Risky driving and pedunculopontine nucleus-thalamic cholinergic denervation in Parkinson disease

BackgroundIt is unknown whether driving difficulty in Parkinson disease (PD) is attributable to nigrostriatal dopaminergic or extranigral non-dopaminergic neurodegeneration.ObjectiveTo investigate in vivo imaging differences in dopaminergic and cholinergic innervation between PD patients with and without a history of risky driving.MethodsThirty non-demented PD subjects (10 women/20 men) completed a driving survey. These subjects had previously undergone (+)-[¹¹C] dihydrotetrabenazine vesicular monoamine transporter 2 and [¹¹C] methyl-4-piperidinyl propionate acetylcholinesterase PET imaging. Acetylcholinesterase PET imaging assesses cholinergic terminal integrity with cortical uptake largely reflecting basal forebrain and thalamic uptake principally reflecting pedunculopontine nucleus integrity.ResultsEight of thirty subjects reported a history of risky driving (been pulled over, had a traffic citation, or been in an accident since PD onset) while 22 had no such history (safe drivers). There was no difference in striatal dihydrotetrabenazine vesicular monoamine transporter uptake between risky and safe drivers. There was significantly less thalamic acetylcholinesterase activity in the risky drivers compared to safe drivers (0.0513 ± 0.006 vs. 0.0570 ± 0.006, p = 0.022) but no difference in neocortical acetylcholinesterase activity. Using multivariable logistic regression, decreased thalamic acetylcholinesterase activity remained an independent predictor of risky driving in PD even after controlling for age and disease duration.ConclusionsRisky driving is related to pedunculopontine nucleus-thalamic but not neocortical cholinergic denervation or nigrostriatal dopaminergic denervation in PD. This suggests that degeneration of the pedunculopontine nucleus, a brainstem center responsible for postural and gait control, plays a role in the ability of PD patients to drive.     

The effect of medication and the role of postural instability in different components of freezing of gait (FOG)

Freezing of gait (FOG) is associated with gait asymmetry and arrhythmicity, cognitive impairment in Parkinson's disease (PD). However, the role of postural instability (PI) in and the effect of dopaminergic medication (meds) on FOG are unclear. We investigated the effect of meds on FOG using a validated metric, Stepping in Place (SIP) and the relationship between PI and FOG.MethodsWe assessed static posturography (off meds), SIP, UPDRS-III (off/on meds) and the FOG-questionnaire (FOG-Q) in 15 freezers/15 non-freezers and 14 healthy controls.ResultsUPDRS-III, rigidity, tremor (P < 0.01) and axial subscores (P < 0.05) improved with meds in freezers. Only UPDRS-III and tremor improved in non-freezers (P < 0.01). Meds improved freezing episode (FE) frequency, duration and stride duration in freezers (P < 0.01). Over 73% of freezers did not freeze on meds, although one freezer had more and longer duration FEs. Meds did not improve SIP cycle asymmetry and arrhythmicity, which remained greater in freezers compared to other groups on and off meds (P < 0.01, P < 0.05 respectively). Center of pressure (CoP) mediolateral displacement and velocity (V_CoP) in both directions were larger in freezers (P < 0.05). FOG-Q was correlated with CoP anteroposterior displacement and mediolateral V_CoP (R = 0.42; R = 0.40, P < 0.05).The improvement of FOG frequency and duration but not of gait asymmetry and arrhythmicity on meds suggests that both dopaminergic and non-dopaminergic networks contribute to FOG. The correlations between postural instability and FOG severity and SIP asymmetry on meds, suggest that as the disease progresses, postural instability interferes with gait symmetry and lead to on meds FOG and falls.     

Parkinsonism in fragile X-associated tremor/ataxia syndrome (FXTAS): Revisited

BackgroundParkinsonian features have been used as a minor diagnostic criterion for fragile X-associated tremor/ataxia syndrome (FXTAS). However, prior studies have examined parkinsonism (defined as having bradykinesia with at least rest tremor or postural instability) mostly in premutation carriers without a diagnosis of FXTAS. The current study was intended to elaborate this important aspect of the FXTAS spectrum, and to quantify the relationships between parkinsonism, FXTAS clinical staging and genetic/molecular measures.MethodsThirty eight (38) FXTAS patients and 10 age-matched normal controls underwent a detailed neurological examination that included all but one item (i.e. rigidity) of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS).ResultsThe FXTAS patient group displayed substantially higher prevalence of parkinsonian features including body bradykinesia (57%) and rest tremor (26%), compared to the control group. Furthermore, parkinsonism was identified in 29% of FXTAS patients. Across all patients, body bradykinesia scores significantly correlated with FXTAS clinical stage, FMR1 mRNA level, and ataxic gait of cerebellar origin, while postural instability was associated with intention tremor.InterpretationParkinsonian features in FXTAS appear to be characterized as bradykinesia concurrent with cerebellar gait ataxia, postural instability accompanied by intention tremor, and frequent rest tremor, representing distinctive patterns that highlight the need for further clinical studies including genetic testing for the FMR1 premutation. The association between FMR1 mRNA level and bradykinesia implicates pathophysiological mechanisms which may link FMR1 mRNA toxicity, dopamine deficiency and parkinsonism in FXTAS.     

A comparison of Parkinson's disease symptoms and self-reported functioning and well being

This study was designed to determine if the presence of tremor, rigidity, bradykinesia and postural instability and gait abnormalities differentially influence Parkinson's disease patients' ratings of quality of life as measured by the Parkinson's Disease Questionnaire (PDQ-39). A regression analysis indicated that the presence of postural instability and gait abnormalities and bradykinesia were strongly predictive of PDQ-39 quality of life scores. The presence of tremor and rigidity had little effect on patients' ratings of quality of life.     

Cerebral cortical areas in which thickness correlates with severity of motor deficits of Parkinson’s disease

The pathology of Parkinson’s disease (PD) is not confined to the nigrostriatal dopaminergic pathway, but also involves widespread cerebral cortical areas. Such non-nigrostriatal lesions may contribute to disabling dopa-resistant parkinsonian motor deficits. We performed cortical thickness analysis to identify cerebral cortical brain areas in which thickness correlates with the severity of parkinsonian motor deficits. We performed T1-weighted brain magnetic resonance imaging studies in 142 PD patients. Motor scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) were measured, and subscores were calculated for bradykinesia, rigidity, tremor, and axial motor deficits. Using FreeSurfer software, we studied cortical areas in which thickness correlates with disease duration or the severity of parkinsonian motor deficits. The cortical thickness of the parieto-temporal association cortex, including the inferior parietal and posterior parietal cortices, showed a negative correlation with disease duration, total UPDRS motor score, and UPDRS subscores for bradykinesia and axial motor deficits. We found no cortical areas in which thickness correlated with subscores for tremor and rigidity. In addition to nigrostriatal dopaminergic deficit, progressive thinning of the parieto-temporal sensory association cortices related to disease duration seems to be related in part to the exacerbation of bradykinesia and the axial motor symptoms of PD.     

Reduced arm swing 16 years before the diagnosis of young onset Parkinson’s disease – A case report

ObjectiveTo report a case of reduced arm swing at age 21 in a patient diagnosed with Parkinson’s disease at age 37.Parkinson’s disease has both motor and non-motor symptoms. The motor symptoms of Parkinson’s disease include bradykinesia, resting tremor, rigidity and postural instability. Sometimes the non-motor symptoms may antedate the motor symptoms by years, but the final diagnosis of Parkinson’s disease still rests upon the presence of motor symptoms. Bradykinesia is the most common and most disabling symptom of Parkinson’s disease. Reduced arm swing is one of the manifestations of bradykinesia and may be reported in the beginning of the course of disease. Reduced arm swing may be first noticed by spouse or family members during walking or while performing activities of daily living. Our patient was diagnosed with Parkinson’s disease at the age of 37 years. His wife noticed that the patient had reduced right arm swing when she met him on their first date at the age of 21, 16 years before the patient was diagnosed with Parkinson’s disease. His symptoms of Parkinson’s disease initially started on the right side i.e. the side of reduced arm swing.     

Clinical features and nigrostriatal dysfunction in patients with combined postural and resting tremors

BackgroundThe characteristics of clinical features and nigrostriatal dopaminergic dysfunction in patients with combined postural and resting tremors have been less clearly reported.MethodsThe present study examined 43 patients with a visible persistent bilateral postural tremor and a unilateral/bilateral resting tremor involving the hands and forearms. The patients had experienced tremors for more than 3 years, with no evidence of Parkinson's disease or other parkinsonian disorders. Visual and quantitative analyses of [¹⁸F] N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane (FP-CIT) PET in 36 patients were performed. Seventeen age-matched normal controls were also studied.ResultsOn visual analysis, 28 patients (78%) showed normal [¹⁸F] FP-CIT uptake and eight (22%) showed significantly reduced uptake, suggesting nigrostriatal dopaminergic neuronal degeneration. The reduced [¹⁸F] FP-CIT uptake was significantly associated with earlier age-at-onset of tremor and asymmetric presentation of resting tremor. On quantitative analysis, there were statistically significant differences in the [¹⁸F] FP-CIT uptake ratio in the posterior putamen between patients with reduced uptake (2.37 ± 1.83) and patients with normal uptake (6.39 ± 1.35) (P < 0.001). However, posterior putamen uptake levels in patients with normal [¹⁸F] FP-CIT uptake on visual analysis were similar to those in normal controls (7.22 ± 1.29) (P = 0.291).ConclusionThe nigrostriatal dopaminergic dysfunction in patients with combined postural and resting tremors may be associated with earlier age-at-onset of tremor and asymmetric pattern of resting tremor, which might help to correctly diagnose patients with mixed tremors.     

Nigrostriatal dopaminergic function in subjects with isolated action tremor

BackgroundIsolated action tremor (IAT) is the hallmark clinical feature of essential tremor (ET), but it may also be a prominent feature of some individuals with Parkinson’s disease (PD) suggesting a pathogenic relationship between these two disorders.ObjectivesWe investigated the integrity of the striatal presynaptic dopaminergic system in subjects presenting IAT to improve the diagnostic accuracy and to explore any putative relationships between ET and PD.MethodsThe striatal dopaminergic system was examined by means of dopamine transporter imaging using ¹²³I-(fluoropropyl)-2ß-carbomethoxy-3ß-(4-iodophenyl) nortropane ([123I]-FP-CIT) single-photon emission tomography (DAT-SPECT) in a clinical series of individuals with IAT, excluding those with associated resting tremor and bradykinesia.ResultsAmong 167 incidental individuals with IAT eligible for DAT-SPECT (Male/Female = 58.9/41.1%; Age = 67.8 ± 14.3 years), reduced striatal uptake was observed in 114 out of 167 (68.3%), whereas normal striatal binding was observed in the remaining 53 subjects (31.7%). Onset of tremor after 50 years and asymmetrical distribution of tremor were predictive variables of nigrostriatal denervation, whereas gender, family history and the presence of intentional, cephalic or voice tremors were not associated with nigrostriatal denervation.ConclusionsOur findings suggest that IAT is a frequent presenting symptom in a subset of individuals with PD, often misdiagnosed as ET, and that DAT-SPECT can help differentiate between these two disorders. Current diagnostic criteria for ET should be revised to include asymmetry and late-onset tremor as predictors of nigrostriatal denervation.     

The relation between cognition and motor dysfunction in drug‐naive newly diagnosed patients with Parkinson's disease

Recent studies have reported cognitive decline to be common in the early phase of Parkinson's disease. Imaging data connect working memory and executive functioning to the dopamine system. It has also been suggested that bradykinesia is the clinical manifestation most closely related to the nigrostriatal lesion. Exploring the relationship between motor dysfunction and cognition can help us find shared or overlapping systems serving different functions. This relationship has been sparsely investigated in population‐based studies of untreated Parkinson's disease. The aim of the present study was to investigate the association between motor signs and cognitive performance in the early stages of Parkinson's disease before the intake of dopaminergic medication. Patients were identified in a population‐based study of incident cases with idiopathic parkinsonism. Patients with the postural instability and gait disturbances phenotype were compared with patients with the tremor‐dominant phenotype on demographics and cognitive measures. Associations between cognitive and motor scores were investigated, with age, education, and sex controlled for. Bradykinesia was associated with working memory and mental flexibility, whereas axial signs were associated with episodic memory and visuospatial functioning. No significant differences in the neuropsychological variables were found between the postural instability and gait disturbances phenotype and the tremor phenotype. Our results indicate a shared system for slow movement and inflexible thinking that may be controlled by a dopaminergic network different from dopaminergic networks involved in tremor and/or rigidity. The association between axial signs and memory and visuospatial function may point to overlapping systems or pathologies related to these abilities. © 2011 Movement Disorder Society     

Treatments of Parkinson disease: circa 2003

Parkinson disease (PD) is a progressive degenerative neurological disorder characterized by resting tremor, bradykinesia, cogwheel rigidity, and postural instability.1 In the later stages, approximately 25% or more of patients develop cognitive compromise. The cardinal pathological features of PD are degeneration of dopaminergic neurons in the substantia nigra pars compacta and their axons, which project principally to the caudate and putamen, and the presence of eosinophilic intracytoplasmic inclusions, Lewy bodies.2-3 Although the loss of neurons is most conspicuous in the substantia nigra pars compacta, neuronal loss and/or Lewy bodies are found in other brain regions (eg, the locus coeruleus, entorhinal region, and amygdala),2 which suggests that treatments that target only the nigrostriatal dopaminergic system, though they may substantially benefit patients, are unlikely to completely resolve the deficits of PD.     

REM sleep behavior disorder and motor dysfunction in Parkinson's disease – A longitudinal study

ObjectivesLongitudinal assessment of a Parkinson's disease (PD) cohort, to investigate the evolution or REM sleep behavior symptoms (RBD) over time and to test the relation between RBD at onset and motor dysfunction progression.MethodsAn early stage PD cohort (n = 61) was assessed at two time points, separated by a two years interval. Diagnostic criteria for RBD were: violent behavior during sleep and body movements or vocalization indicative of dream enacting and at least six affirmative answers in the REM sleep behavior disorder screening questionnaire. Motor function assessment was performed with the Unified Parkinson's Disease Scale part II and III (total and partial scores for tremor, bradykinesia, rigidity, gait/postural instability and dysarthria).Results25 Patients had RBD at baseline, vs. 35 at follow-up. Three RBD changed to non-RBD at follow-up, while 10 non-RBD patients developed RBD at follow-up (annual incidence of 12.5%). RBD and non-RBD patients did not differ significantly at baseline or follow-up. The presence of RBD at baseline was significantly related to an increase in UPDRS total and bradykinesia scores over time.DiscussionRBD symptoms can vary over time and have a tendency to increase during the early stages of disease. The presence of RBD symptoms could be a risk factor for motor function deterioration and particularly for bradykinesia worsening.     

Parkinsonian features in hereditary diffuse leukoencephalopathy with spheroids (HDLS) and CSF1R mutations

Atypical Parkinsonism associated with white matter pathology has been described in cerebrovascular diseases, mitochondrial cytopathies, osmotic demyelinating disorders, leukoencephalopathies leukodystrophies, and others. Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal dominant disorder with symptomatic onset in midlife and death within a few years after symptom onset. Neuroimaging reveals cerebral white matter lesions that are pathologically characterized by non-inflammatory myelin loss, reactive astrocytosis, and axonal spheroids. Most cases are caused by mutations in the colony-stimulating factor 1 receptor (CSF1R) gene.We studied neuropathologically verified HDLS patients with CSF1R mutations to assess parkinsonian features. Ten families were evaluated with 16 affected individuals. During the course of the illness, all patients had at least some degree of bradykinesia. Fifteen patients had postural instability, and seven had rigidity. Two patients initially presented with parkinsonian gait and asymmetrical bradykinesia. These two patients and two others exhibited bradykinesia, rigidity, postural instability, and tremor (two with resting) early in the course of the illness. Levodopa/carbidopa therapy in these four patients provided no benefit, and the remaining 12 patients were not treated. The mean age of onset for all patients was about 45 years (range, 18–71) and the mean disease duration was approximately six years (range, 3–11).We also reviewed HDLS patients published prior to the CSF1R discovery for the presence of parkinsonian features. Out of 50 patients, 37 had gait impairments, 8 rigidity, 7 bradykinesia, and 5 resting tremor. Our report emphasizes the presence of atypical Parkinsonism in HDLS due to CSF1R mutations.     

β‐amyloid and postural instability and gait difficulty in Parkinson's disease at risk for dementia

Although motor impairments in Parkinson's disease (PD) are attributed to nigrostriatal dopaminergic denervation, postural instability and gait difficulty (PIGD) features are less responsive to dopaminergic medications. PIGD features are a risk factor also for the development of dementia in PD (PDD). These observations suggest that nondopaminergic mechanisms may contribute to axial motor impairments. The aim was to perform a correlative PET study to examine the relationship between neocortical β‐amyloid deposition ([¹¹C]‐Pittsburgh Compound B), nigrostriatal dopaminergic denervation ([¹¹C]‐dihydrotetrabenazine), and PIGD feature severity in PD patients at risk for dementia. This was a cross‐sectional study of 44 PD patients (11 female and 33 male; 69.5 ± 6.6 years of age; 7.0 ± 4.8 years motor disease duration; mean H & Y stage: 2.7 ± 0.5) who underwent PET, motor feature severity assessment using the Movement Disorder Society revised UPDRS, and the Dementia Rating Scale (DRS). Linear regression (R²_adj = 0.147; F_4,39 = 2.85; P = 0.036) showed that increased PIGD feature severity was associated with increased neocortical [¹¹C]‐Pittsburgh Compound B binding (β = 0.346; t₃₉ = 2.13; P = 0.039) while controlling for striatal [¹¹C]‐dihydrotetrabenazine binding, age, and DRS total score. Increased neocortical β‐amyloid deposition, even at low‐range levels, is associated with higher PIGD feature severity in PD patients at risk for dementia. This finding may explain why the PIGD motor phenotype is a risk factor for the development of PDD. © 2012 Movement Disorder Society     

Diabetes mellitus is independently associated with more severe cognitive impairment in Parkinson disease

BackgroundThere is increasing interest in interactions between metabolic syndromes and neurodegeneration. Diabetes mellitus (DM) contributes to cognitive impairment in the elderly but its effect in Parkinson disease (PD) is not well studied.ObjectiveTo investigate effects of comorbid DM on cognition in PD independent from PD-specific primary neurodegenerations.MethodsCross-sectional study. Patients with PD (n = 148); age 65.6 ± 7.4 years, Hoehn and Yahr stage 2.4 ± 0.6, with (n = 15) and without (n = 133) comorbid type II DM, underwent [¹¹C]methyl-4-piperidinyl propionate (PMP) acetylcholinesterase (AChE) PET imaging to assess cortical cholinergic denervation, [¹¹C]dihydrotetrabenazine (DTBZ) PET imaging to assess nigrostriatal denervation, and neuropsychological assessments. A global cognitive Z-score was calculated based on normative data. Analysis of covariance was performed to determine cognitive differences between subjects with and without DM while controlling for nigrostriatal denervation, cortical cholinergic denervation, levodopa equivalent dose and education covariates.ResultsThere were no significant differences in age, gender, Hoehn and Yahr stage or duration of disease between diabetic and non-diabetic PD subjects. There was a non-significant trend toward lower years of education in the diabetic PD subjects compared with non-diabetic PD subjects. PD diabetics had significantly lower mean (±SD) global cognitive Z-scores (−0.98 ± 1.01) compared to the non-diabetics (−0.36 ± 0.91; F = 7.78, P = 0.006) when controlling for covariate effects of education, striatal dopaminergic denervation, and cortical cholinergic denervation (total model F = 8.39, P < 0.0001).ConclusionDiabetes mellitus is independently associated with more severe cognitive impairment in PD likely through mechanisms other than disease-specific neurodegenerations.     

Factors predicting response to dopaminergic treatment for resting tremor of Parkinson's disease

We aimed to evaluate the clinical factors predicting response to dopaminergic treatment for resting tremor in patients with Parkinson's disease (PD). Eighty‐five PD patients with prominent resting tremor, defined as tremors of score greater than 3 in at least one limb on the Unified Parkinson's Disease Rating Scale (UPDRS), were divided into those responsive or nonresponsive to dopaminergic treatment. Responsiveness was defined as a reduction of at least two points for more than 3 months in the UPDRS tremor score. Of the 85 patients, 36 (42.4%) were responsive and 49 (57.6%) were nonresponsive to dopaminergic treatment. Initial UPDRS III score (P = 0.015) and Hoehn and Yahr stage (P = 0.010) were each significantly higher in the RG than in the NRG. UPDRS subscores for rigidity (P = 0.012), bradykinesia (P = 0.021) and postural impairment (P = 0.018) also correlated with responsiveness to dopaminergic treatment. Resting tremor in PD patients was more responsive to dopaminergic treatment when accompanied by moderate degrees of bradykinesia and rigidity than in patients without other prominent parkinsonian features. © 2007 Movement Disorder Society     

Falls and Parkinson's disease

One hundred patients with Parkinson's disease (PD) and five patients with progressive supranuclear palsy were questioned about the frequency, circumstances, and consequences of falling. Parkinsonian symptoms were scored using the unified rating scale. Thirty-eight percent of parkinsonian patients fell, and 13% fell more than once a week. Broken bones (13%), hospitalization (18%), confinement to wheelchair (3%), and fear of walking occurred. Postural hypotension was uncommon and did not correlate to falling. Sensory loss, dementia, heart disease, and the use of antihypertensive medications were not related to falling. Falling did correlate with postural instability, bradykinesia, and rigidity but not with tremor. Falling was also related to age and duration of disease. The frequency of falling was correlated only to the severity of one parkinsonian symptom, postural instability. Progressive supranuclear palsy patients fell often and had marked postural instability. Factor analysis of parkinsonian characteristics yielded three groups, with tremor being an independent symptom. Frequent fallers and postural instability were not changed by dopaminergic therapy. Some fallers with gait difficulties and bradykinesia were improved with levodopa. Physical therapy was also of benefit to some patients. It is concluded that falling is a common problem in PD and may cause serious disability. Falling may be related to all the major motor signs except for tremor. Frequent falling is caused by postural instability, which is not reversible with dopaminergic therapy.     

Neuroimaging and neurophysiological evaluation of severity of Parkinson’s disease

ObjectivesParkinson’s disease (PD) is a neurodegenerative disease presenting characteristic motor features. Severity is usually assessed by clinical symptoms; however, few objective indicators are available. In this study, we evaluated the utility of dopamine transporter (DAT) imaging and subthalamic nucleus (STN) activities as indicators of PD severity.Materials and methodsTwelve hemispheres of ten patients with PD who underwent deep brain stimulation (DBS) were included in this study. Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part 3 scores were used to evaluate clinical severity. The relationship between specific binding ratio (SBR) of DAT imaging and the root mean square (RMS) of STN micro-electrode recording (MER) was evaluated.ResultsA negative correlation was detected between the MDS-UPDRS part 3 scores and SBR (N = 20, R² = 0.418; P = 0.002). With respect to subscores, rigidity (R² = 0.582; P < 0.001) and bradykinesia (R² = 0.378; P = 0.004) showed negative correlation with SBR, whereas tremor showed no correlation (R² = 0.054; P = 0.324) (N = 20). On the other hand, no correlation was found between MER and the MDS-UPDRS part 3 scores in ten hemispheres of six patients.ConclusionDAT findings may be useful in evaluating PD severity, especially rigidity and bradykinesia.     

Rest tremor correlates with reduced contralateral striatal dopamine transporter binding in Parkinson's disease

IntroductionIn vivo dopamine transporter imaging is a useful tool for distinguishing nigrostriatal pathologies (e.g. Parkinson's disease) from other causes of tremor. However, while many of the motoric features of Parkinson's disease (e.g. bradykinesia, rigidity, hypomimia) correlate well with reduced striatal dopamine transporter binding, the same relationship has not been demonstrated for tremor. We investigated the relationship between striatal dopamine transporter binding and quantitative measures of tremor.Methods23 participants with Parkinson's disease underwent standardised clinical assessment including structured, videotaped clinical examination, tremor neurophysiology study of both upper limbs using accelerometry and surface EMG, and Technitium-99 m TRODAT-1 brain SPECT imaging. Normalised striatal uptake values were calculated. Tremor EMG and accelerometry time series were processed with Fourier transformation to identify peak tremor power within a window of 3–10Hz and to calculate the tremor stability index (TSI).ResultsSpearman correlation analyses revealed an association between tremor power and contralaterally reduced striatal uptake in a number of recording conditions. This association was strongest for rest tremor, followed by postural tremor, with the weakest association observed for kinetic tremor. Lower TSI was also associated with lower contralateral striatal uptake in a number of rest and postural conditions.ConclusionThese data suggest a relationship between Parkinsonian rest tremor and contralateral reduction in striatal dopamine binding. Use of quantitative neurophysiology techniques may allow the demonstration of clinico-pathophysiological relationships in tremor that have remained occult to previous studies.     

The heterogeneity of Parkinson's disease: clinical and prognostic implications

In 334 patients with idiopathic Parkinson's disease, deterioration in mental status paralleled severity of bradykinesia, postural instability, and gait difficulty. Tremor was relatively independent of the other cardinal signs and was associated with relative preservation of mental status, earlier age at onset, family history of parkinsonism, and more favorable prognosis. There seem to be at least two Parkinson's subgroups: one with postural instability and gait difficulty and another with tremor as the dominant feature.     

Clinician versus machine: Reliability and responsiveness of motor endpoints in Parkinson's disease

BackgroundEnhancing the reliability and responsiveness of motor assessments required to demonstrate therapeutic efficacy is a priority for Parkinson's disease (PD) clinical trials. The objective of this study is to determine the reliability and responsiveness of a portable kinematic system for quantifying PD motor deficits as compared to clinical ratings.MethodsEighteen PD patients with subthalamic nucleus deep-brain stimulation (DBS) performed three tasks for evaluating resting tremor, postural tremor, and finger-tapping speed, amplitude, and rhythm while wearing a wireless motion-sensor unit (Kinesia) on the more-affected index finger. These tasks were repeated three times with DBS turned off and at each of 10 different stimulation amplitudes chosen to yield small changes in treatment response. Each task performance was video-recorded for subsequent clinician rating in blinded, randomized order. Test–retest reliability was calculated as intraclass correlation (ICC) and sensitivity was calculated as minimal detectable change (MDC) for each DBS amplitude.ResultsICCs for Kinesia were significantly higher than those for clinician ratings of finger-tapping speed (p < 0.0001), amplitude (p < 0.0001), and rhythm (p < 0.05), but were not significantly different for evaluations of resting or postural tremor. Similarly, Kinesia scores yielded a lower MDC as compared with clinician scores across all finger-tapping subscores (p < 0.0001), but did not differ significantly for resting and postural tremor.ConclusionsThe Kinesia portable kinematic system can provide greater test–retest reliability and sensitivity to change than conventional clinical ratings for measuring bradykinesia, hypokinesia, and dysrhythmia in PD patients.