Amantadine in advanced Parkinson's disease: good use of an old drug.
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Biomedical subjects
C H Adler
Publications and source records attributed to C H Adler.
Stability of reach-to-grasp movement patterns in Parkinson's disease.
The performance of patients with Parkinson's disease on two reach-to-grasp tasks was compared with that of age-matched control subjects. The aim of the study was to determine whether Parkinson's disease patients have problems coordinating concurrently executed tasks within the same system of effectors in a natural context and whether such problems would be exacerbated by increases in task difficulty. We examined how subjects concurrently executed the transport and grasp components of reach-to-grasp movements in the presence of two types of change in task demands: (i) increases in demands for accurate digit pad placement and (ii) use of two reach-to-grasp tasks, i.e. the standard unimanual task and a bimanual task which increased the control and coordination demands relative to the unimanual task. If Parkinson's disease patients have coordination problems they should demonstrate increased impairment with increasing accuracy demands and in the bimanual task; any such differences should be absent or much smaller in the control group. The Parkinson's disease group showed substantial impairments in all conditions, moving about 30% slower than the control group, with much increased jerking and with signs of difficulty controlling the speed of movement. However, there were no consistent indications that the Parkinson's disease group were differentially impaired on the bimanual task nor that movement deficits increased with increasing accuracy requirements. Grasp and transport components were coordinated similarly by Parkinson's disease and control groups in both reach-to-grasp tasks, and the Parkinson's disease group co-ordinated the two limbs in the bimanual task effectively and in a fashion similar to that of the control group. These results are interpreted to mean that higher levels (effector-independent levels) of motor programming are preserved in Parkinson's disease and that execution of a motor programme need not be compromised by increasing the number of muscle-/joint-level degrees of freedom which are used.
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Treatment of restless legs syndrome with gabapentin.
Gabapentin is a well tolerated anticonvulsant, structurally related to gamma-aminobutyric acid, with an unknown mechanism of action. Restless legs syndrome (RLS) is a disorder characterized by sensory and motor symptoms in the legs that is best treated with dopaminergic drugs and opiates. In this open-label study, eight patients with RLS were treated with gabapentin. Four of the eight had a beneficial response, three with almost complete resolution of symptoms for up to 6 months. For a disorder that is often difficult to treat, these results are encouraging, and they suggest that a placebo-controlled trial is warranted.
Acetates↗
Female predominance in spasmodic dysphonia.
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Adult↗
Tolcapone improves motor function and reduces levodopa requirement in patients with Parkinson's disease experiencing motor fluctuations: a multicenter, double-blind, randomized, placebo-controlled trial. Tolcapone Fluctuator Study Group I.
Tolcapone is a potent catechol-O-methyltransferase inhibitor that prolongs the plasma half-life of levodopa. This multicenter, double-blind, placebo-controlled study used two 10-hour clinical evaluations to compare the efficacy and safety of three doses of tolcapone (50, 200, and 400 mg tid) with placebo in patients with Parkinson's disease (PD) experiencing motor fluctuations from levodopa/carbidopa. One hundred fifty-one patients completed the study. Clinical evaluations lasting 10 hours were performed on day -1 and day 42 using United Parkinson's Disease Rating Scale motor subscale and "on/off" and dyskinesia assessments every 30 minutes. Tolcapone significantly reduced "off" time an average of 40% and increased total "on" time by about 25% at all dose levels, as compared to placebo treatment. Levodopa/carbidopa dosage and frequency were significantly reduced. Tolcapone was well tolerated, with patients experiencing typical dopaminergic side effects that could be reduced or eliminated by lowering levodopa/carbidopa dosages. Tolcapone was effective at prolonging the clinical benefit of levodopa and reducing total levodopa requirements in PD patients with motor fluctuations.
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Ropinirole for the treatment of early Parkinson's disease. The Ropinirole Study Group.
A prospective, randomized, placebo-controlled, double-blind, parallel-group, 6-month study assessed the efficacy and safety of ropinirole, a nonergoline D2-dopamine agonist, in patients with early Parkinson's disease (n = 241; Hoehn & Yahr stages I to III) with limited or no prior dopaminergic therapy. Patients (mean age, 62.8 years), stratified by concomitant use of selegiline, were randomized to ropinirole (n = 116) or placebo (n = 125). The starting dose of ropinirole was 0.25 mg tid with titration to at least 1.5 mg tid (maximum dose, 8 mg tid). Primary efficacy endpoint was the percentage improvement in Unified Parkinson's Disease Rating Scale (UPDRS) motor score. Ropinirole-treated patients had a significantly greater percentage improvement in UPDRS motor score than patients who received placebo (+24% vs -3%; p < 0.001). Ropinirole was well tolerated and patient withdrawals were infrequent. Most adverse experiences were related to peripheral dopaminergic activity. Ropinirole monotherapy is an effective and well-tolerated therapeutic option for treatment of early Parkinson's disease.
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Unilateral pallidotomy for Parkinson's disease: comparison of outcome in younger versus elderly patients.
We studied the effects of medial pallidotomy in the first 20 consecutive patients with Parkinson's disease (PD) undergoing this MRI/electrophysiologically guided procedure at our institution. The mean age of patients was 65.5 years (median 66.5) and none suffered any serious complications. Pallidotomy significantly improved motor function in both "on" and "off" states as measured by Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and timed tests (Purdue pegboard and counter tapping) in the arm contralateral to surgery 3 months postoperatively. Patients also improved in terms of activities of daily living, reflected by improved UPDRS activity of daily living and complications of therapy scoring and reduced levodopa-induced dyskinesias; six of 11 patients who could not walk in an "off" state prior to surgery could do so postoperatively. The total UPDRS score improved by 22% from preoperative values. The aforementioned improvements occurred similarly in patients greater than (n = 11) or less than 65 years (n = 9) at surgery. Neuropsychological measures indicated that although the majority of cognitive function remains unchanged in right-handed PD patients following dominant (left) hemisphere pallidotomy, mild specific declines in word generation are present. The findings of this study suggest that unilateral pallidotomy is safe and associated with improved motor functioning in elderly as well as younger PD patients experiencing significant disability despite optimal medical therapy.
Adult↗
Perioperative use of botulinum toxin for movement disorder-induced cervical spine disease.
Patients with cervical dystonia or tics of the nuchal muscles can develop serious cervical spine disease. We report a series of four patients who received botulinum toxin injections to control their movement disorders prior to their required surgery. One patient with cervical tic-induced radiculomyelopathy required botulinum toxin injection postoperatively to facilitate stabilization of the cervical fusion. Two patients with torticollis-induced cervical radiculomyelopathy, and one patient with dystonia-induced C5 fracture, had botulinum toxin injected preoperatively to facilitate postoperative recovery. Botulinum toxin appears to be a useful adjunct in the treatment of cervical movement disorders prior to or following surgery for associated cervical spine disease.
Adult↗
Lesch-Nyhan variant: dystonia, ataxia, near-normal intelligence, and no self-mutilation.
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Adult↗
Adjunctive cabergoline therapy of Parkinson's disease: comparison with placebo and assessment of dose responses and duration of effect.
Adjunctive cabergoline or placebo, in doses up to 5 mg daily, were administered to Parkinson's disease patients with short-duration levodopa responses in a 6-month double-blind trial. The 13 patients randomized to cabergoline and completing the study had significantly improved Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and timed hand-tapping test scores. Serial measurements on test days documented improved scores: (a) before the first levodopa (and cabergoline) dose of the day, (b) at the time of the peak levodopa effect, and (c) at the end of the levodopa response cycle, 5 h after test doses. Continued testing verified that these therapeutic responses were sustained for at least 48 h after the last cabergoline dose. Patients randomized to placebo failed to improve on any of these measures. In a subsequent open-label dose-escalation phase, further improvement was documented as the dosage was gradually raised to 10 mg daily. As in the double-blind phase, levodopa reduction allowed the improvement to occur in the absence of significantly increased dyskinesias. Other side effects were more substantial with higher doses, however, including two of 11 patients with hallucinations and confusion. In summary, adjunctive single-daily-dose cabergoline therapy resulted in long-lasting, dose-related improvement in parkinsonism not seen in patients receiving placebo.
Adult↗
Multicenter, placebo-controlled trial of cabergoline taken once daily in the treatment of Parkinson's disease.
Cabergoline is a dopaminergic agonist relatively specific for the D2 receptor and much longer-acting than other dopamine agonists. We conducted a randomized, placebo-controlled, double-blind study of cabergoline in 188 levodopa/carbidopa-treated patients with suboptimally controlled Parkinson's disease (PD). The cabergoline patients had significantly better Activities of Daily Living (p = 0.032) and Motor Examination (p = 0.031) scores at the conclusion of the trial compared with the placebo group. The daily levodopa dose for the cabergoline patients decreased 18% compared with a 3% reduction for the placebo group (p < 0.001). The amount of time in the "on" state increased more in the cabergoline group (p = 0.022). The side-effect was similar to that seen with other dopamine agonists, and cabergoline was generally well tolerated. We conclude that cabergoline is an effective adjunct to levodopa for the treatment of PD.
Activities of Daily Living↗
Cerebellar ataxia, dystonia, and tremor within a family: variable phenotypes of a single genetic disorder?
We report a non-Jewish, Anglo-Saxon, American family, in which one sibling has dystonia, a second has cerebellar ataxia, and a third has a combination of dystonia and ataxia. All three siblings have pyramidal signs. Their mother and maternal uncle have tremor, and their maternal grandmother may have had a neurodegenerative disorder. Although the inheritance pattern is uncertain, this may represent phenotypic variability resulting from a single gene mutation. The multiple phenotypes within this family do not fit any known inherited neurodegenerative or metabolic disorder.
Adult↗
Treatable gait disorder and polyneuropathy associated with high titer serum IgM binding to antigens that copurify with myelin-associated glycoprotein.
We studied clinical and electrodiagnostic features of 9 patients with very high titers (> 1:10,000) of serum IgM binding to a CNS myelin antigen (CMA) preparation that copurified with myelin-associated glycoprotein (MAG). We found that 8 of the 9 patients had a combined syndrome of gait ataxia and polyneuropathy (GAPN) with late-age onset (mean = 70 years of age). In the 8 GAPN patients progressive difficulty with ambulation led to significant functional disability and frequent falling. Examination showed a wide-based unsteady gait, especially when standing still or turning. There was mild-to-moderate distal sensory loss with involvement of joint position sense only in the toes. Motor changes, when present, were mild and mainly involved distal leg musculature. Treatment of 5 GAPN patients resulted in clear improvement of 2 after intravenous human immunoglobulin and of 3 others after other immunodulating agents. Immune-mediated GAPN syndromes with high titers of serum IgM binding to CMA appear to be treatable causes of gait disorders in older patients.
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A kinematic study of the reach to grasp movement in a subject with hemiParkinson's disease.
The kinematic organization of a reach to grasp movement in a left hemiParkinson subject is compared to that of a control subject. Subjects used the right and left limbs to reach 15, 27 or 40 cm for the grasp of cylinders of 0.7 or 8 cm diameter. In general, the kinematics of the affected limb of the hemiParkinson subject differed from that of the unaffected limb. However, for both arms the hemiParkinson subject showed a delay in the onset of the manipulation component. The subtle dysfunction in the activation of near-simultaneous or sequential movements is thus bilateral, despite unilateral clinical symptomatology.
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Perturbation of the grasp component of a prehension movement in a subject with hemiParkinson's disease.
The response to perturbation of the manipulation component during prehension was assessed for both hands of a hemiParkinson and of a Control subject. With perturbed trials, the hemiParkinson showed the same pattern as the Control: a reorganization of kinematic parameters and no increase of movement time. However, for both limbs of the hemiParkinson subject there was a transition phase from precision grip to whole hand prehension--this was more pronounced for the affected limb. The manipulation component did not show a delay of activation [2]. Thus the global dysfunction in the performance of sequential movement patterns was related to aspects of task predictability.
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Hemifacial spasm: evaluation by magnetic resonance imaging and magnetic resonance tomographic angiography.
We evaluated 37 patients with hemifacial spasm and 16 age-matched control patients with other neurological disorders using magnetic resonance (MR) imaging, MR angiography, and MR tomographic angiography. MR tomographic angiography is a new technique using computer reconstruction of MR angiographic images to create coronal angiotomes that display tissue and arterial structures on the same image. Twenty-four of 37 (64.9%) patients with hemifacial spasm had ipsilateral vascular compression of cranial nerve VII or the pons noted by this technique, whereas only 1 of 16 (6.3%) control patients had compression. MR imaging and MR angiography were less sensitive and less specific in evaluating for vascular compression. This study supports vascular compression of cranial nerve VII or the pons as a cause of hemifacial spasm, and demonstrates MR tomographic angiography's value as an excellent, noninvasive technique to demonstrate the compression.
Adult↗
Tourette's syndrome. Current approaches to recognition and management.
Once thought to be a rare, disabling disorder of psychogenic origin, Tourette's syndrome is now recognized as a chronic neurologic condition that is manageable in most patients. Individualized therapy is the key to helping patients achieve a productive and socially integrated life-style. This article discusses diagnostic criteria, effective management strategies, and promising new drug therapies.
Adolescent↗
Epitope analysis of senile plaque components in the hippocampus of patients with Parkinson's disease.
We conducted an epitope analysis of senile plaque (SP) proteins on hippocampal SPs in patients with Parkinson's disease (PD), using a library of antibodies to proteins implicated in the genesis of hippocampal SPs in Alzheimer's disease (AD). The library included antibodies to the beta-amyloid protein (beta-AP), domains outside the beta-AP in beta-amyloid precursor proteins (beta-APPs), ubiquitin, diverse neuronal cytoskeletal proteins, and polypeptides located mainly in axon terminals. We obtained samples of hippocampus at autopsy from 14 PD patients, 10 of whom were demented. As in the AD hippocampus, the SPs detected by conventional stains in five of the 10 demented subjects contained the beta-AP and flanking domains in beta-APPs as well as epitopes in tau, neurofilament proteins, and synaptophysin. Further, with the exception of the beta-AP, epitopes in the other proteins were confined to the coronas of SPs, while clathrin light chain, microtubule-associated protein 5, and neural cell adhesion molecules were almost undetectable or absent in the neuropil occupied by SPs. The same group of antibodies rarely labeled SPs in the other five demented PD subjects or in the four nondemented PD subjects, and conventional stains for amyloid and neurofibrillary pathology revealed rare SPs in these cases. Hence, when conventional stains reveal lesions diagnostic of AD in PD patients, the molecular features of the hippocampal SPs in these patients are the same as those in SPs of the AD hippocampus.
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