White matter changes in comatose survivors of anoxic ischemic encephalopathy and traumatic brain injury: comparative diffusion-tensor imaging study.

PURPOSE: To analyze white matter pathologic abnormalities by using diffusion-tensor (DT) imaging in a multicenter prospective cohort of comatose patients following cardiac arrest or traumatic brain injury (TBI). MATERIALS AND METHODS: Institutional review board approval and informed consent from proxies and control subjects were obtained. DT imaging was performed 5-57 days after insult in 49 cardiac arrest and 40 TBI patients. To control for DT imaging-processing variability, patients' values were normalized to those of 111 control subjects. Automated segmentation software calculated normalized axial diffusivity (λ1) and radial diffusivity (λ⊥) in 19 predefined white matter regions of interest (ROIs). DT imaging variables were compared by using general linear modeling, and side-to-side Pearson correlation coefficients were calculated. P values were corrected for multiple testing (Bonferroni). RESULTS: In central white matter, λ1 differed from that in control subjects in six of seven TBI ROIs and five of seven cardiac arrest ROIs (all P < .01). The λ⊥ differed from that in control subjects in all ROIs in both patient groups (P < .01). In hemispheres, λ1 was decreased compared with that in control subjects in three of 12 TBI ROIs (P < .05) and nine of 12 cardiac arrest ROIs (P < .01). The λ⊥ was increased in all TBI ROIs (P < .01) and in seven of 12 cardiac arrest ROIs (P < .05). Cerebral hemisphere λ1 was lower in cardiac arrest than in TBI in six of 12 ROIs (P < .01), while λ⊥ was higher in TBI than in cardiac arrest in eight of 12 ROIs (P < .01). Diffusivity values were symmetrically distributed in cardiac arrest (P < .001 for side-to-side correlation) but not in TBI patients. CONCLUSION: DT imaging findings are consistent with the known predominance of cerebral hemisphere axonal injury in cardiac arrest and chiefly central myelin injury in TBI. This consistency supports the validity of DT imaging for differentiating axon and myelin damage in vivo in humans.

Preoperative computed tomography scan may fail to predict perilymphatic gusher.

OBJECTIVES: A stapes gusher is a very rare event in ear surgery, but the consequences for hearing can be dramatic. It can usually be predicted by characteristic radiologic abnormalities. We report 2 cases of gusher without any abnormalities seen on the preoperative computed tomography scans. METHODS: The first case was in a 30-year-old man with a bilateral mixed hearing loss. The gusher occurred after a stapedotomy performed with a microdrill. The oval window was plugged with a vein graft, and a fluoroplastic piston was inserted. The second case was in a 39-year-old woman with a family history of hearing loss who presented with a bilateral mixed hearing loss. The footplate was fractured during the stapedotomy drilling and was covered with a temporalis fascia graft that was fixed with a fluoroplastic piston. RESULTS: The first patient had no cerebrospinal fluid leakage and no vertigo or tinnitus. He did have a sensorineural hearing loss. The second patient had dizziness and tinnitus. Postoperative magnetic resonance imaging scans were performed, but again no features were identified that might have predicted these cases. CONCLUSIONS: Surgeons should be reminded that a preoperative computed tomography scan may fail to detect the risk of a perilymphatic gusher.

Assessment of white matter injury and outcome in severe brain trauma: a prospective multicenter cohort.

BACKGROUND: Existing methods to predict recovery after severe traumatic brain injury lack accuracy. The aim of this study is to determine the prognostic value of quantitative diffusion tensor imaging (DTI). METHODS: In a multicenter study, the authors prospectively enrolled 105 patients who remained comatose at least 7 days after traumatic brain injury. Patients underwent brain magnetic resonance imaging, including DTI in 20 preselected white matter tracts. Patients were evaluated at 1 yr with a modified Glasgow Outcome Scale. A composite DTI score was constructed for outcome prognostication on this training database and then validated on an independent database (n=38). DTI score was compared with the International Mission for Prognosis and Analysis of Clinical Trials Score. RESULTS: Using the DTI score for prediction of unfavorable outcome on the training database, the area under the receiver operating characteristic curve was 0.84 (95% CI: 0.75-0.91). The DTI score had a sensitivity of 64% and a specificity of 95% for the prediction of unfavorable outcome. On the validation-independent database, the area under the receiver operating characteristic curve was 0.80 (95% CI: 0.54-0.94). On the training database, reclassification methods showed significant improvement of classification accuracy (P < 0.05) compared with the International Mission for Prognosis and Analysis of Clinical Trials score. Similar results were observed on the validation database. CONCLUSIONS: White matter assessment with quantitative DTI increases the accuracy of long-term outcome prediction compared with the available clinical/radiographic prognostic score.

Usefulness of multislice computerized tomographic angiography in the postoperative evaluation of patients with clipped aneurysms.

BACKGROUND: The aim of our study was to evaluate the diagnostic efficacy of multislice computed tomographic angiography (MSCTA) regarding exclusion quality after aneurysm clipping. METHODS: Sixty patients (74 aneurysms) underwent microsurgical exclusion using titanium clips. The presence of aneurysm remnants on MSCTA was compared by a neuroradiologist to 2D digital subtraction angiography (DSA), which was considered as a reference examination. The contribution of 3D DSA was assessed in a subpopulation of 29 patients (35 aneurysms). RESULTS: With 2D DSA, six aneurysm remnants (8%) were diagnosed, and only five (7%) by MSCTA. The specificity and sensitivity were 98.5 and 83%, respectively. MSCTA failed to demonstrate one large remnant (>2 mm) because of clip artifacts (six clips). With 3D DSA six supplementary remnants were diagnosed. Two were large remnants blinded by vessel overlaps and clip artifacts. Four were small "dog-eared" remnants (< or =2 mm). No additional treatment was required for small remnants. CONCLUSION: In the postoperative period, MSCTA was considered a useful tool to evaluate the large remnants as well as a non-invasive ulterior examination for suspected bifurcation. Nevertheless, 3D DSA is still required for an accurate evaluation of aneurysms treated by more than three clips.

Relation between brain lesion location and clinical outcome in patients with severe traumatic brain injury: a diffusion tensor imaging study using voxel-based approaches.

The early prediction of consciousness recovery from traumatic brain injury (TBI) is crucial to make decisions about the appropriate use of prolonged intensive care. Diffusion tensor imaging (DTI) has been proposed as a biomarker of white matter injury that could be used in a classification purpose. Instead of region-of-interest-based approach, we applied voxel-based approaches (voxel-based DTI and tract-based spatial statistics) on 30 patients with TBI to identify, without any prior, the brain regions that were specifically damaged in unfavorable 1-year outcome group compared to the favorable one. DTI were acquired at mean 23 days (5-53 days) and two DTI-derived indices, fractional anisotropy (FA) and apparent diffusion coefficient (ADC), were tested. Our results showed that (1) ADC is not a relevant biomarker for early 1-year outcome prognosis; (2) FA measured in inferior longitudinal fasciculus, in cerebral peduncle, in posterior limb of the internal capsule, and in posterior corpus callosum is specifically decreased in unfavorable outcome group compare to the favorable one; (3) a linear discriminant analysis using the FA measured in these four regions showed good classification performance (sensitivity = 86% and specificity = 86%). These findings confirm the relevance of the use of DTI as biomarkers for consciousness recovery after TBI and support the possible use of these biomarkers for early classification of patients.

Experience of diffusion tensor imaging and 1H spectroscopy for outcome prediction in severe traumatic brain injury: Preliminary results.

OBJECTIVE: The objective of the study is to test whether multimodal magnetic resonance imaging can provide a reliable outcome prediction of the clinical status, focusing on consciousness at 1 year after severe traumatic brain injury (TBI). DESIGN: Single center prospective cohort with consecutive inclusions. SETTING: Critical Care Neurosurgical Unit of a university hospital. PATIENTS: Forty-three TBI patients not responding to simple orders after sedation cessation and 15 healthy controls. INTERVENTIONS: A multimodal magnetic resonance imaging combining morphologic sequences, diffusion tensor imaging (DTI), and H proton magnetic resonance spectroscopy (MRS) was performed 24 +/- 11 days after severe TBI. The ability of DTI and MRS to predict 1-year outcome was assessed by linear discriminant analysis (LDA). Robustness of the classification was tested using a bootstrap procedure. MEASUREMENTS AND MAIN RESULTS: Fractional anisotropy (FA) was computed as the mean of values at discrete brain sites in the infratentorial and supratentorial regions. The N-acetyl aspartate/creatine (NAA/Cr) ratio was measured in the thalamus, lenticular nucleus, insular cortex, occipital periventricular white matter, and pons. After 1 year, 19 (44%) patients had unfavorable outcomes (death, persistent vegetative state, or minimally conscious state) and 24 (56%) favorable outcomes (normal consciousness with or without functional impairments). Analysis of variance was performed to compare FA and NAA/Cr in the two outcome groups and controls. FA and MRS findings showed highly significant differences between the outcome groups, with significant variables by LDA being supratentorial FA, NAA/Cr (pons), NAA/Cr (thalamus), NAA/Cr (insula), and infratentorial FA. LDA of combined FA and MRS data clearly separated the unfavorable outcome, favorable outcome, and control groups, with no overlap. Unfavorable outcome was predicted with up to 86% sensitivity and 97% specificity; these values were better than those obtained with DTI or MRS alone. CONCLUSION: FA and NAA/Cr hold potential as quantitative outcome-prediction tools at the subacute phase of TBI.

Quality of life and brain damage after microsurgical clip occlusion or endovascular coil embolization for ruptured anterior communicating artery aneurysms: neuropsychological assessment.

OBJECT: For anterior communicating artery (ACoA) aneurysms, endovascular coil embolization constitutes a safe alternative therapeutic procedure to microsurgical clip occlusion. The authors' aim in this study was to evaluate the quality of life (QOL), cognitive function, and brain structure damage after the treatment of ruptured ACoA aneurysms in a group of patients who underwent microsurgical clipping (36 patients) compared with a reference group who underwent endovascular coiling (14 patients). METHODS: At 14 months posttreatment all patients underwent evaluations by independent observers. These observers evaluated global efficacy, executive functions using a frontal assessment battery of tests (Trail making test, Stroop tasks, dual task of Baddeley, verbal fluency, and Wisconsin Card Sorting test), behavior dysexecutive syndrome (the Inventaire du Syndrome Dysexécutif Comportemental questionnaire [ISDC]), and QOL by using the Reintegration To Normal Living Index. Brain damage was analyzed using MR imaging. RESULTS: In the microsurgical clipping and endovascular coiling groups, the distribution on the modified Rankin Scale (p = 0.19) and mean QOL score (85.4 vs 83.4, respectively) were similar. Moreover, the proportion of executive dysfunctions (19.4 vs 28.6%, respectively) and the mean score on the ISDC questionnaire (8.9 vs 8.5, respectively) were not significant, but verbal memory was more altered in the microsurgical clipping group (p = 0.055). Magnetic resonance imaging revealed that the incidence of local encephalomalacia and the median number of lesions per patient increased significantly in the microsurgical clipping group (p = 0.003). CONCLUSIONS: In the 2 groups, no significant difference was observed regarding QOL, executive functions, and behavior. Despite the significant decrease in verbal memory after microsurgical clipping, the interdisciplinary approach remains a safe and useful strategy.

Lesions in deep gray nuclei after severe traumatic brain injury predict neurologic outcome.

PURPOSE: This study evaluates the correlation between injuries to deep gray matter nuclei, as quantitated by lesions in these nuclei on MR T2 Fast Spin Echo (T2 FSE) images, with 6-month neurological outcome after severe traumatic brain injury (TBI). MATERIALS AND METHODS: Ninety-five patients (80 males, mean age = 36.7y) with severe TBI were prospectively enrolled. All patients underwent a MR scan within the 45 days after the trauma that included a T2 FSE acquisition. A 3D deformable atlas of the deep gray matter was registered to this sequence; deep gray matter lesions (DGML) were evaluated using a semi-quantitative classification scheme. The 6-month outcome was dichotomized into unfavorable (death, vegetative or minimally conscious state) or favorable (minimal or no neurologic deficit) outcome. RESULTS: Sixty-six percent of the patients (63/95) had both satisfactory registration of the 3D atlas on T2 FSE and available clinical follow-up. Patients without DGML had an 89% chance (P = 0.0016) of favorable outcome while those with bilateral DGML had an 80% risk of unfavorable outcome (P = 0.00008). Multivariate analysis based on DGML accurately classified patients with unfavorable neurological outcome in 90.5% of the cases. CONCLUSION: Lesions in deep gray matter nuclei may predict long-term outcome after severe TBI with high sensitivity and specificity.

Intralabyrinthine schwannomas: a case series with discussion of the diagnosis and management.

OBJECTIVE: By extracting cases of intralabyrinthine schwannomas (ILS) from the sum of all vestibular schwannomas, we aim to identify and analyze unique features of its presentation. This allows us to refine the management protocol of this rare condition. DESIGN: This is a retrospective study of all patients seen in the Department of Otorhinolaryngology-Head and Neck Surgery, Rouen University Hospital, with either ILS or ILS with intracanalicular extension (ILS-IAC) between 2001 and 2011. A literature search was performed and results combined to draw conclusions on management strategies. METHOD: Three patients with ILS and 6 patients with ILS-IAC were identified. We retrieved data on age, sex, symptoms, audiometry, imaging, and management. Pure tone audiometry and speech discrimination score were assessed and hearing classification recorded. Facial nerve function and vestibular function were documented throughout. The diagnostic and surveillance imaging (MRI with or without CT) were reviewed. RESULTS: The average age at presentation was 62.8 years and the sex ratio was (male: female) 4:5. An ipsilateral hearing loss was observed in all patients. Eight of 9 patients had tinnitus at presentation, 2 had rotatory vertigo, and 1 patient had a facial palsy and hemifacial spasm. In 2 cases, the labyrinthine extension was initially missed. The patient presenting with a large tumor and facial palsy was operated on without delay. The others underwent MRI surveillance, with 4 requiring surgery at a later stage. No postoperative facial palsies were encountered other than the one that had been present preoperatively. CONCLUSION: Frequency of ILS is underestimated because of poor diagnostic criteria. These tumors have often been described as having features, which resemble Ménière's disease, which is not found in our series. In the absence of tumor progression or disabling symptoms, their management is surveillance/medical, and when surgery is considered, facial paralysis and recurrence rates seem low. The treatment of IAC-ILS differs from that of ILS.

Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study.

BACKGROUND: Mutant mouse models suggest that the chloride channel ClC-2 has functions in ion and water homoeostasis, but this has not been confirmed in human beings. We aimed to define novel disorders characterised by distinct patterns of MRI abnormalities in patients with leukoencephalopathies of unknown origin, and to identify the genes mutated in these disorders. We were specifically interested in leukoencephalopathies characterised by white matter oedema, suggesting a defect in ion and water homoeostasis. METHODS: In this observational analytical study, we recruited patients with leukoencephalopathies characterised by MRI signal abnormalities in the posterior limbs of the internal capsules, midbrain cerebral peduncles, and middle cerebellar peduncles from our databases of patients with leukoencephalopathies of unknown origin. We used exome sequencing to identify the gene involved. We screened the candidate gene in additional patients by Sanger sequencing and mRNA analysis, and investigated the functional effects of the mutations. We assessed the localisation of ClC-2 with immunohistochemistry and electron microscopy in post-mortem human brains of individuals without neurological disorders. FINDINGS: Seven patients met our inclusion criteria, three with adult-onset disease and four with childhood-onset disease. We identified homozygous or compound-heterozygous mutations in CLCN2 in three adult and three paediatric patients. We found evidence that the CLCN2 mutations result in loss of function of ClC-2. The remaining paediatric patient had an X-linked family history and a mutation in GJB1, encoding connexin 32. Clinical features were variable and included cerebellar ataxia, spasticity, chorioretinopathy with visual field defects, optic neuropathy, cognitive defects, and headaches. MRI showed restricted diffusion suggesting myelin vacuolation that was confined to the specified white matter structures in adult patients, and more diffusely involved the brain white matter in paediatric patients. We detected ClC-2 in all components of the panglial syncytium, enriched in astrocytic endfeet at the perivascular basal lamina, in the glia limitans, and in ependymal cells. INTERPRETATION: Our observations substantiate the concept that ClC-2 is involved in brain ion and water homoeostasis. Autosomal-recessive CLCN2 mutations cause a leukoencephalopathy that belongs to an emerging group of disorders affecting brain ion and water homoeostasis and characterised by intramyelinic oedema. FUNDING: European Leukodystrophies Association, INSERM and Assistance Publique-Hôpitaux de Paris, Dutch Organisation for Scientific Research (ZonMw), E-Rare, Hersenstichting, Optimix Foundation for Scientific Research, Myelin Disorders Bioregistry Project, National Institute of Neurological Disorders and Stroke, and Genetic and Epigenetic Networks in Cognitive Dysfunction (GENCODYS) Project (funded by the European Union Framework Programme 7).

Silent ischemic lesions in young adults with first stroke are associated with recurrent stroke.

OBJECTIVE: To determine the association between silent ischemic lesions (SILs) on baseline brain MRI and recurrent stroke in young adults with first-ever ischemic stroke. METHODS: This was a single-center retrospective study of adult patients aged 18-50 years with first-ever ischemic stroke investigated by brain MRI between 2002 and 2009. Silent brain infarcts (SBIs) were defined as focal T2 hyperintensities ≥ 3 mm without corresponding focal symptoms, and leukoaraiosis was defined as focal, multifocal, or confluent hyperintensities on T2-weighted sequences. The primary outcome was recurrent stroke. A forward stepwise Cox regression model was used to determine whether SILs were independently associated with recurrent stroke. RESULTS: A total of 271 eligible patients were identified in the database: 89 did not undergo MRI imaging and 12 patients had inadequate follow-up, leaving a study population of 170 patients. MRI demonstrated SILs in 48 of 170 (28.2) patients. No patients had isolated leukoaraiosis. Hypertension (p = 0.049), migraine with aura (p = 0.02), and cardiovascular disease (p = 0.04) were associated with SIL. Mean follow-up duration was 25 ± 7 months. Among patients with SILs, 11 of 48 (23%) had a recurrent stroke vs 8 of 122 (6.5%) patients without SIL (p = 0.003). After multivariate Cox regression, SILs remained independently associated with recurrent stroke (hazard ratio [HR] 3.2, 95% confidence interval [CI] 1.2-8.6, p = 0.02), as did the combination of SBIs and leukoaraiosis (HR 7.3, 95% CI 2.3-22.9, p = 0.003). CONCLUSIONS: In adults ≤ 50 years old with first-ever ischemic stroke, SILs are common and independently predict recurrent stroke.

Interdisciplinary treatment of ruptured cerebral aneurysms in elderly patients.

OBJECT: The aim of the study was to assess postprocedural neurological deterioration and outcome in patients older than 70 years of age in whom treatment was managed in an interdisciplinary context. METHODS: This prospective longitudinal study included all patients 70 years of age or older treated for ruptured cerebral aneurysm over 10 years (June 1997-June 2007). The population was composed of 64 patients. The neurovascular interdisciplinary team jointly discussed the early obliteration procedure for each aneurysm. Neurological deterioration during the postprocedural 2 months and outcome at 6 months were assessed during consultation according to the modified Rankin Scale (mRS) as follows: favorable (mRS score < or = 2) and unfavorable (mRS score > 2). RESULTS: Aneurysm sac obliteration was performed by microvascular clipping in 34 patients (53.1%) and by endovascular coiling in 30 (46.9%). Postprocedural neurological deterioration occurred in 30 patients (46.9%), related to ischemia in 19 (29.7%), rebleeding in 1 (1.6%), and hydrocephalus in 10 (15.6%). At 6 months, the outcome was favorable in 39 patients (60.9%). By multivariate regression logistic analysis, the independent factors associated with unfavorable outcome were age exceeding 75 years (p = 0.005), poor initial grade (p < 0.0001), and the occurrence of ischemia (p < 0.0001). CONCLUSIONS: The baseline characteristics of SAH in the elderly were only slightly different from those in younger patients. In the elderly, the interdisciplinary approach may be considered useful to decrease the ischemic consequences.