Diffuse white matter lesions in carbon disulfide intoxication: microangiopathy or demyelination

Long-term exposure to carbon disulfide (CS(2)) may induce diffuse encephalopathy with parkinsonism, pyramidal signs, cerebellar ataxia, and cognitive impairments, as well as axonal polyneuropathy. The pathogenic mechanisms of diffuse encephalopathy are unclear, although vasculopathy and toxic demyelination have been proposed. Recently, we have encountered a patient who developed headache, limb tremors, gait disturbance, dysarthria, memory impairment, and emotional lability after long-term exposure to CS(2). The brain magnetic resonance images (MRI) showed diffuse hyperintensity lesions in T(2)-weighted images in the subcortical white matter, basal ganglia, and brain stem. The brain computed tomography perfusion study revealed a diffusely decreased regional cerebral blood flow and prolonged regional mean transit time in the subcortical white matter and basal ganglion. To our knowledge, there have been few reports demonstrating diffuse white matter lesions in chronic CS(2) encephalopathy using brain MRI. In addition, the (99m)Tc-TRODAT-1 single photon emission computed tomography showed a normal uptake of the dopamine transporter, indicating a normal presynaptic dopaminergic pathway. We conclude that diffuse white matter lesions may develop after chronic exposure to CS(2), possibly through microangiopathy. In addition, CS(2) poisoning can be considered as one of the causes of chronic leukoencephalopathy.     

Multiple sclerosis exceptionally presenting as parkinsonism responds to intravenous methylprednisolone

Parkinsonism due to multiple sclerosis (MS) is rare. In previously reported patients with MS-induced parkinsonism, MS manifested first, followed a typical clinical course, and parkinsonism developed later in the course of the illness. We report a 52-year-old male presenting with parkinsonism as the initial manifestation of MS, in whom a subsequent MS relapse consisted of marked deterioration in parkinsonism, a clinical pattern not previously described in MS. A brain MRI demonstrated involvement of the substantia nigra and basal ganglia. This patient illustrates that the clinical presentation and progression of MS may rarely be characterised by predominating parkinsonian features which are reversible by treatment with intravenous methylprednisolone and interferon β1a.     

Carbon disulfide neurotoxicity: Taiwan experience

Carbon disulfide (CS2) intoxication may induce peripheral neuropathy, encephalopathy, and cardiovascular diseases. In our studies, abnormalities of the peripheral nerves including clinical symptoms and electrophysiological findings were still present 3 years after cessation of CS2 exposure. The data indicate that CS2 neuropathy may persist for a period of time. The involvement of central nervous system may continue even longer. Brain magnetic resonance images usually show multiple high signal intensities in the basal ganglia and subcortical white matter suggesting a vascular event particularly in the small vessels. In addition, a patient with diffuse demyelination in the cerebral hemispheres also showed a diffuse decrease of regional cerebral blood flow indicating a microangiopathy. Therefore, CS2 exposure should be considered as a risk factor for strokes and one of the causes for diffuse leucoencephalopathy. Because CS2 may induce parkinsonian features, a differential diagnosis between CS2 parkinsonism and idiopathic parkinsonism is important. In our study, dopamine transporter with 99mTc-TRODAT-1 brain single photon emission computed tomography showed a normal uptake in the corpus striatum. The data suggest a normal presynaptic dopaminergic pathway function and provide useful information in differentiation. The involvement of cardiovascular systems may be due to thrombotic effects rather than atherogenic effects. In addition, absorption of CS2 through skin is also significant particularly in workers with skin lesions.     

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     

Corticosteroid-responsive parkinsonism associated with primary Sjögren's syndrome

A 74-year-old woman with primary Sjögren's syndrome confirmed by salivary gland biopsy presented with parkinsonism. Magnetic resonance imaging (MRI) of the brain revealed multiple small high intensity lesions in the deep white matter, basal ganglia and pons on T₂-weighted images. Treatment with -dopa failed to improve the parkinsonian features. After the initiation of prednisolone 30 mg/day, the parkinsonian signs and symptoms significantly improved. Some lesions on MRI were decreased in size after corticosteroid therapy. These findings suggest that parkinsonism associated with primary Sjögren's syndrome is at least in part attributable to small vessel vasculopathy such as focal inflammation or edema.     

Carbon disulfide encephalopathy: cerebral microangiopathy

To understand cerebral blood circulation after long-term exposure to carbon disulfide (CS2), four patients with encephalopathy and polyneuropathy, who had worked in a viscose rayon plant, were studied. Clinical and laboratory examinations, including brain magnetic resonance images (MRI), computed tomography (CT), CT perfusion, and CT angiography, were carried out. Brain CT and MRI disclosed mild cortical atrophy in all four patients, and multiple lesions in the subcortical white matter, and basal ganglia in three patients. Brain CT angiography and perfusion revealed a statistically significant decrease of cerebral blood flow (CBF) in the total brain parenchyma and basal ganglia, and a decrease of the cerebral blood volume (CBV) in the basal ganglia and a prolonged mean transit time (MTT) in the total brain parenchyma, and the territories of the internal carotid artery (ICA), basal ganglia and occipital lobe. In conclusion, the decrease of CBV and CBF, and the prolonged MTT in the total brain parenchyma, ICA, basal ganglia and occipital lobes, indicated a microangiopathy in patients with CS2 encephalopathy.     

Genetic and DAT imaging studies of familial parkinsonism in a Taiwanese cohort

We here summarize the results of genetic investigations on a series of 82 parkinsonian patients from 60 families in Taiwan. We found 13 parkin patients in 7 families (12%), 2 PINK1 sibs from 1 family, and 1 LRRK2 patient from 1 family with I2012T mutation. We also identified SCA2 in 8 patients from 5 families (8%) and SCA3 in 3 patients from 1 family, all presenting with parkinsonian phenotype. In the available patients with parkin, PINK1, SCA2 and SCA3, the dopamine transporter (DAT) scan revealed that the reduction of uptake was primarily observed in the bilateral putamen, basically sharing a similar pattern with that in idiopathic Parkinson's disease. We concluded that the genetic causes contributed to about 25% of our series of familial parkinsonism. The parkin mutations and SCA2 were the most frequent genetic causes in our series with Chinese ethnicity. The results of DAT scan indicated that bilateral putamen was essentially involved in various genetically-caused familial parkinsonism.     

^99mTc-TRODAT-1 SPECT多巴胺转运体显像在诊断早期帕金森病中的意义

目的探讨99mTc-TRODAT-1 SPECT多巴胺转运体(DAT)显像在诊断早期帕金森病(PD)中的意义.方法对62例早期PD、12例晚期PD及10名正常人进行99mTc-TRODAT-1 SPECT 基底节DAT显像,选取纹状体区和小脑为感兴趣区,计算两者的放射性比值,比较3组间该比值的差异,并分析早期PD患者DAT放射性结合率与H&Y分级及UPDRS评分之间的相关性.结果PD患者基底节99m Tc-TRODAT-1摄取率显著降低,早期PD患者病变较重肢体对侧纹状体放射性摄取率较同侧纹状体显著下降.PD患者纹状体区放射性摄取率与PD患者的H&Y分级呈负相关,而与UPDRS Ⅱ、Ⅲ评分无相关性.结论99mTc-TRODAT-1 SPECT基底节 DAT显像可用于临床早期PD的诊断.     

Impact of subcortical white matter lesions on dopamine transporter SPECT

Subcortical arteriosclerotic encephalopathy (SAE) can affect the nigrostriatal system and presumably cause vascular parkinsonism (VP). However, in patients with SAE, the differentiation of VP from idiopathic Parkinson’s disease (IPS) is challenging. The aim of the present study was to examine the striatal dopamine transporter (DAT) density in patients with parkinsonism and SAE. Fifteen consecutive patients with parkinsonian symptoms displayed SAE, as detected by magnetic resonance imaging (MRI). Fifteen retrospectively chosen, matched patients with diagnosis of IPS without any abnormalities in MRI served as a reference group. DAT SPECT was performed using the tracer ¹²³I-FP-CIT. Scans were acquired on a triple-head SPECT system (Multispect 3, Siemens) and analysed using the investigator-independent BRASS? software (HERMES). In the SAE group, a DAT deficit was observed in 9/15 patients. In contrast, all patients from the IPS group showed a reduced DAT binding (p = 0.008). The specific binding ratios (BR) of putamen contralateral to the side of the more affected limb versus occipital lobe were in trend higher in patients with SAE versus patients in the IPS-group (p = 0.053). Indices for putaminal asymmetry (p = 0.036) and asymmetry caudate-to-putamen (p = 0.026) as well as the ratio caudate-to-putamen (p = 0.048) were significantly higher in IPS patients having no SAE. DAT deficit was less pronounced in patients with SAE and parkinsonism than in patients with IPS without any abnormalities in the MRI. A potential role of DAT SPECT in the differential diagnosis of VP and IPS requires more assessments within prospective studies.     

18F]FDOPA PET and clinical features in parkinsonism due to manganism.

Manganese exposure reportedly causes a clinically and pathophysiologically distinct syndrome from idiopathic Parkinson's disease (PD). We describe the clinical features and results of positron emission tomography with 6-[18F]fluorodopa ([18F]FDOPA PET) of a patient with parkinsonism occurring in the setting of elevated blood manganese. The patient developed parkinsonism associated with elevated serum manganese from hepatic dysfunction. [18F]FDOPA PET demonstrated relatively symmetric and severely reduced [18F]FDOPA levels in the posterior putamen compared to controls. The globus pallidum interna had increased signal on T1-weighted magnetic resonance imaging (MRI) images. We conclude that elevated manganese exposure may be associated with reduced striatal [18F]FDOPA uptake, and MRI may reveal selective abnormality within the internal segment of the pallidum. This case suggests that the clinical and pathophysiological features of manganese-associated parkinsonism may overlap with that of PD.     

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.     

Carbon disulfide vasculopathy: a small vessel disease

We present the clinical manifestations of 4 male patients with acute stroke-like symptoms and polyneuropathy after long-term exposure to carbon disulfide (CS2) in a viscose rayon plant. The ages of onset of polyneuropathy ranged from 42 to 45 years with a duration of CS2 exposure between 6 and 21 years. The ages of onset of stroke were from 42 to 48 years. The risk factors for stroke including heart disease and diabetes were denied, except for smoking in 4, hyperlipidemia in 2 and hypertension in 1. At the initial visit in 1992, only 2 patients developed sudden onset of hemiparesis suggesting a lacunar stroke before the diagnosis of CS2 intoxication. Brain computed tomography (CT) scans showed low-density lesions in the basal ganglia in 2 patients, cortical atrophy in 1 and normal in 1. Brain magnetic resonance image (MRI) study disclosed multiple lesions in the corona radiata and basal ganglia on T(2)-weighted images in 3 patients and cortical atrophy in 1. After the diagnosis, they left their jobs for a CS2-free environment, and improvement of the working conditions was noted. During 5 years follow-up period, another 2 patients also developed an acute episode of stroke with hemiparesis. Brain CT and/or MRI follow-up studies in these 2 patients revealed new lesions in the basal ganglia and corona radiata. Intriguingly, a patient with previous stroke also developed new lesions in the bilateral thalami and brainstem. Carotid Doppler scan, transcranial Doppler scan and/or cerebral angiography did not show any prominent stenosis or occlusion in the major intracranial large arteries. We conclude that encephalopathy may occur in patients after long-term CS2 exposure, probably due to impaired cerebral perfusion. The lesions tend to occur in the basal ganglia, corona radiata and even brainstem, particularly involving the small-sized vessels. In addition, the cerebral lesions may progress even after cessation of CS2 exposure. Therefore, we suggest that CS2 exposure may be a risk factor for stroke.     

Role of dopamine transporter imaging in routine clinical practice.

Functional imaging of the dopamine transporter (DAT) defines integrity of the dopaminergic system and has its main clinical application in patients with mild, incomplete, or uncertain parkinsonism. Imaging with specific single positron emission computerised tomography ligands for DAT (FP-CIT, beta-CIT, IPT, TRODAT) provides a marker for presynaptic neuronal degeneration. Striatal uptake correlates with disease severity, in particular bradykinesia and rigidity, and monitoring of progression assists in clinical trials of potential neuroprotective drugs. DAT imaging is abnormal in idiopathic Parkinson's disease, multiple system atrophy and progressive supranuclear palsy and does not distinguish between these disorders. Dopamine loss is seen even in the earliest clinical presentations of true parkinsonism; a normal scan suggests an alternative diagnosis such as essential tremor, vascular parkinsonism (unless there is focal basal ganglia infarction), drug-induced parkinsonism, or psychogenic parkinsonism. Congruence between working clinical diagnosis and DAT imaging increases over time in favour of baseline DAT imaging results. Additional applications are characterising dementia with parkinsonian features (abnormal results in dementia with Lewy bodies, normal in Alzheimer's disease); and differentiating juvenile-onset Parkinson's disease (abnormal DAT) from dopa-responsive dystonia (normal DAT).     

Parkinsonian Syndrome Complicating Systemic Lupus Erythematosus

Two girls with florid extrapyramidal parkinsonism complicating systemic lupus erythematosus (SLE) are reported. One patient (15 years old) presented with extreme rigidity, irritability, and mutism initially diagnosed as acute psychosis. Examination revealed severe extrapyramidal akinetic mutism, along with marked restlessness. CT and MRI imaging of the brain were unremarkable. EEG revealed moderate generalized disturbance of background activity. ^99mTc-HmPAO SPECT cerebral scanning detected decreased regional cerebral blood flow at the basal ganglia. Dopamine-agonist drugs led to complete recovery after 3 months, along with normalization of EEG and SPECT alterations. The second patient (16 years old) was assessed for progressive bradykinesia and apathy impeding her active daily activities, and she was suspected to have developed depression. Neurologic assessment revealed a parkinsonian syndrome that was less severe than that of the first patient. The EEG showed mild disturbance of background activity, and ^99mTc-HmPAO SPECT demonstrated impaired regional cerebral blood flow over the basal ganglia. A parkinsonian extrapyramidal syndrome complicating SLE should therefore be taken into account in any patient with SLE presenting with marked behavioral alterations, rigidity, or akinetic mutism.     

An update on conventional and advanced magnetic resonance imaging techniques in the differential diagnosis of neurodegenerative parkinsonism

PURPOSE OF REVIEW: The clinical differentiation between Parkinson's disease and atypical parkinsonian disorders (APD) remains a challenge for every neurologist. Conventional magnetic resonance imaging (MRI) and different advanced MRI techniques offer the potential for objective criteria in the differential diagnosis of neurodegenerative parkinsonism. The aim of this article is to review the recent literature on the role of conventional and advanced MRI techniques in the differential diagnosis of neurodegenerative parkinsonian disorders. RECENT FINDINGS: An important role of MRI is the exclusion of symptomatic parkinsonism due to other pathologies. Over the past two decades, conventional MRI and different advanced MRI techniques, including proton magnetic resonance spectroscopy (1H-MRS), diffusion-weighted imaging (DWI), magnetization transfer imaging (MTI) and magnetic resonance volumetry (MRV) have been found to show abnormalities in the substantia nigra and basal ganglia, especially in APD. Recent studies using MRV, MTI, DWI and 1H-MRS to discriminate Parkinson's disease from APD are discussed extensively. SUMMARY: Research findings suggest that novel MRI techniques such as MTI, DWI and MRV have superior sensitivity compared to conventional MRI in detecting abnormal features in neurodegenerative parkinsonian disorders. Whether these techniques will emerge as standard investigations in the work-up of patients presenting with parkinsonism requires further prospective magnetic resonance studies during early disease stages.     

Levodopa-responsive parkinsonism in a patient with Down's syndrome

We report a patient with Down's syndrome (DS) who developed progressive parkinsonian symptomatology at the age of 43 years. His parkinsonism was responsive to levodopa/carbidopa, but he developed end of dose wearing off. We discuss basal ganglia and dopamine abnormalities in DS and suggest that DS may be associated with parkinsonism.     

Dopamine transporter SPECT: How to remove subjectivity?

Clinical criteria enable accurate and reliable diagnosis of parkinsonian syndromes when cardinal clinical features are fully developed. Single photon emission computed tomography (SPECT) investigating the striatal dopamine transporter (DAT) status have been suggested to increase the diagnostic accuracy in uncertain parkinsonian syndromes such as isolated tremor symptoms not fulfilling essential tremor criteria, as well as drug‐induced, vascular and psychogenetic parkinsonism. Several approaches for the analysis of the striatal DAT distribution have been tested for their ability to analyze and quantify SPECT images. Visual assessment of DAT binding and semiquantitative analysis using region of interests have been recommended by Nuclear Medicine Associations to be incorporated in the routine work‐up of DAT‐SPECT. Besides these observer dependent approaches, fully automated image‐analysis techniques have been validated in the clinical setting. Their potential as tools to improve the diagnostic accuracy in patients presenting with parkinsonian features is reviewed here. © 2009 Movement Disorder Society     

The relationship between cerebral vascular disease and parkinsonism: The VADO study

BackgroundThe observation of gait abnormalities, parkinsonism and vascular lesions in elderly patients is often reported as vascular parkinsonism (VP). However the status of striatal dopamine transporter (DAT) and the effects of brain vascular lesions on motor features and levodopa responsiveness are poorly defined.MethodsWe recorded clinical features, chronic response to levodopa and vascular risk factors in a cross-sectional cohort of consecutive elderly patients with possible Parkinson's disease (PD) or VP recruited in 20 centers in Italy.ResultsWe included a total of 158 patients. Onset of motor symptoms was asymmetric in 93 (59%) and symmetric in 65 patients (41%). Symmetric motor onset was associated with greater disease severity. Chronic levodopa response was positive in 75 (47.8%) and negative in 82 patients (52.2%). A negative response to levodopa was associated with greater frequency of symmetric onset of motor symptoms, worst disease severity, absence of dyskinesia and greater number of vascular risk factors. Frontal lobe showed largest vascular load. Striatal DAT was normal in 48 (30.4%) and abnormal in 110 (69.6%) patients. Patients with normal DAT binding showed higher vascular load at MRI. Significant predictive factors of worst disease severity and negative response to levodopa were hypertension, vascular lesions in basal ganglia/periventricular regions, and normal DAT uptake.ConclusionsMultiple cerebral vascular lesions modify clinical presentation and severity in patients with parkinsonism and this is underlined by specific risk factors primarily hypertension. Striatal DAT assessment is helpful in identifying patients where therapy benefit is less likely.     

Suspected MPTP-induced parkinsonism.

The case of an intravenous heroin user who developed parkinsonian symptoms from the age of 28 years is presented. Neuropathologic examination revealed a marked loss of neurons and gliosis with the presence of Lewy bodies in the substantia nigra and locus ceruleus; they stained variably with antibody to ubiquitin and negatively with antibodies to tau and neurofibrillary tangles. Pseudo-Lewy bodies were also seen. Electron microscopy showed features in keeping with other electron microscopic studies of Lewy bodies in idiopathic Parkinson's disease and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced inclusion bodies in monkeys. Given that the deceased was a known heroin user, the rarity of the early age of onset, that MPTP is a recognized cause of parkinsonism in the drug abusing population, the absence of history of exposure to neuroleptics and the neuropathologic features, the parkinsonism was considered to be due to MPTP contamination of heroin. However, given the onset of parkinsonism 11 years prior to death it was not possible to obtain samples of the heroin injected to test for the presence of MPTP. Therefore it could not be absolutely excluded that this was a case of idiopathic Parkinson's disease occurring at a very young age in a heroin abuser. The immunohistochemical and electron microscopic features of Lewy bodies in such a case have not been previously described. The similarity of the neuropathological features to those of idiopathic Parkinson's disease and MPTP-induced parkinsonism further strengthens the hypothesis of MPTP or an MPTP-like agent being a cause of idiopathic Parkinson's disease.     

Clinical and neuropathological study of a familial case of juvenile parkinsonism

This is a detailed autopsy case of rare juvenile parkinsonism with dominant heredity. The patient displayed parkinsonian symptoms which began at the age of 24, and expired in a state of quadriplegia-in-flexion at 35. In the later stage, myoclonic jerks, epileptiform convulsions and dementia appeared. L-dopa was effective only in the early stages. The autopsy revealed severe degeneration and the formation of atypical Lewy bodies in the cerebral cortex, as well as typical lesions of idiopathic parkinsonism with a Lewy body formation in the brain stem. This case was considered to belong essentially to idiopathic parkinsonism. The pathology of juvenile parkinsonism is reviewed briefly.