Michael Schocke

Diffusion-weighted imaging discriminates progressive supranuclear palsy from PD, but not from the parkinson variant of multiple system atrophy

Background and objective: The parkinson variant of multiple system atrophy (MSA-P) and progressive supranuclear palsy (PSP) present with atypical parkinsonism, which may be misdiagnosed as PD, particularly in early disease stages. It was previously shown that diffusion-weighted MRI (DWI) is a sensitive tool to discriminate MSA-P from PD based on increased apparent diffusion coefficients (ADCs) in the putamen. In this study DWI was evaluated in 10 patients with PSP compared with 13 patients with PD and 12 with MSA-P. Methods: Disease was diagnosed according to established diagnostic criteria and groups were matched for age, disease duration, and Hoehn and Yahr “off” stage. Regional ADCs (rADCs) were determined in different brain regions including basal ganglia, gray matter, white matter, substantia nigra, and pons. Results: In patients with PSP compared with those with PD, rADCs were significantly increased in putamen, globus pallidus, and caudate nucleus. Stepwise logistic regression analysis followed by receiver operating characteristics analysis identified an optimal cut-off value for putaminal rADC, discriminating PSP and PD with a sensitivity of 90% and a positive predictive value of 100%. DWI failed to discriminate PSP and MSA-P. Conclusions: These results show that DWI detects basal ganglia abnormalities in PSP patients within few years of disease onset, discriminating patients with PSP from those with PD, but not from those with MSA-P.

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

Objective and BackgroundRoutine 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. MethodsTen 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. ResultsPatients with MSA-P had higher putaminal rADC (median 0.791 × 103/mm2/s) than both patients with PD (median 0.698 × 103/mm2/s, p < 0.001) and healthy volunteers (median 0.727 × 103/mm2/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. ConclusionDWI, 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.

Survival with full neurologic recovery and no cerebral pathology after prolonged cardiopulmonary resuscitation with vasopressin in pigs

OBJECTIVES We sought to determine the effects of vasopressin and saline placebo in comparison with epinephrine on neurologic recovery and possible cerebral pathology in an established porcine model of prolonged cardiopulmonary resuscitation (CPR). BACKGROUND It is unknown whether increased cerebral blood flow during CPR with vasopressin is beneficial with regard to neurologic recovery or detrimental owing to complications such as cerebral edema after return of spontaneous circulation. METHODS After 4 min of cardiac arrest, followed by 3 min of basic life support CPR, 17 animals were randomly assigned to receive every 5 min either vasopressin (0.4, 0.4 and 0.8 U/kg; n = 6), epinephrine (45, 45 and 200 microg/kg; n = 6) or saline placebo (n = 5). The mean value +/- SEM of aortic diastolic pressure was significantly (p < 0.05) higher 90 s after each of three vasopressin versus epinephrine versus saline placebo injections (60 +/- 3 vs. 45 +/- 3 vs. 29 +/- 2 mm Hg; 49 +/- 5 vs. 27 +/- 3 vs. 23 +/- 1 mm Hg; and 50 +/- 6 vs. 21 +/- 3 vs. 16 +/- 3 mm Hg, respectively). After 22 min of cardiac arrest, including 18 min of CPR, defibrillation was attempted to achieve return of spontaneous circulation. RESULTS All the pigs that received epinephrine and saline placebo died, whereas all pigs on vasopressin survived (p < 0.05). Neurologic evaluation 24 h after successful resuscitation revealed only an unsteady gait in all vasopressin-treated animals; after 96 h, magnetic resonance imaging revealed no cerebral pathology. CONCLUSIONS During prolonged CPR, repeated vasopressin administration, but not epinephrine or saline placebo, ensured long-term survival with full neurologic recovery and no cerebral pathology in this porcine CPR model.

White and gray matter abnormalities in idiopathic rapid eye movement sleep behavior disorder: A diffusion-tensor imaging and voxel-based morphometry study

We applied diffusion‐tensor imaging (DTI) including measurements of mean diffusivity (MD), a parameter of brain tissue integrity, fractional anisotropy (FA), a parameter of neuronal fiber integrity, as well as voxel‐based morphometry (VBM), a measure of gray and white matter volume, to detect brain tissue changes in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD).

Voxel‐based morphometry detects cortical atrophy in the Parkinson variant of multiple system atrophy

To determine magnetic resonance imaging (MRI) patterns of brain atrophy in parkinsonian syndromes, we applied voxel‐based morphometry (VBM) to segmented gray matter, white matter, and cerebrospinal fluid compartments of T1‐weighted brain volumes of 12 patients with probable multiple system atrophy–parkinson variant (MSA‐P) and 12 Parkinsons disease patients, comparing them with 12 normal controls matched for age. In comparison to controls, a cortical atrophy pattern was observed in MSA‐P patients with significant clusters of volume loss in primary sensorimotor cortices bilateral, supplementary motor areas bilateral, right premotor cortex, prefrontal cortex bilateral (middle frontal gyri) and insular cortices bilateral; subcortical atrophy occurred bilaterally in caudate nuclei and putamen as well as in the midbrain. Furthermore, an enlargement of the cerebrospinal fluid compartment was found in the lateral ventricles, third ventricle, perimesencephalic and cerebellomedullar cavities. In PD patients, significant atrophy only occurred in left caudate head with enlargement of left lateral ventricle. Comparing MSA‐P to PD patients, MSA‐P showed a similar cortical pattern of atrophy as compared to controls. We conclude that VBM reveals selective cortical atrophy in patients with MSA‐P affecting primary and higher order motor areas as well as prefrontal and insular cortices. Further studies are required to determine clinical and/or subclinical correlates of cortical atrophy in MSA‐P.

Trace of diffusion tensor differentiates the Parkinson variant of multiple system atrophy and Parkinson's disease.

We have recently shown that diffusion-weighted magnetic resonance (MR) imaging (DWI) discriminates patients with the Parkinson variant of multiple system atrophy (MSA-P) from those with Parkinsons disease (PD) by regional apparent diffusion coefficients (rADC) in the putamen. Because rADCs measured in one direction may underestimate diffusion-related pathologic processes, we investigated the diffusivity in different brain areas by trace of diffusion tensor (Trace(D)) in a new cohort of patients with MSA-P and PD. We studied 11 MSA-P, 17 PD patients, and 10 healthy volunteers matched for age and disease duration. Regional ADCs in three orthogonal directions and Trace(D) values were determined in selected brain regions including the basal ganglia, gray matter, white matter, substantia nigra, and pons. MSA-P patients had significantly higher putaminal and pallidal rTrace(D) values as well as rADCs in y- and z-direction than both PD patients and healthy volunteers. Moreover, putaminal Trace(D) discriminated completely MSA-P from both PD and healthy volunteers. The rADCs in the y- and z-direction provided a complete or near complete separation. In conclusion, our study confirms the results of previous studies of our group that patients with MSA-P show an increased putaminal diffusivity due to neuronal loss and gliosis. Because rADCs in one direction are dependent on the slice orientation relative to the directions of fiber tracts, Trace(D) imaging appears to be more accurate in the separation of MSA-P from PD.

A widespread distinct pattern of cerebral atrophy in patients with alcohol addiction revealed by voxel-based morphometry

Background: Patients with alcohol addiction show a number of transient or persistent neurological and psychiatric deficits. The complexity of these brain alterations suggests that several brain areas are involved, although the definition of the brain alteration patterns is not yet accomplished. Aim: To determine brain atrophy patterns in patients with alcohol dependence. Methods: Voxel-based morphometry (VBM) of grey matter (GM) and white matter (WM) was performed in 22 patients with alcohol dependence and in 22 healthy controls matched for age and sex. Results: In patients with alcohol dependence, VBM of GM revealed a significant decrease in density (p<0.001) in the precentral gyrus, middle frontal gyrus, insular cortex, dorsal hippocampus, anterior thalamus and cerebellum compared with controls. Reduced density of WM was found in the periventricular area, pons and cerebellar pedunculi in patients with alcohol addiction. Conclusions: Our findings provide evidence that alcohol addiction is associated with altered density of GM and WM of specific brain regions. This supports the assumption that alcohol dependence is associated with both local GM dysfunction and altered brain connectivity. Also, VBM is an effective tool for in vivo investigation of cerebral atrophy in patients with alcohol addiction.

Imaging early practice effects in arithmetic.

A better understanding of learning processes in arithmetic in healthy adults can guide research into learning disabilities such as dyscalculia. The goal of the present functional magnetic resonance imaging study was to investigate the ongoing process of learning itself. No training was provided prior to the scanning session. Training consisted in a higher frequency of repetition for one set of complex multiplication problems (repeated) and a lower frequency for the other set (novel). Repeated and novel problems were presented randomly in an event-related design. We observed activation decreases due to training in fronto-parietal areas and the caudate nucleus, and activation increases in temporo-parietal regions such as the left angular gyrus. Training effects became significant after approximately eight repetitions of a problem and remained stable over the course of the experiment. The change in brain activation patterns observed was similar to the results of previous neuroimaging studies investigating training effects in arithmetic after a week of extensive training. The paradigm employed seems to be a suitably sensitive tool to investigate and compare learning processes on group level for different populations. Furthermore, on a more general level, the early and robust changes in brain activation in healthy adults observed here indicate that repeating stimuli can profoundly and quickly affect fMRI results.

Voxel based morphometry reveals a distinct pattern of frontal atrophy in progressive supranuclear palsy

Background: Frontal lobe atrophy is a well known neuropathological feature of progressive supranuclear palsy (PSP), accompanied by characteristic neuropsychological deficits. Objective: To determine subregional frontal lobe atrophy patterns in patients with PSP using voxel based morphometry (VBM). Methods: VBM is an observer unbiased volumetry which allows the investigation of the entire brain. An optimised protocol for normalisation, segmentation, and correction for volume changes in preprocessing was used. Grey matter, white matter, and cerebrospinal fluid (CSF) partitions in 12 patients with probable PSP were compared with 12 healthy controls matched for age and sex. Results: In PSP patients, the following cortical areas were decreased in volume (pcorr<0.05): the prefrontal cortex, predominantly the medial frontal gyri and a cluster in the left lateral middle frontal gyrus; the insular region including the frontal opercula; both supplementary motor areas; and the left medio-temporal area (V5). White matter comparisons revealed a volume reduction in both frontotemporal regions and the mesencephalon. Analysis of the CSF compartment showed no significant regional changes between the groups. Conclusions: Frontal atrophy in PSP predominantly involves mesio-frontal targets of striatal projections. This atrophy pattern probably accounts for cardinal PSP associated behavioural deficits.

Model-based imaging of cardiac electrical excitation in humans

Activation time (AT) imaging from electrocardiographic (ECG) mapping data has been developing for several years. By coupling ECG mapping and three-dimensional (3-D) + time anatomical data, the electrical excitation sequence can be imaged completely noninvasively in the human heart. In this paper, a bidomain theory-based surface heart model AT imaging approach was applied to single-beat data of atrial and ventricular depolarization in two patients with structurally normal hearts. In both patients, the AT map was reconstructed from sinus and paced rhythm data. Pacing sites were the apex of the right ventricle and the coronary sinus (CS) ostium. For CS pacing, the reconstructed AT pattern on the endocardium of the right atrium was compared with the CARTO map in both patients. The localization errors of the origins of the initial endocardial breakthroughs were determined to be 6 and 12 mm. The sites of early activation and the areas with late activation were estimated with sufficient accuracy. The reconstructed sinus rhythm sequence was in good qualitative agreement with the pattern previously published for the isolated Langendorff-perfused human heart.