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To clarify the precise location and timing of the mo tor cortical activation in voluntary movement, dipole source analysis integrating multiple constraints wa conducted for the movement-related cortical potentia (MRCP). Six health...
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To clarify the precise location and timing of the mo tor cortical activation in voluntary movement, dipole source analysis integrating multiple constraints wa conducted for the movement-related cortical potentia (MRCP). Six healthy subjects performed single self paced extensions of the right index finger at about 15-intervals during EEG and event-related fMRI acquisi tions. EEG was recorded from 58 scalp electrodes, and fMRI of the entire brain was obtained every 2.6 s. Coordinates of the two methods were coregistered us ing anatomical landmarks. During dipole source mod eling, a realistic three-layer head model was used as a volume conductor. To identify the number of uncorre lated source s in the MRCP, principal component (PC analysis was performed, which was consistent with the existence of six sources in the left (Lt SM1) and right (Rt SMI) sensorimotor and medial frontocentral (MFC) areas. After dipoles were seeded at the acti vated spots revealed by fMRI, dipole orientations were fixed based on the interpretation of the topography of distribution of the PC. The strength of the six dipoles (three dipoles in Lt SMI, two in Rt SMI, and one in MFC) was then computed over time. Within the bilat eral SM1, activation of the precentral gyrus occurs bilaterally with similar strength from -1.2 s, followed by that of the precentral bank from -0.5 s with con tralateral preponderance. Subsequently, the postcen tral bank becomes active only on the contralateral side at 0.1 s after movement. Activation of the MFC shows timing similar to that of the bilateral precentral gyri These deduced patterns of activation are consis tent with previous studies of electrocorticography in humans.
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Writer's cramp is a type of idiopathic focal dystonia with incompletely understood pathophysiology. Recent studies provide evidence that one element might be a sensory processing defect. We performed a PET study with O(15) H(2)O t...
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Writer's cramp is a type of idiopathic focal dystonia with incompletely understood pathophysiology. Recent studies provide evidence that one element might be a sensory processing defect. We performed a PET study with O(15) H(2)O to find out in which brain areas activity correlates with the severity of writer's cramp symptoms. METHODS: We studied 10 patients with writer's cramp and 10 age- and gender-matched control subjects. There were seven conditions, each repeated twice: rest, writing, tapping with index finger for 2, 3, 4, and 5 min. For each scan, we obtained EMG recordings from the flexor digitorum superficialis (FDS), extensor indicis proprius (EIP) muscles, and a subjective score of severity of dystonia. Scans were realigned, normalized, smoothed, and analyzed using SPM99. Analysis included both intra- and intergroup comparisons and a correlation analysis where we used EMG recordings and subjective dystonia score as covariates. RESULTS: Random effect analysis of the writing task showed overactivity of the primary sensory cortex and no significant underactivity. Correlation analysis of dystonia patients showed activation of SI when we used the subjective dystonia score as a covariate, and activation of both the SI and primary motor cortex when the normalized EMG score of FDS was used. CONCLUSION: While some overactivity of MI is not surprising, overactivity of SI is more dramatic and suggests a primary deficit in processing sensory feedback. Writer's cramp may arise in part as a dysfunction of sensory circuits, which causes defective sensorimotor integration resulting in co-contractions of muscles and overflow phenomena.
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Dementia is a common disabling complication in patients with Parkinson's disease (PD). The underlying molecular causes of Parkinson's disease with dementia (PDD) are poorly understood. To identify candidate genes and molecular pat...
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Dementia is a common disabling complication in patients with Parkinson's disease (PD). The underlying molecular causes of Parkinson's disease with dementia (PDD) are poorly understood. To identify candidate genes and molecular pathways involved in PDD, we have performed whole genome expression profiling of susceptible cortical neuronal populations. Results show significant differences in expression of 162 genes (P < 0.01) between PD patients who are cognitively normal (PD-CogNL) and controls. In contrast, there were 556 genes (P < 0.01) significantly altered in PDD compared to either healthy controls or to PD-CogNL cases. These results are consistent with increased cortical pathology in PDD relative to PD-CogNL and identify underlying molecular changes associated with the increased pathology of PDD. Lastly, we have identified expression differences in 69 genes in PD cortical neurons that occur before the onset of dementia and that are exacerbated upon the development of dementia, suggesting that they may be relevant presymptomatic contributors to the onset of dementia in PD. These results provide new insights into the cortical molecular changes associated with PDD and provide a highly useful reference database for researchers interested in PDD.
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BACKGROUND/AIMS: Previously we have shown that functional declines in Parkinson's disease (PD) and Alzheimer's disease (AD) correlate to global measures of cognitive decline. We now determine if the correlation between cognitive i...
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BACKGROUND/AIMS: Previously we have shown that functional declines in Parkinson's disease (PD) and Alzheimer's disease (AD) correlate to global measures of cognitive decline. We now determine if the correlation between cognitive impairment and functional ability in PD is similar to that in AD using individual cognitive measures. METHODS: 93 PD subjects and 124 AD/MCI subjects underwent the Functional Assessment Staging (FAST), the Global Deterioration Scale (GDS), and a neuropsychological battery. RESULTS: In PD subjects, the FAST and GDS correlated significantly with Rey Auditory Verbal Learning Test (AVLT), Controlled Oral Word Association (COWA), Animal Fluency, and Stroop but not with Clock Draw or Judgment Line Orientation (JLO). In AD/MCI subjects, FAST and GDS correlated with all neuropsychological components except Stroop. In the AD/MCI group, the UPDRS significantly correlated with the FAST, GDS, MMSE, and all neuropsychological parameters except the Stroop. In the PD group, the motor UPDRS significantly correlated significantly with FAST, GDS, MMSE and all neuropsychological parameters except Digit Span, Stroop, Clock Draw and JLO. CONCLUSIONS: Similar to AD, functional decline in PD correlates with multiple measures of cognitive impairment. Some differences between PD and AD may be explained by the influence of motor disability and declines in visuospatial function in PD.
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The objective of the study was to determine the safety and efficacy of increasing doses of Rotigotine CDS in patients with advanced Parkinson's disease. The development of motor complications in Parkinson's disease has been linked...
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The objective of the study was to determine the safety and efficacy of increasing doses of Rotigotine CDS in patients with advanced Parkinson's disease. The development of motor complications in Parkinson's disease has been linked to intermittent stimulation of dopamine receptors. Continuous, noninvasive, dopaminergic stimulation has not been available to date. Rotigotine CDS is a lipid-soluble D2 dopamine agonist in a transdermal delivery system that could fill this void. This inpatient study consisted of a 2-week dose escalation phase followed by a 2-week dose maintenance phase at the highest dose (80 cm2). Each individual's L-Dopa dose was back-titrated as feasible. The primary outcome measure was L-Dopa dose, and secondary outcome measures included early morning "off"-L-Dopa Unified Parkinson's Disease Rating Scale motor scores by a blinded evaluator and motor fluctuation data obtained from patient diaries ("on" without dyskinesia, "on" with dyskinesia, and "off"). Seven of 10 subjects provided data that could be evaluated. There were two administrative dropouts, and one individual was eliminated from the study because of recrudescence of hallucinations. The median daily L-Dopa dose decreased from 1,400 to 400 mg (p = 0.018, Wilcoxon test). Unified Parkinson's Disease Rating Scale motor scores were unchanged. Although diary variables improved in most individuals, only the reduction in "off" time attained statistical significance. Adverse effects were mild and consisted mainly of dopaminergic side effects and local skin reactions. The data suggest that Rotigotine CDS is an effective treatment for advanced Parkinson's disease and permits patients to substantially lower L-Dopa doses without loss of antiparkinsonian efficacy. Full-scale controlled clinical trials are warranted. In addition to potential therapeutic benefits, this drug can be used to test the hypothesis that continuous dopaminergic stimulation from the initiation of Parkinson's disease therapy will limit the development of motor complications.
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Previous studies showed that there are certain features suggestive of a psychogenic disorder, and Fahn and Williams proposed criteria for psychogenic movement disorders. Data on the sensitivity and specificity of these criteria ar...
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Previous studies showed that there are certain features suggestive of a psychogenic disorder, and Fahn and Williams proposed criteria for psychogenic movement disorders. Data on the sensitivity and specificity of these criteria are lacking. We expanded on the Fahn and Williams criteria to create a new set of diagnostic criteria. We retrospectively reviewed 79 patients in a movement disorders specialty clinic. We applied the proposed diagnostic criteria to both cases and controls and analyzed sensitivity and specificity. The diagnostic criteria correctly identified "clinically probable" (or better) psychogenic movement disorders with a sensitivity of 83% and specificity of 100%. For "clinically possible" or greater, sensitivity was 97% and specificity was 96%. In addition, a significantly higher proportion of patients with psychogenic disease were female and reported either a family history of neurological disease or other exposure to neurological disease (P = 0.001 and 0.01, respectively). The diagnostic criteria are simple to apply and have high sensitivity and specificity for psychogenic movement disorders. Also, we report a correlation between previous exposure to a disease model and psychogenic disease.
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Patients with Parkinson's disease are at risk for pulmonary complications as a consequence of both the underlying disease pathology and the side effects of medication. Degeneration of the substantia nigra and subsequent loss of do...
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Patients with Parkinson's disease are at risk for pulmonary complications as a consequence of both the underlying disease pathology and the side effects of medication. Degeneration of the substantia nigra and subsequent loss of dopaminergic neurons may produce changes in ventilatory parameters. Upper airway obstruction and chest wall restriction are both common, and both may respond to levodopa. However, therapy for Parkinson's may also contribute to pulmonary morbidity. Overtreatment with levodopa causes respiratory dyskinesia that may be difficult to differentiate from complications of the disease itself. Therapy with ergot derivatives may cause pleuropulmonary fibrosis. Pneumonia resulting from the respiratory complications remains a significant cause of morbidity and mortality in Parkinson's disease.
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Olfactory dysfunction in Parkinson's disease (PD) is an association that has been well documented in the medical literature, although the underlying pathophysiologic mechanism has not been clearly elucidated. In the Sun Health Res...
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Olfactory dysfunction in Parkinson's disease (PD) is an association that has been well documented in the medical literature, although the underlying pathophysiologic mechanism has not been clearly elucidated. In the Sun Health Research Institute Brain and Body Donation Program, subjects were tested for olfactory function. Olfaction was impaired in subjects with clinically probable PD but not those with essential tremor (ET), restless legs syndrome (RLS), or mild cognitive impairment. In the elderly control population there were no differences between genders and the UPSIT score decreased by 3.2 points per decade. These data confirm previous findings in PD, ET, and RLS, and expand the data for an elderly control population.
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Brain-derived neurotrophic factor (BDNF) stimulates neuronal growth and protects nigral dopamine neurons in animal models of Parkinson disease (PD). Therefore, BDNF is a candidate gene for PD. The authors investigated five single-...
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Brain-derived neurotrophic factor (BDNF) stimulates neuronal growth and protects nigral dopamine neurons in animal models of Parkinson disease (PD). Therefore, BDNF is a candidate gene for PD. The authors investigated five single-nucleotide polymorphisms in 597 cases of familial PD. Homozygosity for the rare allele of the functional BDNF G196A (Val66Met) variant was associated with a 5.3-year older onset age (p = 0.0001). These findings suggest that BDNF may influence PD onset age.
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