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1.
Neurology ; 60(4): 601-5, 2003 Feb 25.
Article in English | MEDLINE | ID: mdl-12601099

ABSTRACT

BACKGROUND: The pathophysiologic mechanisms underlying parkinsonian tremor remain unclear. The response to dopaminergic treatment is variable and nondopaminergic mechanisms may play a role in tremor generation. Midbrain raphe 5-HT(1A) binding provides a functional measure of serotonergic system integrity. With PET, the aim of this study was to examine regional cerebral (11)C-WAY 100635 binding to 5-HT(1A) receptors in patients with PD and to correlate it with severity of tremor. METHODS: (11)C-WAY 100635 PET was performed on 23 patients with PD and eight age-matched healthy volunteers. Brain 5-HT(1A) receptor binding was computed using compartmental modeling with a cerebellar reference tissue input function. RESULTS: The authors found mean 27% reduction in the midbrain raphe 5-HT(1A) binding potential in patients with PD compared to healthy volunteers (p < 0.001). They also showed that Unified Parkinson's Disease Rating Scale composite tremor scores, but not rigidity or bradykinesia, correlate with 5-HT(1A) binding in the raphe (p < 0.01). CONCLUSIONS: These findings support previous indirect evidence that serotonergic neurotransmission is decreased in PD in vivo. The authors hypothesize that the reduction in raphe 5-HT(1A) binding represents receptor dysfunction or loss of cell bodies due to Lewy body degeneration in PD, or both. An association between 5-HT(1A) receptor availability in the raphe and severity of parkinsonian tremor was also found.


Subject(s)
Parkinson Disease/diagnostic imaging , Parkinson Disease/physiopathology , Piperazines , Pyridines , Receptor, Serotonin, 5-HT1A/metabolism , Tremor/physiopathology , Carbon Radioisotopes , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Middle Aged , Parkinson Disease/complications , Raphe Nuclei/diagnostic imaging , Raphe Nuclei/metabolism , Raphe Nuclei/physiopathology , Serotonin 5-HT1 Receptor Antagonists , Serotonin Antagonists , Tomography, Emission-Computed , Tremor/diagnosis , Tremor/etiology
2.
Arch Neurol ; 58(11): 1846-51, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11708994

ABSTRACT

BACKGROUND: Progressive supranuclear palsy (PSP) is generally considered to be a sporadic disease; however, occasional cases of familial PSP have been described. The rarity of reports of familial PSP may be attributed in part to an inability to detect subclinical disease in affected relatives who subsequently die before symptoms clinically develop. OBJECTIVE: To study regional cerebral dopaminergic function and glucose metabolism in members of 2 large kindreds with familial PSP to identify subclinical cases. METHODS: Three clinically affected members from the 2 PSP kindreds were scanned with both (18)F-dopa and (18)fluorodeoxyglucose ((18)FDG) positron emission tomography (PET). Fifteen asymptomatic first-degree relatives were scanned with (18)F-dopa PET; 10 of them also underwent a second PET study with (18)FDG. RESULTS: All 3 clinically affected PSP patients showed a significant reduction in caudate and putamen (18)F-dopa uptake along with a significant reduction in striatal, lateral, and medial premotor area and dorsal prefrontal cortex glucose metabolism. In 4 of the 15 asymptomatic relatives, caudate and putamen (18)F-dopa uptake was 2.5 SDs lower than the normal mean. These 4 subjects and a fifth asymptomatic relative with normal (18)F-dopa uptake showed a significant reduction of cortical and striatal glucose metabolism in a pattern similar to that of their affected relatives. CONCLUSION: (18)F-dopa and (18)FDG PET allowed us to identify 5 cases with subclinical metabolic dysfunction among 15 subjects (33%) at risk for PSP, suggesting that this approach is useful for characterizing the pattern of aggregation in PSP kindreds.


Subject(s)
Caudate Nucleus/diagnostic imaging , Putamen/diagnostic imaging , Supranuclear Palsy, Progressive/diagnosis , Adult , Aged , Caudate Nucleus/metabolism , Dihydroxyphenylalanine/chemistry , Dihydroxyphenylalanine/metabolism , Dopamine Agents/chemistry , Dopamine Agents/metabolism , Female , Fluorine Radioisotopes/chemistry , Fluorine Radioisotopes/metabolism , Fluorodeoxyglucose F18/metabolism , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Pedigree , Putamen/metabolism , Radiopharmaceuticals/metabolism , Supranuclear Palsy, Progressive/diagnostic imaging , Supranuclear Palsy, Progressive/metabolism , Tomography, Emission-Computed
3.
Mov Disord ; 15(4): 648-57, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10928574

ABSTRACT

Paroxysmal dystonic choreoathetosis (PDC) is an unusual hyperkinetic movement disorder characterized by attacks of chorea, dystonia, and ballism with onset in childhood. We report a large British family with dominantly inherited PDC linked to chromosome 2q and describe the clinical features in 20 affected family members. Attacks were precipitated by a variety of factors, including caffeine, alcohol, or emotion, and could be relieved by short periods of sleep in most subjects. The clinical features in the family are compared with those of 11 other PDC families in the literature and a core phenotype for PDC suggested. CSF monoamine metabolites measured at baseline and during an attack in one subject were found to increase during the attack. Magnetic resonance spectroscopy of brain and basal ganglia performed both during and between attacks was normal. Positron emission tomography using the D2 receptor ligand, 11C-raclopride, showed no abnormalities.


Subject(s)
Athetosis/genetics , Chorea/genetics , Dopamine/physiology , Adult , Athetosis/diagnosis , Athetosis/physiopathology , Brain/physiopathology , Chorea/diagnosis , Chorea/physiopathology , Chromosomes, Human, Pair 2 , Diagnostic Imaging , Female , Genes, Dominant/genetics , Humans , Male , Pedigree , Receptors, Dopamine D2/physiology
4.
Ann Neurol ; 47(4 Suppl 1): S154-8; discussion S158-9, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10762143

ABSTRACT

Dyskinesias are observed in the majority of Parkinson's disease (PD) patients who have been chronically exposed to levodopa, and these may result from supersensitivity of postsynaptic striatal dopamine D1 and D2 receptors following loss of nigral dopaminergic projections. Dyskinetic and nondyskinetic PD patients were studied using 11C-SCH23390 and 11C-raclopride positron emission tomography (PET). No difference in mean putamen or caudate D1 or D2 receptor binding between the two patient subgroups was found, suggesting that dyskinesias are unlikely to arise from a primary disturbance of dopamine receptor availability. When dyskinetic and nondyskinetic patients were studied with 11C-diprenorphine PET, the former showed a significant reduction (p < 0.05) in striatal and thalamic opioid site availability, compatible with the presence of raised levels of endogenous opioid peptides. H2(15)O PET activation studies of patients with focal limb dyskinesias showed that resting levels of regional cerebral blood flow after oral levodopa were increased during dyskinesias in lentiform nuclei, motor, premotor and dorsal prefrontal cortex. These results suggest that dyskinesias are associated with derangement of basal ganglia opioid transmission, resulting in overactivity of basal ganglia-frontal projections.


Subject(s)
Dyskinesia, Drug-Induced/diagnostic imaging , Tomography, Emission-Computed , Dopamine Agents/adverse effects , Humans , Levodopa/adverse effects , Parkinson Disease/drug therapy
5.
Gut ; 46(4): 546-52, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10716686

ABSTRACT

BACKGROUND/AIMS: To measure cerebral benzodiazepine receptor binding using (11)C-flumazenil positron emission tomography in patients with stable chronic hepatic encephalopathy, who were also characterised by proton magnetic resonance spectroscopy. METHODS: Six abstinent patients of mean age 61 years with alcohol related cirrhosis and grade I-II hepatic encephalopathy and 11 matched healthy volunteers were studied. Each patient's encephalopathy was defined according to clinical, psychometric, electroencephalographic, and magnetic resonance spectroscopy criteria. Using positron emission tomography, the brain volume of distribution of (11)C-flumazenil was obtained; this reflects benzodiazepine receptor availability. Proton magnetic resonance spectra were acquired at 1.5 T using a multivoxel technique; peak area ratios were calculated for choline, glutamine/glutamate, N-acetylaspartate, and creatine resonances. RESULTS: The mean volume of distribution of (11)C-flumazenil was significantly higher in the cortex, cerebellum, and the basal ganglia in the patients compared with controls (p<0.001). In the patient group, the mean glutamine/glutamate to creatine ratio was significantly increased and the mean choline to creatine ratio was significantly decreased in all brain areas, compared with healthy volunteers. However, the N-acetylaspartate to creatine ratio was unchanged compared with controls. CONCLUSIONS: The spectroscopy results reflect the cerebral metabolic derangement associated with hepatic encephalopathy. Stable grade I-II chronic hepatic encephalopathy in alcohol related cirrhosis may be associated with increased cerebral benzodiazepine receptor availability. However, a direct effect of previous chronic exposure to alcohol cannot be excluded.


Subject(s)
Brain/metabolism , Hepatic Encephalopathy/metabolism , Liver Cirrhosis, Alcoholic/metabolism , Receptors, GABA-A/metabolism , Adult , Aged , Case-Control Studies , Female , Hepatic Encephalopathy/diagnosis , Hepatic Encephalopathy/diagnostic imaging , Humans , Liver Cirrhosis, Alcoholic/diagnosis , Liver Cirrhosis, Alcoholic/diagnostic imaging , Magnetic Resonance Spectroscopy , Male , Middle Aged , Tomography, Emission-Computed
6.
Brain ; 123 ( Pt 2): 340-52, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10648441

ABSTRACT

Regional cerebral phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) was performed in 10 non- demented Parkinson's disease patients and nine age-matched control subjects. Five of the patients undergoing (31)P-MRS and four additional Parkinson's disease patients had cerebral 2-[(18)F]fluoro-2-deoxy-D-glucose PET ((18)FDG-PET), the results of which were compared with those of eight age-matched control subjects. All Parkinson's disease patients underwent neuropsychological testing including performance and verbal subtests of the Wechsler Adult Intelligence Scale-Revised, Boston Naming Test, Controlled Oral Word Association test (FAS Test) and California Learning Test to exclude clinical dementia. (31)P MR spectra from right and left temporo-parietal cortex, occipital cortex and a central voxel incorporating basal ganglia and brainstem were obtained. (31)P MR peak area ratios of signals from phosphomonoesters (PMEs), inorganic phosphate (P(i)), phosphodiesters (PDEs), alpha-ATP, gamma-ATP and phosphocreatine (PCr) relative to beta-ATP were measured. Relative percentage peak areas of PMEs, P(i), PDEs, PCr, and alpha-, beta- and gamma-ATP signals were also measured with respect to the total (31)P-MRS signal. Significant bilateral increases in the P(i)/beta-ATP ratio were found in temporoparietal cortex (P = 0.002 right and P = 0.014 left cortex) for the non-demented Parkinson's disease patients compared with controls. In the right temporoparietal cortex, there was also a significant increase in the mean relative percentage P(i) (P = 0.001). (18)FDG-PET revealed absolute bilateral reductions in glucose metabolism after partial volume effect correction in posterior parietal and temporal cortical grey matter (P < 0.01 and P < 0.05, respectively) for the Parkinson's disease group, using both volume of interest analysis and statistical parametric mapping. There were significant correlations between right temporoparietal P(i)/beta-ATP ratios and estimated reductions in performance IQ (r = 0.96, P < 0.001). Left temporoparietal P(i)/beta-ATP ratios correlated with full scale IQ and verbal IQ (r = -0.82, P = 0.006, r = -0.86, P = 0.003, respectively). In summary, temporoparietal cortical hypometabolism was seen in non-demented Parkinson's disease patients with both (31)P-MRS and (18)FDG-PET, suggesting that both glycolytic and oxidative pathways are impaired. This dysfunction may reflect either the presence of primary cortical pathology or deafferentation of striato-cortical projections. (31)P-MRS and (18)FDG-PET may both provide useful predictors of future cognitive impairment in a subset of Parkinson's disease patients who go on to develop dementia.


Subject(s)
Occipital Lobe/physiopathology , Parkinson Disease/physiopathology , Temporal Lobe/physiopathology , Aged , Case-Control Studies , Dementia/etiology , Dementia/physiopathology , Female , Fluorodeoxyglucose F18 , Glucagon/metabolism , Humans , Magnetic Resonance Spectroscopy , Male , Middle Aged , Occipital Lobe/diagnostic imaging , Occipital Lobe/metabolism , Oxidation-Reduction , Parkinson Disease/diagnostic imaging , Phosphorus Isotopes , Temporal Lobe/diagnostic imaging , Temporal Lobe/metabolism , Tomography, Emission-Computed
7.
Brain ; 122 ( Pt 12): 2353-63, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10581228

ABSTRACT

Using serial [(11)C]SCH 23390- and [11C]raclopride-PET, we have measured the rate of loss of striatal dopamine D1 and D2 receptor binding over a mean of 40 months in nine asymptomatic adult Huntington's disease mutation carriers, four patients with symptomatic disease, seven mutation-negative controls and three subjects at risk for the disease. Eight of the nine asymptomatic Huntington's disease mutation carriers had serial [11C]raclopride-PET and showed a mean annual loss of striatal D2 binding of 4.0%. Only five of these eight, however, showed active progression, and they had a mean annual loss of D2 binding of 6.5%. All nine asymptomatic mutation carriers had serial [11C]SCH 23390-PET and showed a mean annual loss of striatal D1 binding of 2. 0%. Four of these subjects demonstrated active progression and they had a mean annual loss of 4.5%. Our four symptomatic Huntington's disease patients showed a mean annual loss of D2 binding of 3.0% and of D1 binding of 5.0%. Loss of striatal D1 and D2 binding was significantly greater in the known mutation carriers than in the combined at-risk and gene-negative groups (P < 0.05). At follow-up PET all subjects were clinically assessed using the Unified Huntington's Disease Rating Scale. Scores for motor function and total functional capacity correlated with PET measures of striatal dopamine receptor binding both in the asymptomatic mutation carriers (D1, P < 0.01) and across the combined asymptomatic and clinically affected Huntington's disease mutation carrier group (D1 and D2, P < 0.001). We conclude that PET measures of striatal D1 and D2 dopamine binding can be used to identify asymptomatic Huntington's disease mutation carriers who are actively progressing and who would thus be suitable for putative neuroprotective therapies. Measures of disease progression rates in Huntington's disease patients and asymptomatic mutation carriers will be of critical importance in future trials of experimental restorative treatments.


Subject(s)
Corpus Striatum/metabolism , Huntington Disease/metabolism , Receptors, Dopamine D1/metabolism , Receptors, Dopamine D2/metabolism , Adult , Aged , Benzazepines/metabolism , Corpus Striatum/diagnostic imaging , Disease Progression , Dopamine Antagonists/metabolism , Female , Humans , Huntington Disease/genetics , Huntington Disease/physiopathology , Male , Middle Aged , Prospective Studies , Raclopride/metabolism , Retrospective Studies , Tomography, Emission-Computed
8.
J Neurol Neurosurg Psychiatry ; 67(1): 20-6, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10369817

ABSTRACT

OBJECTIVES: To investigate whether proton magnetic resonance spectroscopy (1H MRS) can detect cortical dysfunction in non-demented patients with Parkinson's disease, and to correlate changes with cognitive function on formal neuropsychological testing. METHODS: Multivoxel 1H MRS was performed in 17 patients with levodopa treated idiopathic Parkinson's disease with out clinical dementia, and 10 age match ed control subjects. Measurements of N-acetylaspartate (NAA)/choline (Cho), NAA/creatine+phosphocreatine (Cr), and Cho/Cr were obtained from right and left temporoparietal cortex and occipital cortex. Fourteen patients with Parkinson's disease underwent a full battery of neuropsychological testing including performance and verbal subtests of the WAIS-R, Boston naming test, FAS test, and California verbal learning test. RESULTS: There were significant temporoparietal cortex reductions in NAA/Cr ratios in right and left averaged spectra of the patients with Parkinson's disease (p=0.012 after Bonferroni correction) and in spectra contralateral to the worst clinically affected limbs of the patients with Parkinson's disease compared with controls (p = 0.003 after Bonferroni correction). There was a significant correlation between reduction in NAA/Cr ratios and measures of global cognitive decline, occurring independently of motor impairment (p=0.019). CONCLUSIONS: This study suggests that 1H MRS can detect temporoparietal cortical dysfunction in non-demented patients with Parkinson's disease. Further longitudinal studies are needed to investigate whether these 1H MRS changes are predictive of future cognitive impairment in the subset of patients with Parkinson's disease who go on to develop dementia, or occur as part of the normal Parkinson's disease process.


Subject(s)
Brain/metabolism , Parkinson Disease/metabolism , Aged , Humans , Magnetic Resonance Spectroscopy , Middle Aged , Neuropsychological Tests , Parkinson Disease/psychology , Protons
9.
Metab Brain Dis ; 14(1): 45-55, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10348313

ABSTRACT

Animal studies have suggested an increased striatal glutamate activity in Parkinson's disease models, although this has not been substantiated in magnetic resonance spectroscopy studies in patients. Our initial aim was to assess glutamate and glutamine levels in the striatum of patients with idiopathic Parkinson's disease, using multivoxel proton magnetic resonance spectroscopy techniques. Since data were collected from other areas of the brain without a priori selection, information on the cortex was also obtained. Twelve healthy volunteers, seven dyskinetic and five non-dyskinetic patients were studied. Peak area ratios of choline-containing compounds (Cho), glutamine and glutamate (Glx) and N-acetyl moieties including N-acetylaspartate (NAx), relative to creatine (Cr) were calculated. Spectra were analysed from the corpus striatum, the occipital cortex and the temporo-parietal cortex. The median Glx/Cr ratio was unaltered in the striatal spectra of Parkinson's disease patients compared to healthy controls. However, the more severely affected patients had significantly reduced NAx/Cr ratios in spectra localised to the temporo-parietal cortex, compared to healthy controls. Furthermore, the entire patient population had significantly reduced Cho/Cr ratios in spectra from the temporo-parietal cortex, compared to the reference population. We found no evidence of increased striatal glutamate in either dyskinetic or non-dyskinetic Parkinson's disease. However, the low NAx/Cr and Cho/Cr ratios in the temporo-parietal cortex may indicate the presence of subclinical cortical dysfunction.


Subject(s)
Cerebral Cortex/metabolism , Corpus Striatum/metabolism , Parkinson Disease/metabolism , Aged , Aspartic Acid/analogs & derivatives , Aspartic Acid/metabolism , Cerebral Cortex/pathology , Choline/metabolism , Corpus Striatum/pathology , Creatine/metabolism , Female , Glutamic Acid/metabolism , Glutamine/metabolism , Humans , Magnetic Resonance Spectroscopy , Male , Middle Aged , Movement Disorders/etiology , Parietal Lobe/metabolism , Parkinson Disease/complications , Parkinson Disease/diagnosis , Reference Values , Temporal Lobe/metabolism
10.
Neurology ; 52(5): 932-7, 1999 Mar 23.
Article in English | MEDLINE | ID: mdl-10102408

ABSTRACT

OBJECTIVE: To use PET to study striatal dopaminergic function in restless legs syndrome (RLS). BACKGROUND: RLS is a common disorder experienced by as much as 5% of the population. It has been suggested that this condition is associated with a disturbance of dopaminergic transmission. METHODS: The authors measured nigrostriatal terminal dopamine storage with 18F-dopa and striatal D2 receptor binding with 11C-raclopride PET in 13 RLS patients, five of whom were receiving treatment with L-dopa at the time of scanning. RLS results were compared with those of age-matched control subjects. RESULTS: Mean caudate and putamen 18F-dopa uptake were mildly reduced in the RLS patients compared with control subjects, and this reached significance (p = 0.04) in the putamen. Mean D2 binding was reduced in the caudate (p = 0.01) and the putamen (p = 0.008) in RLS patients compared with control subjects. Six of the 13 RLS patients had caudate and putamen D2 binding reduced below the control range. Three other RLS patients showed only reduced putamen D2 binding. There were no significant differences in striatal 18F-dopa uptake or D2 binding between L-dopa-naive and L-dopa-treated RLS patients. CONCLUSIONS: These PET findings support the hypothesis of central dopaminergic dysfunction in RLS.


Subject(s)
Corpus Striatum/metabolism , Dihydroxyphenylalanine/analogs & derivatives , Dopamine/metabolism , Restless Legs Syndrome/diagnostic imaging , Salicylamides , Aged , Carbon Radioisotopes , Corpus Striatum/diagnostic imaging , Female , Humans , Kinetics , Male , Middle Aged , Raclopride , Restless Legs Syndrome/metabolism , Syndrome , Tomography, Emission-Computed
11.
J Neurol Neurosurg Psychiatry ; 66(3): 380-5, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10084539

ABSTRACT

A 36 year old man, who sustained a skull fracture in 1984, was unconscious for 24 hours, and developed signs of Parkinson's syndrome 6 weeks after the injury. When assessed in 1995, neuroimaging disclosed a cerebral infarction due to trauma involving the left caudate and lenticular nucleus. Parkinson's syndrome was predominantly right sided, slowly progressive, and unresponsive to levodopa therapy. Reaction time tests showed slowness of movement initiation and execution with both hands, particularly the right. Recording of movement related cortical potentials suggested bilateral deficits in movement preparation. Neuropsychological assessment disclosed no evidence of major deficits on tests assessing executive function or working memory, with the exception of selective impairments on the Stroop and on a test of self ordered random number sequences. There was evidence of abulia. The results are discussed in relation to previous literature on basal ganglia lesions and the effects of damage to different points of the frontostriatal circuits.


Subject(s)
Brain Injuries/pathology , Parkinson Disease/pathology , Adult , Brain/diagnostic imaging , Brain/pathology , Brain Injuries/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Parkinson Disease/diagnostic imaging , Tomography, Emission-Computed
12.
Mov Disord ; 12(6): 1035-8, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9399232

ABSTRACT

We present the case of a 36-year-old woman with a right temporal hematoma and an overlying subdural hematoma following rupture of a right middle cerebral artery aneurysm. Three weeks after recovering consciousness, she developed a levodopa-responsive parkinsonian syndrome involving the right limbs. A year after the vascular event, she reported subjective improvement in her parkinsonism, which has remained stable since. 18F-dopa positron-emission tomography showed a marked reduction of uptake in the left putamen, raising the possibility that the intracranial hemorrhage unmasked latent Parkinson's disease. To the best of our knowledge, this is the first case of parkinsonism associated with spontaneous acute intracerebral and subdural hematomas.


Subject(s)
Hematoma/complications , Parkinson Disease, Secondary/complications , Parkinson Disease, Secondary/diagnostic imaging , Tomography, Emission-Computed , Acute Disease , Adult , Antiparkinson Agents/therapeutic use , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/surgery , Corpus Striatum/diagnostic imaging , Female , Fluorine Radioisotopes , Hematoma/diagnostic imaging , Hematoma/surgery , Humans , Levodopa/therapeutic use , Parkinson Disease, Secondary/drug therapy , Radiography
13.
Neurology ; 49(3): 717-23, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9305330

ABSTRACT

Dyskinesias are usually seen in Parkinson's disease (PD) patients after several years of L-dopa therapy. Their presence has been attributed to supersensitivity of striatal D1 and D2 receptors. We have used PET to assess striatal D2 receptor binding in untreated PD patients and striatal D1 and D2 binding in L-dopa-treated PD patients. Untreated patients showed a 14% increase in mean D2 receptor binding in the putamen contralateral to the more affected limbs (p < 0.02). Treated patients were segregated into subgroups according to the presence or absence of dyskinesias. There were no differences in mean caudate and putamen D1 and D2 binding between dyskinetic and nondyskinetic patients, matched for duration of clinical disease. Both dyskinetic and nondyskinetic PD subgroups showed a similar 16% reduction of mean caudate D2 binding (p < 0.01) with normal D2 binding in putamen. Mean caudate and putamen D1 binding potentials of both subgroups were reduced by 10% compared with those of controls, though this trend did not reach significance. Putamen D1 binding, however, showed a negative correlation with duration and L-dopa treatment (p < 0.03). These findings suggest that, while exposure of PD patients to L-dopa may be associated with reductions in caudate D2 and caudate and putamen D1 receptor, dyskinesias are unlikely to result from alterations in striatal dopamine receptor binding.


Subject(s)
Corpus Striatum/drug effects , Levodopa/therapeutic use , Movement Disorders/drug therapy , Parkinson Disease/drug therapy , Receptors, Dopamine D1/metabolism , Receptors, Dopamine D2/metabolism , Adult , Aged , Carbon Radioisotopes , Corpus Striatum/metabolism , Female , Humans , Male , Middle Aged , Movement Disorders/diagnosis , Parkinson Disease/diagnosis , Raclopride , Salicylamides
14.
Mov Disord ; 12(5): 691-6, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9380049

ABSTRACT

The regional metabolic rate of glucose was estimated using 18F-labeled 2-deoxyglucose and positron-emission tomography (PET) in eight patients with corticobasal degeneration (CBD). Measures of cerebral glucose metabolism in these patients were compared with those for nine age-matched normal controls and eight patients with progressive supranuclear palsy (PSP). Compared with that in the normal controls, the CBD patients showed significantly reduced cerebral glucose metabolism in the contralateral hemisphere to the clinically most affected side in the dorsolateral frontal, medial frontal, inferior parietal, sensorimotor, and lateral temporal cortex, as well as in the corpus striatum and the thalamus. In comparison with that in PSP, in CBD the glucose metabolism in the contralateral hemisphere was significantly decreased in the inferior parietal, sensorimotor, lateral temporal cortex, and the corpus striatum. These results confirm the marked asymmetric cerebral involvement in CBD and suggest that there are significant differences between CBD and PSP in the cerebral metabolism in some cerebral regions such as the inferior parietal cortex and sensorimotor cortex, which might reflect the differences in their clinical characteristics.


Subject(s)
Basal Ganglia Diseases/metabolism , Brain/metabolism , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Glucose/metabolism , Neurodegenerative Diseases/metabolism , Aged , Analysis of Variance , Atrophy , Brain/pathology , Case-Control Studies , Female , Humans , Male , Middle Aged , Supranuclear Palsy, Progressive/metabolism , Tomography, Emission-Computed
15.
Brain ; 120 ( Pt 8): 1301-13, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9278624

ABSTRACT

Supplementary motor area and right dorsal prefrontal cortex activation in Parkinson's disease is selectively impaired during volitional limb movements. Since posteroventral pallidotomy improves motor performance in Parkinson's disease patients 'off' medication (i.e. off medication for 9-12 h), we hypothesized that it would also concomitantly increase supplementary motor area and dorsal prefrontal cortex activation. Six Parkinson's disease patients with a median total motor Unified Parkinson's Disease Rating Scale (UPDRS) of 52.5 (range 34-66) 'off' medication underwent unilateral right posteroventral pallidotomy. The patients had H2(15)O PET when 'off' medication before and 3-4 months after surgery. Each PET study comprised four to six measurements of regional cerebral blood flow either at rest or while performing regularly paced joystick movements in freely selected directions (forward, backward, left or right) using the left hand. Pre- and postoperative scans were performed in an identical manner and the associated levels of activation were compared using statistical parametric mapping. After pallidotomy, the median total motor UPDRS score 'off' medication decreased by 34.7% (P = 0.03) and mean response times of joystick movements following the pacing tones improved by 13.8% (P = 0.08). Relative increases in activation of the supplementary motor area and right dorsal prefrontal cortex were observed during joystick movements (P < 0.001). Decreased activation was seen in the region of the right pallidum (P = 0.001). We conclude that pallidotomy reduces pallidal inhibition of thalamocortical circuits and reverses, at least partially, the impairment of supplementary motor area and dorsal prefrontal cortex activation associated with Parkinson's disease.


Subject(s)
Globus Pallidus/surgery , Motor Cortex/physiology , Parkinson Disease/surgery , Prefrontal Cortex/physiology , Volition/physiology , Adult , Aged , Female , Globus Pallidus/physiopathology , Humans , Male , Middle Aged , Motor Cortex/diagnostic imaging , Movement/physiology , Oxygen Radioisotopes , Parkinson Disease/physiopathology , Postoperative Period , Prefrontal Cortex/diagnostic imaging , Preoperative Care , Psychomotor Performance/physiology , Thalamus/physiology , Tomography, Emission-Computed , Water
16.
Neurology ; 49(1): 183-9, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9222188

ABSTRACT

Posttraumatic encephalopathy (PTE) is characterized by a combination of upper motor neuron, basal ganglia, cerebellar, and psychiatric disturbances. A "striatal" variant, with predominant posttraumatic parkinsonism (PTP), is uncommon and may be difficult to distinguish from idiopathic Parkinson's disease (PD). We report the clinical characteristics of six patients clinically presumed to have PTP who were investigated with 18F-dopa PET. We compared their findings with those of age-matched controls and a group of idiopathic PD patients without a history of head trauma. The PTP patients showed a uniform 40% reduction (p < 0.0001) of mean 18F-dopa uptake in caudate and putamen compared with controls. Their mean putamen uptake was significantly higher than that seen in the PD group (p < 0.004) while mean caudate uptake was lower. The PTP mean caudate:putamen Ki ratio (0.97) was similar to that of controls (1.10) but significantly lower than that of the PD group (1.90) (p < 0.0001). These results suggest that although PTP may appear clinically similar to PD, 18F-dopa PET may help to differentiate it in vivo by demonstrating uniform nigrostriatal involvement as opposed to relative sparing of caudate function. These data also provide support for the view that delayed neurologic sequelae may follow cumulative head trauma.


Subject(s)
Brain/metabolism , Dihydroxyphenylalanine/analogs & derivatives , Dopamine/metabolism , Fluorine Radioisotopes , Parkinson Disease/physiopathology , Wounds and Injuries/physiopathology , Aged , Brain/diagnostic imaging , Humans , Male , Middle Aged , Time Factors , Tomography, Emission-Computed
17.
Mov Disord ; 12(3): 354-9, 1997 May.
Article in English | MEDLINE | ID: mdl-9159730

ABSTRACT

Two patients with presumed encephalitis lethargica are presented with clinical features suggestive of two forms of the disease described by Von Economo: One patient had a psychosis and a mute-akinetic syndrome associated with myoclonus. The second patient presented with a psychosis and fever, developing severe dyskinesias involving the mouth, trunk and limbs, together with respiratory irregularities and presumed hypothalamic disturbance and disturbance of consciousness. In both cases, initial cerebrospinal fluid (CSF) examination revealed an elevated white cell count (predominantly lymphocytes), elevated protein in case 2, and oligoclonal bands in both cases. Computed tomography (CT) brain scan was normal but in both cases EEG revealed diffuse slow wave activity. A 18F-Dopa positron emission tomography (PET) scan in case 2 was normal. The medical management of both patients is discussed. In case 1, L-Dopa improved the akinesia, while the myoclonus responded to clonazepam. In case 2, the severe dyskinesias failed to respond to a number of drugs, and she ultimately required paralysis to relieve her almost continuous movements. Both patients responded rapidly and dramatically to intravenous methylprednisolone. We suggest that steroid treatment should be considered in the acute phase of patients with features suggestive of encephalitis lethargica.


Subject(s)
Encephalitis/diagnosis , Sleep Stages , Acyclovir/administration & dosage , Acyclovir/therapeutic use , Adult , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , Encephalitis/drug therapy , Female , Humans , Injections, Intravenous , Methylprednisolone/administration & dosage , Methylprednisolone/therapeutic use , Movement Disorders/diagnosis , Myoclonus/diagnosis
18.
Ann Neurol ; 41(2): 222-9, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9029071

ABSTRACT

There is increasing evidence for familial aggregation in Parkinson's disease (PD). It is possible that some asymptomatic relatives of PD patients have subclinical nigral Lewy body pathology and their identification could help determine the true prevalence of the disease. We used 18F-dopa positron emission tomography to investigate nigrostriatal dopaminergic terminal function in asymptomatic members of 7 unrelated kindreds in which at least 2 members had parkinsonism. Eight (25%) of the 32 asymptomatic relatives showed abnormal putamen 18F-dopa uptake (2.5 standard deviations below the normal mean). When discriminant function analysis was applied, all of these 8 subjects plus another 3 were classified with high probability as having PD. On neurological examination, 5 of the 32 relatives scanned had an isolated mild postural tremor and 2 of these 5 had reduced putamen uptake. Our findings provide further support for a role of inheritance in the etiology of PD and suggest that the penetrance for nigrostriatal dopaminergic dysfunction in familial clusters of PD is higher than the prevalence of clinical parkinsonism reported in epidemiological surveys.


Subject(s)
Brain/pathology , Dihydroxyphenylalanine/metabolism , Dopamine/metabolism , Parkinson Disease/genetics , Parkinson Disease/pathology , Adult , Brain/diagnostic imaging , Female , Humans , Male , Middle Aged , Tomography, Emission-Computed
19.
J Neural Transm Suppl ; 51: 37-48, 1997.
Article in English | MEDLINE | ID: mdl-9470127

ABSTRACT

Parkinsonism and dementia are present in a number of neurodegenerative conditions. They may be a manifestation of isolated brain stem (Parkinson's disease) or diffuse Lewy body disease (DLBD), or be secondary to combined Lewy body and Alzheimer's disease (AD) pathologies. Positron emission tomography (PET) studies show a resting pattern of fronto-temporo-parietal hypometabolism in both, AD and in parkinsonism-dementia (PD-dementia) patients, even when only isolated brain stem Lewy body disease is found at pathology. We have studied three patients fulfilling clinical criteria for diagnosis of DLBD. Their 18F-fluorodeoxyglucose (FDG) PET results showed an AD pattern of fronto-temporo-parietal hypometabolism, though these patients had only mild cognitive dysfunction. Parkinsonism associated with apraxia is observed in corticobasal degeneration (CBD) while impairment of frontal functions, such as planning and sorting, is seen in patients with progressive supranuclear palsy (PSP). PET studies in CBD patients have shown an asymmetric hypometabolism of cortex and thalamus contralateral to the affected limbs, while in PSP patients there is a global metabolic reduction most pronounced in frontal areas and the basal ganglia. These results suggest that metabolic PET studies can help to distinguish PD-dementia, PSP and CBD, but are unable to distinguish PD-dementia from AD. Further studies with post-mortem confirmation are required to establish if DLBD is associated with a distinctive pattern of resting hypometabolism.


Subject(s)
Cerebrovascular Circulation/physiology , Dementia/physiopathology , Parkinson Disease/physiopathology , Tomography, Emission-Computed , Aged , Dementia/diagnostic imaging , Female , Humans , Male , Parkinson Disease/diagnostic imaging
20.
Clin Neuropharmacol ; 19(4): 314-20, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8828994

ABSTRACT

Forty-four patients with disabling writer's cramp (WC) and one with a musician's cramp were treated with botulinum toxin (BT) injections for a mean period of 12 (range, 3-48) months. The forearm muscles causing the dystonic position were identified by inspection while writing; BT was then administered under electromyographic (EMG) guidance. The degree of improvement in writing and amelioration of pain were rated with self-assessment scales. Patients reported significant improvement in writing after 56% treatment sessions (TS) and in pain after 62% TS. Mild weakness occurred after 32% TS. Twenty-nine patients discontinued treatment, generally after the initial BT injection. In 16 patients who remained on treatment with a mean follow-up of 21 (range, 3-48) months, the improvement in writing and pain was present after 76 and 79% of the TS, respectively. We conclude that BT injections offered a worthwhile and sustained functional improvement to 36% of our patients with WC.


Subject(s)
Botulinum Toxins/therapeutic use , Dystonia/drug therapy , Hand/physiopathology , Muscle Cramp/drug therapy , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Writing
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