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Parkinson's disease is characterised by symptoms and signs which relate to tremor, rigidity and bradykinesis. The signs may be mild in the early stages of the disorder but the diagnosis can be established by careful neurological examination directed at proper evaluation of the essential features. The lack of any specific abnormality on special investigation leaves the responsibility for diagnosis with the clinician.
The present study addressed the question of whether the emergence and severity of levodopa-induced dyskinesia was related to the therapeutic benefits derived from levodopa. Eight PD patients with clinically observed levodopa-induced dyskinesia were studied prior to and for two hours following a single dose of Sinemet (carbidopa/levodopa). Quantitative instrumental procedures were used to assess upper extremity dyskinesia, rigidity and bradykinesia. Results indicated that all patients exhibited significant reduction in their parkinsonism within 45 minutes following treatment. Reduction in bradykinesia, but not rigidity appeared to coincide with the emergence of dyskinesia. There was a significant relationship between severity of dyskinesia and the degree of improvement in movement velocity but not rigidity. Further analyses revealed that this relationship depended largely on the age of the patient. These findings are discussed as they pertain to a unified model of basal ganglia movement disorders which places dyskinesia and bradykinesia at opposite extremes along a continuum.
An extreme syndrome of the trephined after decompressive craniectomy is reported here. The most extensive clinical syndrome observed was established over 4 weeks and consisted of bradypsychia, dysartria, and limb rigidity with equine varus feet predominating on the right. The syndrome was aggravated when the patient was sitting with the sequential appearance over minutes of a typical parkinsonian levodopa-resistant tremor starting on the right side, extending to all four limbs, followed by diplopia resulting from a left abducens nerve palsy followed by a left-sided mydriasis. All signs recovered within 1-2 h after horizontalisation. It was correlated with an orthostatic progressive sinking of the skin flap, MRI and CT scan mesodiencephalic distortion without evidence of parenchymal lesion. Brain stem auditory evoked potential wave III latency increases were observed on the right side on verticalisation of the patient. EEG exploration excluded any epileptic activity. Symptoms were fully recovered within 2 days after cranioplasty was performed. The cranioplasty had to be removed twice due to infection. Bradypsychia, speech fluency, limb rigidity and tremor reappeared within a week after removal of the prosthesis. While waiting for sterilisation of the operative site, the symptoms were successfully prevented by a custom-made transparent suction-cup helmet before completion of cranioplasty.
The influence of the type, duration, severity and levodopa treatment of Parkinson's disease on autonomic involvement has been assessed. The Valsalva manoeuvre, deep breathing, handgrip and orthostatic tests were performed in 50 patients with Parkinson's disease and in a control group of 30 healthy subjects. No attempt was made to classify further patients with parkinsonian features into groups such as the Shy-Drager syndrome or multiple system atrophy. All test results were significantly smaller in patients than in healthy subjects. The diastolic pressure increase during handgrip was significantly smaller in akinetic-rigid than in tremor-akinetic-rigid type patients. The Valsalva ratio and orthostatic test results were significantly smaller in patients with longer duration than in those with shorter duration of disease. All test results except those of the orthostatic test were significantly smaller in patients with the more severe form than in those with the less severe form of disease. Comparing test results of levodopa-treated and -untreated patients no significant differences were found. Our studies in parkinsonian patients suggest that (1) sympathetic impairment is more pronounced in akinetic-rigid than in tremor-akinetic-rigid type patients; (2) sympathetic impairment occurs early, whereas parasympathetic impairment develops later; (3) sympathetic and parasympathetic impairment parallels the severity of disease; (4) orthostatic parameters are more duration-sensitive than severity-sensitive; (5) chronic levodopa treatment does not markedly influence cardiovascular autonomic responses.
Since alpha adrenergic antagonists are known to protect rats from the extrapyramidal effects of reserpine, the purpose of this study was to examine the relative contribution of alpha-2 receptors in modifying the reserpine-induced syndrome. Rats were pretreated with either clonidine, yohimbine, phentolamine, methysergide or SKF-7265. Thirty minutes later they were given reserpine (20 mg/kg) and evaluated using eleven categories of behavioral responses for three hours. Yohimbine, an alpha-2 antagonist, was the most effective agent in protecting against the reserpine effects. Phentolamine and SKF-7265, which block both alpha-1 and alpha-2 receptors, were also effective. Clonidine, an alpha-2 agonist, and methysergide a serotonin antagonist, were not. In all cases the alpha blocking drugs prevented the motor responses but did not alter the autonomic responses induced by reserpine. The results show not only the efficacy of alpha adrenergic antagonists in protecting against reserpine rigidity but more importantly that the blockade of alpha-2 receptors may be the functionally important action. These results are consistent with the view that some descending motor pathways are controlled by an adrenergic mechanism and suggest that alpha-2 receptors are an important component.
A 27 year-old patient developed a progressive neurological multisystem disorder. Initial signs were cerebellar ataxia and dementia, followed by rigidity and oculomotor dysfunction. Myoclonus was not present. MRI showed a marked atrophy of the spinal cord, the cerebellum, and mild (sub)cortical atrophy. CSF contained oligoclonal bands, but no anti-glutamic acid dehydrogenase antibodies. He died 33 months after onset of symptoms. Autopsy revealed widespread neuropathological alterations including perivascular lymphocytic cutting, neuronal cell loss, and micro/astrogliosis the distribution of which corresponded to the changes seen in MRI. The diagnosis of progressive encephalomyelitis with rigidity was pathohistologically confirmed. Brain samples were negative for neurotrophic viruses tested by polymerase chain reaction. A new variant of this rare disorder is described initially presenting with ataxia and dementia, but without myoclonus.
1 (+/-)-10-(3-Dimethylamino-2-methylpropyl)-2-valeroylphenothiazine hydrochloride (M & B 18,706) has been compared with dimethothiazine, chloropromazine, diazepam and baclofen for potency in reducing decerebrate rigidity in the cat and rat and for activity in causing ataxia or sedation.2 When given intravenously M & B 18,706 had seven times the potency of dimethothiazine and one-half the potency of chlorpromazine in reducing the rigidity of the intercollicular decerebrate cat. When administered orally M & B 18,706 and chlorpromazine were equi-potent in reducing rigidity but M & B 18,706 was less effective than chlorpromazine in producing ataxia in this species.3 In the rat, M & B 18,706 had one-quarter the potency of chlorpromazine for reducing decerebrate rigidity but had from 1/20th to 1/200th its potency in tests for sedative or tranquillizing activity.4 M & B 18,706, like dimethothiazine and chlorpromazine, had little effect on the rigidity of ischaemic decerebrate cats and failed to inhibit polysynaptic spinal reflexes.5 M & B 18,706 had intravenous potency comparable to chlorpromazine in reducing the pressor action of noradrenaline in the spinal cat.
CONTEXT: Diagnosis of Parkinson disease (PD) remains challenging. An accurate diagnosis is important because effective symptomatic treatment for PD is available. OBJECTIVE: To systematically review the literature for information on the precision and accuracy of the clinical examination for diagnosing PD. DATA SOURCES: MEDLINE database was searched for all English-language articles related to the diagnosis of PD published from January 1966 through April 2001. The reference lists of all articles retrieved were searched for additional relevant sources. STUDY SELECTION: Studies in which patients presented with 1 or more typical features of PD were included if the final diagnosis was confirmed by a suitable criterion standard and data could be extracted to determine the accuracy of 1 or more symptoms or signs. Variability in descriptions of symptoms and signs made it impossible to combine data across existing studies for most findings. DATA SYNTHESIS: We identified 6 studies that met our criteria. The positive (presence) likelihood ratios (LRs) for tremor as a symptom of PD ranged from 1.3 to 17 (range of negative [absence] LRs, 0.24 to 0.60). Tremor as a sign of PD produced a range of positive LRs from 1.3 to 1.5 (negative LRs, 0.47 to 0.61). Clinical features useful in the diagnosis of PD include a history of the combination of symptoms of rigidity and bradykinesia (positive LR, 4.5; negative LR, 0.12); a history of loss of balance (range of positive LRs, 1.6 to 6.6; range of negative LRs, 0.29 to 0.35), symptoms of micrographia (range of positive LRs, 2.8 to 5.9; range of negative LRs, 0.30 to 0.44), and a history of shuffling gait (range of positive LRs, 3.3 to 15; range of negative LRs, 0.32 to 0.50). Trouble with certain tasks such as turning in bed (positive LR, 13; negative LR, 0.56), opening jars (positive LR, 6.1; negative LR, 0.26), and rising from a chair (range of positive LRs, 1.9 to 5.2; range of negative LRs, 0.39 to 0.58). Useful signs include the glabella tap test (positive LR, 4.5; negative LR, 0.13), difficulty walking heel-to-toe (positive LR, 2.9; negative LR, 0.32), and rigidity (range of positive LRs, 0.53 to 2.8; range of negative LRs, 0.38 to 1.6). Significant selection bias was detected in all studies included for review. CONCLUSIONS: Symptoms of tremor, rigidity, bradykinesia, micrographia, shuffling gait, and difficulty with the tasks of turning in bed, opening jars, and rising from a chair should be carefully reviewed in all patients with suspected PD. The glabella tap and heel-to-toe tests also should be assessed.
Several pathogenic mutations in the leucine-rich repeat kinase 2 (LRRK2; PARK8) gene recently have been identified in familial and sporadic parkinsonism. We screened 435 Norwegian patients diagnosed with Parkinson's disease and 519 control subjects for the presence of 7 LRRK2 mutations. Nine patients from seven families were found to be heterozygote carriers of the LRRK2 6055G>A (G2019S) mutation. Twelve of 28 first-degree relatives also carried the mutation, but only 1 had Parkinson's disease. The clinical features included asymmetric resting tremor, bradykinesia, and rigidity with a good response to levodopa and could not be distinguished from idiopathic Parkinson's disease.
To determine the diagnostic accuracy of Kernig's sign, Brudzinski's sign, and nuchal rigidity for meningitis, 297 adults with suspected meningitis were prospectively evaluated for the presence of these meningeal signs before lumbar puncture was done. Kernig's sign (sensitivity, 5%; likelihood ratio for a positive test result [LR(+)], 0.97), Brudzinski's sign (sensitivity, 5%; LR(+), 0.97), and nuchal rigidity (sensitivity, 30%; LR(+), 0.94) did not accurately discriminate between patients with meningitis (>/=6 white blood cells [WBCs]/mL of cerebrospinal fluid [CSF]) and patients without meningitis. The diagnostic accuracy of these signs was not significantly better in the subsets of patients with moderate meningeal inflammation (>/=100 WBCs/mL of CSF) or microbiological evidence of CSF infection. Only for 4 patients with severe meningeal inflammation (>/=1000 WBCs/mL of CSF) did nuchal rigidity show diagnostic value (sensitivity, 100%; negative predictive value, 100%). In the broad spectrum of adults with suspected meningitis, 3 classic meningeal signs did not have diagnostic value; better bedside diagnostic signs are needed.
Whether or not zopiclone, a new sleep-inducing drug, exerted a similar effect to that of benzodiazepines was examined. The drug inhibited crossed extensor reflexes in chicks and augmented the dorsal root-dorsal root reflexes in rats without affecting the mono- and polysynaptic reflexes. The site of its action was considered to be located in the spinal cord since the effect on the dorsal root reflex was observed also in the spinal rats. Zopiclone selectively reduced the phasic responses of anemic decerebrate rigidity like benzodiazepines in rats. Despite the structural difference from the benzodiazepines, zopiclone dose-dependently inhibited [3H]flunitrazepam binding in rat brain membranes, although the potency was weaker. These results suggested that zopiclone exerts CNS actions via benzodiazepine receptors.
OBJECTIVE: The mixed dopamine D2/D3 receptor agonist pramipexole is effective as monotherapy in early Parkinson's disease and as adjunctive therapy in advanced disease. Clinical trials suggest that the benefits of pramipexole may extend beyond the relief of motor symptoms (akinesia, rigidity and tremor at rest) to amelioration of depressive symptoms in Parkinson's disease. The aim of this study was to confirm the beneficial effects of pramipexole on the core symptoms of Parkinson's disease (with a focus on tremor), as well as to assess its antidepressant activity, during routine clinical practice. The study also aimed to demonstrate the practicability of the Snaith-Hamilton Pleasure Scale (SHAPS-D), the Tremor Impact Scale (TIS) and the Short Parkinson's Evaluation Scale (SPES) under conditions of routine clinical practice. STUDY DESIGN: This was a prospective observational study. PATIENTS: Data for 657 outpatients with Parkinson's disease were collected from German hospitals and specialist practices. The majority of patients were in Hoehn & Yahr stage II or III and were receiving levodopa. METHODS: Pramipexole (Sifrol) was initiated at a dosage of 0.375 mg/day (using a three-times-daily schedule) and titrated upwards, as required, at weekly intervals over a 4-week period to a maximum dosage of 4.5 mg/day (three times daily). Clinical evaluation was performed at baseline, at the end of the titration phase and at the end of maintenance therapy. Patients were assessed via the German questionnaire versions of the physician-assessed SPES, the self-evaluated TIS and the SHAPS-D. Changes in scale scores were evaluated nonparametrically, using the Wilcoxon-matched pairs test. Cronbach's alpha was used as a measure for item consistency. RESULTS: Pramipexole significantly improved SPES subscores for motor symptoms, complications of therapy, psychological status and activities of daily living. Pramipexole also reduced the detrimental effect of tremor on activities of daily living and social interactions, as assessed by patients via the TIS. As indicated by the results of the SHAPS-D questionnaire, pramipexole significantly reduced anhedonia in patients who had associated depression. Internal consistency of SPES subscales was found to be unaltered between the initial evaluation and follow-up. Likewise, internal consistency for TIS and SHAPS-D was demonstrated. Pramipexole was well tolerated and accepted by the vast majority of physicians and patients. CONCLUSION: In addition to ameliorating the core symptoms of akinesia and rigidity in Parkinson's disease, pramipexole improves tremor and depressive symptoms in routine clinical practice. The SPES, TIS and SHAPS-D were found to be useful instruments with validity in this study.
Decerebrate rigidity (DR) in humans results from a midbrain lesion and is manifested by an exaggerated extensor posture of all extremities. It is characterized by shortening and lengthening reactions and can be modified by tonic neck, labyrinthine (Magnus-de Kleijn), and phasic spinal reflexes. These criteria, and not extensor posture alone, reflect the observations of Sherrington and should form the basis of the clinical examination; however, the experimental-anatomical lesion and physiological findings can never be reproduced exactly in humans. "Tonic and cerebellar fits" are not the equivalent of DR, but are forms of muscle spasm that result in an extensor attitude. They are caused by irritation and excitation of the brain stem. The most common cause of DR in humans is trauma. The incidence of DR in head-injured patients may be as high as 40%, resulting in an average mortality rate of 80%; the presence of an extensor posture increases the mortality from 20 to 70%. The surgical removal of an intracranial lesion does not improve the high mortality rate in patients with craniocerebral trauma who are decerebrate. Although the Glasgow coma scale (GCS) does not consider the specific type of central nervous system abnormality caused by trauma, it is an accurate and accepted assessment of outcome after coma lasting longer than 6 hours. DR is a factor in the best motor response of the GCS and should be assigned major importance in the prognosis of comatose head-injured patients.
We investigated the effect of an anticholinergic (biperiden) and a dopamine agonist (apomorphine) on tremor, rigidity, and akinesia in patients with idiopathic Parkinson's disease. In a standardized, crossover study design 17 patients received single-dose challenges of 5 mg biperiden intravenously and a previously determined dose of apomorphine subcutaneously on 2 consecutive days. Resting (RT), postural (PT), and action tremor (AT) were assessed using spectral analysis of accelerometer data, and Unified Parkinson's Disease Rating Scale (UPDRS) scores for rigidity and akinesia were determined before and after administration of the study drug. Both single-dose challenges significantly reduced the amplitude of RT, PT, and AT, but only apomorphine significantly reduced UPDRS scores for rigidity and akinesia. In only one patient was tremor reduced by the dopamine agonist but not by the anticholinergic. We found that anticholinergic and dopaminergic agents are both effective in reducing tremor in IPD, and there was no evidence for a selective anticholinergic responsiveness of parkinsonian tremor. Akinesia and rigidity, on the other hand, were not improved by biperiden. We therefore conclude that dopaminergic substances are as effective as anticholinergics in patients with parkinsonian tremor and additionally improve other parkinsonian signs.
The structural organization and neuronal circuit of the basal ganglia were reviewed, and the neural mechanisms for the clinical syndromes of Parkinson's disease were discussed. Dopamine depletion in parkinsonian patients causes an increase in neuronal activities in the globus pallidus internal segment and the substantia nigra pars reticulata, resulting in an inhibition of neurons in the thalamus and pedunculopontine nucleus, and developing akinesia and rigidity. Distorted integral information processes in the striatum and different involvement patterns of the two pathways of the information flow, the direct and indirect pathways, may cause diversity of the extrapyramidal syndromes in basal ganglia diseases. Also discussed was an instructional role of dopamine in generating a relevant voluntary movement by modulating the striatal neurons.
Extrapyramidal symptoms (EPS) occur more frequently in dementia of the Alzheimer's type (DAT) than in normal aging. Other late-life mental disorders, however, have also been associated with EPS. To examine whether EPS are increased in DAT patients relative to neuropsychiatric control subjects, the authors compared EPS in 127 neuroleptic-free elderly patients diagnosed with either DAT, major depressive disorder (MDD), or a psychotic disorder (SCHIZ/DELUS). They also examined whether depressive or psychotic symptoms were associated with EPS independently of diagnosis. Severity of parkinsonian rigidity was found to be independently associated with DAT. Rank order of rigidity was DAT > MDD > SCHIZ/DELUS. Bradykinesia, although not associated with diagnostic group, was positively correlated with withdrawn depression. These findings suggest that rigidity is associated with DAT independently of any concurrent psychotic or depressive process, whereas bradykinesia does not appear to be specific to DAT among late-life neuropsychiatric illnesses.
We report a patient with probable Parkinson's disease who experienced a temporary worsening of his symptoms and signs after cigarette smoking. Deterioration of tremor, rigidity, and writing disturbance began soon after the inhalation of cigarette smoke and persisted for 15 minutes. Chewing nicotine gum also induced a brief worsening of the patient's symptoms. Aggravation of parkinsonian symptoms after cigarette smoking appeared to be caused by nicotine alone, although the mechanism for this effect remains unclear.
INTRODUCTION: Parkinson's disease is an idiopathic disorder of the extrapyramidal system. It has a worldwide prevalence but data from developing countries is scanty. We describe the clinical spectrum of the disease from Pakistan, a developing country. METHODS: Patients with Parkinson's disease, over a period of 11 years, were identified by ICD-9 coding system of the hospital medical records. Demographical characteristics, clinical features, laboratory investigations and radiological investigations were recorded and analysed. RESULTS: A total of 80 patients were identified. 50 (63 percent) were males and 30 (37 percent) were females. Mean age of onset of the disease was 54 years. 47 (59 percent) patients had onset of illness during the sixth or seventh decade of life. Mean duration of illness at the time of presentation was five years. Rigidity, bradykinesia, tremors, hypomimia, primitive reflexes, difficulty in performing fine work and walking difficulty were the most common clinical features. 52 (65 percent) patients had stage I or II (Hoehn-Yahr staging) disease at the time of presentation. 56 (70 percent) patients had predominantly unilateral symptoms. 15 (19 percent) patients had cognitive impairment. Cognitive decline was more common in the elderly and in patients with disease duration of longer than ten years. CONCLUSION: Parkinson's disease is more common in males. Tremor, rigidity, walking difficulty, bradykinesia and difficulty in performing fine work are the commonest clinical features. Disease severity increases with duration of the disease. Cognitive impairment is not uncommon in these patients and is associated with disease duration and age of onset of the illness.