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PubMed2001

Clinical correlates of action tremor in Parkinson disease.

BACKGROUND: Action tremor is often noted in patients with Parkinson disease (PD), yet the clinical correlates of this type of tremor have been the focus of few studies. It is not clear whether this action tremor is a manifestation of the underlying basal ganglia disease. OBJECTIVE: To determine whether the severity of action tremor in PD is associated with age, age at disease onset, disease duration, levodopa dose, severity of rest tremor, or other motor (ie, bradykinesia, rigidity) and nonmotor manifestations of PD. METHODS: Patients with PD (N = 197) were ascertained as part of a familial aggregation study. All patients underwent a neurological examination. Rest tremor was rated with the Unified Parkinson Disease Rating Scale; and action tremor, with the Washington Heights-Inwood Genetic Study of Essential Tremor Rating Scale. RESULTS: Action tremor was present in 184 (93.4%) of 197 patients. Four patients (2%) met criteria for definite essential tremor. The action tremor score was not associated with age, age at onset, or disease duration. The action tremor score was associated with the rest tremor score (r = 0.37; P<.001), and more strongly with the ipsilateral than contralateral rest tremor score. The association between the action tremor score and the rest tremor score was diminished but still significant (r = 0.21, P<.02) even when we excluded these 63 patients with re-emergent tremor. Neither the action nor the rest tremor score was associated with the bradykinesia or rigidity scores, Hoehn and Yahr scale score, or modified Mini-Mental State Examination score. CONCLUSIONS: Action tremor was associated with rest tremor in PD, suggesting that, at least in part, action tremor is a manifestation of the underlying basal ganglia disease. Neither tremor was associated with other motor and nonmotor manifestations of PD. This in turn suggests that tremor in PD may represent an underlying pathophysiological process different from these other manifestations.

Adult↗

PubMed2000

Progression of parkinsonian signs in Alzheimer's disease.

OBJECTIVE: To describe the progression of parkinsonian signs in persons with AD. BACKGROUND: Parkinsonian signs are common in AD and appear to be related to morbidity and mortality. However, little is known about individual patterns of progression of parkinsonian signs. METHODS: A cohort of 410 people with clinically diagnosed AD underwent annual clinical evaluations over a 4-year period, with over 90% of survivors participating in follow-up. The entire motor portion of the Unified Parkinson's Disease Rating Scale (UPDRS) was administered at each evaluation. Previously established measures of four parkinsonian signs were derived from the UPDRS. Scores ranged from 0 to 100 and represented the percent obtained of the total possible item score. RESULTS: A growth curve approach was used to estimate individual paths of change. Rates of change in bradykinesia (4.5% increase per year), rigidity (6.0% increase per year), and gait disorder/postural reflex impairment (8.9% increase per year) were substantial and positively correlated (median r = 0.69). Change in tremor was minimal, mostly confined to postural tremor, and weakly correlated with change in other signs (median r = 0.16). The rate of progression in each sign was highly variable across individuals and not strongly related to demographic factors or use of neuroleptic medications. CONCLUSIONS: Parkinsonian signs other than tremor progress rapidly in AD but at widely differing rates.

Aged↗

PubMed2001

Subthalamic nucleus stimulation for Parkinson disease: benefits observed in levodopa-intolerant patients.

OBJECT: A blinded evaluation of the effects of subthalamic nucleus (STN) stimulation was performed in levodopa-intolerant patients with Parkinson disease (PD). These patients (Group I, seven patients) were moderately or severely disabled (Hoehn and Yahr Stages III-V during the off period), but were receiving only a small dose of medication (levodopa-equivalent dose [LED] 0-400 mg/day) because they suffered unbearable side effects. The results were analyzed in comparison with those obtained in patients with advanced PD (Group II, seven patients) who were severely disabled (Hoehn and Yahr Stages IV and V during the off period), but were treated with a large dose of medication (500-990 mg/day). METHODS: The patients were evaluated twice at 6 to 8 months after surgery. To determine the actual benefits afforded by STN stimulation to their overall daily activities, the patients were maintained on their medication regimen with optimal doses and schedules. Stimulation was turned off overnight for at least 12 hours. It was turned on in the morning (or remained turned off), and each patient's best and worst scores on the Unified Parkinson's Disease Rating Scale during waking daytime activity were recorded as on- and off-period scores, respectively. The order of assessment with respect to whether stimulation was occurring was determined randomly. The STN stimulation markedly improved daily activity and total motor scores in Group I patients. The percentage time of immobility (Hoehn and Yahr Stages IV and V) became 0% in patients who were intermittently immobile while not receiving stimulation. Improvements were demonstrated in tremor, rigidity. akinesia, and gait subscores. The STN stimulation produced less marked but still noticeable improvements in the daily activity and total motor scores in Group II patients. The percentage time of immobility as well as the LED was reduced in patients who displayed intermittent immobility with pronounced motor fluctuations while not receiving stimulation. Improvements were demonstrated in tremor, rigidity, and dyskinesia subscores in these patients. In contrast, STN stimulation did not improve the overall daily activities at all in patients who had become unresponsive to a tolerable dose of levodopa and were continuously immobile, even though these patients' tremor and rigidity subscores were still improved by stimulation. CONCLUSIONS: Consistent with earlier findings, the great benefit of STN stimulation in levodopa-intolerant patients is that STN stimulation can reduce the level of required levodopa medication. This suggests that STN stimulation could be a therapeutic option for patients with less-advanced PD by allowing levodopa medication to be maintained at as low a dose as possible, and to prevent adverse reactions to the continued use of large-dose levodopa.

Adult↗

PubMed2004

Anomalies of asymmetry of clinical signs in parkinsonism.

Parkinson's disease (PD) is characterized by a minimum of two of three features: tremor, rigidity, and bradykinesia. Asymmetry of these features is often considered to support a diagnosis of PD in contrast to other parkinsonian syndromes. All major manifestations of PD are often more pronounced on the side first manifesting features of PD. Significant dissociation of features on the contralateral side, along with other variants of presentation involving the contralateral side, are rarely observed. To determine the frequency and significance of unusual asymmetry in parkinsonism, we retrospectively examined 613 patients clinically diagnosed as idiopathic PD for presence of unusual asymmetries of clinical features. Three groups of patients with unusual asymmetrical clinical findings were identified. Group 1 comprised 10 patients followed for an average of 6 years presenting with rest tremor most prominent in one lower limb and contralateral upper limb. Group 2 comprised 24 patients followed for an average of 5.5 years with action tremor most prominent on the side contralateral to the side of most prominent rest tremor. Group 3 comprised 33 patients followed for an average of 10 years who had parkinsonian signs of greatest severity on one side but subsequently, over an average of 5.4 years, became gradually more prominent on the opposite side. In Group 3, 15 of 33 patients (45%) demonstrated evolution to a rigid form of parkinsonism with disappearance of rest tremor over an average of 7.1 years after presentation. A small percentage (11%) of Parkinson's patients in our clinic demonstrated anomalous asymmetrical clinical findings, which indicates that (1) the disease process may begin in different topographic sites on each side; (2) rest tremor and action tremor may have different anatomical bases; (3) the disease process may progress at different rates on different sides; and (4) tremor becomes less pronounced with progression of disease in some patients with Parkinsonism.

Activities of Daily Living↗

PubMed1993

Neurochemical substrates of rigidity and chorea in Huntington's disease.

Huntington's disease is a progressive degenerative neurological disorder which produces a characteristic movement disorder termed chorea. Although chorea is associated with dysfunction of the basal ganglia, the underlying mechanisms by which dyskinesias such as chorea are produced, are poorly understood. Recent studies in primates have led to experimental models of chorea with postulated involvement of specific neural pathways. In the present study we attempted to determine the validity of the experimental models by measuring concentrations of gamma-aminobutyric acid (GABA), glutamate, substance P and met-enkephalin in the basal ganglia of Huntington's disease patients who manifested either chorea or rigidity/bradykinesia within 6 months of death. We also characterized changes in the Huntington's disease patients according to pathological grade, since this may be a confounding factor. We analysed post-mortem brain tissue from 12 controls, and 11 grade 3 and 12 grade 4 Huntington's disease patients. The grade 3 and 4 cases consisted of eight adult-onset choreic, nine adult-onset rigid and six juvenile-onset rigid patients. We also analysed the putamen and globus pallidus from 11 grade 2 adult onset choreic Huntington's disease patients. A model of chorea based on experimental studies in primates proposes that a loss of striatal GABAergic inhibitory projections to the globus pallidus externa leads to increased activity of the inhibitory globus pallidus externa GABAergic neurons which project to the subthalamic nucleus. It is believed that the loss of GABAergic inputs to the globus pallidus externa precedes a loss of GABAergic input to the globus pallidus interna, which occurs later in the disease and is associated with the development of rigidity and bradykinesia. In the choreic Huntington's disease patients whom we studied, there was a greater loss of GABA in the globus pallidus externa than in the globus pallidus interna, and the globus pallidus interna: globus pallidus externa GABA ratio was significantly increased compared with rigid patients. There were also increases in GABA in the subthalamic nucleus in the choreic patients, although this did not reach significance. A differential loss of met-enkephalin in the globus pallidus externa compared with substance P loss in the globus pallidus interna was not observed in either the choreic patients with advanced disease or the grade II patients. There was a significant increase in GABA concentrations in the ventroanterior nucleus of the thalamus in the choreic patients compared with rigid/bradykinetic patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1996

Time course of physical and psychological responses to selegiline monotherapy in newly diagnosed, idiopathic parkinsonism.

RATIONALE: Poor specificity of face-value endpoints and the poor sensitivity of gross clinical examination may have militated against demonstrating prophylaxis by selegiline. METHODS: Objective measures of the four cardinal signs were used as primary outcome criteria in a randomised, double-blind, placebo-controlled, parallel group study of selegiline monotherapy in 25 newly diagnosed elderly sufferers from idiopathic parkinsonism, stratified for sex and Hoehn and Yahr functional staging. RESULTS: There was a significant interaction between time and nature of treatment with respect to rigidity. The effect of time during active treatment was highly significant: rigidity decreased by 1.3% per week. The worsening of rigidity on placebo was not statistically significant. Neuronal rescue is a possible explanation for the long term, progressive improvement produced by selegiline. No significant treatment effect was seen on the other cardinal signs. However, there was a significant quadratic time trend for arousal on active treatment suggesting tolerance to this effect. CONCLUSION: The difference in time course between the psychostimulant and physical effects suggests more than one mode of action.

Aged↗

PubMed1998

Progressive pseudobulbar paresis, early choreiform movements, and later rigidity: appearance in two sets of dizygotic twins in the same family.

In a family with two sets of dizygotic twins, three, possibly all four, siblings were affected by the same disorder. The parents were unrelated and the illness seemed limited to one generation. Onset was in the early to mid-20s with tics and choreiform movements, dysarthria, and dysphagia. Two twins had epilepsy. There was a marked dyscoordination of bulbar musculature reminiscent of pseudobulbar paresis. Involuntary movements were prominent during the first years, but then disappeared and were replaced by an akinetic-rigid parkinsonian appearance in the late stage. The intellect remained largely intact. Tendon reflexes were reduced. Varying degrees of peripheral nerve changes were seen. Two patients died after 22-24 years from causes indirectly related to the main illness. Marked degenerative changes were found in the caudate nucleus and putamen. Acanthocytes in significant numbers could not be detected in peripheral blood. Lipoproteinelectrophoresis was normal. Creatine kinase levels were moderately raised in one patient, normal in the others. Although certain clinical resemblances exist with neuroacanthocytosis, the exact nosologic status of the disorder has not been determined.

Adult↗

PubMed2002

[Muscarinic receptors of the neostriatum -- important targets of regulation of instrumental movement and posture].

Chronic experiments with 10 dogs were conducted to study effects of bilateral microinjections of the nonselective agonist of the muscarinic receptors carbachol, nonselective blocker of the muscarinic receptors scopolamine and selective blocker M1 of the muscarinic receptors pyrensepine on the instrumental defensive reflex in the neostriatum to sustain a given flexion amplitude and posture adjustment. Microinjections of carbachol were found to increase tone and stem the phase of the reflex, make posture adjustment more orderly and amplitudinous. Repeated microinjections gave the instrumental movement a ramp-like form. Chronic carbachol microinjections (over several years) resulted in akinesis and rigidity in dogs. However, these led to impairment of the diagonal pattern of posture adjustment as in pathologic so in normal dogs. These developments were partially meliorated by dopamine, scopolamine and pyrensepine which sharply increased the phase component of the instrumental movement. These findings are interpreted in the light of the concept of two neostriatum efferent outputs with opposite effects on respective targets and the muscarinic and dopamine receptors as their triggers and blockers. Results of the experiment bring to the conclusion that activation or blockage of the muscarinic receptors in the neostriatum can modify an existing motor behavior and compensate motor pathology in dogs.

Animals↗

PubMed1989

Juvenile parkinsonism with marked diurnal fluctuation.

We presented a report on four cases of juvenile parkinsonism with a marked diurnal fluctuation of symptoms and dystonia. Among parkinsonian signs, rigidity fluctuated the most and increasing rigidity by passive or active movements or emotional stress was observed. When we analyzed patients previously reported, in addition to our own new patients, apart from the diurnal fluctuation and predominant occurrence in females, many similarities to Yokochi's third group of juvenile parkinsonism were found. In the previous reports, the patients with the marked fluctuation of parkinsonian symptoms have not always shown dystonia. The changes of symptoms in relation to menstruation and pregnancy were other characteristic features in our three female patients. Here we proposed that for the present, it is preferable to call this disorder "juvenile parkinsonism with a marked diurnal fluctuation."

Adult↗

PubMed1983

Hyperekplexia.

Hyperekplexia is a hereditary neurologic disorder manifested by an exaggerated startle response, generalized muscular rigidity, and prominent nocturnal myoclonus. The distinctive features of this syndrome constitute an unusual clinical entity that is easily mistaken for other disorders. The study of a family provided additional data on various aspects of this condition. The proband was 3 months old when he was referred for persistent generalized stiffness since birth; this stiffness was associated with an exaggerated startle response and intermittent apnea. Similar symptoms in infancy and prominent nocturnal myoclonus with an excessive startle response in adulthood were described in other family members for five generations. Various features of the disorder indicate a relationship to the syndrome of the "jumping Frenchmen of Maine," latah, miryachit, and other unusual startle reactions.

Humans↗

PubMed2006

Neonatal rigid-akinetic syndrome and dentato-olivary dysplasia.

This report describes a male infant who presented since birth with rigidity and hypokinesia. Severe developmental delay, episodic central hypoventilation, and drug-resistant epilepsy progressively added to the extrapyramidal signs in the following months and led to the patient's death at 10 months of age. Neuroradiologic and neurometabolic evaluations were negative. Normal cerebrospinal metabolites excluded a defect in dopamine metabolism, and treatment with levodopa failed to improve his motor symptoms. Neuropathologic findings demonstrated dentato-olivary dysplasia. While isolated dentato-olivary dysplasia has been described in a few cases of Ohtahara syndrome, to our knowledge, the association with infantile parkinsonism has not been previously reported.

Cerebellar Nuclei↗

PubMed1980

[Syndrome of femorolumbar extension rigidity].

Under observation there were 43 patients aged 10 to 22 years and showing the syndrome of femorolumbar extension rigidity. On surgical verification it was found that 5 pateints had productive epiduritis, 20 protrusions and prolapses of the discs complicated with productive epiduritis in the lumbar division of the vertebral column; 11 had tumours in the lumbar, 3 in the thoracic, 3 in the cervical divisions of the vertebral column. The syndrome was frequently accompanied by dysplasia of the lumbar division. This syndrome is similar to meningeal contractures; it manifests in reflectory disturbances of the extensor tone, and can be classed with traction syndromes. An adequate treatment method consists in surgical mobilization of the spinal cord, its radicles, and the dural sac.

Adolescent↗

PubMed1997

Dose comparison of remifentanil and alfentanil for loss of consciousness.

BACKGROUND: This study evaluated the efficacy and safety of remifentanil, a potent mu agonist opioid with a rapid onset and offset of effect, as a sole induction agent for loss of consciousness (LOC) and compared it with alfentanil. METHODS: Remifentanil and alfentanil were administered intravenously over 2 min in ascending doses (remifentanil 2, 3, 4, 5, 6, 8, 10, 15, 20 microg/kg; alfentanil 40, 60, 80, 100, 120, 160, 200 microg/kg) to unpremedicated healthy patients. Patients were observed for rigidity and LOC for 30 s after the end of infusion. If patients had not lost consciousness, 2 mg x kg(-1) x min(-1) thiopental was administered until LOC was achieved. Arterial blood samples, obtained at specified time intervals, were analyzed for remifentanil and alfentanil whole-blood concentration. Blood pressure and heart rate were also recorded at preset time intervals. RESULTS: Neither drug could reliably produce LOC. With both drugs, there was a dose-dependent decrease in thiopental requirements and a dose-dependent increase in the incidence and severity of rigidity (P < 0.05). The median effective dose (ED50) for LOC with remifentanil was 12 microg/kg, and for alfentanil it was 176 mcrog/kg. The median effective concentration (EC50; whole-blood concentration) of remifentanil was 53.8 ng/ml and for alfentanil it was 1,012 ng/ml. Minimal hemodynamic changes were observed after either drug was given. CONCLUSIONS: Remifentanil is 15 times more potent than alfentanil, based on the ED50 to achieve loss of response to a verbal command and 20 times more potent than alfentanil based on the EC50. Neither opioid is suitable as a sole induction agent.

Adult↗

PubMed2003

How do parkinsonian signs return after discontinuation of subthalamic DBS?

OBJECTIVE: To study the reappearance of the clinical signs of PD when subthalamic nucleus (STN) deep brain stimulation (DBS) was turned off. METHOD: The authors studied 35 patients treated with STN DBS 6.7 +/- 3.3 months (mean +/- SD) after implantation. All were clinically improved. Twenty-four had not required any antiparkinsonian medication for many months and 11 were in "practically defined off" conditions when studied. Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were assessed at baseline and 5, 15, 30, 60, 90, 120, 150, 180, and 240 minutes after switching off STN DBS. RESULTS: A sequential pattern of return of parkinsonian signs was observed, with a fast worsening of tremor within minutes, followed by a smoother, slower worsening of bradykinesia and rigidity over half an hour to an hour, and finally a slow and steady worsening of axial signs over 3 to 4 hours. Ninety percent of the UPDRS motor score worsening was reached after 2 hours. When switching STN DBS "on" again, all motor UPDRS subscores improved with a similar pattern, but faster than their rate of worsening, especially for axial signs. CONCLUSIONS: STN DBS may act by different mechanisms on the four major parkinsonian signs. At least 3 hours off STN DBS is needed to estimate the clinical effect of stimulation.

Disease Progression↗

PubMedDate not supplied

Should levodopa therapy for Parkinson's disease be started early or late? Clinical course of the major tetrad in 122 parkinsonian patients treated with levodopa over 14 years.

The study was carried out to clarify whether levodopa should be started early or late in the course of Parkinson's disease. In this study, 122 patients treated with levodopa over 14 years were included. The time course of each of the four major signs (rigidity, static tremor, akinesia and postural instability) and Yahr stage was investigated in three groups, Yahr stage I/II group, Yahr stage III group and Yahr stage IV/V group, taking into consideration the time period preceding the initiation of levodopa therapy. When the time periods in years since onset of symptoms were matched, no significant differences were recognized among the three groups. There seemed to be no benefit in delaying levodopa therapy but, rather, levodopa therapy should be started as early as possible. The declining efficacy often recognized during levodopa therapy was thought probably due to progression of Parkinson's disease itself rather than to levodopa.

Drug Administration Schedule↗

PubMed2006

[Posttraumatic meningitis: incidence, bacteriology, and outcomes].

BACKGROUND AND PURPOSE: The aim of our study was to search for the incidence, the responsible organisms and the favoring causes of death of post-traumatic meningitis (PTM). METHODS: This retrospective study was conducted over a seven-year period (January 1st, 1996 - December 31, 2002) in the ICU and the neurosurgery department of the Habib-Bourguiba University Hospital, Sfax, Tunisia. RESULTS: Over the study period, 38 patients presented PTM (0.96% of patients hospitalized for head injury), 92% of them had received antibiotic prophylaxis on admission. Mean time between head injury and the diagnosis of PTM was 9+/- 8 days (range: 2-34 days). The most common isolated organisms were multidrug resistant A. baumanii, and K. pneumoniae and reduced susceptibility S. pneumoniae. Factors predictive of prognosis in the 14 days following the diagnosis of meningitis were Glasgow coma score (GCS) on the day of diagnosis of PTM, absence of nuchal rigidity, CSF protein, CSF/blood glucose ratio, and S. pneumoniae as the causal agent of PTM. CONCLUSIONS: Antibioprophylaxis in patients with head trauma must be avoided to prevent the emergence of multidrug resistant bacteria when PTM occurs. GCS on the day of diagnosis of PTM, CSF protein concentration, CSF/blood glucose ratio, and S. pneumoniae as the causal agent of PTM are predictive factors of mortality of patients with PTM.

Adolescent↗

PubMedDate not supplied

Progressive supranuclear palsy: report of two cases (author's transl).

Two cases of progressive supranuclear palsy (PSP) are reported in two men (49 and 75years old) who for one and four years respectively had sudden falling while walking. Rigidity of the neck was an carly feature that prgressed to involve the upper trunk while "subcortical dementia", dysarthria and dysphagia appeared. They had a complete paralysis of vertical eye movements and slow horizontal voluntary eye movements. Oculocephalic reflexes were intact. On caloric stimulation vestibulo-ocular responses were present but only slow saccadic eye movements were observed. With surface electrodes eye movements were studied during the REM phase of sleep. Our patients had both vertical and horizontal eye movements during paradoxal sleep. This findings is in keeping with a supranuclear ophtalmoplegia, and may help in antemorten diagnosis of PSP.

Aged↗

PubMed1994

Persistent neuroleptic-induced rigidity and dystonia in AIDS dementia complex: a clinico-pathological case report.

Patients with AIDS dementia complex (ADC) appear to have an increased likelihood of developing acute onset parkinsonism and dystonia when treated with dopamine antagonists. It has been hypothesized, based on clinical evidence, that hypersensitivity to these drugs in ADC is probably related to direct invasion of the basal ganglia by the HIV virus and a secondary alteration in dopaminergic mechanisms. We report the first pathological description of a patient with ADC who developed acute onset, generalized rigidity and dystonia after a brief trial of low dose neuroleptic therapy administered for psychotic symptoms. An unusual clinical feature of this case was the persistence of his movement disorder. Pathological examination revealed a generalized encephalitic process with substantial neuronal loss observed primarily in the medial and lateral globus pallidus. Correlation with a current model of basal ganglia pathophysiology and other disorders with pallidal lesions is discussed. Clinical and pathological features of this case confirm the previous contention and indicate that dopamine antagonists should be utilized with extreme caution in patients with ADC.

AIDS Dementia Complex↗