Substantia nigra echogenicity is correlated with nigrostriatal impairment in Machado-Joseph disease

BackgroundSeveral studies have demonstrated increased substantia nigra (SN) echogenicity in Parkinson's disease (PD) and Machado-Joseph disease (MJD). Pathological substrate of PD is characterized by dopaminergic nigrostriatal cell loss, also found in MJD. Also, SN hyperechogenicity might be associated with nigrostriatal dysfunction in PD, when comparing dopamine transporter binding with SN echogenicity. The present study aimed to correlate the SN echogenic size and striatal dopamine transporter density in MJD patients.MethodsWe performed TCS in 30 subjects and SPECT with [^99mTc]-TRODAT-1 in 18 subjects with MJD. Fifteen healthy subjects matched for age and gender formed a control group. TCS and [^99mTc]-TRODAT-1 SPECT findings from both MJD patients and control subjects were compared.ResultsThere were no differences regarding age (p = 0.358) or gender (p = 0.566) between groups (MJD versus control group). Mean DAT binding potentials and SN echogenicity were significantly different between groups. There was a significant negative correlation with regard to the SN echogenic size and the ipsilateral striatal TRODAT-1 uptake: the higher the SN echogenicity, the lower the DAT uptake in the ipsilateral cerebral hemisphere.ConclusionIncrease in SN echogenic size likely correlates with presynaptic dopaminergic nigrostriatal dysfunction in MJD, suggesting a concurrent in vivo pathophysiological mechanism.     

Dopamine transporter binding in chronic manganese intoxication

Abstract. Chronic exposure to manganese may induce parkinsonism similar to idiopathic Parkinsons disease (PD). However, clinical manifestations of manganism also have some features different from PD. The mechanisms of manganese-induced parkinsonism remain not fully understood. ^99mTc-TRODAT-1 is a cocaine analogue that can bind to the dopamine transporter (DAT) site reflecting the function of presynaptic dopaminergic terminals. The purpose of this study was to evaluate DAT function using ^99mTc-TRODAT-1 to investigate the integrity of the presynaptic dopaminergic terminals in manganese-induced parkinsonism. Brain ^99mTc-TRODAT-1 single photon emission computed tomography was performed in 4 patients with chronic manganese intoxication in a ferromanganese smelting plant in Taiwan. Twelve PD patients and 12 healthy volunteers served as abnormal and normal controls, respectively. Clinically, all manganism patients had a bradykinetic-rigid syndrome. The scores of the Unified Parkinsons Disease Rating Scale ranged between 19 and 64. The uptake values of the ^99mTc-TRODAT-1 were 0.868±0.136 in the right corpus striatum and 0.865±0.118 in the left, as compared with 0.951±0.059 and 0.956±0.058, respectively for the normal controls. The data were significantly higher than 0.250±0.070 and 0.317±0.066 respectively for the PD patients. Interestingly, there was a mild decrease in the uptake of ^99mTc-TRODAT-1 in the putamen and the ratio of putamen and caudate when compared with the normal controls. Although the DAT shows a slight decrease in the putamen of manganism patients as compared with that of the normal controls, the data indicate that the presynaptic dopaminergic terminals are not the main target of chronic manganese intoxication. In addition ^99mTc-TRODAT-1 SPECT can provide a useful, convenient and inexpensive tool for differentiation between chronic manganism and PD.     

99mTc-TRODAT-1 SPECT study in early Parkinson's disease and essential tremor

OBJECTIVE: The clinical differentiation between early Parkinson's disease (PD) and essential tremor (ET) could be difficult, therefore, the aim of this study was to investigate 99mTc-TRODAT-1 SPECT as an applicable tool in this field. METHODS: 99mTc-TRODAT-1 single photon emission computed tomography (SPECT) was performed in 10 healthy volunteers, 27 patients with idiopathic PD (Hoehn and Yahr 1-1.5) and 12 patients with ET. The ratio of striatal (99m)Tc-TRODAT-1 binding was calculated as the index of (striatum - occipital cortex)/occipital cortex. RESULTS: Compared with the striatal 99mTc-TRODAT-1 uptake in the ET group (0.49 +/- 0.07) or healthy controls (0.54 +/- 0.18), there was a significant decrease in the bilateral striatums of early PD, with a greater reduction in the contralateral striatum (0.27 +/- 0.08) than ipsilateral one (0.36 +/- 0.10, P < 0.01). Its sensitivity and specificity of differentiating early PD from ET was 96.4% and 91.7% respectively. CONCLUSION: 99mTc-TRODAT-1 SPECT can detect the dysfunction of nigrostriatal system in patients with early PD and provided a feasible tool to help differentiate early PD from ET.     

Substantia nigra echogenicity: A structural correlate of functional impairment of the dopaminergic striatal projection in Parkinson's disease

Transcranial sonography (TCS) reveals abnormal spatial extension of substantia nigra (SN) echogenicity in a high proportion of patients with Parkinson's disease (PD). It has been proposed that this abnormality represents a structural trait that is mechanistically distinct from degeneration of dopaminergic nigrostriatal projection neurons. We sought to clarify the relationship between sonographic abnormalities of SN and dysfunction of striatal dopaminergic neurotransmission. We studied 50 patients with PD. The spatial extension of the echogenic SN area was compared with the activity of presynaptic striatal dopamine reuptake transporters, assessed in the same patients by I‐123‐2‐beta‐carbomethoxy‐3‐beta‐(4‐iodophenyl)‐tropane (β‐CIT) single‐photon emission computed tomography (SPECT). Extension of echogenic SN area correlated (inversely) with striatal activity of presynaptic dopamine reuptake transporter in PD patients (R = ?0.417; P = 0.003) and with the equivalent levodopa dose (R = 0.380; P = 0.006; linear regression analysis). Findings support the hypothesis that in PD abnormal extension of echogenic SN area provides a direct structural marker of degeneration of SN neurons. Therefore, in PD, TCS and β‐CIT assess pathophysiologically related phenomena. © 2009 Movement Disorder Society     

Drug-naive patients with Parkinson’s disease in Hoehn and Yahr stages I and II show a bilateral decrease in striatal dopamine transporters as revealed by [123I]β-CIT SPECT

Ten healthy subjects and 16 patients with early Parkinson’s disease (PD) were examined with single photon emission computed tomography (SPECT) and [¹²³I]β-CIT, a ligand for the dopamine (DA) transporter. Only drug-naive patients were examined since the expression of and binding to DA transporters may be influenced by dopaminergic medication. The main finding was a significant reduction in [¹²³I]β-CIT binding in the ipsi- and contralateral striatal regions, especially in the putamen, which showed a mean reduction of 65% of the control mean. Discriminant function analysis of the putaminal [¹²³I]β-CIT binding measures classified 100% of the cases in the correct group. Disease severity correlated negatively and highly significantly with the binding measures. Tremor ratings did not correlate with the SPECT measures, whereas rigidity, and to a lesser extent bradykinesia, did. Patients with unilateral PD showed a bilateral loss of striatal DA transporters. Our findings indicate that with [¹²³I]β-CIT SPECT it is possible to diagnose PD in subjects with very mild symptoms and signs. Moreover, finding a bilateral loss of striatal DA transporters in patients with unilateral PD also suggests that it may be possible to identify subjects in the preclinical phase of the disease. Received: 12 February 1997 Received in revised form: 12 September 1997 Accepted: 16 September 1997     

Comparative study of the substantia nigra echogenicity and 123I-Ioflupane SPECT in patients with synucleinopathies with and without REM sleep behavior disorder

ObjectivesHyperechogenicity of the substantia nigra (SN) and abnormal dopamine transporter-single-photon emission computed tomography (DAT-SPECT) are biomarkers commonly used in the assessment of prodromal synucleinopathy. Our goals were as follows: (1) to compare echogenicity of SN in idiopathic rapid eye movement (REM) behavior disorder (iRBD), Parkinson's disease (PD) without RBD (PD-noRBD), PD with RBD (PD + RBD), and control subjects; and (2) to examine association between SN degeneration assessed by DAT-SPECT and SN echogenicity.Patients/methodsA total of 61 subjects with confirmed iRBD were examined using Movement Disorders Society-unified PD rating scale (MDS-UPDRS), TCS (transcranial sonography) and DAT-SPECT. The results were compared with 44 patients with PD (25% PD + RBD) and with 120 age-matched healthy subjects.Results and conclusionThe abnormal SN area was found in 75.5% PD, 23% iRBD and 7.3% controls. Median SN echogenicity area in PD (0.27 ± 0.22 cm²) was higher compared to iRBD (0.07 ± 0.07 cm²; p < 0.0001) and controls (0.05 ± 0.03 cm²; p < 0.0001). SN echogenicity in PD + RBD was not significantly different from PD-noRBD (0.30 vs. 0.22, p = 0.15).Abnormal DAT-SPECT was found in 16 iRBD (25.4%) and 44 PD subjects (100%). No correlation between the larger SN area and corresponding putaminal binding index was found in iRBD (r = −0.13, p = 0.29), nor in PD (r = −0.19, p = 0.22).The results of our study showed that: (1) SN echogenicity area in iRBD was higher compared to controls, but the hyperechogenicity was present only in a minority of iRBD patients; (2) SN echogenicity and DAT-SPECT binding index did not correlate in either group; and (3) SN echogenicity does not differ between PD with/without RBD.     

Substantia nigra hyperechogenicity in healthy controls: a [18Fluoro] Dopa-PET follow-up study

In order to assess nigrostriatal function over time in healthy subjects with substantia nigra hyperechogenicity (SN+) believed to be at higher risk for Parkinson’s disease (PD), ten healthy SN+ subjects underwent [¹⁸Fluoro] Dopa positron emission tomography (PET) twice—at baseline and after a mean of 7.3 years. Neurological examination took place at study inclusion followed by a structured telephone interview focusing on early Parkinsonian symptoms at the time point of second PET study and 3.5 years later. The [¹⁸Fluoro] Dopa uptake remained unchanged in eight of ten participants. In the other two subjects marked unilateral reduction of putaminal [¹⁸Fluoro] Dopa uptake ratios appeared over the time, followed by complaints of a clinically manifest PD in one. We suggest that the progressive pathological PET findings in 20 % and PD conversion in 10 % of our cohort may be in accordance with the presumed proportion of SN+ individuals eventually developing PD based on SN+ prevalence of 10 % within the healthy population, being ten times higher than PD prevalence in the age of over 60 years. Our findings hint towards a significance of SN+ indicating a high risk for PD in some extrapyramidally healthy SN+ individuals.     

Normal dopamine transporter binding in dopa responsive dystonia

We report the clinical manifestations of dopa responsive dystonia (DRD) in 2 patients from the same family. The brain magnetic resonance images (MRI) were normal. The dopamine transporter (DAT) imaging with ^99mTc-TRODAT-1 was performed in the 2 probands, 8 patients with young onset Parkinson disease (YOPD) and 16 normal controls. The ratios of ^99mTc-TRODAT-1 brain SPECT in the striatum were 2.40 ± 0.12 (right) and 2.30 ± 0.17 (left) in these 2 DRD patients as compared with 1.38 ± 0.18 (right), 1.41 ± 0.20 (left) in YOPD patients, and 2.15 ± 0.35 (right), 2.14 ± 0.32 (left) in normal controls respectively. A normal DAT uptake was found in DRD suggesting a normal presynaptic nigrostriatal dopaminergic terminal. We conclude that a normal DAT in parkinsonian patients can differentiate DRD from YOPD. In addition, DAT with ^99mTc-TRODAT-1 is a reliable and convenient tool to study the function of the presynaptic dopaminergic axonal terminals. Received: 18 October 2001 Received in revised form: 1 February 2002 Accepted: 6 February 2002     

Lack of effect of polymorphisms in dopamine metabolism related genes on imaging of TRODAT-1 in striatum of asymptomatic volunteers and patients with Parkinson's disease.

SPECT scanning using (99)Tc-TRODAT-1, a ligand that binds to dopamine transporters, may be useful for detection of early Parkinson's disease (PD), diagnosis of presymptomatic individuals, and monitoring disease progression. Understanding whether genetic factors contribute to inter-individual variability is crucial for interpreting imaging results in the context of disease pathophysiology. We tested whether polymorphisms in the genes for catechol-O-methyltransferase (COMT), monoamine-oxidase B (MAO-B), and the dopamine transporter (DAT) influence dopamine uptake parameters in the striatum in vivo in asymptomatic volunteers and patients with PD as measured with (99)Tc-TRODAT-1. (99)Tc-TRODAT-1 binding declined with age in both asymptomatic volunteers and PD patients, and depended on disease duration in PD patients. We found no significant association between COMT, MAO-B, and DAT polymorphisms and results of (99)Tc-TRODAT-1 testing in asymptomatic volunteers or patients with PD. In PD patients, the age of disease onset and speed of progression did not differ based on these polymorphisms. These results demonstrate that these specific genetic variations do not alter the fidelity of (99)Tc-TRODAT-1 as a measure of dopaminergic function in asymptomatic volunteer individuals or patients with PD.     

Role of dopaminergic treatment in dopamine receptor down-regulation in advanced Parkinson disease: a positron emission tomographic study

BACKGROUND: In patients with advanced Parkinson disease (PD) who are undergoing long-term treatment with a dopaminergic medication, a down-regulation of striatal dopamine D2 receptor expression has been demonstrated and interpreted as a consequence of either the disease itself or dopaminergic drug administration. OBJECTIVE: To compare, using positron emission tomography, the striatal binding of raclopride carbon C 11, a dopamine D2 receptor ligand, in PD patients who completely discontinued dopaminergic therapy (off drug) with that in PD patients who continued receiving dopaminergic therapy (on drug) after undergoing subthalamic nucleus stimulation. MAIN OUTCOME MEASURES: The positron emission tomographic data were acquired in off-stimulation and, for 12 hours, off-medication conditions. Five off-drug PD patients, 7 on-drug PD patients, and 8 healthy subjects participated. RESULTS: In off-drug PD patients, the putaminal raclopride C 11 binding was 24% higher than in on-drug PD patients. The same tendency was noted for the caudate nucleus, but was not significant (P=.07). Compared with control subjects, the putaminal raclopride C 11 binding was increased by 21% in off-drug and was normal in on-drug PD patients. Compared with controls, the caudate raclopride C 11 binding was reduced by 23% in on-drug and was normal in off-drug PD patients. Further analysis using statistical parametric mapping showed a significant increase of binding bilaterally in the caudate nucleus and putamen in off-drug compared with on-drug PD patients (P=.002 at cluster level). CONCLUSIONS: The down-regulation of dopamine D2 receptors probably relates to the long-term and intermittent administration of dopaminergic treatments rather than to disease progression. This phenomenon is reversed by the complete withdrawal of dopaminergic drugs. Furthermore, an up-regulation of putaminal dopamine D2 receptors is demonstrated in late-stage PD after dopaminergic drug withdrawal.     

Reversible abnormal functional neuroimaging presentations in polycythemia vera with chorea

We report a case of polycythemia vera with chorea in which the brain metabolism and dopamine system were investigated using 2-[¹⁸F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET) and ^99mTc-labeled tropane dopamine transporter (^99mTc-TRODAT-1) single photon emission computed tomography (SPECT). Along with normalization of the hematocrit and clinical symptoms after consecutive phlebotomies, the FDG PET scan and ^99mTc-TRODAT-1 SPECT images returned towards normal. It is hypothesized that the development of polycythemia chorea is associated with a reversible alteration in the corticobasal ganglia metabolism and disturbed dopaminergic function.     

An magnetic resonance imaging T2*‐weighted sequence at short echo time to detect putaminal hypointensity in Parkinsonisms

At 1.5 T, T2*‐weighted gradient echo (GE) sequences are more sensitive in revealing mineral deposition in the basal ganglia than standard T2 weighted sequences. T2*‐weighted GE sequences, however, may detect putaminal hypointensities either in patients affected by parkinsonian syndromes or in healthy subjects. The aim of this study was to identify the magnetic resonance imaging (MRI) T2*‐weighted sequence which more specifically detected putaminal hypointensities differentiating atypical parkinsonian syndromes from Parkinson's disease (PD) and control subjects. In a sample of 38 healthy subjects, we performed three T2*‐weighted GE sequences at increasing time echo (TE; TE = 15 millisecond, TE = 25 millisecond, and echoplanar at TE = 40 millisecond; T2* sequences study). The sequence not showing any putaminal abnormality in the healthy subjects was then used to assess putaminal signal intensity in 189 patients with PD, 20 patients with multiple system atrophy (MSA), 41 patients with progressive supranuclear palsy (PSP), and in 150 age and sex‐matched control subjects. In the T2* sequences study, the T2*‐weighted TE = 15 (T2*/15) did not show any putaminal abnormalities in the healthy subjects. This sequence detected putaminal hypointensities in a significantly higher proportion of patients with MSA (35%, P < 0.05) and PSP (24.4%, P < 0.05) than in patients with PD (5.3%), but in none of the controls. The sensitivity of putaminal hypointensity in T2*/15 sequence was 25.4% for PD, 43.9% for PSP, and 55% for MSA versus controls whereas the specificity was 93.2% for all groups. Despite the suboptimal sensitivity, the high specificity of the T2*/15 sequence performed on routine MRI suggests its usefulness in clinical practice for identifying putaminal hypointensities associated with parkinsonian disorders. © 2010 Movement Disorder Society     

Reproducibility of brain dopamine transporter binding with Tc-99m TRODAT-1 SPECT in healthy young men

Single photon emission computed tomography (SPECT) with Tc-99m TRODAT-1 as ligand can be used to evaluate striatal dopamine transporters (DAT) in young subjects. The purpose of this study was to evaluate the reproducibility of (99m)Tc-TRODAT-1 SPECT in DAT binding in healthy young men. Fourteen healthy young men were recruited. The test-retest studies were performed 1week apart. Specific uptake ratios (SUR) of the striatum (ST) and its subregions, the caudate (CA) and the putamen (PU), were measured using the occipital cortex as the reference tissue. The reliability of the two measurements between test and retest, showed significant correlations for the ST, CA and PU, was demonstrated by calculating the intraclass correlation coefficient (ICC). Thus, (99m)Tc-TRODAT-1 SPECT might provide a reproducible and reliable tool in clinical management of young patients with DAT-related disorders.     

The interaction between dopamine transporter function,gender differences,and possible laterality in depression

The Dopamine Transporter (DAT) can reflect the general state of striatal dopamine activity. This current study examined the role of DAT in depressed patients before and after bupropion treatment. Twenty-three patients with major depression were treated with bupropion for 8 weeks. Before and after the treatment, they and 20 normal subjects received the radioligand ^99mTc-TRODAT-1 single photon emission tomography scan (SPECT). Subjects were assessed with the Hamilton Depression Rating Scale. All DAT images were spatially normalized to an averaged brain template, and the specific binding ratios of the striatum, caudate, and putamen were calculated according the formulae of: [region counts] / [occipital counts] - 1. Depressed patients had greater DAT availability on both sides of the striatum. DAT binding was significantly decreased in the striatum after bupropion treatment. Women had higher initial and final DAT binding in the right and left caudate when compared to depressed men. DAT binding decreased in all areas of the brain in women after successful antidepressant treatment, but only in the right caudate of men. Depressed patients had a greater availability of DAT; it was decreased after bupropion treatment.Women seemed to have more DAT availability.     

Dopamine transporter dysfunction in Han Chinese people with chronic methamphetamine dependence after a short-term abstinence

Single-photon emission-computed tomography (SPECT) after the administration of ^99mTc-TRODAT-1 was performed on healthy subjects and subjects with methamphetamine (METH)dependence at time 1 (T1) after 24–48 h of abstinence, time 2 (T2) after 2 weeks of abstinence, and time 3 (T3) after 4 weeks of abstinence. In contrast to values in controls, the values of the striatal DAT specific uptake ratios (SURs) in subjects with METH dependence were significantly lower at T1 (n=25), T2 (n=9), and T3 (n=8); a mild increase in SURs was observed at T2 and T3, but values were still significantly lower than those in controls. In subjects with METH dependence, there was a trend for a negative correlation of striatal DAT SURs and craving for METH at T1. METH craving, anxiety and depression scores significantly decreased from T1 to T2 to T3. We conclude that Han Chinese people with METH dependence experience significant striatal DAT dysfunction, and that these changes may be mildly reversible after 4 weeks of abstinence, but that DAT levels still remain significantly lower than those in healthy subjects. The mild recovery of striatal DAT may parallel improvements in craving, anxiety and depression.     

Diffusion-weighted MRI differentiates the Parkinson variant of multiple system atrophy from PD

OBJECTIVE AND BACKGROUND: Routine MRI as well as MR volumetry and MRS have been shown to contribute to the differential diagnosis of the Parkinson variant of multiple system atrophy (MSA-P) and PD. However, it is currently unknown whether diffusion-weighted imaging (DWI) discriminates these disorders. METHODS: Ten patients with MSA-P (mean age, 64 years) were studied, 11 with PD (mean age, 64 years), and seven healthy volunteers (mean age, 59 years) matched for age and disease duration. Regional apparent diffusion coefficients (rADC) were determined in different brain regions including basal ganglia, gray matter, white matter, substantia nigra, and pons. RESULTS: Patients with MSA-P had higher putaminal rADC (median 0.791 x 10(3)/mm(2)/s) than both patients with PD (median 0.698 x 10(3)/mm(2)/s, p < 0.001) and healthy volunteers (median 0.727 x 10(3)/mm(2)/s, p < 0.001). There were no significant differences in putaminal rADC between patients with PD and healthy volunteers. Moreover, none of the putaminal rADC values in the PD and control group surpassed the lowest value in the MSA-P group. There were no significant group differences in the rADC values in other brain regions such as pons, substantia nigra, globus pallidus, caudate nucleus, thalamus, or gray and white matter. Putaminal rADC values correlated significantly with Unified PD Rating Scale OFF scores in patients with MSA as measured by the Spearman rank test. CONCLUSION: DWI, even if measured in the slice direction only, is able to discriminate MSA-P and both patients with PD and healthy volunteers on the basis of putaminal rADC values. The increased putaminal rADC values in Parkinson variant of multiple system atrophy are likely to reflect ongoing striatal degeneration, whereas most neuropathologic studies reveal intact striatum in PD. Diffusion-weighted imaging may represent a useful diagnostic tool that can provide additional support for a diagnosis of Parkinson variant of multiple system atrophy.     

Sonographic discrimination of dementia with Lewy bodies and Parkinson's disease with dementia

Objective To study the use of transcranial sonography (TCS) in discriminating between patients with dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). Methods Fourteen patients with DLB, 31 with PDD and 73 with PD without dementia (PDnD) were studied with TCS. Results All assessable patients with DLB, 97% with PDD, and 94% with PDnD showed at least unilateral hyperechogenicity of substantia nigra (SN). However, bilateral marked SN hyperechogenicity was present in 80% of DLB patients but only in one third of PDD and PDnD patients, and was associated with younger age at disease onset in PD but not in DLB. An asymmetry index ≥ 1.15 of bilateral SN echogenic sizes, estimated by division of larger size by smaller size, was found in 69% of PDD patients but only 20% of DLB patients. Combination of SN echogenic sizes, asymmetry indices and onset age discriminated PDD from DLB with a sensitivity of 96%, a specificity of 80% and a positive predictive value of 93%. TCS of brainstem raphe, thalami, lenticular nuclei, caudate nuclei and ventricle widths did not discriminate between DLB and PDD. Compared with PDnD patients, DLB and PDD patients exhibited significantly larger widths of third ventricle and of frontal horns. In PDD patients, scores on the Unified Parkinson's Disease Rating Scale correlated with widths of third ventricle and of frontal horns. Conclusions SN hyperechogenicity is typical for PDD and DLB.However, size, asymmetry and relation of SN hyperechogenicity to age at disease onset discriminate PDD from DLB.     

Diagnostic value of brain MRI and 18F‐FDG PET in the differentiation of parkinsonian type multiple system atrophy from Parkinson’s disease

Background and purpose: Differentiation between parkinsonian type multiple system atrophy (MSA‐P) and Parkinson’s disease (PD) is important but often difficult. We investigated the diagnostic value of brain magnetic resonance imaging (MRI) and ¹⁸F‐fluorodeoxyglucose positron emission tomography (¹⁸F‐FDG PET) in differentiating MSA‐P from PD. Methods: Twenty‐four patients with MSA‐P (16 probable and 8 possible) and eight patients with PD were included in this study. Results: For analysis using the putaminal findings, the sensitivities were 58.3% by visual analysis of brain MRI, 95.8% by visual analysis of ¹⁸F‐FDG PET, and 79.2% by statistical parametric mapping (SPM) analysis of ¹⁸F‐FDG PET in differentiating MSA‐P from PD; the specificity was 100% for each analysis. Using the putaminal findings, visual analysis of ¹⁸F‐FDG PET had a higher sensitivity compared with brain MRI (P = 0.004) and SPM analysis of ¹⁸F‐FDG PET revealed a tendency towards higher sensitivity compared with brain MRI (P = 0.063). For analysis using both putaminal and infratentorial findings, the sensitivities were 79.2% by visual analysis of brain MRI, 95.8% by visual analysis of ¹⁸F‐FDG PET, 95.8% by SPM analysis of ¹⁸F‐FDG PET in differentiating MSA‐P from PD; the specificity was 100% for each analysis. Conclusion: Both brain MRI and ¹⁸F‐FDG PET showed diagnostic usefulness in differentiating MSA‐P from PD, with ¹⁸F‐FDG PET being more sensitive than brain MRI.     

Neurophysiological Studies and Non-Motor Symptoms Prior to Ataxia in a Patient with Machado–Joseph Disease: Trying to Understand the Natural History of Brain Degeneration

Spinocerebellar ataxia type 3 or Machado–Joseph disease is the most common spinocerebellar ataxia. In this neurological disease, anatomical, physiological, clinical, and functional neuroimaging demonstrate a degenerative process besides the cerebellum. We performed neurophysiological and neuroimaging studies—polysomnography, transcranial sonography, vestibular-evoked myogenic potential, single-photon emission computed tomography (SPECT) with ^99mTc-TRODAT-1, and a formal neuropsychological evaluation in a patient with sleep complaints and positive testing for Machado–Joseph disease, without cerebellar atrophy, ataxia, or cognitive complaints. Polysomnography disclosed paradoxical high amplitude of submental muscle, characterizing REM sleep without atonia phenomenon. Transcranial sonography showed hyperechogenicity of the substantia nigra. There was an absence of vestibular-evoked myogenic potentials on both sides in the patient under study, in opposite to 20 healthy subjects. Brain imaging SPECT with ^99mTc-TRODAT-1 demonstrated a significant lower DAT density than the average observed in six healthy controls. Electroneuromyography was normal. Neuropsychological evaluation demonstrated visuospatial and memory deficits. Impairment of midbrain cholinergic and pontine noradrenergic systems, dysfunction of the pre-synaptic nigrostriatal system, changes in echogenicity of the substantia nigra, and damage to vestibulo-cervical pathways are supposed to occur previous to cerebellar involvement in Machado–Joseph disease.     

Transcranial brain sonography in Parkinson's disease with restless legs syndrome

Substantia nigra (SN) hyperechogenicity assessed by transcranial brain sonography (TCS) is a characteristic finding in idiopathic Parkinson's disease (PD). In contrast, SN hypoechogenicity on TCS has been recently demonstrated in restless legs syndrome (RLS). RLS is one of the most common sleep problems in PD, but the pathophysiologic relationship between these two disorders has not been thoroughly elucidated. We compared the SN echogenicities of PD patients with and without RLS to investigate whether comorbid RLS in PD affects SN echogenicity and to explain the echogenic differences between idiopathic RLS (iRLS) and secondary PD–related RLS (pRLS). Sixty‐three PD patients (median age 64.6 ± 10.6 years), 40 iRLS patients (53.1 ± 11.7 years), and 40 healthy controls (69.1 ± 2.3 years) were enrolled in our study. All subjects answered a sleep questionnaire and underwent TCS. PD patients were subdivided into two groups, PD with RLS (PD+RLS, n = 26) and PD without RLS (PD‐RLS, n = 37), and the sonographic findings of each group were compared. Although significant hyperechogenicity was detected in both the SN and SN/midbrain ratios in both PD subgroups compared with the controls and the iRLS group (P < 0.001), there were no significant differences in SN echogenicity between the PD+RLS and PD‐RLS groups. Meanwhile, iRLS patients showed significant SN hypoechogenicity. In conclusion, comorbid RLS in PD did not have an impact on the sonographic SN findings. These results suggest that the pathogenesis of pRLS and iRLS involve different mechanisms. Further study will be required to clarify the association between RLS and PD. © 2010 Movement Disorder Society