Bauke M. de Jong

Typical cerebral metabolic patterns in neurodegenerative brain diseases

The differential diagnosis of neurodegenerative brain diseases on clinical grounds is difficult, especially at an early disease stage. Several studies have found specific regional differences of brain metabolism applying [18F]‐fluoro‐deoxyglucose positron emission tomography (FDG‐PET), suggesting that this method can assist in early differential diagnosis of neurodegenerative brain diseases.

Striatal dopa and glucose metabolism in PD patients with freezing of gait

In Parkinsons disease (PD), freezing suggests sudden and transient blocks of motor behavior during initiating or continuous repetitive movements. Its underlying pathophysiology remains unclear. The objective of this study is to compare striatal dopamine metabolism and cerebral glucose metabolism between PD patients with and without freezing of gait (FOG). A total of 10 PD patients with FOG at off and 7 PD patients without FOG underwent brain positron emission tomography with 18[F]‐6‐fluoro‐levodopa (FDOPA) and 18[F]‐fluordesoxyglucose (FDG). Striatum decarboxylase activity was expressed by metabolic influx constants of the striatum related to the occipital lobe (Kocc). FDG uptake in caudate and putamen was normalized to global FDG uptake. Region of interest (ROI) analysis of striatal regions was used, as well as voxel‐based analysis by statistical parametric mapping (SPM). ROI analysis did not reveal differences in striatal FDOPA and FDG uptake between the groups. SPM showed lower putaminal FDOPA uptake (P = 0.05 uncorrected) with increased FDG uptake (P = 0.01 uncorrected) in freezing PD, whereas caudate uptake of the two tracers was reduced. Freezing‐related cortical FDG decrease was found in (right) parietal regions. In conclusion, in freezing PD, caudate uptake of FDG and FDOPA was reduced, whereas putamen FDOPA decrease was associated with FDG increase. Right hemisphere circuitry seemed to be more affected in freezing patients.

Cerebral activation during motor imagery in complex regional pain syndrome type 1 with dystonia.

&NA; The pathogenesis of dystonia in Complex Regional Pain Syndrome type 1 (CRPS‐1) is unclear. In primary dystonia, functional magnetic resonance imaging (fMRI) has revealed changes in cerebral networks during execution of movement. The aim of this study was to determine cerebral network function in CRPS‐1 patients with dystonic postures. Cerebral processing related to both execution and imagining of hand movements in patients and controls was assessed with fMRI. Eight CRPS‐1 patients with dystonic postures of the right upper extremity and 17 age‐matched healthy controls were studied. Compared with controls, imaginary movement of the affected hand in patients showed reduced activation ipsilaterally in the premotor and adjacent prefrontal cortex, and in a cluster comprising frontal operculum, the anterior part of the insular cortex and the superior temporal gyrus. Contralaterally, reduced activation was seen in the inferior parietal and adjacent primary sensory cortex. There were no differences between patients and controls when they executed movements, nor when they imagined moving their unaffected hand. The altered cerebral activation pattern in patients with CRPS‐1 linked dystonia most likely reflects an interface between pain‐associated circuitry and higher order motor control, which points at a specific mechanistic pathophysiology of this type of dystonia.

Regional cortical grey matter loss in Parkinson's disease without dementia is independent from visual hallucinations.

In our previous functional magnetic resonance imaging study, Parkinsons disease (PD) patients with visual hallucinations (VH) showed reduced activations in ventral/lateral visual association cortices preceding image recognition, compared with both PD patients without VH and healthy controls. The primary aim of the current study was to investigate whether functional deficits are associated with grey matter volume changes. In addition, possible grey matter differences between all PD patients and healthy controls were assessed. By using 3‐Tesla magnetic resonance imaging (MRI) and voxel‐based morphometry (VBM), we found no differences between PD patients with (n = 11) and without VH (n = 13). However, grey matter decreases of the bilateral prefrontal and parietal cortex, left anterior superior temporal, and left middle occipital gyrus were found in the total group of PD patients, compared with controls (n = 14). This indicates that previously demonstrated functional deficits in PD patients with VH are not associated with grey matter loss. The strong left parietal reduction in both nondemented patient groups was hemisphere specific and independent of the side of PD symptoms.

Validation of parkinsonian disease-related metabolic brain patterns.

The objective of this study was to validate disease‐related metabolic brain patterns for Parkinsons disease, multiple system atrophy, and progressive supranuclear palsy.

Handedness correlates with the dominant parkinson side: A systematic review and meta-analysis

Parkinsons disease (PD) characteristically presents with asymmetrical symptoms, contralateral to the side of the most extensive cerebral affection. This intriguing asymmetry, even included in the definition for diagnosing PD, however, is still part of a mystery. The relation with handedness as a common indicator of cerebral asymmetry might provide a clue in the search for causal factors of asymmetrical symptom onset in PD. This possible relationship, however, is still under debate. The objective of this study was to establish whether a relation between handedness and dominant PD side exists. We searched for cross‐sectional or cohort studies that registered handedness and onset side in PD patients in PubMed, EMBASE, and Web of Science from their first record until 14 February 2011. Data about handedness and dominant PD side was extracted. Authors who registered both but not described their relation were contacted for further information. Odds ratios (ORs) were analyzed with a fixed effect Mantel‐Haenszel model. Heterogeneity and indications of publication bias were limited. Our electronic search identified 10 studies involving 4405 asymmetric PD patients. Of the right‐handed patients, 2413 (59.5%) had right‐dominant and 1644 (40.5%) had left‐dominant PD symptoms. For the left‐handed patients this relation was reversed, with 142 (40.8%) right‐dominant and 206 (59.2%) left‐dominant PD symptoms. Overall OR was 2.13 (95% confidence interval [CI], 1.71–2.66). Handedness and symptom dominance in PD are firmly related with each other in such a way that the PD symptoms emerge more often on the dominant hand‐side. Possible causal factors are discussed.

Changed patterns of cerebral activation related to clinically normal hand movement in cervical dystonia

OBJECTIVES The relief of cervical dystonia by sensory tricks points at complex sensorimotor interaction. The relation between such stimulus-induced normalization of posture and parietal activation [Naumann M, Magyar-Lehmann S, Reiners K, Erbguth F, Leenders KL. Sensory tricks in cervical dystonia: perceptual dysbalance of parietal cortex modulates frontal motor programming. Ann Neurol 2000;47:322-8] further supports the idea of disturbed higher-order motor control and suggests that the organization of movement is affected beyond the level of a local output channel. Dysbalance beyond a restricted output channel is also supported by the spread of focal dystonia to adjacent body parts. In this fMRI study, we aimed to determine whether cervical dystonia patients have indeed different patterns of cerebral activation during clinically normal hand performance. PATIENTS AND METHODS By means of statistical parametric mapping (SPM) of 3T fMRI results, task-related cerebral activations measured in eight cervical dystonia patients were compared to data of nine healthy volunteers. RESULTS Compared to controls, the patient group showed a relative reduction of activations in bilateral parietal, left premotor and cingulate cortex regions during imagining of movement, while activation of right (ipsilateral) putamen, insula and cingulate cortex was impaired during movement execution. CONCLUSION Cervical dystonia appears to concern a general disorganization of cerebral motor control, which indicates a pre-dystonic state of clinically normal hand movements. The latter may imply an increased vulnerability for deteriorating triggers such as minor accidents.

Abnormal Parietal Function in Conversion Paresis

The etiology of medically unexplained symptoms such as conversion disorder is poorly understood. This is partly because the interpretation of neuroimaging results in conversion paresis has been complicated by the use of different control groups, tasks and statistical comparisons. The present study includes these different aspects in a single data set. In our study we included both normal controls and feigners to control for conversion paresis. We studied both movement execution and imagery, and we contrasted both within-group and between-group activation. Moreover, to reveal hemisphere-specific effects that have not been reported before, we performed these analyses using both flipped and unflipped data. This approach resulted in the identification of abnormal parietal activation which was specific for conversion paresis patients. Patients also showed reduced activity in the prefrontal cortex, supramarginal gyrus and precuneus, including hemisphere-specific activation that is lateralized in the same hemisphere, regardless of right- or left-sided paresis. We propose that these regions are candidates for an interface between psychological mechanisms and disturbed higher-order motor control. Our study presents an integrative neurophysiological view of the mechanisms that contribute to the etiology of this puzzling psychological disorder, which can be further investigated with other types of conversion symptoms.

55Cobalt (Co) as a PET-tracer in stroke, compared with blood flow, oxygen metabolism, blood volume and gadolinium-MRI

Several studies have shown the feasibility of divalent cobalt (Co)-isotopes (55Co and 57Co) in imaging of neuronal damage in stroke, multiple sclerosis, cerebral tumors and traumatic brain injury. Little is known how regional Co uptake relates to other pathophysiological changes after stroke. Therefore, we compared 55Co-PET with functional parameters such as regional cerebral blood flow (rCBF) using C(15)O(2), regional oxygen metabolism (rCMRO(2)) using 15O(2), regional cerebral blood volume (rCBV) and post-gadolinium (Gd) T(1)w-MRI to assess the permeability of the blood-brain-barrier (BBB). Sixteen patients (10 female; six male) aged 43 to 84 (mean 69) years with first ever stroke, as shown by CT or MRI, were examined with 55Co-PET and C(15)O(2)-, 15O(2)- and C(15)O-PET in one single session, in a period varying from 0 to 30 days after stroke-onset. Regions of infarction on C(15)O(2)- and 15O(2)-PET (defined by rCMRO(2)<65% or rCBF<45% of the contralateral value) were subsequently superimposed on the 55Co-PET scan. Clinical status was established using the Orgogozo stroke scale, which was assessed both at day 1 and at discharge (at least 6 weeks after day 1). Accumulation of 55Co was seen in eight out of 16 patients, occurring in areas showing a diminished oxygen metabolism, was only partially related to blood flow, and was located mainly outside the extent of the infarction or luxury perfusion as seen on post-Gd T(1)w-MRI. Statistical analysis showed a negative correlation between the Orgogozo score at discharge and the uptake of radioactive cobalt.

Direct comparison between regional cerebral metabolism in progressive supranuclear palsy and Parkinson's disease

The differentiation between progressive supranuclear palsy (PSP) and Parkinsons disease (PD) may be difficult, especially in the early stages of disease. Positron emission tomography potentially provides a tool for making such a distinction. To identify key features in the spatial distributions of cerebral glucose metabolism, 18F‐fluorodeoxyglucose (FDG) measurements of 10 patients with probable or possible PSP were directly compared with those of 9 PD patients. This analysis was done with statistic parametric mapping. After normalization of global brain uptake, in PSP, relative uptake of FDG was reduced in the caudal (motor) part of the anterior cingulate gyrus (Brodmanns area BA 24; P < 0.05, corrected for multiple comparisons). At a lower threshold, an additional decrease was present in the dorsal mesencephalon. In PD, relative hypometabolism was seen in extrastriate visual, ventrolateral temporal, posterior parietal, and orbitofrontal regions. Only reduction in the right fusiform gyrus and the lateral extrastriate visual cortex reached statistical significance. We concluded that particularly the reduction of medial frontal metabolism may be a valuable diagnostic imaging parameter in distinguishing PSP from PD. For PD, a possible association between occipitotemporal FDG decrease and vulnerability to hallucinations is suggested.