Brigitte Holst

Quantitative T2 Values Predict Time From Symptom Onset in Acute Stroke Patients

BACKGROUND AND PURPOSE We hypothesize that in comparison to diffusion-weighted imaging, quantitative T2 values (qT2) are more directly related to water uptake in ischemic tissue, depending on time from symptom onset. We measured the increase of qT2 in the infarct core to quantify the correlation between time from symptom onset and change in qT2. METHODS Thirty-six patients with acute ischemic stroke in the territory of the proximal middle cerebral artery underwent MRI including diffusion-weighted imaging, fluid-attenuated inversion recovery, and a triple-echo T2 sequence (calculation of T2 maps) within 6 hours after symptom onset. Regions of decreased apparent diffusion coefficient <550 x 10(-9) mm(2)/sec were defined and superimposed onto the corresponding T2 map and the unaffected side in the horizontally flipped maps. Differences of T2/apparent diffusion coefficient values between affected and unaffected side were calculated (differences of T2/differences of apparent diffusion coefficient). Fluid-attenuated inversion recovery images were rated for lesion visibility. RESULTS Differences of T2 showed a significant correlation with time from symptom onset (R=0.580; P<0.001). T2 values measured in patients with visible fluid-attenuated inversion recovery lesions were significantly higher than in those without visible hyperintensity (P<0.001). The accuracy of qT2 to predict a time from symptom onset <3 hours was 0.794, whereas the corresponding accuracy for visual assessment of fluid-attenuated inversion recovery images was 0.676. CONCLUSIONS T2 values demonstrated a strong correlation with time from onset, suggesting different pathophysiologic mechanisms than diffusion restriction. Whereas fluid-attenuated inversion recovery only provides binary information on lesion visibility, T2 values correlate well with time from symptom onset, and are free from operator bias, increasing reproducibility to determine time from symptom onset.

Brain Iron Deposition Fingerprints in Parkinson's Disease and Progressive Supranuclear Palsy

It can be difficult to clinically distinguish between classical Parkinsons disease (PD) and progressive supranuclear palsy. Previously, there have been no biomarkers that reliably allow this distinction to be made. We report that an abnormal brain iron accumulation is a marker for ongoing neurodegeneration in both conditions, but the conditions differ with respect to the anatomical distribution of these accumulations. We analyzed quantitative T2′ maps as markers of regional brain iron content from PD and progressive supranuclear palsy patients and compared them to age‐matched control subjects. T2‐weighted and T2*‐weighted images were acquired in 30 PD patients, 12 progressive supranuclear palsy patients, and 24 control subjects at 1.5 Tesla. Mean T2′ values were determined in regions‐of‐interest in the basal ganglia, thalamus, and white matter within each hemisphere. The main findings were shortened T2′ values in the caudate nucleus, globus pallidus, and putamen in progressive supranuclear palsy compared to PD patients and controls. A stepwise linear discriminant analysis allowed progressive supranuclear palsy patients to be distinguished from PD patients and the healthy controls. All progressive supranuclear palsy patients were correctly classified. No progressive supranuclear palsy patient was classified as a healthy control, no healthy controls were incorrectly classified as having progressive supranuclear palsy, and only 6.7% of the PD patients were incorrectly classified as progressive supranuclear palsy. Regional decreases of T2′ relaxation times in parts of the basal ganglia reflecting increased brain iron load in these areas are characteristic for progressive supranuclear palsy but not PD patients.

MRI Correlates of Disability in African-Americans with Multiple Sclerosis

Objectives Multiple sclerosis (MS) in African-Americans (AAs) is characterized by more rapid disease progression and poorer response to treatment than in Caucasian-Americans (CAs). MRI provides useful and non-invasive tools to investigate the pathological substrate of clinical progression. The aim of our study was to compare MRI measures of brain damage between AAs and CAs with MS. Methods Retrospective analysis of 97 AAs and 97 CAs with MS matched for age, gender, disease duration and age at MRI examination. Results AA patients had significantly greater T2- (p = 0.001) and T1-weighted (p = 0.0003) lesion volumes compared to CA patients. In contrast, measurements of global and regional brain volume did not significantly differ between the two ethnic groups (p>0.1). Conclusions By studying a quite large sample of well demographically and clinically matched CA and AA patients with a homogeneous MRI protocol we showed that higher lesion accumulation, rather than pronounced brain volume decrease might explain the early progress to ambulatory assistance of AAs with MS.

Vascular events after transsylvian selective amygdalohippocampectomy and impact on epilepsy outcome

Epilepsy surgery is a standard treatment option for medically intractable temporal lobe epilepsy. Selective amygdalohippocampectomy (SAH) and anterior temporal lobectomy (ATL) are two of the standard surgical procedures in these cases. We conducted a retrospective analysis of patients treated with SAH via a modified transsylvian approach in our epilepsy center between 2008 and 2011, and we analyzed the impact of adjacent procedure‐related infarctions on seizure outcome in these patients.

T1- Thresholds in Black Holes Increase Clinical-Radiological Correlation in Multiple Sclerosis Patients.

BACKGROUND Magnetic Resonance Imaging (MRI) is an established tool in diagnosing and evaluating disease activity in Multiple Sclerosis (MS). While clinical-radiological correlations are limited in general, hypointense T1 lesions (also known as Black Holes (BH)) have shown some promising results. The definition of BHs is very heterogeneous and depends on subjective visual evaluation. OBJECTIVE We aimed to improve clinical-radiological correlations by defining BHs using T1 relaxation time (T1-RT) thresholds to achieve best possible correlation between BH lesion volume and clinical disability. METHOD 40 patients with mainly relapsing-remitting MS underwent MRI including 3-dimensional fluid attenuated inversion recovery (FLAIR), magnetization-prepared rapid gradient echo (MPRAGE) before and after Gadolinium (GD) injection and double inversion-contrast magnetization-prepared rapid gradient echo (MP2RAGE) sequences. BHs (BHvis) were marked by two raters on native T1-weighted (T1w)-MPRAGE, contrast-enhancing lesions (CE lesions) on T1w-MPRAGE after GD and FLAIR lesions (total-FLAIR lesions) were detected separately. BHvis and total-FLAIR lesion maps were registered to MP2RAGE images, and the mean T1-RT were calculated for all lesion ROIs. Mean T1 values of the cortex (CTX) were calculated for each patient. Subsequently, Spearman rank correlations between clinical scores (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite) and lesion volume were determined for different T1-RT thresholds. RESULTS Significant differences in T1-RT were obtained between all different lesion types with highest T1 values in visually marked BHs (BHvis: 1453.3±213.4 ms, total-FLAIR lesions: 1394.33±187.38 ms, CTX: 1305.6±35.8 ms; p<0.05). Significant correlations between BHvis/total-FLAIR lesion volume and clinical disability were obtained for a wide range of T1-RT thresholds. The highest correlation for BHvis and total-FLAIR lesion masks were found at T1-RT>1500 ms (Expanded Disability Status Scale vs. lesion volume: rBHvis = 0.442 and rtotal-FLAIR = 0.497, p<0.05; Multiple Sclerosis Functional Composite vs. lesion volume: rBHvis = -0.53 and rtotal-FLAIR = -0.627, p<0.05). CONCLUSION Clinical-radiological correlations in MS patients are increased by application of T1-RT thresholds. With the short acquisition time of the MP2RAGE sequences, quantitative T1 maps could be easily established in clinical studies.

Maraviroc as possible treatment for PML-IRIS in natalizumab-treated patients with MS

Progressive multifocal leukoencephalopathy (PML) is a serious complication of natalizumab treatment in patients with relapsing-remitting MS (RRMS)1 with 638 confirmed cases as of March 2016. Therapeutic re-establishment of cerebral immune surveillance in PML management is complicated by immune reconstitution inflammatory syndrome (IRIS), an exuberant inflammatory response that aggravates damage caused by John Cunningham virus (JCV) infection and ultimately leads to a combined PML/IRIS syndrome.2 Currently, plasma exchange (PLEX) for the elimination of natalizumab and reconstitution of immune surveillance is used as standard of care, although this might lead to rebound MS activity or enhanced IRIS. Here, we report 2 cases of patients with PML/IRIS who did not receive PLEX, but were instead treated with the CCR5 antagonist maraviroc that has been associated with an amelioration of IRIS.3

Ruxolitinib treatment in a patient with neuromyelitis optica: A case report

Neuromyelitis optica spectrum disorder (NMOSD) is a rare relapsing autoimmune demyelinating disease of the CNS that predominantly affects the optic nerves and the spinal cord.1 Because of the severity and poor recovery of attacks, aggressive immunosuppressive agents are used early in the clinical course to reduce relapse frequency. Apart from classical immunosuppressant agents, biologicals such as rituximab, eculizumab, or tocilizumab have been used for relapse prevention.2 Based on retrospective data, 17–53% of patients have break-through relapses under the most commonly used treatments azathioprine, mycophenolate mofetil, or rituximab.3

Unexplained loss of vision in a child: consider bilateral primary optic nerve sheath meningioma.

A 4-year-old girl gradually lost her vision to become practically blind at the age of 10 years. Examinations at several medical centers had been unable to establish an etiology. Traditional investigation using cerebral magnetic resonance imaging (MRI) initially showed normal results; however, later on it showed progressive atrophy of both optical nerves without recognizable cause. Subsequently, MRI including adequate orbital sequences, contrast-enhanced sequences, and fat suppression demonstrated bilateral primary optic nerve sheath meningioma, a rare but treatable tumor of childhood. The patient underwent neurosurgery and to date retains minimal vision. Adequate neuroradiological investigation of unexplained optic atrophy is advocated.

Quantitative T2′ imaging in patients with clinically isolated syndrome

The T2′ imaging has been shown to be sensitive to oxygen saturation changes in normal appearing white and grey matter (NAWM, NAGM) in patients with relapsing‐remitting multiple sclerosis (RRMS). We aimed to explore the presence and extent of T2′ changes in patients with a clinically isolated syndrome (CIS) and a possible association of T2′ with conventional magnetic resonance imaging and clinical outcomes.

T1 Recovery Is Predominantly Found in Black Holes and Is Associated with Clinical Improvement in Patients with Multiple Sclerosis

BACKGROUND AND PURPOSE: Quantitative MR imaging parameters help to evaluate disease progression in multiple sclerosis and increase correlation with clinical disability. We therefore hypothesized that T1 values might be a marker for ongoing tissue damage or even remyelination and may help increase clinical correlation. MATERIALS AND METHODS: MR imaging was performed in 17 patients with relapsing-remitting MS at baseline and after 12 months of starting immunotherapy with dimethyl fumarate. On baseline images, lesion segmentation was performed for normal-appearing white matter, T2 hyperintense (FLAIR lesions), T1 hypointense (black holes), and contrast-enhancing lesions, and T1 relaxation times were obtained at baseline and after 12 months. Changes in clinical status were assessed by using the Expanded Disability Status Scale and Symbol Digit Modalities Test at both dates (Expanded Disability Status Scale-difference/Symbol Digit Modalities Test-diff). RESULTS: The highest T1 relaxation time at baseline was measured in black holes (1460.2 ± 209.46 ms) followed by FLAIR lesions (1400.38 ± 189.1 ms), pure FLAIR lesions (1327.5 ± 210.04 ms), contrast-enhancing lesions (1205.59 ± 199.95 ms), and normal-appearing white matter (851.34 ± 30.61 ms). After 12 months, T1 values had decreased significantly in black holes (1369.4 ± 267.81 ms), contrast-enhancing lesions (1079.57 ± 183.36 ms) (both P < .001), and normal-appearing white matter (841.98 ± 36.1 ms, P = .006). With the Jonckheere-Terpstra Test, better clinical scores were associated with decreasing T1 relaxation times in black holes (P < .05). CONCLUSIONS: T1 relaxation time is a useful quantitative MR imaging technique, which helps detect changes in MS lesions with time. We assume that these changes are associated with the degree of myelination within the lesions themselves and are pronounced in black holes. Additionally, decreasing T1 values in black holes were associated with clinical improvement.