Plasma neurofilament light admission levels and development of axonal pathology in mild traumatic brain injury.

BACKGROUND: It is known that blood levels of neurofilament light (NF-L) and diffusion-weighted magnetic resonance imaging (DW-MRI) are both associated with outcome of patients with mild traumatic brain injury (mTBI). Here, we sought to examine the association between admission levels of plasma NF-L and white matter (WM) integrity in post-acute stage DW-MRI in patients with mTBI. METHODS: Ninety-three patients with mTBI (GCS ≥ 13), blood sample for NF-L within 24 h of admission, and DW-MRI ≥ 90 days post-injury (median = 229) were included. Mean fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated from the skeletonized WM tracts of the whole brain. Outcome was assessed using the Extended Glasgow Outcome Scale (GOSE) at the time of imaging. Patients were divided into CT-positive and -negative, and complete (GOSE = 8) and incomplete recovery (GOSE < 8) groups. RESULTS: The levels of NF-L and FA correlated negatively in the whole cohort (p = 0.002), in CT-positive patients (p = 0.016), and in those with incomplete recovery (p = 0.005). The same groups showed a positive correlation with mean MD, AD, and RD (p < 0.001-p = 0.011). In CT-negative patients or in patients with full recovery, significant correlations were not found. CONCLUSION: In patients with mTBI, the significant correlation between NF-L levels at admission and diffusion tensor imaging (DTI) measurements of diffuse axonal injury (DAI) over more than 3 months suggests that the early levels of plasma NF-L may associate with the presence of DAI at a later phase of TBI.

Association of cognitive-linguistic deficits to diffusion tensor imaging parameters in moderate to severe traumatic diffuse axonal injury.

Cognitive-linguistic functions are an essential part of adequate communication competence. Cognitive-linguistic deficits are common after traumatic diffuse axonal injury (DAI). We aimed to examine the integrity of perisylvian white matter tracts known to be associated with linguistic functions in individuals with DAI and their eventual association with poor cognitive-linguistic outcomes. Diffusion tensor imaging (DTI) results of 44 adults with moderate-to-severe DAI were compared with those of 67 controls. Fractional anisotropy (FA) values of the superior longitudinal fasciculus (SLF), arcuate fasciculus (AF), SLF with frontal connections to the lower parietal cortex, and AF with temporal connections to the lower parietal cortex were measured using tractography. The associations between white matter integrity FA values and cognitive-linguistic deficits were studied in the DAI group. Cognitive-linguistic deficits were determined based on our earlier study using the novel KAT test. No previous studies have examined the associations between white matter integrity and cognitive-linguistic deficits determined using the KAT test. Patients with DAI showed lower FA values in all left-side tracts than the controls. Unexpectedly, the poor cognitive-linguistic outcome in the language comprehension and production domains was associated with high FA values of several tracts. After excluding five cases with the poorest cognitive-linguistic performance, but with the highest values in the DTI variables, no significant associations with DTI metrics were found. The association between white matter integrity and cognitive-linguistic functioning is complex in patients with DAI of traumatic origin, probably reflecting the heterogeneity of TBI.

A comparison of diffusion tensor imaging tractography and constrained spherical deconvolution with automatic segmentation in traumatic brain injury.

Detection of microstructural white matter injury in traumatic brain injury (TBI) requires specialised imaging methods, of which diffusion tensor imaging (DTI) has been extensively studied. Newer fibre alignment estimation methods, such as constrained spherical deconvolution (CSD), are better than DTI in resolving crossing fibres that are ubiquitous in the brain and may improve the ability to detect microstructural injuries. Furthermore, automatic tract segmentation has the potential to improve tractography reliability and accelerate workflow compared to the manual segmentation commonly used. In this study, we compared the results of deterministic DTI based tractography and manual tract segmentation with CSD based probabilistic tractography and automatic tract segmentation using TractSeg. 37 participants with a history of TBI (with Glasgow Coma Scale 13-15) and persistent symptoms, and 41 healthy controls underwent deterministic DTI-based tractography with manual tract segmentation and probabilistic CSD-based tractography with TractSeg automatic segmentation.Fractional anisotropy (FA) and mean diffusivity of corpus callosum and three bilateral association tracts were measured. FA and MD values derived from both tractography methods were generally moderately to strongly correlated. CSD with TractSeg differentiated the groups based on FA, while DTI did not. CSD and TractSeg-based tractography may be more sensitive in detecting microstructural changes associated with TBI than deterministic DTI tractography. Additionally, CSD with TractSeg was found to be applicable at lower b-value and number of diffusion-encoding gradients data than previously reported.

Structural Brain Connectivity Correlates with Outcome in Mild Traumatic Brain Injury.

We investigated the topology of structural brain connectivity networks and its association with outcome after mild traumatic brain injury, a major cause of permanent disability. Eighty-five patients with mild traumatic brain injury underwent magnetic resonance imaging (MRI) twice, about three weeks and eight months after injury, and 30 age-matched orthopedic trauma control subjects were scanned. Outcome was assessed with Extended Glasgow Outcome Scale on average eight months after injury. We performed constrained spherical deconvolution-based probabilistic streamlines tractography on diffusion MRI data and parcellated cortical and subcortical gray matter into 84 regions based on T1-weighted data to reconstruct structural brain connectivity networks weighted by the number of streamlines. Graph theoretical methods were employed to measure network properties in both patients and controls, and correlations between these properties and outcome were calculated. We found no global differences in the network properties between patients with mild traumatic brain injury and orthopedic control subjects at either stage. We found significantly increased betweenness centrality of the right pars opercularis in the chronic stage compared with control subjects, however. Further, both global and local network properties correlated significantly with outcome. Higher normalized global efficiency, degree, and strength as well as lower small-worldness were associated with better outcome. Correlations between the outcome and the local network properties were the most prominent in the left putamen and the left postcentral gyrus. Our results indicate that both global and local network properties provide valuable information about the outcome already in the acute/subacute stage and, therefore, are promising biomarkers for prognostic purposes in mild traumatic brain injury.

Cognitive-Linguistic outcome in moderate to severe diffuse axonal injury and association with fatigue.

PURPOSE: Individuals with traumatic brain injury (TBI) often have persistent cognitive-linguistic deficits that negatively influence their life. Our objective was to examine the cognitive-linguistic outcome in individuals with moderate to severe diffuse axonal injury (DAI) with a novel test battery. As fatigue is a common symptom affecting the lives of individuals with DAI, we also wanted to assess whether the self-reported fatigue was associated with cognitive-linguistic abilities. METHODS: Selected cognitive-linguistic subtests of the Finnish KAT test and The Mental Fatigue Scale (MFS) were applied to 48 adults with moderate to severe DAI and 27 healthy controls. The majority of the participants with DAI were in the chronic stage. The groups were compared using ANCOVA. Linear regressions were used to analyze the association between MFS and cognitive-linguistic outcomes. RESULTS: The participants with DAI had significantly poorer scores than the controls in most cognitive-linguistic variables and reported significantly more fatigue. Two of the four cognitive-linguistic composite variables were associated with the degree of self-reported fatigue. CONCLUSIONS: Cognitive-linguistic deficits are common in individuals with moderate to severe DAI, and The Finnish KAT test is a valuable tool to detect those. Fatigue was associated with linguistic working memory and language production.

Alterations in Microstructure and Local Fiber Orientation of White Matter Are Associated with Outcome after Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) can have long-lasting consequences. We investigated white matter (WM) alterations at 6-12 months following mTBI using diffusion tensor imaging (DTI) and assessed if the alterations associate with outcome. Eighty-five patients with mTBI underwent diffusion-weighted magnetic resonance imaging (MRI) on average 8 months post-injury and patients' outcome was assessed at the time of imaging using the Glasgow Outcome Scale-Extended (GOS-E). Additionally, 30 age-matched patients with extracranial orthopedic injuries were used as control subjects. Voxel-wise analysis of the data was performed using a tract-based spatial statistics (TBSS) approach and differences in microstructural metrics between groups were investigated. Further, the susceptibility of the abnormalities to specific fiber orientations was investigated by analyzing the first eigenvector of the diffusion tensor in the voxels with significant differences. We found significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD) and radial diffusivity (RD) in patients with mTBI compared with control subjects, whereas no significant differences were observed in axial diffusivity (AD) between the groups. The differences were present bilaterally in several WM regions and correlated with outcome. Moreover, multiple clusters were found in the principal fiber orientations of the significant voxels in anisotropy, and similar orientation patterns were found for the diffusivity metrics. These directional clusters correlated with patients' functional outcome. Our study showed that mTBI is associated with WM changes at the chronic stage and these alterations occur in several WM regions. In addition, several significant clusters of WM alterations in specific fiber orientations were found and these clusters were associated with outcome.

A patient with Korsakoff syndrome of psychiatric and alcoholic etiology presenting as DSM-5 mild neurocognitive disorder.

Background: Wernicke's encephalopathy (WE) and Korsakoff syndrome (KS) are underdiagnosed. The DSM-5 has raised the diagnostic threshold by including KS in the major neurocognitive disorders, which requires that the patient needs help in everyday activities. Methods: We report clinical, neuropsychological, and radiological findings from a patient who developed Wernicke-Korsakoff syndrome as a result of alcohol use and weight loss due to major depression. We assess the diagnosis in the context of the scientific literature on KS and according to the DSM-IV and the DSM-5. Results: The patient developed ataxia during a period of weight loss, thus fulfilling current diagnostic criteria of WE. WE was not diagnosed, but the patient partially improved after parenteral thiamine treatment. However, memory problems became evident, and KS was considered. In neuropsychological examination, the Logical Memory test and the Word List test were abnormal, but the Verbal Pair Associates test was normal (Wechsler Memory Scale-III). There were intrusions in the memory testing. The Wisconsin Card Sorting Test was broadly impaired, but the other test of executive functions (difference between Trail Making B and Trail Making A tests) was normal. There was atrophy of the mammillary bodies, the thalamus, the cerebellum, and in the basal ganglia but not in the frontal lobes. Diffusion tensor imaging showed damage in several tracts, including the uncinate fasciculi, the cinguli, the fornix, and the corona radiata. The patient remained independent in everyday activities. The patient can be diagnosed with KS according to the DSM-IV. According to the DSM-5, the patient has major neurocognitive disorders. Conclusions: Extensive memory testing is essential in the assessment of KS. Patients with a history of WE and typical clinical, neuropsychological, and radiological KS findings may be independent in everyday activities. Strict use of the DSM-5 may worsen the problem of Wernicke-Korsakoff syndrome underdiagnosis by excluding clear KS cases that do not have very severe functional impairment.

Diffusion parameters of the core of cingulum are associated with age-related ventricular enlargement: a diffusion tensor tractography study.

PURPOSE: To evaluate the influence of the size of lateral ventricles on diffusion parameters of the normal cingulate bundle. METHODS: Eighty normal subjects (17-55 years) underwent MRI at 3 T including diffusion tensor imaging. Superior (SC) and inferior (IC) cingulum were analyzed separately. Mean diffusivity (MD0.30) and fractional anisotropy (FA0.30) were measured by tractography at FA threshold 0.30; further diffusion parameters were analyzed by tractography-based core analysis in volumes of 3.0 cm3/1.5 cm3. The diffusion parameters were correlated with corresponding cross-sectional coronal areas of lateral ventricles. The analysis was performed also separately for young (17-34) and middle-aged (35-55) subjects. RESULTS: FA0.30 values did not correlate with ventricular size, but there was a weak negative correlation (r = - 0.225) between MD0.30 of SC and ventricular size. In all controls and in the older age group, ventricular size correlated positively with core FA of SC (r = 0.262/r = 0.391) and negatively with mean diffusivity (r = - 0.324/r = - 0.303) and radial diffusivity (λ2: r = - 0.238/r = - 0.277; λ3: r = - 0.353/r = - 0.424) of the core of SC. In the younger age group, only the mean diffusivity of SC correlated with ventricular size (r = - 0.273). Ventricular size was not associated with axial diffusivity. The core parameters of IC did not correlate with ventricular size. CONCLUSION: Radial diffusivity of the core of cingulum decreases in age-dependent ventricular enlargement, which can be related to tissue compaction with stretching of axons and diminution of extracellular spaces. The phenomenon, which is reverse to the assumed effect of age-related myelin loss, can influence on DTI parameters in middle-aged subjects.

Korsakoff Syndrome in Non-alcoholic Psychiatric Patients. Variable Cognitive Presentation and Impaired Frontotemporal Connectivity.

Background: Non-alcoholic Wernicke's encephalopathy and Korsakoff syndrome are greatly underdiagnosed. There are very few reported cases of neuropsychologically documented non-alcoholic Korsakoff syndrome, and diffusion tensor imaging (DTI) data are scarce. Methods: We report clinical characteristics and neuropsychological as well as radiological findings from three psychiatric patients (one woman and two men) with a history of probable undiagnosed non-alcoholic Wernicke's encephalopathy and subsequent chronic memory problems. Results: All patients had abnormal neuropsychological test results, predominantly in memory. Thus, the neuropsychological findings were compatible with Korsakoff syndrome. However, the neuropsychological findings were not uniform. The impairment of delayed verbal memory of the first patient was evident only when the results of the memory tests were compared to her general cognitive level. In addition, the logical memory test and the verbal working memory test were abnormal, but the word list memory test was normal. The second patient had impaired attention and psychomotor speed in addition to impaired memory. In the third patient, the word list memory test was abnormal, but the logical memory test was normal. All patients had intrusions in the neuropsychological examination. Executive functions were preserved, except for planning and foresight, which were impaired in two patients. Conventional MRI examination was normal. DTI showed reduced fractional anisotropy values in the uncinate fasciculus in two patients, and in the corpus callosum and in the subgenual cingulum in one patient. Conclusions: Non-alcoholic Korsakoff syndrome can have diverse neuropsychological findings. This may partly explain its marked underdiagnosis. Therefore, a strong index of suspicion is needed. The presence of intrusions in the neuropsychological examination supports the diagnosis. Damage in frontotemporal white matter tracts, particularly in the uncinate fasciculus, may be a feature of non-alcoholic Korsakoff syndrome in psychiatric patients.

High angular resolution diffusion-weighted imaging in mild traumatic brain injury.

We sought to investigate white matter abnormalities in mild traumatic brain injury (mTBI) using diffusion-weighted magnetic resonance imaging (DW-MRI). We applied a global approach based on tract-based spatial statistics skeleton as well as constrained spherical deconvolution tractography. DW-MRI was performed on 102 patients with mTBI within two months post-injury and 30 control subjects. A robust global approach considering only the voxels with a single-fiber configuration was used in addition to global analysis of the tract skeleton and probabilistic whole-brain tractography. In addition, we assessed whether the microstructural parameters correlated with age, time from injury, patient's outcome and white matter MRI hyperintensities. We found that whole-brain global approach restricted to single-fiber voxels showed significantly decreased fractional anisotropy (FA) (p = 0.002) and increased radial diffusivity (p = 0.011) in patients with mTBI compared with controls. The results restricted to single-fiber voxels were more significant and reproducible than those with the complete tract skeleton or the whole-brain tractography. FA correlated with patient outcomes, white matter hyperintensities and age. No correlation was observed between FA and time of scan post-injury. In conclusion, the global approach could be a promising imaging biomarker to detect white matter abnormalities following traumatic brain injury.

Non-alcoholic Korsakoff syndrome in psychiatric patients with a history of undiagnosed Wernicke's encephalopathy.

Wernicke's encephalopathy is often undiagnosed, particularly in non-alcoholics. There are very few reports of non-alcoholic patients diagnosed with Korsakoff syndrome in the absence of a prior diagnosis of Wernicke's encephalopathy and no studies of diffusion tensor imaging in non-alcoholic Korsakoff syndrome. We report on three non-alcoholic psychiatric patients (all women) with long-term non-progressive memory impairment that developed after malnutrition accompanied by at least one of the three Wernicke's encephalopathy manifestations: ocular abnormalities, ataxia or unsteadiness, and an altered mental state or mild memory impairment. In neuropsychological examination, all patients had memory impairment, including intrusions. One patient had mild cerebellar vermis atrophy in MRI taken after the second episode of Wernicke's encephalopathy. The same patient had mild hypometabolism in the lateral cortex of the temporal lobes. Another patient had mild symmetrical atrophy and hypometabolism of the superior frontal lobes. Two patients were examined with diffusion tensor imaging. Reduced fractional anisotropy values were found in the corona radiata in two patients, and the uncinate fasciculus and the inferior longitudinal fasciculus in one patient. Our results suggest that non-alcoholic Korsakoff syndrome is underdiagnosed. Psychiatric patients with long-term memory impairment may have Korsakoff syndrome and, therefore, they should be evaluated for a history of previously undiagnosed Wernicke's encephalopathy.

Diffusion tensor tractography-based analysis of the cingulum: clinical utility and findings in traumatic brain injury with chronic sequels.

INTRODUCTION: To evaluate the clinical utility of quantitative diffusion tensor tractography (DTT) and tractography-based core analysis (TBCA) of the cingulum by defining the reproducibility, normal values, and findings in traumatic brain injury (TBI). METHODS: Eighty patients with TBI and normal routine MRI and 78 controls underwent MRI at 3T. To determine reproducibility, 12 subjects were scanned twice. Superior (SC) and inferior (IC) cingulum were analyzed separately by DTT (fractional anisotropy (FA) thresholds 0.15 and 0.30). TBCA was performed from volumes defined by tractography with gradually changed FA thresholds. FA values were correlated with clinical and neuropsychological data. RESULTS: The lowest coefficient of variation was obtained at DTT threshold 0.30 (2.0 and 2.4 % for SC and IC, respectively), but in proportion to standard deviations of normal controls, the reproducibility of TBCA was better in SC and similar to that of DTT in IC. In patients with TBI, volume reduction with loss of peripheral fibers was relatively common; mean FA was mostly normal in these tractograms. The frequency of FA reductions (>2 SD) was in DTT smaller than in TBCA, in which FA decrease was present in 42 (13.1 %) of the 320 measurements. Central FA values in SC predicted visuoperceptual ability, and those in left IC predicted cognitive speed, language, and communication ability (p < 0.05). CONCLUSION: Tractography-based measurements have sufficient reproducibility for demonstration of severe abnormalities of the cingulum. TBCA is preferential for clinical FA analysis, because it measures corresponding areas in patients and controls without inaccuracies due to trauma-induced structural changes.

Interpretation of magnetic resonance imaging in the chronic phase of traumatic brain injury: what is missed in the original reports?

PRIMARY OBJECTIVE: To find eventual differences in detecting the late stage TBI findings in MRI between two neuroradiologists and to compare the results with the original reports. METHODS AND PROCEDURE: Two neuroradiologists with different levels of experience (R1 and R2) reviewed 89 cranial 1.5 T MRI examinations of patients with clinically evident TBI. They recorded the nature, location and side of the finding and stated their view of traumatic axonal injury (TAI). The original reports were reviewed accordingly. MAIN OUTCOMES AND RESULTS: TAI was reported as being evident or possible in 51 patients with TBI. However, only 30 (76%) of these concerned the same patients. R1 reported more contusion findings, but both found the same number of spot-like haemorrhages. The most striking difference was in the reporting of localized atrophy. R1 reported atrophy in 51/178 (29%) frontal lobes, whereas R2 in 14/178 (8%). Many of the findings were missed in the original reports. CONCLUSIONS: The interpretation of TBI findings in late stage MRI yields significant variability between neuroradiologists. This may endanger diagnostics and lead to false treatment decisions and medico-legal problems. Standardized quantitative imaging analysis programs and advances in MRI technology should be utilized to improve radiological TBI diagnosis.

Diffusion tensor tractography of the uncinate fasciculus: pitfalls in quantitative analysis due to traumatic volume changes.

PURPOSE: To demonstrate the sensitivity of quantitative diffusion tensor tractography to traumatic injury of the uncinate fasciculus (UF), and to evaluate the effect of volume changes on the accuracy of quantitative analysis. MATERIALS AND METHODS: Diffusion tensor imaging (DTI) was performed at 3 T for 110 patients with traumatic brain injury (TBI) and 60 control subjects. Volume, mean diffusivity (MD), and mean fractional anisotropy (FA) of the UF were measured by means of tractography. The influence of FA threshold on mean FA values was determined and the values were further related to the tract volume. RESULTS: In patients with TBI, 16% of the volumes and 29% of the FA values were decreased and 25% of the MD values were increased (>2 SD from the mean of controls). Small tracts (6% of trajectories) often had normal mean FA, but low volume-related FA values. Large UFs often had decreased mean FA values, but normal volume-related central values (3% of trajectories). CONCLUSION: Posttraumatic FA and MD changes and volume reductions are common in the tractography of UF. Trauma-induced volume changes can cause misleading whole-tract mean FA values. Therefore, additional volume-based analysis of the central part is beneficial for clinical assessment.

Quantitative diffusion-tensor tractography of long association tracts in patients with traumatic brain injury without associated findings at routine MR imaging.

PURPOSE: To evaluate whether quantitative diffusion-tensor tractography can show abnormalities in long association tracts of subjects with symptoms after traumatic brain injury without any visible signs of intracranial or intraparenchymal abnormalities of obvious traumatic origin at routine magnetic resonance (MR) imaging and to determine the number and type of these abnormalities. MATERIALS AND METHODS: The study was approved by the local ethics committee, and informed consent was obtained from all subjects. Diffusion-tensor tractography was performed at 3.0 T in 106 consecutive clinical patients with traumatic brain injury without abnormalities at conventional MR imaging (age, 16-56 years) and 62 age- and sex-matched control subjects. Volume, mean apparent diffusion coefficient (ADC), and mean fractional anisotropy (FA) were measured in the following tracts: uncinate fasciculus, superior cingulum, temporal cingulum, superior longitudinal fasciculus, arcuate fasciculus, inferior fronto-occipital fasciculus, and inferior longitudinal fasciculus. Statistical analyses were based on repeated-measures analysis of covariance. RESULTS: In control subjects, tract volumes showed large variability whereas FA and ADC showed small variability. In several tracts, mean FA values correlated negatively with the respective volumes. In patients with brain injury, FA values were reduced in both uncinate fasciculi, both inferior fronto-occipital fasciculi, and in the right inferior longitudinal fasciculus compared with control subjects (P < .05). Diffusivity was increased in half of the tracts (P < .05). The tract volumes were not significantly reduced. CONCLUSION: Quantitative diffusion-tensor tractography is able to show posttraumatic FA and ADC abnormalities in patients with normal findings at conventional MR imaging in several association tracts, most commonly the uncinate fasciculus. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112570/-/DC1.

Lower brain diffusivity in postpartum period compared to late pregnancy: results from a prospective imaging study of multiple sclerosis patients.

INTRODUCTION: A positive correlation has been observed between multiple sclerosis (MS) disease activity status and the apparent diffusion coefficient (ADC) of the brain. Moreover, the relapse frequency of MS has been reported to decrease during pregnancy and increase postpartum. The aim of this study was to evaluate whether ADC histograms correlate with MS activity during pregnancy and postpartum, with a leading hypothesis that the ADC would increase postpartum compared to pregnancy. METHODS: Magnetic resonance imaging, as well as diffusion-weighted imaging, was performed in 19 patients with relapsing-remitting MS once during the third trimester and once 4-12 weeks postpartum. Brain tissue was extracted from nonbrain tissue with an automated computer program, and whole-brain histograms were generated. New or growing T2 lesions in postpartum images were counted on T2-weighted images. RESULTS: In conventional brain magnetic resonance imaging, a significant increase in T2-lesion load was seen in postpartum images; 58% of patients showed signs of disease activity on their postpartum scan. Despite of this, and contrary to the original hypothesis, whole-brain ADC values were significantly lower in the postpartum period compared to the time of pregnancy. CONCLUSION: This is the first study to address the ADC of the brain during pregnancy and postpartum period. We hypothesize that the higher ADC values observed during pregnancy in this study reflect the physiological status of the cerebral vasculature during pregnancy (generalized vasodilatation of downstream resistance arterioles and an increase of endothelial permeability), which overwhelm the alterations in ADC values normally seen related to MS activity.

Reliability of diagnosis of traumatic brain injury by computed tomography in the acute phase.

The purpose of our study was to determine the accuracy and reliability of the computed tomographic (CT) diagnosis of acute traumatic brain injury (TBI) and to evaluate the inter-observer variation of CT reports of acute TBI between two experienced neuroradiologists and a neuroradiologist in training. One hundred cranial CT examinations of suspected TBI were chosen randomly from those taken during 1 year at a university central hospital, with institutional ethics committee approval. Two neuroradiologists and one neuroradiologist in training read the scans independently and were blinded to the clinical data. The original reports of radiologists on call, who were either radiology residents or general radiologists, were reviewed. Main outcome measures were false-positive and false-negative findings, and the congruency of different readers' reports. The reference standard was a group consensus formed by three neuroradiologists. Radiologists on call missed a significant number of brain contusions (67%), but with regard to intraventricular and subarachnoid hemorrhages and edema, their accuracy was moderate. They reported practically no false-positive brain contusion findings, and all readers found subdural hemorrhages reliably. The two experienced neuroradiologists had the smallest number of false-negative findings, but their reports differed significantly. Of the other neuroradiologists' mistakes, 75% were false-positive, nearly all of these concerning contusions, whereas the other made random mistakes. In conclusion, there was a marked variation between readers in the detection of brain contusion findings on acute brain CT. Experience increased accuracy, yet even between the reports of the most experienced readers, there were marked differences.

Association of injury severity, MRI-results and ApoE genotype with 1-year outcome in mainly mild TBI: a preliminary study.

PRIMARY OBJECTIVE: To study the ability of MRI findings, apolipoprotein E (ApoE) genotype, the Glasgow Coma Score (GCS) and duration of post-traumatic amnesia (PTA) to predict the 1-year outcome in traumatic brain injury (TBI). RESEARCH DESIGN: A prospective study in unselected emergency room patients with an acute TBI, followed for 1 year. METHODS AND PROCEDURES: Thirty-three consecutive patients were studied. The TBI severity was assessed with GCS and duration of PTA. Brain MRI scans were obtained within approximately 1 week post-injury. The ApoE genotypes were determined by standard methods. The outcome was evaluated with the Head Injury Symptom Checklist and the Glasgow Outcome Scale (extended) 1 year after the injury. The prognostic value of the explanatory variables was evaluated with multiple linear regression analysis. MAIN OUTCOMES AND RESULTS: The presence of traumatic axonal injury lesions or contusions in MRI and duration of PTA were independent predictors of poor outcome. The ApoE genotype and GCS were not associated with outcome. CONCLUSIONS: In multivariate models, the duration of PTA and acute MRI are the best predictors of 1-year outcome in TBI, whereas the prognostic values of GCS and ApoE are modest. The dominating role of GCS in assessing TBI severity should be questioned.

Neurological symptoms and natural course of xeroderma pigmentosum.

We have prospectively followed 16 Finnish xeroderma pigmentosum (XP) patients for up to 23 years. Seven patients were assigned by complementation analysis to the group XP-A, two patients to the XP-C group and one patient to the XP-G group. Six of the seven XP-A patients had the identical mutation (Arg228Ter) and the seventh patient had a different mutation (G283A). Further patients were assigned to complementation groups on the basis of their consanguinity to an XP patient with a known complementation group. The first sign of the disease in all the cases was severe sunburn with minimal sun exposure in early infancy. However, at the time the diagnosis was made in only two cases. The XP-A patients developed neurological and cognitive dysfunction in childhood. The neurological disease advanced in an orderly fashion through its successive stages, finally affecting the whole nervous system and leading to death before the age of 40 years. Dermatological and ocular damage of the XP-A patients tended to be limited. The two XP-C patients were neurologically and cognitively intact despite mild brain atrophy as seen by neuroimaging. The XP-G patients had sensorineural hearing loss, laryngeal dystonia and peripheral neuropathy. The XP-C patients had severe skin and ocular malignancies that first presented at pre-school age. They also showed immunosuppression in cell-mediated immunity. Neurological disease appears to be associated with the complementation group and the failure of fibroblasts to recover RNA synthesis following UV irradiation, but not necessarily to the severity of the dermatological symptoms, the hypersensitivity of fibroblasts to UVB killing or the susceptibility of keratinocytes to UVB-induced apoptosis.

MRI changes and ApoE genotype, a prospective 1-year follow-up of traumatic brain injury: a pilot study.

PRIMARY OBJECTIVE: To examine the association between apolipoprotein E (ApoE) genotype and visibility of traumatic brain lesions during the first year after traumatic brain injury (TBI). RESEARCH DESIGN: A prospective 1-year follow-up study in unselected victims of TBI. METHODS: The number and extent of contusions, ventricular size index and semi-quantitative score of other traumatic intraparenchymal lesions were determined with MRI approximately 1 week and 1 year after TBI and the results were analysed in relation to the ApoE genotype in 33 patients after acute non-trivial TBI. RESULTS: The ApoE genotype was not associated with the visible changes occurring during this follow-up. CONCLUSIONS: The presence of ApoE4 was not associated with MRI changes during the first year after TBI. This suggests that if the ApoE4 is associated with an unfavourable outcome after TBI, the processes responsible for the repair of visible lesions are not dependent on ApoE genotype.