Dopaminergic function in spinocerebellar ataxia type 6 patients with and without parkinsonism

Journal of Neurology - Although pure cerebellar ataxia is usually emphasized as the characteristic clinical feature of spinocerebellar ataxia type 6 (SCA6), parkinsonism has been repeatedly...     

Cerebrotendinous xanthomatosis patients with and without parkinsonism: Clinical characteristics and neuroimaging findings

Parkinsonism in cerebrotendinous xanthomatosis (CTX) is rare. There are no published studies with imaging findings of dopamine transporter using ^99mTc‐[2‐[[2‐[[[3‐(4‐chlorophenyl)‐8‐methyl‐8‐azabicyclo [3,2,1] oct‐2‐yl] methyl] (2‐mercaptoethyl) amino] ethyl] amino]‐ethanethiolato(3‐)‐N2,N2,S2,S2]oxo‐[1R‐(exo‐exo)] (^99mTc‐TRODAT‐1) SPECT in CTX patients. This report is on the clinical details of five genetically‐proven CTX patients (two with and three without parkinsonism). Imaging findings using cranial magnetic resonance (MR) imaging and ^99mTc‐TRODAT‐1 SPECT are also shown. Clinical correlation of neuroimaging findings and clinical presentations was made. A literature review of the clinical and neuroimaging features of eight CTX patients with parkinsonism reported in the English literature is also presented. The parkinsonian features of our two cases and the other eight reported cases occurred before the age of 50 years. The MR imaging study showed variable findings, in which, besides the common diffuse cerebral and cerebellar white matter lesions shown in CTX, several focal brain lesions were also noted. Of the focal lesions, substantia nigra abnormalities were seen only in the two cases with parkinsonism. The ^99mTc‐TRODAT‐1 SPECT study showed different degrees of unilateral or bilateral abnormalities in the striatal binding in both visual and semiquantitative assessments. parkinsonism can be one of the neurologic presentations of CTX. Even though abnormal findings of the substantia nigra were detected in both of our CTX patients with parkinsonism, basal ganglion lesions have not been uniformly described in MR imaging findings of reported CTX patients with parkinsonism. ^99mTc‐TRODAT‐1 SPECT study can be of value in the detection of striatal involvement, and the study results also suggest pre‐synaptic dopamine neuron involvement in CTX patients with parkinsonism. © 2010 Movement Disorder Society     

Rest and postural tremors in patients with Parkinson's disease

The mild tremor of twenty-four patients with Parkinson's disease (PD) was quantified in four conditions: finger-rest, finger-postural, hand-rest and hand-postural. Tremor characteristics such as amplitude, median power frequency, power dispersion, and power percentage within the 4-7 Hz band were correlated across conditions. Results show that all tremor characteristics were well correlated across conditions (Spearman's Rank), signifying that presence of PD rest tremor was accompanied with a postural tremor having similar characteristics to that of rest tremor. The present results suggest that neural mechanisms involved in PD rest tremor do remain active in the postural condition, even in patients with mild tremor.     

Sleep disturbances in patients with parkinsonism

Altered sleep and vigilance are among the most frequent symptoms, besides parkinsonism, in movement disorders. As many as 60% of patients with Parkinson's disease (PD) experience insomnia, 15-59% show rapid eye movement (REM) sleep behavior disorders (RBDs), and 30% show excessive daytime sleepiness. Insomnia is a distressing difficulty to maintain sleep, which is exacerbated by motor disability, painful dystonia, restless legs, dysuria, anxiety and depressed mood. Improving night-time motor control by overnight treatment with levodopa, transdermal or long-acting dopamine agonists, or bilateral subthalamus stimulation, can improve sleep continuity. RBDs are violent, enacted dreams that expose the patient or their sleeping partner to night-time injuries. A striking improvement of parkinsonism is observed during these behaviors in PD. RBDs are thought to be caused by lesions in the REM sleep atonia system, and can, in association with other early markers of neurodegenerative diseases, such as olfactory, cognitive and autonomic disturbances, precede parkinsonism by several years. Daytime sleepiness, often with a narcolepsy-like phenotype, is a common occurrence in PD, owing to lesions in the arousal systems of the brain. The use of dopamine agonists increases the risk of sleep attacks, especially when driving, suggesting a drug-disease interaction.     

FMR1 gene expansion and scans without evidence of dopaminergic deficits in parkinsonism patients

PurposeTo determine if patients with parkinsonism and fragile X mental retardation 1 (FMR1) gene expansions have a striatal dopamine deficit similar to Parkinson disease (PD) patients.ScopeThe authors studied three patients with parkinsonism carrying small expansions in the FMR1 gene (41–60 CGG) with [¹²³I]β-CIT SPECT imaging. The patients responded to dopaminergic medications, but had preserved dopamine transporter density.ConclusionsThese results suggest that parkinsonism associated with smaller FMR1 expansions may be related to mechanisms other than pre-synaptic dopaminergic changes and may represent a potential explanation for at least some parkinsonian cases with scans without evidence of dopaminergic deficits (SWEDD).     

EEG findings in patients with vascular parkinsonism

Objectives– To investigate whether the conventional and quantitative EEGs of patients with vascular parkinsonism (VP) differ from those of idiopathic Parkinson's disease (PD) patients. Material and methods– The EEGs of 13 patients with vascular parkinsonism and 14 patients with idiopathic Parkinson's disease were scored on a simple scale regarding aspects of conventional EEG variables. Alpha band power asymmetry and EEG slowing (increased delta and theta power) were calculated by the neurometrics method of quantitative EEG data evaluation. Results– Analysis of both conventional and quantitative EEG data shows that VP patients had significantly less EEG slowing than PD patients. Conclusion– This study shows that the EEG in a group of patients with vascular parkinsonism differ from a patient group with idiopathic Parkinson's disease. Our results indicate that VP patients are not PD patients with subcortical vascular lesions, because then they would have had at least as much EEG slowing as PD patients.     

Intellectual changes in patients with MPTP-induced parkinsonism

We studied six patients with MPTP-induced parkinsonism to assess intellectual function, attention, reaction time, and depression. Eight controls with a similar history of drug abuse also participated. General intellectual function, construction, category naming, and frontal lobe function were worse in the patients; other aspects of performance were comparable. All affected women but none of the men were depressed, usually before onset of parkinsonism. The pattern of intellectual deficit in the MPTP patients was similar to that of idiopathic Parkinson's disease. Since MPTP-induced parkinsonism probably represents a purely dopaminergic deficiency, these findings suggest that changes in the dopamine system are responsible for at least some of the intellectual changes of idiopathic Parkinson's disease.     

Degenerative parkinsonism in patients with psychogenic parkinsonism: A dopamine transporter imaging study

Objectives

To evaluate patients with “clinically established” psychogenic parkinsonism (PsyP) using single-photon emission computer tomography (SPECT) with the technetium-99m labeled tracer TRODAT-1, a dopamine transporter (DAT) ligand, and investigate whether these patients have an underlying degenerative parkinsonism.

Patients and methods

Five patients with PsyP were assessed using demographic data, standard clinical scales for Parkinson's Disease (PD), and a neuropsychiatric interview. DAT imaging using SPECT with TRODAT-1 was performed, and values for caudate/putamen DAT binding potentials (BP) registered. Patients with PsyP were matched with PD (n = 5) and healthy control subjects (n = 5).

Results

The mean age (years-old) at first evaluation in the PsyP group was 37.4 ± 3.7, and the mean disease duration (years) was 3.9 ± 1.2. DAT BPs (means ± standard deviations) on right/left caudate were, respectively, 0.69 ± 0.18 and 0.70 ± 0.18 in the PD group versus 1.17 ± 0.06 and 1.12 ± 0.10 in the control group. DAT BPs on right/left putamen were, respectively, 0.48 ± 0.10 and 0.45 ± 0.06 in the PD group versus 1.10 ± 0.10 and 1.21 ± 0.43 in the control group. Two out of five patients from the PsyP group had values for DAT BP in the putamen under the cut-off (≤0.70) for controls, implying pre-synaptic dopaminergic deficit.

Conclusions

Our data in this small group of patients suggest that DAT imaging is a tool that may help in the identification of underlying degenerative parkinsonism in PsyP.     

Difference in severity of sleep apnea in patients with rapid eye movement sleep behavior disorder with or without parkinsonism

ObjectiveRapid eye movement sleep behavior disorder (RBD) is a common sleep disturbance in patients with neurodegenerative disorders. We aimed to compare sleep parameters among the different types of RBD patients.MethodsA total of 122 patients with dream enactment behavior were screened. Of these, 92 patients who were diagnosed with RBD by polysomnography were included in this study. Enrolled patients with RBD were classified into four groups based on the following diagnoses: idiopathic RBD (iRBD); RBD with Parkinson disease (PD-RBD); multiple system atrophy (MSA) with RBD (MSA-RBD); and dementia with Lewy bodies (DLB) with RBD (DLB-RBD). Various clinical and polysomnographic parameters were compared.ResultsAmong the 92 patients with RBD, 35 had iRBD, 25 had PD-RBD, 17 had MSA-RBD, and 15 had DLB-RBD. The mean apnea−hypopnea index of atypical parkinsonism with RBD (AP-RBD) group was 16.2 ± 17.7 events/h (MSA-RBD, 14.0 ± 16.6; DLB-RBD, 18.8 ± 19.1), which was significantly higher than the other groups (p < 0.05). The proportion of patients with 100% supine sleep in the AP-RBD group (44%) was higher than that in the iRBD group (14%; p = 0.030). The proportion of OSA with 100% supine sleep position was significantly higher in the MSA-RBD and DLB-RBD groups than in the iRBD group (p = 0.042 and p = 0.029, respectively).ConclusionOur study demonstrated that patients in the MSA-RBD and DLB-RBD groups had a tendency to sleeping in the supine position and a higher vulnerability to OSA compared to other RBD groups. Further cohort studies are needed to evaluate the influence of these factors on the development of parkinsonism.     

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.     

Reduced striatal [123 I]FP-CIT binding in SCA2 patients without parkinsonism

Degeneration of substantia nigra has been described in spinocerebellar ataxia type 2 (SCA2). In this study, dopamine transporter (DAT) density with [123 I]FP-CIT SPECT was studied in six SCA2 patients with no parkinsonian signs, six Parkinson's disease (PD) patients, and six controls. Marked striatal DAT loss was found in both SCA2 and PD patients. However, a more severe reduction in the caudate and a higher putamen to caudate ratio distinguished SCA2 from PD patients, suggesting a more uniform nigrostriatal impairment in SCA2. Striatal DAT density of SCA2 patients correlated with the severity of cerebellar ataxia.     

Accuracy of self-reported disability in patients with parkinsonism

For the patient, the most important aspect of parkinsonism is the degree to which the disease interferes with daily living. The patient's self-report may be the only way in which such information can be obtained. Depression and cognitive impairment, however, may influence that self-report. In the present study, three ratings of disability, from the patient, a relative, and an independent observer, showed high levels of agreement. The patients' cognitive function made a small but significant contribution to the accuracy of their self-report judged against the relative's rating. Depression, however, played no role. Agreement between patients and relatives for individual items on the disability questionnaire was reasonably high. The results suggest that patients with parkinsonism can provide accurate self-report of their level of disability, even in the presence of depression and cognitive impairment.     

Prevalence and correlates of parkinsonism in patients with primary depression

The authors examined the prevalence, clinical correlates, and longitudinal changes of parkinsonism in 94 patients with primary depression and 20 healthy control subjects. Parkinsonism was present in 20% of patients with primary depression. This syndrome was significantly associated with older age, more severe depression, and more severe cognitive impairment. In a subgroup of depressed patients, parkinsonism was reversible upon recovery from the mood disorder.     

Nigrostriatal dysfunction in patients with amyotrophic lateral sclerosis and parkinsonism

The pathomechanism of amyotrophic lateral sclerosis (ALS) with parkinsonism (ALS-P) has not been clarified. We report two patients with ALS-P who showed dysfunction of the nigrostriatal system. The first patient showed tremor dominant, asymmetric parkinsonism which was more severe on the right side, while the second patient exhibited predominant freezing of gait. Both patients showed reduced uptake of [1?F] N-(3-fluoropropyl)-2?-carbon ethoxy-3?-(4-iodophenyl) nortropane (1?F-FP-CIT) in the posterior parts of bilateral putamina on positron emission tomography (PET). Based on our PET findings, we suggest that presynaptic nigrostriatal dysfunction may be involved in the pathomechanism of parkinsonism combined with ALS.     

Treatment of parkinsonism with N-n-propyl norapomorphine and levodopa (with or without carbidopa).

The effects of the concomitant administration of N-n-propyl norapomorphine (NPA) and levodopa, with and without carbidopa, were studied in 12 patients with unsatisfactory symptom control. Double-blind evaluation of the effects of NPA with suboptimal doses of levodopa or levodopa plus carbidopa (Sinemet) showed a mean overall improvement of 44% (20% to 74%) in nine patients and improvement of the "on-off" effect in five. Dyskinesia diminished in some patients after diminution of basal medication. In three patients, plasma dopa and growth hormone patterns did not differ substantially with and without NPA. The magnitude and timing of the therapeutic and side effects did not correlate with the pattern of growth hormone secretion, which suggests that this hormone might not be instrumental in the induction of these effects. N-n-propyl norapomorphine is a useful adjunct in the long-term management of patients with unsatisfactory response to levodopa.