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Biomedical subjects

Richard B Dewey

Publications and source records attributed to Richard B Dewey.

16 recordsLinked to original sources
PubMed2005

Clinical course in Parkinson's disease with elevated homocysteine.

Elevated homocysteine (Hcy), prevalent in Parkinson's disease (PD), is potentially a modifiable risk factor for neurologic deterioration. We measured cognitive, affective and motor changes over 2 years in a cohort of people with early PD. Subjects whose Hcy had been elevated (>14 micromol/L, n = 31) at baseline were compared with the rest (n = 66). Overall progression in 2 years did not significantly differ (p = 0.20). Four subjects with elevated and one with normal Hcy had died (p = 0.03). We conclude that hyperhomocysteinemia does not predict significantly worse progression over 2 years in early PD. The data raised the possibility of higher mortality, but the number of deaths was small.

Affect↗
PubMed2004

Management of motor complications in Parkinson's disease.

Motor fluctuations in Parkinson's disease (PD) typically develop after 4-6 years of therapy, and affect approximately half of all patients. The wearing-off effect is the most common type, and "delayed-on," "no-on," and "on-off" effects, as well as dyskinesias, may also develop as the disease progresses. Collectively, motor fluctuations represent a significant source of disability in advanced PD patients, and their mitigation is a major goal of patient management. Adjunctive medications, including dopamine agonists, amantadine, MAO-B inhibitors, and COMT inhibitors, each may reduce the frequency or duration of "off" periods, but none does so completely, and each contributes its own side effects which may limit optimal dosing. Surgery is another strategy to reduce "off" time, and both pallidotomy and deep brain stimulation of the globus pallidus or the subthalamic nucleus have been shown to be highly effective in this regard. However, surgery may be contraindicated in elderly advanced patients who could most benefit from its effect on "off" time. The unmet need for treatment of "off" episodes suggests the potential utility of an agent such as apomorphine injectable, which can reliably trigger an "on" response within 10-15 minutes of injection.

Antiparkinson Agents↗
PubMed2004

Elevated plasma homocysteine level in patients with Parkinson disease: motor, affective, and cognitive associations.

BACKGROUND: An elevated plasma homocysteine (Hcy) level has been prospectively associated with an increased risk of vascular and degenerative dementias. An Hcy elevation is prevalent in patients with Parkinson disease (PD) in part because levodopa metabolism produces Hcy. The clinical relevance of an elevated Hcy level in patients with PD is unknown. OBJECTIVE: To determine if hyperhomocysteinemia in patients with PD is associated with depression or with cognitive or physical impairments. DESIGN: Ninety-seven people with a mean (SD) PD duration of 3.6 (1.6) years completed the Beck Depression Inventory, a battery of 11 cognitive tests, and the motor and function components of the Unified Parkinson's Disease Rating Scale. Normalized scores for the affective, cognitive, and physical measures were compared between those with a normal Hcy level (n = 66) and those with hyperhomocysteinemia (n = 31) (Hcy level, >1.89 mg/L [>14 micro mol/L]), controlling for age, sex, disease duration, and treatment. RESULTS: Subjects with an elevated Hcy level were slightly older (68 vs 62 years), but had similar plasma concentrations of vitamin B(12) and folate. Hyperhomocysteinemic patients were more depressed (P =.02) and had worse cognition (P<.01), but the physical measure did not differ. CONCLUSIONS: Patients with PD and hyperhomocysteinemia are more likely to be depressed and to perform worse on neuropsychometric tasks compared with normohomocysteinemic patients. Further research is warranted to see if hyperhomocysteinemia is a reversible risk factor for neuropsychiatric burden in patients with PD.

Aged↗
PubMed2004

Modest increase in plasma homocysteine follows levodopa initiation in Parkinson's disease.

Levodopa, typically ingested chronically at high daily doses, is predictably methylated by means of a series of reactions using B vitamins, which convert methionine to homocysteine. Elevated total plasma homocysteine (tHcy), a risk factor for dementia, has been found in PD patients using levodopa. We prospectively measured the effects on plasma tHcy and B vitamins of levodopa initiation, and measured the effects of dose changes and of treatment with dopamine agonists and entacapone. We collected paired plasma samples, at baseline and again after several months treatment, from patients initiating levodopa (n = 30), from patients whose levodopa dose was doubled (n = 15), halved or stopped (n = 14), from patients starting or stopping entacapone (n = 15) and from patients initiating or doubling dopamine agonist monotherapy (n = 16). Vitamin B12, folate, and tHcy concentrations were measured. Baseline tHcy concentration of 8.7 (2.8) micromol/L increased to 10.1 (3.1) micromol/L (P = 0.004) an average of 94 (range 36 to 200) days after initiation of 604 (240 to 1050) mg/day of L-dopa. Average concentration of vitamin B12 fell from 380 to 291 pmol/ L (P = 0.01). Patients who doubled their daily levodopa dose experienced tHcy elevations from 9.5 to 11.1 micromol/L (P = 0.05). Levodopa reduction, agonist treatment, and entacapone treatment did not have significant effects. Levodopa elevates tHcy and lowers vitamin B12 concentration to modest degrees. The clinical implications, if any, have not yet been determined.

Aged↗
PubMed2004

An unusual variant of the dorsal midbrain syndrome in MS: clinical characteristics and pathophysiologic mechanisms.

Patients with MS exhibit a broad diversity of ocular motor syndromes. We describe a patient with relapsing-remitting MS who developed an unusual variation of the dorsal midbrain syndrome, characterized by monocular convergent-retraction nystagmus in the right eye, accompanied by divergent-retraction nystagmus in the fellow eye upon attempted upward gaze. Examination also revealed a skew deviation with a left hyperdeviation and severe adduction limitation in the left eye during attempted right gaze. We propose that a left INO accounted for the inability of the left eye to adduct (and result in convergent-retraction) during attempted upward saccades. We consider the pathophysiologic mechanisms responsible for our observations and review important details of the dorsal midbrain ocular motor circuitry.

Adult↗
PubMed2003

A new measure of dysconjugacy in INO: the first-pass amplitude.

BACKGROUND: The ratios of abducting to adducting eye movements (versional dysconjugacy index, VDI) for saccadic velocity and acceleration have been useful measures by which to objectively characterize internuclear ophthalmoparesis (INO). Amplitude measures of dysconjugacy have been less useful, given that many patients maintain the ability to ultimately reach a centrifugal fixation target and that traditional amplitude measures of VDI have focused on this 'final amplitude' (FA) position. METHODS: We utilized infrared oculography to define a new amplitude measure of dysconjugacy in 42 multiple sclerosis (MS) patients with INO. The first-pass amplitude (FPA)-VDI is the ratio of abduction/adduction eye movement amplitudes computed at the time when the abducting eye initially achieves the centrifugal horizontal fixation target. RESULTS: FPA-VDI values were significantly more sensitive and specific than FA-VDI values in demonstrating dysconjugacy in INO, and there was a 14-fold increase in dysconjugacy as measured by FPA-VDI Z-scores when compared to FA-VDI Z-scores. CONCLUSION: Consideration of velocity (pulse) and amplitude (step) components of dysconjugacy in patients with INO can provide a greater understanding of the dynamic aspects of this syndrome. We propose to characterize the relationship between the pathophysiology of INO and neuroradiologic measures of tissue injury in MS.

Diagnostic Techniques, Ophthalmological↗
PubMed2003

Tremor response to polarity, voltage, pulsewidth and frequency of thalamic stimulation.

BACKGROUND: Thalamic deep brain stimulation ameliorates essential and parkinsonian tremors refractory to medications. Stimulus voltage, polarity configuration, frequency, and pulsewidth can each be adjusted in order to optimize tremor control and maximize battery life. The relative impacts of these programmable variables have not previously been quantified. METHODS: The thalamus of 11 patients (bilaterally in 2) was studied 4 to 59 months postoperatively. The stimulator was inactivated and medications withheld for 12 hours, and optimal electrode contacts were selected. Stimulation followed at a range of voltages (0, 1, 2, 3, or 4 V), pulsewidths (60, 90, or 120 micros), and frequencies (130, 160, or 185 Hz) for both monopolar and bipolar configurations. Seventy-eight combinations of variables were programmed in random sequence. Postural and action tremors were measured with an electromagnetic tracker, tremor was subjectively graded, and side effects were noted. RESULTS: Voltage was consistently predictive of tremor response. Mean postural tremor amplitude in PD fell from 6.4 cm at 0 V to 2.6, 1.0, 0.3, and 0 cm at 1 through 4 V (bipolar configuration). The voltage response curve for essential tremor was flatter. The monopolar configuration was 10 to 25% more effective than bipolar. The longest pulsewidth tested was up to 30% more effective than the shortest, but frequency changes had little effect on tremor amplitude. Side effects occurred only with monopolar stimulation, and the only setting that was intolerable for the majority was 4 V, 120 micros, and 185 Hz. CONCLUSION: Bipolar deep brain stimulation at 90 micros, 130 Hz, adjusting the voltage up to 3 V, tends to be effective and well tolerated. Monopolar provides similar benefits for lower voltage, but side effects become common at 3 or 4 V.

Aged↗
PubMed2003

Adult polyglucosan body disease associated with lewy bodies and tremor.

BACKGROUND: Adult polyglucosan body disease (PGBD) is rare and typically presents with upper and lower motor neuron involvement and neurogenic bladder. Extrapyramidal features are unusual in PGBD and are presumed secondary to widespread pathology that includes the basal ganglia. There are no prior reports of Lewy bodies in PGBD. OBJECTIVE: To report a unique finding of Lewy bodies in a patient with PGBD. REPORT OF A CASE A 46-year-old woman initially presented with a 4-year history of resting tremor. The tremor responded to levodopa therapy. Several months later, she developed upper and lower motor neuron involvement and other clinical features of PGBD. A sural nerve biopsy specimen revealed intra-axonal polyglucosan bodies that confirmed the clinical diagnosis. Bulbar and limb weakness progressed, and she developed dementia. She died 6 years after onset. At autopsy, extensive polyglucosan body formation was found in many regions of the central nervous system. In addition, numerous alpha-synuclein staining Lewy bodies were observed in the substantia nigra, accompanied by marked neuron depopulation. CONCLUSIONS: To our knowledge, this is the first report of adult PGBD associated with Lewy bodies and levodopa-responsive tremor. Although polyglucosan bodies were seen in substantia nigra, it is most likely that our patient had coexisting Parkinson disease.

Basal Ganglia Diseases↗
PubMed2003

A randomized trial of amantadine in Huntington disease.

CONTEXT: Huntington chorea, like levodopa-induced dyskinesias, may be responsive to amantadine hydrochloride treatment. OBJECTIVES: To measure the effect of amantadine treatment on Huntington chorea and to test a hypothesis that the adventitious movements are associated with reduced central proprioception that can be corrected by amantadine treatment. DESIGN: A randomized placebo-controlled cross-over trial with 2 weeks of treatment. SETTING: A tertiary referral center. PARTICIPANTS: Twenty-four subjects with Huntington disease took amantadine hydrochloride, 100 mg 3 times daily for 2 weeks, and placebo for 2 weeks. METHODS: Chorea of the face, trunk, and limbs while seated was videotaped at baseline and after each study phase. Segments were viewed in random order by blinded reviewers and scored. Proprioception was determined using arm restraints in which the right and left elbows were set at slightly different angles, and the errors in selecting the more extended elbow over 40 trials were recorded. RESULTS: The chorea score was not correlated with a proprioception deficit. Neither chorea nor proprioception were significantly affected by amantadine therapy. The chorea score was 9.6 (3.1) points at baseline and 9.7 (3.7) points when the patient was receiving amantadine therapy. The 95% confidence interval for the difference between placebo effect and amantadine effect was -1.43 to 1.0 points. Despite this, 19 subjects felt improved during the amantadine phase compared with 6 subjects improved in the placebo phase (P =.006) and the quality of life was better (P<.001). CONCLUSIONS: Elbow proprioception was not shown to be related to Huntington chorea. Amantadine hydrochloride treatment at doses of 300 mg/d had no effect, on average, for Huntington chorea, although most patients felt subjectively better during the short course of amantadine treatment.

Amantadine↗
PubMed2003

Distinguishing neurogenic from non-neurogenic detrusor overactivity: a urodynamic assessment of lower urinary tract symptoms in patients with and without Parkinson's disease.

OBJECTIVES: To examine the urodynamic (UDS) attributes of detrusor overactivity (DO) in patients with Parkinson's disease in comparison to DO in men without neurologic disease, in whom DO is presumably outlet obstruction induced. METHODS: The UDS database was reviewed for three groups of patients: group 1, men with lower urinary tract symptoms (LUTS) and no known neurologic condition with DO (n = 22); group 2, men with Parkinson's disease and LUTS (n = 39); and group 3, women with Parkinson's disease and LUTS (n = 18). Statistical analysis was used to compare the UDS parameters and diagnoses among the groups and to test for associations between Parkinson's disease duration, Hoehn and Yahr score, and UDS findings. RESULTS: Patients with Parkinson's disease had a significantly lower median volume at first detrusor contraction than those with non-neurogenic DO. The percentage of group 1 patients with urge incontinence was significantly lower than that found in the other two groups (9.1% versus 53.8% and 55.6%, P <0.001 and 0.002, respectively). No statistically significant correlation between the duration or severity of Parkinson's disease and UDS parameters was found. CONCLUSIONS: Men with non-neurogenic LUTS are less likely to have urge incontinence on UDS than either men or women with Parkinson's disease. DO owing to Parkinson's disease occurs earlier during filling compared with non-neurogenic DO, especially in women. The duration and severity of Parkinson's disease are not predictive of the nature or severity of UDS abnormalities.

Aged↗
PubMed2002

Contributions of dopaminergic drugs and disease severity to daytime sleepiness in Parkinson disease.

BACKGROUND: Excessive daytime somnolence is a common report among patients who have Parkinson disease (PD). The relative contributions of disease severity and of the various dopaminergic drugs are unclear. OBJECTIVE: To separate and quantify the contributions of disease markers and drug doses. METHODS: Patients seen during a 7-month period at a center for movement disorders completed the Epworth Sleepiness Scale. Treatment subgroups were compared. The relationship to sedation of age; dopaminergic drug classes and doses; Hoehn and Yahr stage; duration of disease; total score on the motor subsection of the Unified Parkinson Disease Rating Scale; and the presence or absence of dementia, depression, or hallucinations was calculated using simple and multiple regression and t tests. RESULTS: The Epworth Sleepiness Scale scores were higher among patients with PD (mean [SD], 10.8 [5.3]; n = 368) compared with patients with other neurological disorders (mean, 8.5 [5.1]; n = 243; P<.001). A model containing the Hoehn and Yahr stage, levodopa dose, and use of a dopamine agonist was the best at predicting the total score of Epworth Sleepiness Scale in patients who have PD, but accounted for only 9% of the interindividual variance. The parameter estimates (SE) corresponded to a 1.02 (0.03)-point increase per Hoehn and Yahr stage, a 0.14 (0.06)-point increase per 100-mg increase in levodopa dose over 24 hours, and a 2.33 (0.57)-point increase with use of an agonist. There was no statistically significant dose response for agonists. No statistically significant difference in sedation among the commonly used dopamine agonists was found. CONCLUSIONS: Somnolence in patients with PD, which is on average 25% higher than in other neurological diseases, is related to PD stage, levodopa dose, and the use of a dopamine agonist. However, most of the variability in sedation levels in patients with PD as well as in controls is the result of, as yet, unidentified factors.

Aged↗
PubMed2002

Randomized trial comparing primidone initiation schedules for treating essential tremor.

Early side effects are common when primidone is used to treat essential tremor, with as many as one-third of patients failing to tolerate the tablets. Lower doses can be prescribed initially using a suspension formulation. We suspected suspension initiation would result in fewer early side effects, allow better acclimatization, and improve compliance. Forty patients with essential tremor were randomized to begin primidone treatment using either 2.5 mg doses in the suspension form or 25 mg doses in the tablet form. Doses gradually increased over 3 weeks to 150 mg/day. This was a double-blind, double-dummy trial. Medication cessation due to side effects was designated the primary end-point. Four patients in the suspension group and two in the tablet group dropped out due to early side effects, resulting in a relative risk of 1.9 (95% confidence interval 0.4 to 9.2). Side effects in the first 48 hours of treatment were equally common, affecting seven subjects in each group. Treatment benefits were the same in both groups. We concluded that use of a very low initial dose and a graduated titration schedule in suspension formulation did not appear to improve primidone tolerability. If anything, compliance tended to be worse when compared with the tablet formulation, though the study was under-powered to reject the null hypothesis of equivalence.

Administration, Oral↗
PubMed2002

Ventralis intermedius thalamotomy can succeed when ventralis intermedius thalamic stimulation fails: report of 2 cases for tremor.

In 2 patients with essential tremor, thalamotomy in the ventralis intermedius (VIM) provided lasting tremor relief after thalamic stimulation of the VIM failed. These cases illustrate that the effects of deep brain stimulation might not be those of simple inhibition, and that thalamotomy should be considered when deep brain stimulation does not succeed.

Aged↗
PubMedDate not supplied

Movement disorders after head injury: diagnosis and management.

Head injury can cause extrapyramidal movement disorders such as tremors, parkinsonism, dystonia, chorea, myoclonus, and tics. Pure adventitious movements are rare, but combinations with paresis, spasticity, apraxia, or ataxia occur in approximately 20% of cases of severe head injury, in many cases appearing or evolving in the months following the injury. Tremors may improve in time but many of the other syndromes tend to persist. Reversible causes such as medications or metabolic derangements are occasionally identifiable. Some of these adventitious movements can be improved using neuroactive drugs, botulinum toxin injections, or stereotactic brain surgery.

Adult↗