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Biomedical subjects

R L Rodnitzky

Publications and source records attributed to R L Rodnitzky.

At least 19 recordsLinked to original sources
PubMed2006

Driving with distraction in Parkinson disease.

OBJECTIVE: To assess the effects of auditory-verbal distraction on driving performance in Parkinson disease (PD). METHODS: We tested licensed, currently active drivers with mild-to-moderate PD (n = 71) and elderly controls with no neurologic disease (n = 147) on a battery of cognitive, visual, and motor tests. While they drove on a four-lane interstate freeway in an instrumented vehicle, we determined at-fault safety errors and vehicle control measures during a distracter task (Paced Auditory Serial Addition Task [PASAT]) and on an uneventful baseline segment. RESULTS: Compared with controls, drivers with PD committed more errors during both baseline and distraction, and drove slower with higher speed variability during distraction. Although the average effect of distraction on driving performance compared with baseline was not different between the groups, the drivers with PD showed a more heterogeneous response to distraction (p < 0.001): the error count increased in 28.2% of drivers with PD (vs 15.8% in controls), decreased in 16.9% (vs 3.4%), and remained stable in 54.9% (vs 80.8%). The odds of increase in safety errors due to distraction was higher in the PD group even after adjusting for baseline errors, level of engagement in PASAT, sex, and education (odds ratio [95% CI] = 2.62 [1.19 to 5.74], p = 0.016). Decreased performance on tests of cognitive flexibility, verbal memory, postural control, and increased daytime sleepiness predicted worsening of driving performance due to distraction within the PD group. CONCLUSION: The quantitative effect of an auditory-verbal distracter task on driving performance was not significantly different between Parkinson disease (PD) and control groups. However, a significantly larger subset of drivers with PD had worsening of their driving safety errors during distraction. Measures of cognition, motor function, and sleepiness predicted effects of distraction on driving performance within the PD group.

Accidents, Traffic↗
PubMed2005

Visual dysfunction in Parkinson disease without dementia.

OBJECTIVE: To determine the profiles of visual dysfunction and their relationship to motor and cognitive dysfunction and to disability in mild to moderate Parkinson disease (PD) without dementia. METHODS: Seventy-six independently living participants with mild to moderate PD and 161 neurologically normal older adults were studied using a comprehensive battery to assess visual acuity, contrast sensitivity (CS), visual speed of processing and attention, spatial and motion perception, visual and verbal memory, visuoconstructional abilities, executive functions, depression, and motor function. RESULTS: Participants with PD scored significantly worse on all tests of vision and cognition compared with normal elderly persons. Reduced CS contributed to deficits on tests of spatial and motion perception and attention in participants with PD. Impairments in visual attention and spatial perception predicted worse cognitive function. Worse performances on tests of visual speed of processing and attention, spatial and motion perception, visual construction, and executive functions correlated with measures of postural instability and gait difficulty (in the Motor section of the Unified Parkinson's Disease Rating Scale). Impairments in motor function, visual memory, mood, and executive functions predicted worse disability as measured by Schwab-England Activities of Daily Living Scale. CONCLUSIONS: Patients with mild to moderate Parkinson disease showed impaired visual perception and cognition compared with elderly control subjects. Visual dysfunction contributes to parkinsonian disability through its influences on cognition and locomotion.

Aged↗
PubMed2001

Neuropathology of two members of a German-American kindred (Family C) with late onset parkinsonism.

We present genealogical and longitudinal clinical observations and autopsy findings of a previously reported kindred, Family C (German-American), with late-onset autosomal dominant parkinsonism with evidence for linkage on chromosome 2p13. The clinical phenotype includes the cardinal features of idiopathic Parkinson's disease. In addition, postural tremor and dementia are detected in some individuals. Two members of the kindred, one affected and one unaffected have recently come to autopsy. The unaffected family member was an 82-year-old woman whose brain showed only mild age-related pathology and no evidence of subclinical Lewy body disease. In contrast, the affected family member was an 83-year-old man whose brain had neuronal loss, gliosis and Lewy bodies in the substantia nigra and other monoaminergic brain stem nuclei, as well as the basal forebrain and amygdala. Lewy bodies and Lewy neurites had a distribution typical of cases of idiopathic Parkinson's disease. Thus, the clinical and pathological findings in this family with autosomal dominant parkinsonism are similar to those of sporadic Parkinson's disease.

Aged↗
PubMed1999

Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-responsive cervical dystonia.

OBJECTIVE: To determine the safety and efficacy of botulinum toxin type B (BoNT/B) in patients with cervical dystonia (CD). BACKGROUND: BoNT/B is a form of chemodenervation therapy for the treatment of patients with CD. METHODS: The authors performed a 16-week, randomized, multicenter, double-blind, placebo-controlled trial of BoNT/B in patients with CD who continue to respond to botulinum toxin type A. Placebo, or 5,000 U or 10,000 U of BoNT/B was administered in two to four muscles involved clinically in CD. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at week 4 was the primary efficacy measure. Clinical assessments and adverse events were recorded for treatment day 1 and at weeks 2, 4, 8, 12, and 16. RESULTS: A total of 109 patients were enrolled randomly across all three treatment groups. The mean improvement in the TWSTRS-Total scores in each group at week 4 was 4.3 (placebo), 9.3 (5,000 U), and 11.7 (10,000 U). For the prospectively defined primary contrast (10,000 U versus placebo), highly significant differences were noted for the primary (TWSTRS-Total, baseline to week 4, p = 0.0004) and supportive secondary (Patient Global Assessment, baseline to week 4, p = 0.0001) outcome measures. Improvement in pain, disability, and severity of CD occurred for patients who were treated with BoNT/B when compared with placebo-treated patients. Overall, improvements associated with BoNT/B treatment were greatest for patients who received the 10,000-U dose. The duration of treatment effect for BoNT/B was 12 to 16 weeks for both doses. CONCLUSION: Botulinum toxin type B (NeuroBloc) is safe and efficacious at 5,000 U and 10,000 U for the management of patients with cervical dystonia.

Adult↗
PubMed1999

Can calcium antagonists provide a neuroprotective effect in Parkinson's disease?

Although major strides forward have been made in the symptomatic treatment of Parkinson's disease (PD), effective neuroprotective therapies have not yet been perfected. The role of calcium in neurotoxicity, and specifically in mediating the process of apoptosis, raises the possibility that calcium antagonists may have a salutary effect on conditions such as PD in which apoptosis may be the ultimate mode of cell death. Several lines of evidence support this notion including the reported effect of calcium antagonists on other human diseases involving apoptosis and animal studies demonstrating the ability of calcium antagonists to protect substantia nigra neurons from the toxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). The common calcium antagonists in use for the treatment of cardiovascular diseases have the potential to modify calcium neurotoxicity in PD since they block L-type calcium channels which are predominantly responsible for regulating intracellular calcium in midbrain dopaminergic cells. The widespread use of these agents affords the opportunity to discern their effect on PD through population studies. Preliminary investigations of this type have been performed to date, suggesting that calcium antagonist use may be less common in hypertensive PD patients than in non-PD hypertensive patients. More extensive investigations of this type, and prospective studies of calcium antagonist use in PD will be required to determine if these agents truly have a salutary effect on Parkinsonism.

Apoptosis↗
PubMed1998

The health burdens of Parkinson's disease.

Parkinson's disease (PD) is likely to have a substantial impact on an individual's health-related quality of life (HRQL), health-related resource use, and productivity. Data about the health burdens of PD by disease stage are fundamental to understanding the effectiveness of care, both from a clinical and a fiscal point of view. This study's goal was to describe the associations of patient-reported HRQL and economic characteristics with PD stage. We hypothesized that later stages of PD would be associated with poorer HRQL, greater health-related resource use, and lower work productivity than early stages of PD. We used a cross-sectional analysis to study 193 PD patients attending two hospital-based neurology clinics. Self-administered questionnaires and in-person interviews measured clinical features, functional status, general health perceptions, well-being, overall HRQL, work productivity, and health-related resource use. Consistent, strong associations were found between stage and functional status, general health perceptions, well-being, and overall HRQL even after controlling for age, gender, and comorbid conditions. Most resource use and work productivity measures were also associated with disease stage. However, physician services use was not. This study confirms that the burdens of illness are progressively higher for PD patients with early, moderate, and advanced illness. The results suggest that such important facets of the health burden as HRQL and health-related resource use may be seriously misjudged if not carefully measured but inferred from clinical observations alone.

Activities of Daily Living↗
PubMed1998

The usefulness of the Functional Status Questionnaire and Medical Outcomes Study Short Form in Parkinson's disease research.

Parkinson's disease (PD) has no cure and is a progressive neurological disorder with treatment aimed at the maintenance of function and limitation of the symptoms. No extensive studies of the disease's impact on health-related quality of life (HRQoL) have been conducted. The purpose of this study was to assess the potential usefulness of the Medical Outcomes Study Short Form (SF-36) and the Functional Status Questionnaire (FSQ) in Parkinson's disease research. This cross-sectional study of 193 PD patients who visited two hospital-based neurology clinics used self-administered in-clinic and take-home questionnaires to ascertain the demographic and environmental characteristics of the subjects and to gain health profile measures from the SF-36 and the FSQ. The two health profiles provide important HRQoL information supplementary to the traditional signs and symptoms evaluated by the Unified Parkinson's Disease Rating Scale (UPDRS). Many of the HRQoL measures discriminate progressive stages of disease in this study group and distinguish those with complications of therapy from subjects without complications.

Activities of Daily Living↗
PubMed1998

Visual dysfunction in Parkinson's disease.

Several abnormalities of visual function have been demonstrated in Parkinson's disease (PD) by both electrophysiologic and psychophysical testing. Prolonged visual evoked potential latencies and abnormal electroretinographic patterns, both of which respond to levodopa therapy, have been demonstrated in Parkinson's disease patients and in primates with experimental parkinsonism suggesting that retinal dopamine deficiency is an important factor in the pathogenesis of PD visual dysfunction. Abnormalities of color perception, especially in the blue-green axis, and of visual contrast sensitivity (VCS) have also been well documented in PD patients. Although VCS impairment is likely related to retinal dopaminergic dysfunction, the fact that this visual abnormality is orientation-specific raises the possibility of visual cortex involvement as well. Visual abnormalities in PD are usually clinically occult and not likely to be uncovered during a routine neurological examination or by ordinary high contrast visual acuity testing. The clinician must be aware, however, that several forms of disability ranging from gait freezing to visual hallucinations may be linked to an underlying impairment of visual function in Parkinson's disease.

Color Perception↗
PubMed1997

Botulinum toxin type B: a double-blind, placebo-controlled, safety and efficacy study in cervical dystonia.

We enrolled and treated 122 patients with idiopathic cervical dystonia in a double-blind, placebo-controlled safety and efficacy study of botulinum toxin type B (BotB). Both A-responsive and A-resistant patients were enrolled. Patients received intramuscular injections of either BotB (2,500 U, 5,000 U, or 10,000 U) or placebo. The primary outcome measure of efficacy was the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at 4 weeks following study drug administration. Secondary measures of efficacy were TWSTRS-Severity, -Disability, and -Pain subscale scores, and Analog Pain Assessment, Investigator Global Assessment, Patient Global Assessment, and Sickness Impact Profile scores. Duration of effect was estimated with an intent-to-treat analysis of responders. Safety measures included clinical parameters, laboratory tests, and adverse events. The primary and most of the secondary analyses indicated a statistically significant treatment effect and a dose response. BotB is safe, well tolerated, and efficacious in the treatment of cervical dystonia at the doses tested.

Adult↗
PubMed1996

Localization of the gene for rapidly progressive autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration to chromosome 17q21.

Rapidly progressive autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration (PPND) is a neurodegenerative disorder which begins later in life (> 30 years of age) and is characterized by rapidly progressive parkinsonism, dystonia, dementia, perservative vocalizations and pyramidal tract dysfunction. The disease is observed in a large American family that includes almost 300 members in nine generations with 34 affected individuals. In this kindred evidence for linkage to chromosome 17q21 was obtained with a maximum lod score of 9.08 for the D17S958 locus. Multilocus analysis positions the disease gene in an approximately 10 cM region between D17S250 and D17S943. Notably, the disease locus for a clinically distinct familial neurodegenerative disease named 'disinhibition-dementia-parkinsonism-amyotrophy complex' (DDPAC) was recently mapped to the same region of chromosome 17, suggesting that PPND and DDPAC may possibly originate from mutations in the same gene.

Adult↗
PubMed1996

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↗
PubMed1994

Ranitidine-induced cranial dystonia.

We report a case of cranial dystonia related to the administration of ranitidine. The symptoms started shortly after institution of treatment, resolved after discontinuation, and recurred upon repeat administration of the drug. Although there have been a few reports of abnormal involuntary movements related to other histamine2 antagonists, this is only the second reported instance due to ranitidine and the first reported instance of dystonia related to the drug. The pathophysiology of this effect is unclear, but a central cholinergic effect of this agent may be a contributing factor.

Aged↗
PubMed1992

Rapidly progressive autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration.

We describe a family with nearly 300 members over 8 generations with 32 affected individuals who have an autosomal dominant neurodegenerative disease characterized by progressive parkinsonism with dystonia unrelated to medications, dementia, ocular motility abnormalities, pyramidal tract dysfunction, frontal lobe release signs, perseverative vocalizations, and urinary incontinence. The course is exceptionally aggressive; symptom onset and death consistently occur in the fifth decade. Positron emission tomographic studies with [18F]6-fluoro-L-dopa (6FD) were performed in 4 patients and 7 individuals at risk for development of the disease. All affected subjects had markedly reduced striatal uptake of 6FD (p less than 0.001). All individuals at risk had normal striatal uptake, but high 6FD uptake rate constants were noted in 3 of the 7 studied. Autopsy findings revealed severe neuronal loss with gliosis in substantia nigra, pontine tegmentum, and globus pallidus, with less involvement of the caudate and the putamen. There were no plaques, tangles, Lewy bodies, or amyloid bodies. This kindred appears to represent a neurodegenerative disease not heretofore described. We propose the following name for this new genetic disease: autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration.

Adult↗
PubMed1992

Botulinum toxin enhancement of postoperative immobilization in patients with cervical dystonia. Technical note.

Postoperative immobilization in patients with cervical dystonia requiring fusion presents a unique management problem. Two patients with severe degenerative cervical spine disease secondary to chronic repetitive motion are reported. Both required a surgical fusion and postoperative immobilization. Botulinum toxin was injected intramuscularly to assist in immobilization. The technique used is described.

Adult↗
PubMed1992

Neurologic complications of drugs. Tardive dyskinesias, neuroleptic malignant syndrome, and cocaine-related syndromes.

Drugs, either self-administered or prescribed by physicians, can result in substantial neurologic disability in psychiatric patients. It is clear that the use of neuroleptic agents to treat psychiatric illness may result in a variety of tardive movement disorders. Most commonly, these take the form of orobuccal dyskinesias, but choreic movements of the trunk and extremities, dystonic postures, myoclonus, tics, parkinsonism, and akathisic syndromes also may occur. The choreic tardive syndromes are thought to occur more commonly in the elderly female population, but tardive variants may affect a different population. The neuroleptic malignant syndrome carries a significant mortality and remains a diagnostic and therapeutic challenge. Early detection and vigorous treatment reduces the morbidity and mortality from this condition. Stroke, seizures, and various movement disorders may complicate the illicit use of cocaine and complicate the rehabilitation of those patients dependent on its use. The unsatisfactory treatment of tardive syndromes, neuroleptic malignant syndrome, and cocaine-induced neurologic disease underscores our incomplete understanding of the neurochemistry of dopamine, the function of newly discovered dopamine receptors, and the role they play in maintaining normal emotional and motoric function. For now, awareness of the varied neurologic syndromes related to neurotransmitter-modulating agents should provide the impetus for careful use of these agents and for the continued development of improved drugs for the treatment of psychiatric disease.

Age Factors↗
PubMed1992

The use of Sinemet CR in the management of mild to moderate Parkinson's disease.

The pharmacokinetic advantage of controlled-release carbidopa-levodopa (Sinemet CR) is its slow dissolution and gradual absorption, resulting in more sustained plasma levodopa levels and higher plasma troughs. In patients with moderately severe disease, the benefits include less severe "wearing-off," a modest increase in daily "on" time, and fewer daily doses. Bioavailability of Sinemet CR levodopa is less than that of standard Sinemet, so a slightly higher total daily levodopa dose is required to achieve a comparable effect; but because Sinemet CR is absorbed much more slowly than is the standard preparation, dosing frequency can be reduced by up to half. For most patients, titration will be required after the transition has been made from standard to controlled-release Sinemet. The effect of Sinemet CR on dyskinesias is often difficult to predict and, in individual patients, may depend on the temporal pattern of dyskinesias being experienced. Success in using this new preparation depends on understanding its pharmacokinetic properties, judicious patient selection, and an effective program of patient education.

Carbidopa↗
PubMed1992

Periodic, aperiodic, and rhythmic motor disorders of sleep.

A variety of spontaneous movements can occur during sleep. Most are unassociated with identifiable CNS pathology and are presumed to be caused by sleep-related modulation of CNS motor control systems. Individual dyskinesias occurring during sleep can be characterized not only by their frequency, rhythmicity, and anatomic predilections, but also by the stage of sleep in which they characteristically occur. Wake-pattern movement disorders improve during sleep but, contrary to common belief, they do not entirely disappear. Instead, these disorders reemerge in attenuated form, often during nonrapid eye movement sleep. The identification and proper characterization of the various sleep-related dyskinesias are greatly aided by careful polysomnographic study.

Bruxism↗