Christoph Preul

The first evaluation of brain shift during functional neurosurgery by deformation field analysis

Stereotactic surgery is based on a high degree of accuracy in defining and localising intracranial targets and placing surgical tools. Brain shift can influence its accuracy significantly. Deep brain stimulation of the subthalamic nucleus can markedly change the quality of life of patients with advanced Parkinson’s disease, but the outcome depends on the quality of electrode placement. A patient is reported in whom the placement of the second electrode was not successful. Deformation field analysis of pre- and postoperative three dimensional magnetic resonance images showed an intraoperative brain movement of 2 mm in the region of the subthalamic nucleus (the target point). Electrode repositioning resulted in efficient stimulation effects. This case report shows the need to reduce risk factors for intraoperative brain movement and demonstrates the ability of deformation field analysis to quantify this complication.

Spontaneous Slow Hemodynamic Oscillations are Impaired in Cerebral Microangiopathy

Small-vessel disease or cerebral microangiopathy (CMA) is a common finding in elderly people. It is related to a variety of vascular risk factors and may finally lead to subcortical ischemic vascular dementia. Because vessel stiffness is increased, we hypothesized that slow spontaneous oscillations are reduced in cerebral hemodynamics. Accordingly, we examined spontaneous oscillations in the visual cortex of 13 patients suffering from CMA, and compared them with 14 agematched controls. As an imaging method we applied functional near-infrared spectroscopy, because it is particularly sensitive to the microvasculature. Spontaneous low-frequency oscillations (LFOs) (0.07 to 0.12 Hz) were specifically impaired in CMA in contrast to spontaneous very-low-frequency oscillations (0.01 to 0.05 Hz), which remained unaltered. Vascular reagibility was reduced during visual stimulation. Interestingly, changes were tightly related to neuropsychological deficits, namely executive dysfunction. Vascular alterations had to be attributed mainly to the vascular risk factor arterial hypertension. Further, results suggest that the impairments might be, at least partly, reversed by medical treatment such as angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. Results indicate that functional near-infrared spectroscopy may detect changes in the microvasculature due to CMA, namely an impairment of spontaneous LFOs, and of vascular reagibility. Hence, CMA accelerates microvascular changes due to aging, leading to impairments of autoregulation.

Stroke Pattern Interpretation: The Variability of Hypertensive versus Amyloid Angiopathy Hemorrhage

Introduction: It is commonly felt that cerebral amyloid angiopathy (CAA) related intracerebral hemorrhage (ICH) can be distinguished from hypertension (HTN)-related ICH by certain typical features on computerized tomography (CT) and magnetic resonance imaging (MRI). The purpose of this study was to investigate the performance of clinicians who were asked to differentiate between CAA and HTN based on hemorrhage pattern interpretation and to assess the feasibility of such classification. Methods: The admission scans from 83 patients who were admitted to our service with an acute ICH were presented to 5 clinicians in a randomized and blinded fashion (1 junior, and 1 senior neurosurgical resident, 1 attending neurosurgeon, and 2 neurosurgeon-neuroradiologists). There were no patients who received oral anticoagulants other than low-dose aspirin, or who suffered from vascular malformations or tumors. Scans from 41 patients with a histologically proven diagnosis of CAA and from 42 patients with a clear history of HTN were investigated. Hematoma evacuation was done in all CAA patients and in 59% of HTN patients (n = 25). Results: The overall average classification accuracy was 66.8% (range: 62.7–69.9). For correct HTN classification it was 69.5% (range: 64.3–81), and 63.9% for CAA, respectively (range: 48.9–75.6). There were negligible differences in classification accuracy among all observers. Patients with a CAA-related ICH were significantly older than patients with a HTN-related ICH (74 vs. 66.5 years, p < 0.05). There was a significantly higher number of hematomas >30 ml in CAA (85.3%) when compared with HTN (59.5%). No basal ganglionic hemorrhage was seen in CAA, but in 40.5% in HTN. Intraventricular hemorrhage was seen in 24.4% in CAA, and in 26.2% in HTN. Two patients (4.9%) with CAA, and 7 patients with HTN (16.7%) presented with cerebellar hematomas. Conclusions: Three of 10 scans were not correctly diagnosed regardless of the examiner’s level of training. This calls into question the reliability of classifying the underlying pathological condition based on hemorrhage pattern interpretation on CT or MRI. The definite diagnosis of CAA- versus HTN-related hemorrhage requires a histopathological confirmation and should not be based solely on hemorrhage pattern interpretation.

Do quiescent arachnoid cysts alter CNS functional organization? A fMRI and morphometric study

Objective: To investigate whether congenital and clinically quiescent arachnoid cysts (AC) in the left temporal fossa alter the functional organization of adjacent cortices. Methods: fMRI mapping was applied in five right-handed asymptomatic patients to determine the functional organization of language. Moreover, morphometry was performed in each patient to gain the size of cortical surface areas and cortical thickness values in the neighboring brain adjacent to the AC and explicitly in the left opercular region. Results: Four patients showed a clear left hemisphere language dominance regardless of the cyst size; a mixed laterality of language organization was found in the remaining patient. An interesting dissociation of morphometric data was assessed when comparing strongly language-related cortices in the inferior frontal gyrus with the entire neighboring cortices. Morphometry in the neighboring brain regions of the AC showed 1) overall reduced cortical surface areas and 2) a decrease in cortical thickness compared to the homologous right side. However, the surface area of the fronto-opercular region in the left inferior frontal gyrus—i.e., the pars triangularis and the pars opercularis—was larger on the left as compared to the right side. Both structures have earlier been identified to represent the morphologic substrate of language dominance in the left hemisphere. Conclusion: Arachnoid cysts do not disturb the normal asymmetry of hemisphere language organization despite delicate locations adjacent to the left inferior frontal gyrus.

Morphology-based cortical thickness estimation

We describe a new approach to estimating the cortical thickness of human brains using magnetic resonance imaging data. Our algorithm is part of a processing chain consisting of a brain segmentation (skull stripping), as well as white and grey matter segmentation procedures. In this paper, only the grey matter segmentation together with the cortical thickness estimation is described. In contrast to many existing methods, our estimation method is voxel-based and does not use any surface meshes. While this fact poses a principal limit on the accuracy that can be achieved by our method, it offers tremendous advantages with respect to practical applicability. In particular, it is applicable to data sets showing severe cortical atrophies that involve areas of high curvature and extremely thin gyral stalks. In contrast to many other methods, it is entirely automatic and very fast with computation times of a few minutes. Our method has been used in two clinical studies involving a total of 27 patients and 23 healthy subjects.

Morphometry demonstrates loss of cortical thickness in cerebral microangiopathy

ObjectiveTo evaluate the role of MR morphometry in the characterization of cerebral microangiopathy (CMA) in relation to clinical and neuropsychological impairment.Subjects and Methods3D MR images of 27 patients and 27 age–matched controls were morphometrically analysed for regional thickness. The normalized values were related to the patients’ clinical and neuropsychological scores. The patients were categorised according to the amount of structural MR signal changes. A ventricle index reflecting internal atrophy was related to MR morphology and cortical thickness as an indicator for external atrophy.ResultsCortical thickness was significantly reduced in the patients group (3.03mm ± 0.26 vs. 3.22mm ± 0.13 in controls, p = 0.001). The severest loss of cortical thickness occurred in severe CMA. Internal and external atrophy evolved in parallel and both showed a significant relationship with structural MR–abnormalities (p < 0.05; r = –0.7; r = 0.67; r = –0.74, respectively). Neuropsychological performance correlated strongly with the loss of cortical thickness.ConclusionsCortical thickness was identified as the most sensitive parameter to characterize CMA. A strong correlation was found of morphometric parameters to the severity of CMA based on a score derived from T2–weighted MRI. The degree of cortical atrophy was directly related to the degree of neuropsychological impairment. Our findings suggest that the cortical thickness is a valid marker in the structural and clinical characterization of CMA.

Characterization of Cortical Thickness and Ventricular Width in Normal Aging: A Morphometric Study at 3 Tesla

To describe loss of cortical thickness and ventricular enlargement during normal aging in a sample of 525 neurologically and psychiatrically inconspicuous subjects (17–68 years old).

Serum S100B Protein is Specifically Related to White Matter Changes in Schizophrenia

Background: Schizophrenia can be conceptualized as a form of dysconnectivity between brain regions.To investigate the neurobiological foundation of dysconnectivity, one approach is to analyze white matter structures, such as the pathology of fiber tracks. S100B is considered a marker protein for glial cells, in particular oligodendrocytes and astroglia, that passes the blood brain barrier and is detectable in peripheral blood. Earlier Studies have consistently reported increased S100B levels in schizophrenia. In this study, we aim to investigate associations between S100B and structural white matter abnormalities. Methods: We analyzed data of 17 unmedicated schizophrenic patients (first and recurrent episode) and 22 controls. We used voxel based morphometry (VBM) to detect group differences of white matter structures as obtained from T1-weighted MR-images and considered S100B serum levels as a regressor in an age-corrected interaction analysis. Results: S100B was increased in both patient subgroups. Using VBM, we found clusters indicating significant differences of the association between S100B concentration and white matter. Involved anatomical structures are the posterior cingulate bundle and temporal white matter structures assigned to the superior longitudinal fasciculus. Conclusions: S100B-associated alterations of white matter are shown to be existent already at time of first manifestation of psychosis and are distinct from findings in recurrent episode patients. This suggests involvement of S100B in an ongoing and dynamic process associated with structural brain changes in schizophrenia. However, it remains elusive whether increased S100B serum concentrations in psychotic patients represent a protective response to a continuous pathogenic process or if elevated S100B levels are actively involved in promoting structural brain damage.

Intact serotonergic and dopaminergic systems in two cases of orthostatic tremor.

JO N 3 02 3 A previous single-photon emission computed tomography (SPECT) study demonstrated striatal dopamine transporter (DAT) deficits in OT [2] but also patients with normal presynaptic nigrostriatal pathway have been reported [3]. OT has been suggested to arise from a central oscillator involving the brainstem or cerebellum [4–7]. Interestingly, neuropathological changes in essential tremor have also been found in brainstem and cerebellar structures [8]. An association between the severity of parkinsonian rest tremor and the reduction of serotonin receptor (5-HT1A) binding potential in the midbrain raphe has been shown in a positron emission tomography (PET) study which might indicate a role of the serotonergic system in the generation of tremor [9, 10]. Although imaging of presynaptic pathways by measuring the serotonin transporter (SERT) availability has been performed in different neuropsychiatric disorders including Parkinson’s disease [11, 12] where in advanced patients a regionally widespread loss of brain serotonergic innervation was found [13], studies of the serotonergic system in OT do not exist. Here, we report for the first time two cases of OT with normal SERT availability and intact nigrostriatal dopaminergic pathways suggesting a normal function of these monaminergic neurotransmitter systems. Two patients (A: 61 years, male, B: 61 years, female) presented to our neurologic department with a 5 (A) and 10 (B) year history of progressive instability when standing. Their past medical histories were unremarkable except hypertension that was treated adequately. The family history of patient A remained uninformative, the father of patient B had suffered from Parkinson’s disease. On neurological examination both patients disFlorian Wegner Karl Strecker David Boeckler Armin Wagner Christoph Preul Donald Lobsien Osama Sabri Swen Hesse

Correlation of cognitive status, MRI- and SPECT-imaging in CADASIL patients

Although there is evidence for correlations between disability and magnetic resonance imaging (MRI) total lesion volume in autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the significance of structural MRI abnormalities for cognitive dysfunction remains controversial. We performed detailed neuropsychological testing, high resolution MRI, and Tc‐99m‐ethyl cysteinate‐dimer SPECT in three CADASIL patients. MR‐images were rated independently by two investigators for the presence of white matter lesions, lacunar infarcts, microbleeds, and ventricular enlargement. Cortical atrophy was quantified by the use of automatic morphometric assessment of the cortical thickness. In addition, laboratory and patients’ history data were collected in order to assess the individual vascular risk factor profile. The differences in cognitive performance between the three patients are neither explained by structural‐, or functional neuroimaging, nor by the patient‐specific vascular risk factor profiles. The neuroradiologically least affected patient met criteria for dementia, whereas the most severely affected patient was in the best clinical and cognitive state. Conventional structural and functional neuroimaging is important for the diagnosis of CADASIL, but it is no sufficient surrogate marker for the associated cognitive decline. Detailed neuropsychological assessment seems to be more useful, particularly with respect to the implementation of reliable outcome parameters in possible therapeutic trials.