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1.
Neurology ; 89(9): 900-908, 2017 Aug 29.
Article in English | MEDLINE | ID: mdl-28768844

ABSTRACT

OBJECTIVE: To assess the prognostic value of MOG antibodies (abs) in the differential diagnosis of acquired demyelinating syndromes (ADS). METHODS: Clinical course, MRI, MOG-abs, AQP4-abs, and CSF cells and oligoclonal bands (OCB) in children with ADS and 24 months of follow-up were reviewed in this observational prospective multicenter hospital-based study. RESULTS: Two hundred ten children with ADS were included and diagnosed with acute disseminated encephalomyelitis (ADEM) (n = 60), neuromyelitis optica spectrum disorder (NMOSD) (n = 12), clinically isolated syndrome (CIS) (n = 101), and multiple sclerosis (MS) (n = 37) after the first episode. MOG-abs were predominantly found in ADEM (57%) and less frequently in NMOSD (25%), CIS (25%), or MS (8%). Increased MOG-ab titers were associated with younger age (p = 0.0001), diagnosis of ADEM (p = 0.005), increased CSF cell counts (p = 0.011), and negative OCB (p = 0.012). At 24-month follow-up, 96 children had no further relapses. Thirty-five children developed recurrent non-MS episodes (63% MOG-, 17% AQP4-abs at onset). Seventy-nine children developed MS (4% MOG-abs at onset). Recurrent non-MS episodes were associated with high MOG-ab titers (p = 0.0003) and older age at onset (p = 0.024). MS was predicted by MS-like MRI (p < 0.0001) and OCB (p = 0.007). An MOG-ab cutoff titer ≥1:1,280 predicted a non-MS course with a sensitivity of 47% and a specificity of 100% and a recurrent non-MS course with a sensitivity of 46% and a specificity of 86%. CONCLUSIONS: Our results show that the presence of MOG-abs strongly depends on the age at disease onset and that high MOG-ab titers were associated with a recurrent non-MS disease course.


Subject(s)
Encephalomyelitis, Acute Disseminated/immunology , Multiple Sclerosis/immunology , Myelin-Oligodendrocyte Glycoprotein/blood , Myelin-Oligodendrocyte Glycoprotein/immunology , Neuromyelitis Optica/immunology , Adolescent , Autoantibodies , Biomarkers/metabolism , Child , Child, Preschool , Diagnosis, Differential , Disease Progression , Encephalomyelitis, Acute Disseminated/blood , Encephalomyelitis, Acute Disseminated/cerebrospinal fluid , Encephalomyelitis, Acute Disseminated/diagnostic imaging , Female , Follow-Up Studies , Humans , Infant , Magnetic Resonance Imaging , Male , Multiple Sclerosis/blood , Multiple Sclerosis/cerebrospinal fluid , Multiple Sclerosis/diagnostic imaging , Neuromyelitis Optica/blood , Neuromyelitis Optica/cerebrospinal fluid , Neuromyelitis Optica/diagnostic imaging , Oligoclonal Bands , Prognosis , Prospective Studies
2.
Neuro Oncol ; 16(1): 92-102, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24311637

ABSTRACT

BACKGROUND: Due to the redundancy of molecular pathways simultaneously involved in glioblastoma growth and angiogenesis, therapeutic approaches intervening at multiple levels seem particularly appealing. METHODS: This prospective, multicenter, single-arm phase II trial was designed to evaluate the antitumor activity of sunitinib, an oral small-molecule inhibitor of several receptor tyrosine kinases, in patients with first recurrence of primary glioblastoma using a continuous once-daily dosing regimen. Patients received a starting dose of sunitinib 37.5 mg, followed by a maintenance dose between 12.5 mg and 50 mg depending on drug tolerability. The primary endpoint was a 6-month progression-free survival (PFS) rate. Secondary endpoints included median PFS, overall survival (OS), safety/toxicity, quality of life, and translational studies on the expression of sunitinib target molecules. RESULTS: Forty participants were included in this study, and no objective responses were detected. PFS6 was 12.5%, median PFS 2.2 months, and median OS 9.2 months. Five participants (12.5%) showed prolonged stable disease ≥6 months with a median PFS of 16.0 months (range, 6.4-41.4 mo) and a median OS of 46.9 months (range, 21.2-49.2 mo) for this subgroup. c-KIT expression in vascular endothelial cells (n = 14 participants) was associated with improved PFS. The most common toxicities were fatigue/asthenia, mucositis/dermatitis, dysesthesias, gastrointestinal symptoms, cognitive impairment, leukoctopenia, and thrombocytopenia. Two participants (5%) terminated treatment due to toxicity. CONCLUSION: Continuous daily sunitinib showed minimal antiglioblastoma activity and substantial toxicity when given at higher doses. High endothelial c-KIT expression may define a subgroup of patients who will benefit from sunitinib treatment by achieving prolonged PFS. ClinicalTrials.gov Identifier: NCT00535379.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Brain Neoplasms/drug therapy , Glioblastoma/drug therapy , Indoles/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Pyrroles/therapeutic use , Adult , Aged , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Drug Administration Schedule , Female , Follow-Up Studies , Glioblastoma/mortality , Glioblastoma/pathology , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Prospective Studies , Sunitinib , Survival Rate
3.
J Nucl Med ; 52(6): 856-64, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21622893

ABSTRACT

UNLABELLED: The objective of this study was to compare MRI response assessment with metabolic O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET response evaluation during antiangiogenic treatment in patients with recurrent high-grade glioma (rHGG). METHODS: Eleven patients with rHGG were treated biweekly with bevacizumab-irinotecan. MR images and (18)F-FET PET scans were obtained at baseline and at follow-up 8-12 wk after treatment onset. MRI treatment response was evaluated by T1/T2 volumetry according to response assessment in neurooncology (RANO) criteria. For (18)F-FET PET evaluation, an uptake reduction of more than 45% calculated with a standardized uptake value of more than 1.6 was defined as a metabolic response (receiver-operating-characteristic curve analysis). MRI and (18)F-FET PET volumetry results and response assessment were compared with each other and in relation to progression-free survival (PFS) and overall survival (OS). RESULTS: At follow-up, MR images showed partial response in 7 of 11 patients (64%), stable disease in 2 of 11 patients (18%), and tumor progression in 2 of 11 patients (18%). In contrast, (18)F-FET PET revealed 5 of 11 metabolic responders (46%) and 6 of 11 nonresponders (54%). MRI and (18)F-FET PET showed that responders survived significantly longer than did nonresponders (10.24 vs. 4.1 mo, P = 0.025, and 7.9 vs. 2.3 mo, P = 0.015, respectively). In 4 patients (36.4%), diagnosis according to RANO criteria and (18)F-FET PET was discordant. In these cases, PET was able to detect tumor progression earlier than was MRI. CONCLUSION: In rHGG patients undergoing antiangiogenic treatment, (18)F-FET PET seems to be predictive for treatment failure in that it contributes important information to response assessment based solely on MRI and RANO criteria.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/drug therapy , Glioma/diagnostic imaging , Glioma/drug therapy , Radiopharmaceuticals , Tyrosine/analogs & derivatives , Adult , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Astrocytoma/drug therapy , Astrocytoma/pathology , Astrocytoma/surgery , Bevacizumab , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Combined Modality Therapy , Disease-Free Survival , Female , Glioma/surgery , Humans , Image Processing, Computer-Assisted , Irinotecan , Magnetic Resonance Imaging , Male , Middle Aged , Nervous System Diseases/etiology , Nervous System Diseases/physiopathology , Positron-Emission Tomography , Postoperative Complications/physiopathology , Predictive Value of Tests , Retrospective Studies , Survival Analysis , Treatment Failure , Ultrasonography
4.
J Clin Pathol ; 63(4): 359-61, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20354208

ABSTRACT

Prominent leukoaraiosis is common in the clinical routine setting. In addition to microatheroma and hypertensive small vessel disease (lipohyalinosis), a large number of rare but clinically relevant differential diagnoses have to be considered. A man in his 60s presented with left pontine infarction and subsequent rapidly deteriorating leukoaraiosis associated with dementia. Standard non-invasive examination did not enable the correct diagnosis to be obtained. A brain biopsy sample revealed a combination of diffuse infiltrating and intravascular large B cell central nervous system (CNS) lymphoma, which has not previously been described in literature. Despite immediate treatment with state of the art chemotherapy, the patient died 3 months after the onset of symptoms. Diffuse infiltrating and intravascular primary CNS lymphoma is a rare cause of rapidly progressive leukoencephalopathy and stroke mediated by neoplastic microvessel occlusion and inflammatory tissue damage. This report intends to increase awareness among neurologists and other stroke physicians about this disease in order to accelerate diagnosis and initiation of treatment.


Subject(s)
Central Nervous System Neoplasms/complications , Leukoencephalopathies/etiology , Lymphoma, Large B-Cell, Diffuse/complications , Central Nervous System Neoplasms/diagnosis , Disease Progression , Fatal Outcome , Humans , Leukoencephalopathies/diagnosis , Lymphoma, Large B-Cell, Diffuse/diagnosis , Magnetic Resonance Imaging , Male , Middle Aged
5.
Mult Scler ; 15(12): 1481-8, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19965519

ABSTRACT

Neutralizing antibodies against interferon-beta are associated with a reduction of the efficacy of this drug. Continuing treatment leads to a decline or even loss of neutralizing antibodies over years. No strategies are currently available to shorten the period of neutralizing antibody positivity. The objective of this study was to investigate the effect of switching between high and low immunogenic interferon-beta products on neutralising antibody titres. Twenty-four patients treated with the subcutaneously administered interferon-beta 1b or 1a and high titres of neutralizing antibodies were included. At baseline interferon-beta therapy was interrupted for 3 months and two pulses of high dose methylprednisolone were applied. Patients were then randomized to receive either the previous interferon-beta preparation or the low immunogenic intramuscular interferon-beta 1a. The primary end-point was the change of neutralizing antibody titres 12 months after randomization. Twelve patients were switched to interferon-beta 1a intramuscularly and 12 patients remained on previous treatment. Median neutralizing antibody titres were 846 NU at baseline and 196 NU at the end of the study. The median change of neutralizing antibody titres did not differ significantly between therapy switchers and non-switchers. Baseline and final neutralizing antibody titres correlated significantly. In conclusion, neither switching nor continuous therapy with any subcutaneous interferon-beta preparation significantly changed neutralizing antibody titres.


Subject(s)
Antibodies, Neutralizing/blood , Immunologic Factors/administration & dosage , Immunologic Factors/immunology , Interferon-beta/administration & dosage , Interferon-beta/immunology , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Adult , Austria , Drug Administration Schedule , Glucocorticoids/administration & dosage , Humans , Infusions, Intravenous , Injections, Intramuscular , Injections, Subcutaneous , Interferon beta-1a , Interferon beta-1b , Magnetic Resonance Imaging , Methylprednisolone/administration & dosage , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/immunology , Multiple Sclerosis, Relapsing-Remitting/pathology , Pulse Therapy, Drug , Recurrence , Time Factors , Treatment Outcome
6.
Parkinsonism Relat Disord ; 14(8): 595-9, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18328766

ABSTRACT

The purpose of this study was to evaluate the accuracy of stereotactic electrode placement in patients undergoing deep brain stimulation by using pre- and postoperative computed tomography (CT). Twenty-three patients with movement disorders (Parkinson's disease (n=7), tremor (n=9), dystonia (n=7)) treated with bilateral deep brain stimulation (DBS) (overall 46 target points) were investigated. The target point of the electrode was planned stereotactically in combination with a preoperative stereotactic helical computed tomography (CT). A postoperative CT, which was carried out still in the operating room while the patient had the stereotactic frame on the head, was performed in order to control the position of the electrodes in relation to the previously planned target point. The position of the four electrode contacts was measured according to the Talairach space (AC-PC line) and compared with the coordinates of the planned target point. The mean spatial distance of planned target perpendicular to the electrode was 1.32+/-0.75mm. These results show the high accuracy of stereotactic implantation of DBS electrodes assisted by pre- and postoperative image fusion with computed tomography (CT).


Subject(s)
Deep Brain Stimulation , Electrodes , Movement Disorders/diagnostic imaging , Stereotaxic Techniques , Tomography, X-Ray Computed/methods , Deep Brain Stimulation/methods , Evaluation Studies as Topic , Female , Humans , Intraoperative Period , Male , Middle Aged , Monitoring, Intraoperative , Movement Disorders/classification , Movement Disorders/therapy , Neurosurgical Procedures , Retrospective Studies
8.
Epilepsia ; 46(11): 1754-63, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16302855

ABSTRACT

PURPOSE: The study aims to explore the contribution of the hippocampal formation to the retained language-comprehension network in patients with unilateral mesial temporal lobe epilepsy (TLE). METHODS: We performed a functional magnetic resonance (MRI) study based on a language comprehension paradigm in 45 right-handed patients with unilateral mesial TLE and 35 healthy control subjects. Activations in the hippocampal formations in both hemispheres were analyzed for each subject as well as for groups of left TLE, right TLE, and controls. RESULTS: In sum, 82% of TLE patients displayed hippocampal activations. A significant difference in hippocampal activation between left and right TLE was found: Right TLE patients showed increased activity in the left hippocampal formation compared with left TLE patients. In contrast, patients with left TLE did not show increased activity in the right hippocampal formation compared with right TLE patients. In comparison with a healthy control group, right TLE patients activated the left hippocampal formation to a greater extent, whereas patients with left TLE did not activate the right hippocampal formation to a greater degree. These findings point to an increased involvement of the left hippocampal formation during a language-comprehension task in right TLE patients. In contrast, left TLE in right-handed patients seems not associated with an enhanced involvement of the right hippocampal formation in retained language comprehension. CONCLUSIONS: These findings suggest that effective language comprehension in right-handed subjects with TLE depends on the involvement of the left hippocampal formation and underline the risks of postoperative language decline in patients with left TLE.


Subject(s)
Epilepsy, Temporal Lobe/diagnosis , Epilepsy, Temporal Lobe/physiopathology , Functional Laterality/physiology , Hippocampus/physiology , Hippocampus/physiopathology , Language Tests , Language , Adolescent , Adult , Aged , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Semantics , Temporal Lobe/physiopathology
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