symptoms (e.g., cognitive impairment, mood disorders, autonomic dysfunction and sleep disorders). While dopaminergic agents such as L-3,4-dihydroxyphenylalanine (L-DOPA) and dopamine D2 agonists are widely used for the treatment of PD, there is still high clinical unmet need for novel medications that overcome the limitations of current therapies. Evidence is now accumulating that the serotonergic nervous system is involved in the pathophysiological basis of PD and can provide benefits in the treatment of PD through its diverse functions. Among 5-HT receptor subtypes, 5-HT1A, 5-HT2, 5-HT3 and 5-HT6 receptors play an important role in modulating extrapyramidal motor disorders. In addition, 5-HT1A, 5-HT2, 5-HT3, 5-HT4 and 5-HT6 receptors are implicated in modulation of cognitive impairment, mood disorders (e.g., depression and anxiety) and/or psychosis, which are frequently observed in patients with PD. Specifically, stimulation of 5-HT1A receptors seems to be effective for multiple PD symptoms including parkinsonism, L-DOPA-induced dyskinesia, cognitive impairment, mood disorders and neurodegeneration of dopamine neurons. Blockade of 5-HT2 receptors is also likely to improve parkinsonism, depressive mood and cognitive impairment. In addition, it was recently demonstrated that 5-HT2A inverse agonists can alleviate PD psychosis. All these findings emphasize the therapeutic roles of the serotonergic system in PD and stimulate new insight into novel treatments by modulating 5-HT1A and 5-HT2 receptors.
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PMID:New insight into the therapeutic role of the serotonergic system in Parkinson's disease. 2645 57

Parkinsonian signs are common in patients with Alzheimer's disease (AD) of mild degree and predict functional decline, but their relationship with gait speed and balance is unclear. The aims of this study were to describe characteristics of patients with parkinsonian signs among 98 patients with AD of mild degree (with no comorbid Parkinson's disease), and to examine associations between parkinsonian signs with gait speed and balance. A cross sectional study at a memory clinic was conducted. Presence of each parkinsonian sign (bradykinesia, rigidity and tremor) was derived from the UPDRS, regular gait speed was recorded over 10m and balance were assessed using the Mini-Balance Evaluation Systems Test (Mini-BESTest). Bradykinesia was present in 30.6% of the sample, rigidity in 13.3% and tremor only in one patient. Patients with bradykinesia were older, had worse cognitive impairment and worse gait and balance performance than those without bradykinesia. More men than women had rigidity. Bradykinesia was significantly associated with mini-BESTest after adjusting for demographic factors (p<0.001, explaining 13.3% of the variance), but was not significantly associated with gait speed. Rigidity was not associated with either gait speed or balance. We conclude that assessment of bradykinesia should be included in examination of balance control in patients with AD of mild degree.
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PMID:The importance of parkinsonian signs for gait and balance in patients with Alzheimer's disease of mild degree. 2915 79


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