Christian Brenneis

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.

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.

Language Lateralization in Temporal Lobe Epilepsy: A Comparison between fMRI and the Wada Test

Summary:  Purpose: Recent studies have claimed that language functional magnetic resonance imaging (fMRI) can identify language lateralization in patients with temporal lobe epilepsy (TLE) and that fMRI‐based findings are highly concordant with the conventional assessment procedure of speech dominance, the intracarotid amobarbital test (IAT).

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.

Voxel based morphometry reveals specific gray matter changes in primary dystonia.

The present study assessed patterns of brain tissue alterations in different types of primary dystonia using voxel‐based morphometry (VBM). Nine patients with primary generalized dystonia (GD), 11 patients with primary cervical dystonia (CD), and 11 patients with primary focal hand dystonia (FHD) as well as 31 age and gender‐matched controls were included. When compared with healthy controls, patients with primary dystonia (n = 31) showed gray matter volume increase bilaterally in the globus pallidus internus, nucleus accumbens, prefrontal cortex, as well as unilaterally in the left inferior parietal lobe. This is the first study using VBM in patients with different types of primary dystonia, showing a common pattern of gray matter changes.

Case report: severe heat stroke with multiple organ dysfunction – a novel intravascular treatment approach

IntroductionWe report the case of a patient who developed a severe post-exertional heat stroke with consecutive multiple organ dysfunction resistant to conventional antipyretic treatment, necessitating the use of a novel endovascular device to combat hyperthermia and maintain normothermia.MethodsA 38-year-old male suffering from severe heat stroke with predominant signs and symptoms of encephalopathy requiring acute admission to an intensive care unit, was admitted to a ten-bed neurological intensive care unit of a tertiary care hospital. The patient developed consecutive multiple organ dysfunction with rhabdomyolysis, and hepatic and respiratory failure. Temperature elevation was resistant to conventional treatment measures. Aggressive intensive care treatment included forced diuresis and endovascular cooling to combat hyperthermia and maintain normothermia.ResultsAnalyses of serum revealed elevation of proinflammatory cytokines (TNF alpha, IL-6), cytokines (IL-2R), anti-inflammatory cytokines (IL-4) and chemokines (IL-8) as well as signs of rhabdomyolysis and hepatic failure. Aggressive intensive care treatment as forced diuresis and endovascular cooling (CoolGard® and CoolLine®) to combat hyperthermia and maintain normothermia were used successfully to treat this severe heat stroke.ConclusionIn this case of severe heat stroke, presenting with multiple organ dysfunction and elevation of cytokines and chemokines, which was resistant to conventional cooling therapies, endovascular cooling may have contributed significantly to the reduction of body temperature and, possibly, avoided a fatal result.

Survival and long-term functional outcome in 1,155 consecutive neurocritical care patients*

Objective:To analyze survival, mortality, and long-term functional disability outcome and to determine predictors of unfavorable outcome in critically ill patients admitted to a neurologic intensive care unit (neuro-ICU). Design:Retrospective cohort study with post–neuro-ICU health-related evaluation of functional long-term outcome. Setting:Ten-bed neuro-ICU in a tertiary care university hospital. Patients:A consecutive cohort of 1,155 patients admitted to a neuro-ICU during a 36-month period. Interventions:None. Measurements and Main Results:A total of 1,155 consecutive patients, of whom 41% were women, were enrolled in the study. The predominant reasons for neuro-ICU care were cerebrovascular diseases, such as intracerebral hemorrhage (20%), subarachnoid hemorrhage (16%), and complicated, malignant ischemic stroke (15%). A total of 213 patients (18%) died in the neuro-ICU. The Glasgow Outcome Scale and modified Rankin scale were dichotomized into two groups determining unfavorable vs. favorable outcome (Glasgow Outcome Scale scores 1–3 vs. 4–5 and modified Rankin scale scores 2–6 vs. 0–1). Factors associated with unfavorable outcome in the unselected cohort according to logistic regression analysis were admission diagnosis, age (p < .01), and a higher score in the simplified Therapeutic Intervention Scoring System (TISS-28) at time of admission (p < .01). Functional long-term outcome was evaluated by telephone interview for 662 patients after a median follow-up of approximately 2.5 yrs by evaluating modified Rankin scale and Glasgow Outcome Scale scores. Factors associated with unfavorable functional long-term outcome were admission diagnosis, sex, age of >70 yrs (odds ratio, 8.45; 95% confidence interval, 4.52–15.83; p < .01), TISS-28 of >40 points at admission (odds ratio, 4.05; 95% confidence interval, 2.54–6.44; p < .01), TISS-28 of >40 points at discharge from the neuro-ICU (odds ratio, 3.50; 95% confidence interval, 1.51–8.09; p < .01), and length of stay (odds ratio, 1.01; 95% confidence interval, 1.00–1.03; p = .02). Conclusion:We found admission diagnosis, age, length of stay, and TISS-28 scores at admission and discharge to be independent predictors of unfavorable long-term outcome in an unselected neurocritical care population.

Cortical atrophy in the cerebellar variant of multiple system atrophy: a voxel-based morphometry study.

This study aimed to determine in vivo the atrophy patterns in clinically established cerebellar variant of multiple‐system atrophy (MSA‐C) using voxel‐based morphometry (VBM). Thirteen patients with MSA‐C (12 probable, 1 possible) and 13 healthy controls matched for age and sex were included. High‐resolution MR images were acquired with a 1.5 T scanner. Images were normalized onto a study‐specific template, segmented into the tissue compartments, modulated with the Jacobian determinants, and finally smoothed with a Gaussian kernel filter of 10 mm. The general linear model was used to assess statistical differences in gray and white matter. Infratentorial atrophy was observed in the cerebellar hemispheres, vermis, mesencephalon, and pons of MSA‐C patients. Supratentorial volume loss was found in orbitofrontal and mid‐frontal regions as well as in temporomesial and insular areas of both hemispheres. A negative correlation was observed between a cerebellar ataxia score and the volume of cerebellar hemispheres, peduncles, and pons. To compare this atrophy pattern to that of spinocerebellar ataxia (SCA2), which was previously reported by our group, a conjunction analysis was assessed. We observed a volume loss shared by both disorders comprising the cerebellum, vermis, pons, mesencephalon, orbitofrontal, mid‐frontal, and temporomesial cortex of both hemispheres as well as the left insular cortex.

Pharmacokinetics of Intravenous Linezolid in Cerebrospinal Fluid and Plasma in Neurointensive Care Patients with Staphylococcal Ventriculitis Associated with External Ventricular Drains

ABSTRACT The pharmacokinetic profile of linezolid in cerebrospinal fluid (CSF) in five neurointensive care patients with staphylococcal ventriculitis was studied. The mean area under concentration-time curve (± standard deviation) was 63 ± 18.9 mg · h/liter, with a CSF-to-plasma ratio of 0.8 ± 0.3. Times above MIC in CSF were 99.8% and 57.2% for pathogens with MICs of 2 mg/liter and 4 mg/liter, respectively.

Influence of red blood cell transfusion on mortality and long-term functional outcome in 292 patients with spontaneous subarachnoid hemorrhage*

Objective:To analyze the influence of red blood cell (RBC) transfusions on mortality and outcome of patients with spontaneous subarachnoid hemorrhage (SAH) and to determine predictors of unfavorable neurologic long-term outcome in this patient population. Design:Cohort study with post–intensive care unit (ICU) prospective evaluation of functional long-term outcome. Setting:Ten-bed neuro-ICU in a tertiary care university hospital. Patients:A consecutive cohort of 292 patients with spontaneous SAH admitted to a neuro-ICU during a 70-month period. Interventions:None. Measurements and Main Results:A total of 292 consecutive patients with SAH were enrolled in the study. At admission, mean hemoglobin was 13.3 g/dL (±sd 1.8 g/dL), comparable in all Hunt and Hess groups (p = 0.61 by analysis of variance). Seventy-nine patients received at least one unit of RBC transfusion in the study period. In-ICU mortality was 20.5% (n = 60). Binary logistic regression analysis comparing survivors with nonsurvivors found only higher Hunt and Hess grades (i.e., Hunt and Hess 3–5) to be significantly (p < 0.01) associated with mortality in the neuro-ICU, whereas transfusion, sex, and even age had no significant influence. Functional long-term outcome was assessed after a mean of 3.3 years (sd ±1.7 years) by evaluating modified Rankin Scale (mRS) and Glasgow Outcome Scale (GOS). More than 41% of all patients have almost fully recovered (i.e., mRS 0–1; GOS 4–5). Factors associated with unfavorable long-term outcome (i.e., GOS 1–3 and mRS 2–6) were age (odds ratio 1.06; 95% confidence interval 1.03–1.09; p < 0.01), Hunt and Hess Grade (odds ratio 11.43; 95% confidence interval 4.1–31.9; p < 0.01) but not transfusion (p = 0.46). Conclusion:Transfusion of RBCs was not associated with in-neuro-ICU mortality or unfavorable long-term outcome. Of all patients with SAH, >41% have almost fully recovered with favorable neurologic long-term outcome.