Martin Skalej

Magnetic resonance imaging-based volumetry differentiates idiopathic Parkinson's syndrome from multiple system atrophy and progressive supranuclear palsy.

By using three‐dimensional magnetic resonance imaging–based volumetry, we studied atrophy of the caudate nucleus, putamen, brainstem, and cerebellum in patients with idiopathic Parkinsons syndrome (IPS, n = 11), progressive supranuclear palsy (PSP, n = 6), and multiple system atrophy with predominant parkinsonism (MSA‐P, n = 12) or ataxia (MSA‐C, n = 17). Patients were compared with a total of 46 controls, of whom 16 were age matched. Mean striatal, cerebellar, and brainstem volumes were normal in patients with IPS. We found significant reductions in mean striatal and brainstem volumes in patients with MSA‐P, MSA‐C, and PSP, whereas patients with MSA‐C and MSA‐P also showed a reduction in cerebellar volume. On an individual basis, volumes of structures in patients with MSA and PSP showed an extensive overlap with the normal range with the exception of brainstem volumes in patients with MSA‐C. Therefore, groups could not be discriminated on the basis of individual structure volumetry. Application of stepwise discriminant analysis, however, allowed discrimination of all 12 patients with MSA‐P, 15 of 17 patients with MSA‐C, and 5 of 6 patients with PSP from the normal and IPS cohorts. However, patients with IPS could not be separated from controls and patients with MSA‐P could not be separated from patients with PSP. In conclusion, total intracranial volume–normalized magnetic resonance imaging–based volumetric measurements provide a sensitive marker to discriminate typical and atypical parkinsonism. Ann Neurol 1999;45:65–74

Increased Prevalence of Diverse N -Methyl-D-Aspartate Glutamate Receptor Antibodies in Patients With an Initial Diagnosis of Schizophrenia: Specific Relevance of IgG NR1a Antibodies for Distinction From N -Methyl-D-Aspartate Glutamate Receptor Encephalitis

CONTEXT Evidence for symptomatic convergence of schizophrenia and N-methyl-D-aspartate glutamate receptor (NMDA-R) encephalitis highlights the need for an assessment of antibody prevalence and specificity for distinct disease mechanisms in patients with a diagnosis of schizophrenia among glutamatergic pathophysiologic abnormalities in psychiatric disorders. OBJECTIVES To compare the specificity and prevalence of NMDA-R antibodies in schizophrenia (DSM-IV criteria) with those of other psychiatric diagnoses and to determine whether antibody subtypes characterize overlap with and distinction from those in NMDA-R encephalitis. DESIGN Serum from 459 patients admitted with acute schizophrenia, major depression (MD), and borderline personality disorder (BLPD) or individuals serving as matched controls was obtained from our scientific blood bank. To explore epitope specificity and antibody subtype, IgA/IgG/IgM NMDA-R (NR1a or NR1a/NR2b) and α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPA-R) (GluR1/GluR2) serum antibodies were determined. PARTICIPANTS Two hundred thirty matched healthy controls were compared with patients (unmedicated for at least 6 weeks) with schizophrenia (n = 121), MD (n = 70), or BLPD (n = 38). MAIN OUTCOME MEASURES The primary outcome was the overall number of seropositive cases for NMDA-R and AMPA-R antibodies; the secondary outcome was disease specificity of IgA/IgG/IgM antibodies and epitope specificity for clinical subgroups. RESULTS Diverse NMDA-R antibodies were identified in 15 subjects, primarily those with an initial schizophrenia diagnosis (9.9%), opposed to MD (2.8%), BLPD (0), and controls (0.4%). Retrospectively, 2 patients initially classified as having catatonic or disorganized schizophrenia were reclassified as having misdiagnosed NMDA-R encephalitis (presence of specific serum and cerebrospinal fluid IgG NR1a antibodies). In all other seropositive cases, the antibodies consisted of classes IgA and/or IgM or were directed against NR1a/NR2b (not against NR1a alone). None of the patients or controls had antibodies against AMPA-R. CONCLUSIONS Acutely ill patients with an initial schizophrenia diagnosis show an increased prevalence of NMDA-R antibodies. The repertoire of antibody subtypes in schizophrenia and MD is different from that with NMDA-R encephalitis. The latter disorder should be considered as a differential diagnosis, particularly in young females with acute disorganized behavior or catatonia.

CNS late effects after ALL therapy in childhood. Part I: Neuroradiological findings in long-term survivors of childhood ALL—an evaluation of the interferences between morphology and neuropsychological performance

The effect of cranial irradiation on possible therapy-induced morphological central nervous system (CNS) side effects of children cured from acute lymphoblastic leukemia (ALL) is controversially discussed. In a retrospective multicenter study, 118 former ALL patients in first continuous remission were investigated using cranial computerised tomography (CCT) or magnetic resonance imaging (MRI) scans to evaluate CNS related impairments. Corresponding to the different kinds of CNS prophylaxis, the patient sample was divided: group A (n = 39) receiving intrathecal methotrexate (ITMTX) and systemical medium-high-dose methotrexate (SMHDMTX), group B (n = 41) cranial irradiated (in mean 16.8 Gy) and administering ITMTX and SMHDMTX, group C (n = 38) irradiated (in mean 17.1 Gy) and getting ITMTX. Pathologic scans showed atrophy, leukoencephalopathy, calcifications or grey matter changes. These findings were compared with the neuropsychological test results. Abnormal MRI or CCI scans were found in 61/118 patients (51.7%). Fifteen belonged to group A (38.5%), 23 to B (56.1%) and 23 to C (60.5%). Patients with definite CNS changes show reduced neuropsychological test results. The prevalence of brain alterations seems to appear twice increased after lengthening the posttherapeutic interval in irradiated patients as in nonirradiated patients. Irradiated patients as an age younger than 2 years at diagnosis may show a lower prevalence for developing CNS alterations. CNS alterations are not sex-related. Children treated with cranial irradiation in combination with SMHDMTX and/or ITMTX were at greater risk of developing morphological brain alterations than patients with chemotherapy alone. These alterations are partly correlated with reduced neuropsychological performances and seem to stay with a longer posttherapeutic interval.

Comparing motion- and imagery-related activation in the human cerebellum: a functional MRI study.

Cerebellar activation during execution and imagination of a finger movement was compared. Functional magnetic resonance imaging was used to detect cerebellar activation during execution and imagination of an untrained self‐paced finger‐to‐thumb movement (left and right hand separately). The four fingers were opposed to the thumb in changing sequences freely chosen by the subjects. The activation maps of 10 right‐handed healthy subjects were averaged after transformation into a common coordinate space. Averaged activation maps revealed strong motion‐related bilateral activation in the anterior lobe of the cerebellum and in the paravermal regions of the posterior lobe. Ipsilateral activity predominated significantly. Compared to motion, imagination of the same task produced lower signal changes, and foci were more variable in position and strength. The averaged activation maps showed activity in the same regions as in motion. Activation in the posterior cerebellar lobe was more prominent extending into the lateral hemispheres. Ipsilateral dominance was significant for right‐hand imagery. The left‐hand task only showed marginally stronger ipsilateral activation. The activation pattern observed during execution of the finger‐to‐thumb movement is in agreement with theories of functional cerebellar topography. For imagery, activation at a comparable location may reflect common functionality, e.g., motor preparation and/or timing. Additional activation in the lateral hemispheres may be related to an imagery‐specific function. Hum. Brain Mapping 6:105–113, 1998.

Surpass Flow Diverter in the Treatment of Intracranial Aneurysms: A Prospective Multicenter Study

BACKGROUND AND PURPOSE: Incomplete occlusion and recanalization of large and wide-neck brain aneurysms treated by endovascular therapy remains a challenge. We present preliminary clinical and angiographic results of an experimentally optimized Surpass flow diverter for treatment of intracranial aneurysms in a prospective, multicenter, nonrandomized, single-arm study. MATERIALS AND METHODS: At 24 centers, 165 patients with 190 intracranial aneurysms of the anterior and posterior circulations were enrolled. The primary efficacy end point was the percentage of intracranial aneurysms with 100% occlusion on 6-month DSA. The primary safety end point was neurologic death and any stroke through a minimum follow-up of 6 months. RESULTS: Successful flow-diverter delivery was achieved in 161 patients with 186 aneurysms (98%); the mean number of devices used per aneurysm was 1.05. Clinical follow-up (median, 6 months) of 150 patients (93.2%), showed that the primary safety end point occurred in 18 subjects. Permanent neurologic morbidity and mortality were 6% and 2.7%, respectively. Morbidity occurred in 4% and 7.4% of patients treated for aneurysms of the anterior and posterior circulation, respectively. Neurologic death during follow-up was observed in 1.6% and 7.4% of patients with treated intracranial aneurysms of the anterior and posterior circulation, respectively. Ischemic stroke at ≤30 days, SAH at ≤7 days, and intraparenchymal hemorrhage at ≤7 days were encountered in 3.7%, 2.5%, and 2.5% of subjects, respectively. No disabling ischemic strokes at >30 days or SAH at >7 days occurred. New or worsening cranial nerve deficit was observed in 2.7%. Follow-up angiography available in 158 (86.8%) intracranial aneurysms showed 100% occlusion in 75%. CONCLUSIONS: Clinical outcomes of the Surpass flow diverter in the treatment of intracranial aneurysms show a safety profile that is comparable with that of stent-assisted coil embolization. Angiographic results showed a high rate of intracranial aneurysm occlusion.

Gliomas in Adults

BACKGROUND Primary brain tumors are among the ten most common causes of cancer-related death. There is no screening test for them, but timely diagnosis and treatment improve the outcome. Ideally, treatment should be provided in a highly specialized center, but patients reach such centers only on the referral of their primary care physicians or other medical specialists from a wide variety of fields. An up-to-date account of basic knowledge in this area would thus seem desirable, as recent years have seen major developments both in the scientific understanding of these tumors and in clinical methods of diagnosis and treatment. METHODS Selective search of the pertinent literature (PubMed and Cochrane Library), including the guidelines of the German Societies of Neurosurgery, Neurology, and Radiotherapy. RESULTS AND CONCLUSION Modern neuroradiological imaging, in particular magnetic resonance imaging, can show structural lesions at high resolution and provide a variety of biological and functional information, yet it is still no substitute for histological diagnosis. Gross total resection of gliomas significantly improves overall survival. New molecular markers can be used for prognostication. Chemotherapy plays a major role in the treatment of various different kinds of glioma. The median survival, however, generally remains poor, e.g., 14.6 months for glio-blastoma.

Visualization and quantification of disease progression in multiple system atrophy

To visualize and quantify disease progression in multiple system atrophy (MSA) from cerebellar type (MSA‐C), we combined two magnetic resonance imaging (MRI) techniques, voxel‐based morphometry (VBM) and 3D‐based volumetry. Patients suffering from MSA‐C (n = 14) were imaged twice with an interval of 2.0 ± 0.2 years. We first applied VBM to map brain morphology changes between MSA patients and controls and to identify brain areas that showed a significant amount of atrophy. Using 3D‐based volumetry, we confirmed that in MSA‐C patients, the brainstem including medulla and pons, vermis and cerebellar hemispheres, caudate nucleus and putamen showed significant atrophy compared with controls. Next, we used 3D‐based volumetry to analyze the atrophy rates. Atrophy rates in patients with MSA were significantly different from controls for putamen (−11.4% ± 2.6%/year), vermis (−12.3% ± 2.9%/year), and cerebellar hemispheres (−6.6% ± 1.1%/year). The results show that 3D‐based MRI volumetry is a tool that allows the disease progression of MSA to be followed over a time period of 2 years and suggest that it may serve as a surrogate marker in clinical trials to measure disease progression.

Leukemic red bone marrow changes assessed by magnetic resonance imaging and localized1H spectroscopy

SummaryRed bone marrow of healthy persons has considerable contents of water and lipids. The cellularity and the corresponding fat-water ratio within the marrow show clear changes in hematological diseases. Magnetic resonance (MR) methods use the signals of the protons of water and lipids. This paper gives a comparison between different standard MR techniques and recently developed fat- and water-selective imaging methods, addressing their sensitivity to bone marrow changes in leukemia. Additionally,1H results of spectroscopic methods are presented. The results and conclusions are based on the examination of 26 healthy volunteers and 106 patients with general or focal bone marrow alterations. Standard T1-weighted images did not distinguish bone marrow of young healthy volunteers with relatively high cellularity from acute leukemia. Using fat- and water-selective methods, patients with untreated leukemia showed only water proton signals and no lipid signals from red bone marrow of vertebral bodies and the pelvis. This phenomenon was never observed in healthy volunteers. Following chemotherapy, lipid and water contents normalize in successfully treated patients. Nonresponders did not show significant changes of the fat-water ratio after up to 3 weeks of therapy. Phase contrast imaging provides information about the difference between fat and water fractions within the bone marrow, but quantitative determination of the absolute fat and water fractions requires acquisition of several images and suffers from the susceptibility effects in trabecular bone marrow. The fat-water ratio and additional qualities of water and lipid protons (relaxation times) can be evaluated by volume-selective MR spectroscopy. Typical results of spectra from small-volume elements in hypercellular vertebral bone marrow of leukemic patients before cytotoxic treatment and of normocellular or hypocellular marrow after therapy are demonstrated.

Impact of Stents and Flow Diverters on Hemodynamics in Idealized Aneurysm Models

Cerebral aneurysms constitute a major medical challenge as treatment options are limited and often associated with high risks. Statistically, up to 3% of patients with a brain aneurysm may suffer from bleeding for each year of life. Eight percent of all strokes are caused by ruptured aneurysms. In order to prevent this rupture, endovascular stenting using so called flow diverters is increasingly being regarded as an alternative to the established coil occlusion method in minimally invasive treatment. Covering the neck of an aneurysm with a flow diverter has the potential to alter the hemodynamics in such a way as to induce thrombosis within the aneurysm sac, stopping its further growth, preventing its rupture and possibly leading to complete resorption. In the present study the influence of different flow diverters is quantified considering idealized patient configurations, with a spherical sidewall aneurysm placed on either a straight or a curved parent vessel. All important hemodynamic parameters (exchange flow rate, velocity, and wall shear stress) are determined in a quantitative and accurate manner using computational fluid dynamics when varying the key geometrical properties of the aneurysm. All simulations are carried out using an incompressible, Newtonian fluid with steady conditions. As a whole, 72 different cases have been considered in this systematic study. In this manner, it becomes possible to compare the efficiency of different stents and flow diverters as a function of wire density and thickness. The results show that the intra-aneurysmal flow velocity, wall shear stress, mean velocity, and vortex topology can be considerably modified thanks to insertion of a suitable implant. Intra-aneurysmal residence time is found to increase rapidly with decreasing stent porosity. Of the three different implants considered in this study, the one with the highest wire density shows the highest increase of intra-aneurysmal residence time for both the straight and the curved parent vessels. The best hemodynamic modifications are always obtained for a small aneurysm diameter.

VIVENDI - A Virtual Ventricle Endoscopy System for Virtual Medicine

Virtual Medicine is an emerging and challenging field in Computer Graphics. Numerous visualization methods are used to model and render data of different modalities.