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Hypokinesia, rigidity, and tremor induced by hypothalamic 6-OHDA lesions in the rat.

Bilateral administration of 6-hydroxydopamine in the medial fore-brain bundle at the level of the posterolateral hypothalamus in rats resulted in hypokinesia, muscular rigidity and tremor as determined by various behavioral assessment procedures. These neurological signs were accompanied by marked decreases in the concentrations of dopamine and its main metabolites dihydroxyphenylacetic acid and homovanillic acid in both striatum and nucleus accumbens. Administration of apomorphine (1 mg/kg) or L-Dopa (60 mg/kg) reversed or totally abolished the hypokinesia, rigidity and tremor in lesioned animals. Together, the present findings demonstrate that bilateral intrahypothalamic administration of 6-OHDA results in the appearance of the three cardinal symptoms of Parkinson's disease in rats. This model should prove to be valuable for both the study of the neuropathological processes underlying the neurological signs of this disease and the screening of potential antiparkinson agents.

3,4-Dihydroxyphenylacetic Acid↗

H reflex behavior in Parkinson's disease patients and patients with extrapyramidal and pyramidal signs combined.

The H reflex was elicited in 21 normal subjects, 48 patients with Parkinson's disease (PD) and 22 patients with pyramidal and extrapyramidal signs combined (PESC). In most normal subjects (90.5%), in 29.2% of PD patients and 54.5% of patient with PESC the threshold for sensory fibers was lower than for motor fibers, and the H reflex was obtained before the M response for all duration stimuli in both legs. In 9.5% of normal subjects, 39.6% of PD patients with mild and moderate rigidity (according to the motor part of UPDRS) and 31.8% of patients with PESC, the threshold for the H reflex and M response was the same or the M response threshold was lower in at least one of the legs for short stimulus duration (0.1-0.2 ms). In 31.2% of PD patients (most of them with severe rigidity) and 13.7% of patients with PESC, the threshold for M response was lower for all stimulus duration in at least one of the legs, and it was obtained before H reflex. These very significant differences in behavior of the H reflex in PD patients (Fisher exact test, p<0.0001) that almost disappear in patients with PESC, could be possibly explained by changes in agonist-antagonist inhibition.

Adult↗

Association between mild parkinsonian signs and mild cognitive impairment in a community.

BACKGROUND: Mild parkinsonian signs (MPS) are associated with prevalent and incident dementia but it is not known whether they are associated with mild cognitive impairment (MCI). OBJECTIVE: To determine whether MPS and specific MPS (changes in axial function, rigidity, tremor) are associated with MCI in nondemented community-dwelling older people in northern Manhattan, NY. METHODS: Participants underwent neurologic assessment, including a modified motor portion of the Unified Parkinson Disease Rating Scale. MCI was diagnosed in nondemented participants who had cognitive impairment based on neuropsychological testing and no functional impairment. Participants with MCI were classified as having MCI with memory impairment (MCI+M) vs MCI without memory impairment (MCI-M). RESULTS: MCI was present in 608 (27.3%) of 2,230 participants, including 255 participants with MCI+M and 353 with MCI-M; 1,622 participants did not have MCI. MPS were present in 369 (16.5%) of 2,230 participants. In a univariate logistic regression model, odds of MCI+M (vs no MCI) were 51% higher in participants with MPS compared to those with no MPS (OR = 1.51, 95% CI = 1.09 to 2.09, p = 0.01). Multivariate models yielded similar results (OR = 1.45, 95% CI = 1.03 to 2.05, p = 0.03). Rigidity was present in a higher proportion of participants with MCI+M compared to participants without MCI. CONCLUSIONS: Mild parkinsonian signs, especially rigidity, are associated with amnestic mild cognitive impairment. Mild parkinsonian signs and mild cognitive impairment may share similar pathogeneses. Whether this involves Alzheimer-type pathology, Lewy bodies, or vascular changes in the basal ganglia or basal ganglia circuitry deserves further investigation in postmortem studies.

Age Factors↗

A compensatory mechanism in unilateral akinetic-rigid syndrome: an fMRI study.

The motor mechanisms of a patient with unilateral hand clumsiness in the early stages of akinetic-rigid syndrome were assessed by functional magnetic resonance imaging (fMRI). Movements of the unaffected hand produced activation in the contralateral sensorimotor cortex (SMC) and ipsilateral SMC and superior parietal lobule (SPL). The affected hand activated the bilateral SMCs, supplementary motor areas, and SPLs. We speculated that the bilateral activation indicated recruitment of a pre-existing bilaterally organized large-scale neural network to perform the motor task.

Aged↗

Posttraumatic akinetic-rigid syndrome resembling Parkinson's disease: a report on three patients.

We describe three patients who developed a rapidly evolving posttraumatic akinetic-rigid syndrome (ARS), the clinical manifestations of which were similar to Parkinson's disease, including response to levodopa. Despite initial imaging studies showing traumatic damage to the substantia nigra, the ARS appeared after a delay of 1-5 months after the injury. We stress the importance of magnetic resonance imaging to illustrate nigral damage in all patients in whom head trauma precedes an ARS.

Adult↗

Milacemide therapy for Parkinson's disease.

The clinical effects of central glutamatergic stimulation by the glycine prodrug milacemide were studied in six patients with Parkinson's disease under double-blind, placebo-controlled conditions. When administered as monotherapy at a single oral dose of 1,200 mg, the drug increased overall parkinsonian severity transiently, mostly due to an effect on rigidity. Milacemide did not, however, alter levodopa-induced dyskinesias. These results support the view that drugs acting on the glutamatergic system can influence motor function in patients with extrapyramidal movement disorders and that pharmaceutical agents that selectively block certain subtypes of glutamate receptors may ameliorate parkinsonian symptoms.

Acetamides↗

Clinical and pharmacological evaluation of the effects of piribedil in patients with parkinsonism.

Nine patients with Parkinsonism were studied before and after treatment with piribedil, a dopamine-receptor stimulator. Piribedil appeared to have a slight anti-Parkinsonism effect upon bradykinesia, and possibly upon tremor, but did not improve rigidity. The chief toxic effects were drowsiness and confusion, and two patients experienced nausea. Changes in homovanillic acid in the cerebrospinal fluid indicated that the drug reduced the turnover of endogenous dopamine. In spite of this definite neuropharmacological action, no clear-cut associated clinical benefit was demonstrated. The significance of these findings is discussed.

Aged↗

Diagnostic assessment of haemorrhagic rash and fever.

AIMS: To establish criteria for early distinction between meningococcal disease and other conditions with similar clinical features, and to identify other causes for haemorrhagic rashes accompanied by fever. METHODS: In a prospective study, 264 infants and children hospitalised with fever and skin haemorrhages were studied. RESULTS: We identified an aetiological agent in 28%: 15% had meningococcal disease, 2% another invasive bacterial infection, 7% enterovirus infection, and 4% adenovirus infection. Five clinical variables distinguished between meningococcal disease and other conditions on admission: (1) skin haemorrhages of characteristic appearance; (2) universal distribution of skin haemorrhages; (3) maximum diameter of one or more skin haemorrhages greater than 2 mm; (4) poor general condition (using a standardised observation scheme); and (5) nuchal rigidity. If any two or more of these clinical variables were present, the probability of identifying a patient with meningococcal disease was 97% and the false positive rate was only 12%. This diagnostic algorithm did not identify children in whom septicaemia was caused by other bacterial species.

Adenovirus Infections, Human↗

Frequency of a specific cytochrome P4502D6B (CYP2D6B) mutant allele in clinically differentiated groups of patients with Parkinson disease.

The frequency of the cytochrome P4502D6B CYP2D6B (29B) mutant allele has been determined in three clinically distinct groups of patients with Parkinson disease. No differences in mutation frequency among the patients with the rigidity-akinetic and monosymptomatic tremor forms has been observed compared to the healthy control group, while in the group with akinetic-rigidity tremor symptoms the frequency of heterozygous wt/29B individuals was significantly increased. Therefore, individuals bearing the CYP2D6B mutation appear to be predisposed to the development of this particular form of Parkinson disease, and the presence of the 29B mutation in the genotype may serve as an additional diagnostic criteriaum for the clinical differentiation of patients with Parkinson disease.

Aged↗

Striatal FP-CIT uptake differs in the subtypes of early Parkinson's disease.

In idiopathic Parkinson's disease (PD), a tremor-dominant type (TDT), an akinetic-rigid type (ART), and a mixed type (MT) are distinguished. We compared cerebral [I-123]FP-CIT SPECT in the PD subtypes (67 patients Hoehn and Yahr stage 1:26 with ART, 19 with MT, 22 with TDT). We measured the ratios putamen/occipital lobe binding and caudate nucleus/occipital lobe binding. Parkinsonian motor symptoms were quantified by UPDRS motor scale. In both putamen and caudate nucleus contralateral to the clinically affected body side TDT patients showed a significantly higher FP-CIT uptake than ART or MT patients (ANOVA; p<0.01). Contralateral putamen and caudate nucleus FP-CIT uptake correlated significantly with severity of rigidity (p<0.01) and hypokinesia (p<0.01) but not with severity of resting or postural tremor (p>0.05). The missing correlation between striatal FP-CIT uptake and tremor suggests, that further systems besides the nigrostriatal dopaminergic system may contribute to generation of parkinsonian tremor.

Adult↗

[Corticobasal degeneration. The significance of clinical criteria for establishing the diagnosis].

Neuropathological studies show that about 20% of all patients suffering from an acinetic-rigid syndrome can not be given the diagnosis of idiopathic Parkinson's disease. Among these non-idiopathic Parkinson-syndromes the corticobasal degeneration (CBD) can be regarded as a separate disease entity. The pathological findings of moderate predominantly frontal and parietal cerebral atrophy, cortical Pick-cells and specific corticobasal inclusion bodies are considered valuable features which support the diagnosis. The clinical Characteristics of CBD are demonstrated in 3 patients including an acinetic-rigid syndrome, limb apraxia and "alien limb"-syndrome, as well as reflex myoclonus. Eye movement disorders, dementia and other rare symptoms may also be present. Electrophysiological reflex-testing helps to corroborate diagnosis. These findings and a summary which includes the previously published cases of CBD show that CBD in most cases can be diagnosed intra vitam.

Aged↗

Individual manifestations of Parkinson's disease after ten or more years of levodopa.

Twenty-five consecutive patients with Parkinson's disease, who had been on levodopa for 10 or more years, were studied. Over the 12.9 years of treatment, the average Northwestern Disability Score had increased from 9.6 to 18.9. By this measure, 24 of 25 patients were worse, and one was unchanged. The progression of disability did not involve all pretreatment parkinsonian features equally in any of the patients studied. Instead a distinctive pattern of deterioration was seen: postural reflexes worsened in 24/25, speech in 24/25, and gait in 22/25. In contrast, rigidity was improved or unchanged in 17/25, tremor was improved or unchanged in 17/17, while handwriting was improved or unchanged in 21/22. Finger dexterity which was improved in 5/25, unchanged in 15/25, and worse in 5/25 which seemed to be between these two extremes. These observations demonstrate that some signs of parkinsonism can remain quite responsive to levodopa for more than 10 years while at the same time other manifestations of the disease are no longer as responsive to this form of treatment.

Gait↗

Association of daytime napping and Parkinsonian signs in Alzheimer's disease.

BACKGROUND AND PURPOSE: Excessive daytime sleepiness (EDS) is reported in Alzheimer's disease (AD), with unstable sleep-wake rhythms that worsen with advancing disease stage. EDS is also very common in Parkinson's disease (PD), regardless of disease severity. The purpose of this study was to determine whether more Parkinsonian motor signs exist in AD patients with more reported daytime napping compared to AD patients without daytime napping. PATIENTS AND METHODS: AD patients ((National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association) NINCDS/ADRDA criteria) were prospectively evaluated in a dementia clinic. Parkinsonian motor signs were assessed using a modified motor Unified Parkinson's Disease Rating Scale (mmUPDRS). AD patients were grouped according to daytime napping frequency: (1) minimal napping (AD-Naps), or (2) napping at least once a day (AD+Naps). Wilcoxon rank-sum tests and chi2-tests computed differences between groups for mmUPDRS, nighttime sleep disturbances, and the Mini Mental State Examination (MMSE). Statistical significance was set at P<0.05. RESULTS: AD patients were classified as AD-Naps (n=155) or AD+Naps (n=180). Compared with AD-Naps patients, AD+Naps patients had higher total mmUPDRS scores (P<0.001), higher rigidity scores (P<0.005), and more gait impairment (P<0.001). CONCLUSION: AD patients with more reported daytime napping had more Parkinsonian motor signs, suggesting that this subgroup may have an increased propensity for sleepiness resembling PD. Longitudinal studies with objective measures are needed to determine whether causal relationships exist between sleepiness and Parkinsonism in AD.

Adult↗

Clinical features and mortality in patients with early-onset Alzheimer's disease.

In a population-based study of 198 patients with probable early-onset Alzheimer's disease (AD), we studied the occurrence of extrapyramidal signs (tremors and rigidity), myoclonus, psychosis and seizures, as well as their predictive value for mortality. The presence of tremors was significantly associated with the presence of rigidity. The occurrence of myoclonus was significantly associated with the occurrence of seizures. Psychosis and seizures in AD patients were not associated with mortality. The occurrence of extrapyramidal signs and myoclonus at any point in time during the course of AD increased the risk of mortality significantly. When evaluating their relative importance, extrapyramidal signs appeared to be the most important predictor of mortality.

Adult↗

[Effects on cognitive function and activities of daily living after stereotactic thalamotomy for Parkinson's disease].

Stereotactic thalamotomy was performed in ten patients with Parkinson's disease for the suppression of their tremor. After VL-thalamotomy, contralateral tremor and rigidity disappeared or was significantly reduced. Activities of daily living (ADL) measured by functional independence measure and Parkinson's disability score were improved postoperatively in all patients. There was significant improvement in anxiety index. However, other neuropsychological tests showed no significant change postoperatively. ADL improved after thalamotomy. It is concluded that stereotactic VL-thalamotomy is a useful treatment which improves ADL without cognitive dysfunction.

Activities of Daily Living↗

[A case of progressive supranuclear palsy showing improvement of rigidity, nuchal dystonia and autonomic failure with trazodone].

A 63-year-old man was admitted to the hospital with a 1,5-year history of progressive dementia, supranuclear ophthalmoplegia, pseudobulbar palsy, rigidity and dystonia in the neck and the upper trunk. Magnetic resonance imagings showed severe atrophy of the frontal lobe and the brainstem. He was diagnosed as having progressive supranuclear palsy (PSP). Rigidity, nuchal dystonia, frequent micturition, and profuse sweating ameliorated after trazodone administration. Furthermore, additional administration of L-dopa and droxidopa improved his pseudobulbar palsy, akinesia, and lack of initiative. Single photon emission tomography using IMP after medication showed increased IMP-uptake in the frontal areas and the basal ganglia compared with that before medication. This patient illustrates a substantial role of impairments in the serotonin system in the production of some PSP symptoms.

Autonomic Nervous System Diseases↗

Long-term effects of bilateral subthalamic nucleus stimulation in advanced Parkinson disease: a four year follow-up study.

In this study we aimed to investigate the effects of bilateral STN HFS in patients with advanced Parkinson disease (PD) at long-term, with a minimum follow-up of 4 years. Twenty patients (15 men, five women) were included, with a mean age of 60.9+/-8.1 years. Surgery was performed under local anesthesia. The target was defined on computerized tomography (CT). At 3 months, significant improvements were found on the total Unified Parkinson disease rating scale (UPDRS) III (motor) score, in the medication. off (from 42.3+/-9.3 to 19.5+/-6.4), as well as the medication on (from 18.6+/-12.1 to 10.1+/-5.9) phase. The UPDRS IVa (dyskinesias) and IVb (motor fluctuations) scores decreased significantly. At long-term follow-up, there were still significant improvements on the total UPDRS III motor score (from 42.3+/-9.3 to 24.2+/-13.2), as well as in all motor subscores, in the off phase, during stimulation. In the on phase, the only significant improvement was seen for rigidity. Complications included hypomania to mania in four patients. Our results indicate that HFS STN results in long-lasting improvement of the motor symptoms, ADL activities and functional performance in patients suffering from advanced PD. The stimulation induced behavioural changes need special consideration.

Activities of Daily Living↗

Neuroleptic malignant-like syndrome after abrupt withdrawal of baclofen.

We present the case of a 36-year-old man who presented with a clinically neuroleptic malignant-like syndrome involving disorientation, signs of autonomic dysfunction, rigidity and raised total creatine kinase level, but in the absence of any neuroleptic medication. He had, however, abruptly stopped taking his long-term baclofen in the days prior to presentation. He improved markedly after the reintroduction of baclofen, and we postulate that his clinical syndrome resulted from the sudden withdrawal of this drug. We concur with the concept that neuroleptic malignant syndrome represents a spectrum of disorders, and add it to the list of possible sequelae after abrupt withdrawal of baclofen.

Adult↗