Reliability of the freehand region-of-interest method in quantitative cerebral diffusion tensor imaging.

BACKGROUND: Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique used for evaluating changes in the white matter in brain parenchyma. The reliability of quantitative DTI analysis is influenced by several factors, such as the imaging protocol, pre-processing and post-processing methods, and selected diffusion parameters. The region-of-interest (ROI) method is most widely used of the post-processing methods because it is found in commercial software. The focus of our research was to study the reliability of the freehand ROI method using various intra- and inter-observer analyses. METHODS: This study included 40 neurologically healthy participants who underwent diffusion MRI of the brain with a 3 T scanner. The measurements were performed at nine different anatomical locations using a freehand ROI method. The data extracted from the ROIs included the regional mean values, intra- and inter-observer variability and reliability. The used DTI parameters were fractional anisotropy (FA), the apparent diffusion coefficient (ADC), and axial (AD) and radial (RD) diffusivity. RESULTS: The average intra-class correlation coefficient (ICC) of the intra-observer was found to be 0.9 (excellent). The single ICC results were excellent (> 0.8) or adequate (> 0.69) in eight out of the nine regions in terms of FA and ADC. The most reliable results were found in the frontobasal regions. Significant differences between age groups were also found in the frontobasal regions. Specifically, the FA and AD values were significantly higher and the RD values lower in the youngest age group (18-30 years) compared to the other age groups. CONCLUSIONS: The quantitative freehand ROI method can be considered highly reliable for the average ICC and mostly adequate for the single ICC. The freehand method is suitable for research work with a well-experienced observer. Measurements should be performed at least twice in the same region to ensure that the results are sufficiently reliable. In our study, reliability was slightly undermined by artifacts in some regions such as the cerebral peduncle and centrum semiovale. From a clinical point of view, the results are most reliable in adults under the age of 30, when age-related changes in brain white matter have not yet occurred.

Preexisting conditions in older adults with mild traumatic brain injuries.

OBJECTIVE: This study examined the prevalence of preexisting conditions that could affect premorbid brain health, cognition, and functional independence among older adults with mild traumatic brain injury (MTBI), and the relationship between preexisting conditions, injury characteristics, and emergency department (ED) discharge location (home versus continued care). METHODS: Older adults (N = 1,427; 55-104 years-old; 47.4% men) who underwent head computed tomography (CT) after acute head trauma were recruited from the ED. Researchers documented preexisting medical conditions retrospectively from hospital records. RESULTS: Multiple preexisting conditions increased in frequency with greater age, including circulatory and nervous system diseases and preexisting abnormalities on head CT. Psychiatric and substance use disorders (SUDs) decreased in frequency with greater age. Among participants with uncomplicated MTBI and GCS = 15, preexisting nervous system diseases and preexisting CT abnormalities were associated with higher odds of continued care for all participants, whereas psychiatric disorders and SUDs were only associated with higher odds of continued care among participants <70 years-old. Preexisting circulatory diseases, loss of consciousness, and amnesia were unassociated with discharge location. CONCLUSIONS: Preexisting medical conditions that could affect brain and cognitive health occur commonly among older adults who sustain MTBIs. These conditions can confound research examining post-injury outcomes within this age group.

Global Burden of Small Vessel Disease-Related Brain Changes on MRI Predicts Cognitive and Functional Decline.

Background and Purpose- Cerebral small vessel disease is characterized by a wide range of focal and global brain changes. We used a magnetic resonance imaging segmentation tool to quantify multiple types of small vessel disease-related brain changes and examined their individual and combined predictive value on cognitive and functional abilities. Methods- Magnetic resonance imaging scans of 560 older individuals from LADIS (Leukoaraiosis and Disability Study) were analyzed using automated atlas- and convolutional neural network-based segmentation methods yielding volumetric measures of white matter hyperintensities, lacunes, enlarged perivascular spaces, chronic cortical infarcts, and global and regional brain atrophy. The subjects were followed up with annual neuropsychological examinations for 3 years and evaluation of instrumental activities of daily living for 7 years. Results- The strongest predictors of cognitive performance and functional outcome over time were the total volumes of white matter hyperintensities, gray matter, and hippocampi (P<0.001 for global cognitive function, processing speed, executive functions, and memory and P<0.001 for poor functional outcome). Volumes of lacunes, enlarged perivascular spaces, and cortical infarcts were significantly associated with part of the outcome measures, but their contribution was weaker. In a multivariable linear mixed model, volumes of white matter hyperintensities, lacunes, gray matter, and hippocampi remained as independent predictors of cognitive impairment. A combined measure of these markers based on Z scores strongly predicted cognitive and functional outcomes (P<0.001) even above the contribution of the individual brain changes. Conclusions- Global burden of small vessel disease-related brain changes as quantified by an image segmentation tool is a powerful predictor of long-term cognitive decline and functional disability. A combined measure of white matter hyperintensities, lacunar, gray matter, and hippocampal volumes could be used as an imaging marker associated with vascular cognitive impairment.

Spinal cord injury induces widespread chronic changes in cerebral white matter.

Traumatic spinal cord injuries (SCIs) lead to axonal damage at the trauma site, as well as disconnections within the central nervous system. While the exact mechanisms of the long-term pathophysiological consequences of SCIs are not fully understood, it is known that neuronal damage and degeneration are not limited to the direct proximity of the trauma. Instead, the effects can be detected even in the cerebrum. We examined SCI-induced chronic brain changes with a case-control design using 32 patients and 70 control subjects. Whole-brain white matter (WM) tracts were assessed with diffusion tensor imaging (DTI). In addition, we analysed associations between DTI metrics and several clinical SCI variables. Whole-brain analyses were executed by tract-based spatial statistics (TBSS), with an additional complementary atlas-based analysis (ABA). We observed widespread, statistically significant (P ≤ 0.01) changes similar to neural degeneration in SCI patients, both in the corticospinal tract (CST) and beyond. In addition, associations between DTI metrics and time since injury were found with TBSS and ABA, implying possible long-term post-injury neural regeneration. Using the ABA approach, we observed a correlation between SCI severity and DTI metrics, indicating a decrease in WM integrity along with patient sensory or motor scores. Our results suggest a widespread neurodegenerative effect of SCI within the cerebrum that is not limited to the motor pathways. Furthermore, DTI-measured WM integrity of chronic SCI patients seemed to improve as time elapsed since injury. Hum Brain Mapp 38:3637-3647, 2017. © 2017 Wiley Periodicals, Inc.

Critical neural targets for (the level of) human consciousness: Arousal arrest and unconsciousness after sumatriptan administration.

BACKGROUND: Insufficient understanding of the mechanisms of consciousness can make unconsciousness a diagnostic challenge, directly effecting the treatment and the outcome of the patient. Consciousness is a product of brainstem arousal (wakefulness, the level of consciousness) and cortical information integration (awareness, the contents of consciousness). The thalamus serves as a critical hub in the arousal pathway. The nuclei within the internal medullary lamina, together with the associated thalamocortical connections, have been implicated as being especially important for human consciousness. CASE STUDY: A 17-year old male migraineur developed a sudden episode of unconsciousness after receiving a single dose of intranasal sumatriptan for the treatment of prolonged migraine-associated symptoms. Diffusion-weighted magnetic resonance imaging revealed a small bilateral thalamic infarction affecting the centromedian and parafascicular nuclei and the associated non-specific thalamocortical connections as the likely reason for the impairment of consciousness. With the exception of occasional fatigue due to a persistent lesion on the left thalamus, the patient experienced full recovery. Corresponding to the injury, diffusion tensor tractography imaging revealed a distinctive defect on the thalamocortical fibres originating from the left centromedian/parafascicular nuclei complex. CONCLUSIONS: The presented case offers an outstanding example of the importance of the arousal system and non-specific thalamocortical connectivity for normal waking consciousness.

Acute mild traumatic brain injury is not associated with white matter change on diffusion tensor imaging.

This study was designed to (i) evaluate the influence of age on diffusion tensor imaging measures of white matter assessed using tract-based spatial statistics; (ii) determine if mild traumatic brain injury is associated with microstructural changes in white matter, in the acute phase following injury, in a large homogenous sample that was carefully screened for pre-injury medical, psychiatric, or neurological problems; and (iii) examine if injury severity is related to white matter changes. Participants were 75 patients with acute mild traumatic brain injury (age = 37.2 ± 12.0 years, 45 males and 30 females) and 40 controls (age = 40.6 ± 12.2 yrs, 20 males and 20 females). Age effects were analysed by comparing control subgroups aged 31-40, 41-50, and 51-60 years against a group of 18-30-year-old control subjects. Widespread statistically significant areas of abnormal diffusion tensor measures were observed in older groups. Patients and controls were compared using age and gender as covariates and in age- and gender-matched subgroups. Subgroups of patients with more severe injuries were compared to age-and gender-matched controls. No significant differences were detected in patient-control or severity analyses (all P-value > 0.01). In this large, carefully screened sample, acute mild traumatic brain injury was not associated with diffusion tensor imaging abnormalities detectable with tract-based spatial statistics.

Resilience is associated with fatigue after mild traumatic brain injury.

OBJECTIVE: To examine resilience as a predictor of change in self-reported fatigue after mild traumatic brain injury (MTBI). PARTICIPANTS: A consecutive series of 67 patients with MTBI and 34 orthopedic controls. DESIGN: Prospective longitudinal study. MAIN MEASURES: Resilience Scale, Beck Depression Inventory-Second Edition, and Pain subscale from Ruff Neurobehavioral Inventory 1 month after injury and Barrow Neurological Institute Fatigue Scale 1 and 6 months after injury. RESULTS: Insomnia, pain, and depressive symptoms were significantly correlated with fatigue, but even when these variables were controlled for, resilience significantly predicted the change in fatigue from 1 to 6 months after MTBI. In patients with MTBI, the correlation between resilience and fatigue strengthened during follow-up. In controls, significant associations between resilience and fatigue were not found. CONCLUSION: Resilience is a significant predictor of decrease in self-reported fatigue following MTBI. Resilience seems to be a relevant factor to consider in the management of fatigue after MTBI along with the previously established associated factors (insomnia, pain, and depressive symptoms).

Clinical correlates of retrograde amnesia in mild traumatic brain injury.

PRIMARY OBJECTIVE: The purpose of this study was to examine the clinical significance of retrograde amnesia (RA) in patients with acute mild traumatic brain injuries (MTBI). METHODS AND PROCEDURES: An emergency department sample of patients (n = 75), aged 18-60 years, with no pre-morbid medical or psychiatric conditions, who met the WHO criteria for MTBI were enrolled in this prospective, descriptive, follow-up study. This study examined the presence and duration of RA in relation to socio-demographics, MTBI severity markers including neuroimaging (CT, MRI) and clinical outcomes (Rivermead post-concussion symptoms questionnaire, post-concussion syndrome (PCS) diagnosis and return to work (RTW) status) at 2 weeks, 1 month and 6 months post-injury. MAIN OUTCOMES AND RESULTS: GCS scores and duration of post-traumatic amnesia (PTA) were related to RA. Those with GCS scores of 14 vs. 15 were more likely to have RA (χ(2)(1) = 13.70, p < 0.0001) and a longer duration (Mann-Whitney U = 56.0, p < 0.0001, d = 1.15) of RA. The duration of RA and PTA correlated positively (Spearman ρ(75) = 0.42, p < 0.0001) and those with RA had longer durations of PTA (Mann-Whitney U = 228.5, p = 0.001, d = 1.21). During the follow-up, the presence and duration of RA were not significantly associated with PCS diagnosis or time to RTW. CONCLUSIONS: In this study, the presence and duration of RA was not associated with outcome.

Diffusion tensor imaging of the cervical spinal cord in healthy adult population: normative values and measurement reproducibility at 3T MRI.

BACKGROUND: Compared to diffusion tensor imaging (DTI) of the brain, there is a paucity of reports addressing the applicability of DTI in the evaluation of the spinal cord. Most normative data of cervical spinal cord DTI consist of relatively small and arbitrarily collected populations. Comprehensive normative data are necessary for clinical decision-making. PURPOSE: To establish normal values for cervical spinal cord DTI metrics with region of interest (ROI)- and fiber tractography (FT)-based measurements and to assess the reproducibility of both measurement methods. MATERIAL AND METHODS: Forty healthy adults underwent cervical spinal cord 3T MRI. Sagittal and axial conventional T2 sequences and DTI in the axial plane were performed. Whole cord fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were determined at different cervical levels from C2 to C7 using the ROI method. DTI metrics (FA, axial, and radial diffusivities based on eigenvalues λ1, λ2, and λ3, and ADC) of the lateral and posterior funicles were measured at C3 level. FA and ADC of the whole cord and the lateral and posterior funicles were also measured using quantitative tractography. Intra- and inter-observer variation of the measurement methods were assessed. RESULTS: Whole cord FA values decreased and ADC values increased in the rostral to caudal direction from C2 to C7. Between the individual white matter funicles no statistically significant difference for FA or ADC values was found. Both axial diffusivity and radial diffusivity of both lateral funicles differed significantly from those of the posterior funicle. Neither gender nor age correlated with any of the DTI metrics. Intra-observer variation of the measurements for whole cord FA and ADC showed almost perfect agreement with both ROI and tractography-based measurements. There was more variation in measurements of individual columns. Inter-observer agreement varied from moderate to strong for whole cord FA and ADC. CONCLUSION: Both ROI- and FT-based measurements are applicable methods yielding reproducible results for cervical spinal cord DTI metrics. Normative values for both measurement methods are presented.

Acute assessment of brain injuries in ground-level falls.

OBJECTIVE: The purpose of this study was to characterize traumatic brain injuries (TBI) sustained in ground-level falls (GLFs). The focus was on factors associated with acute computed tomographic (CT) findings. METHODS: The sample included 575 subjects examined and treated at the Tampere University Hospital emergency department (ED). Retrospective data collection consisted of subject- and injury-related data and clinical information from the emergency department. All CT scans were analyzed and systematically coded. RESULTS: Ground-level falls were the mechanism of injury in 48.3% (n = 278) of the subjects. In the GLF group, independent risk factors for acute traumatic CT findings were long-term alcohol abuse, older age, being found on the ground, and left temporoparietal and occipital location of direct head impact. There were no significant differences in the incidence of any intracranial traumatic lesion type between those with GLFs and other causes of TBI. None of the classic clinical TBI severity markers studied were associated with acute traumatic CT findings in patients with GLFs. CONCLUSIONS: Older age and long-term alcohol abuse increase the likelihood of acute intracranial CT abnormalities. The pattern of intracranial traumatic CT findings does not differ from other causes of TBI. Clinical signs and indices of TBI severity did not predict traumatic CT findings.

[Diffusion tensor imaging and sequel of brain injury]. / Diffuusiotensorikuvaus ja aivovamman jälkitila.

By observing the magnitude and direction of thermal motion of water molecules, diffusion tensor imaging (DTI) allows the study of the internal structure and disturbances of the white matter tracts. For instance in neurosurgery, the relation of the corticospinal tract to the tumor to be operated can be defined in this manner when planning the operation. It is hoped that DTI will be beneficial for patients who are not recovering from brain injury in an expected manner, although conventional imaging methods do not reveal any brain damage. Indeed, DTI is able to distinguish brain-damaged patients from healthy controls also in cases of a normal MRI finding.

Repeatability and variation of region-of-interest methods using quantitative diffusion tensor MR imaging of the brain.

BACKGROUND: Diffusion tensor imaging (DTI) is increasingly used in various diseases as a clinical tool for assessing the integrity of the brain's white matter. Reduced fractional anisotropy (FA) and an increased apparent diffusion coefficient (ADC) are nonspecific findings in most pathological processes affecting the brain's parenchyma. At present, there is no gold standard for validating diffusion measures, which are dependent on the scanning protocols, methods of the softwares and observers. Therefore, the normal variation and repeatability effects on commonly-derived measures should be carefully examined. METHODS: Thirty healthy volunteers (mean age 37.8 years, SD 11.4) underwent DTI of the brain with 3T MRI. Region-of-interest (ROI) -based measurements were calculated at eleven anatomical locations in the pyramidal tracts, corpus callosum and frontobasal area. Two ROI-based methods, the circular method (CM) and the freehand method (FM), were compared. Both methods were also compared by performing measurements on a DTI phantom. The intra- and inter-observer variability (coefficient of variation, or CV%) and repeatability (intra-class correlation coefficient, or ICC) were assessed for FA and ADC values obtained using both ROI methods. RESULTS: The mean FA values for all of the regions were 0.663 with the CM and 0.621 with the FM. For both methods, the FA was highest in the splenium of the corpus callosum. The mean ADC value was 0.727 ×10-3 mm2/s with the CM and 0.747 ×10-3 mm2/s with the FM, and both methods found the ADC to be lowest in the corona radiata. The CV percentages of the derived measures were < 13% with the CM and < 10% with the FM. In most of the regions, the ICCs were excellent or moderate for both methods. With the CM, the highest ICC for FA was in the posterior limb of the internal capsule (0.90), and with the FM, it was in the corona radiata (0.86). For ADC, the highest ICC was found in the genu of the corpus callosum (0.93) with the CM and in the uncinate fasciculus (0.92) with FM. CONCLUSIONS: With both ROI-based methods variability was low and repeatability was moderate. The circular method gave higher repeatability, but variation was slightly lower using the freehand method. The circular method can be recommended for the posterior limb of the internal capsule and splenium of the corpus callosum, and the freehand method for the corona radiata.

Serotonergic Antidepressants and Risk for Traumatic Intracranial Bleeding.

Background: Serotonergic antidepressants may predispose to bleeding but the effect on traumatic intracranial bleeding is unknown. Methods: The rate of intracranial bleeding in patients with antidepressant medication was compared to patients not antidepressants in a cohort of patients with acute head injury. This association was examined by using a consecutive cohort of head trauma patients from a Finnish tertiary center emergency department (Tampere University Hospital, Tampere, Finland). All consecutive (2010-2012) adult patients (n = 2,890; median age = 58; male = 56%, CT-positive = 22%, antithrombotic medication users = 25%, antidepressant users = 10%) who underwent head CT due to head trauma in the emergency department were included. Results: Male gender, GCS <15, older age, and anticoagulation were associated with an increased risk for traumatic intracranial bleeding. There were 17.8% of patients not taking antidepressants and 18.3% of patients on an antidepressant who had traumatic intracranial bleeding (p = 0.830). Among patients who were taking antithrombotic medication, 16.6% of the patients not taking antidepressant medication, and 22.5% of the patients taking antidepressant medication, had bleeding (p = 0.239). In a regression analysis, traumatic intracranial hemorrhage was not associated with antidepressant use. Conclusions: Serotonergic antidepressant use was not associated with an increased risk of traumatic intracranial hemorrhage.

Diffusion tensor imaging of the brain in a healthy adult population: Normative values and measurement reproducibility at 3 T and 1.5 T.

BACKGROUND: Diffusion tensor imaging (DTI) is an increasingly used method for investigation of brain white matter integrity in both research and clinical applications. Familiarity with normal variation of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values and measurement reproducibility is essential when DTI measurements are interpreted in clinical patients. PURPOSE: To establish normal values for FA and ADC in a healthy adult population at 1.5 T and 3 T MRI based on region of interest (ROI) analysis, and to study the inter- and intra-observer reproducibility of the measurements. MATERIAL AND METHODS: Forty healthy volunteers (26 women, 14 men, mean age 38.3, SD 11.6 years) underwent conventional MRI and DTI of the brain, 30 with 3 T and 10 with 1.5 T clinical scanners. ROI-based measurements for FA and ADC values were performed in five different anatomic locations of each hemisphere and in three locations within the corpus callosum. Mean values for FA and ADC for each region were calculated. Inter-observer variation of ROI measurements was evaluated by comparing the results of the two observers, intra-observer variation by repeated measurement of 10 subjects by both observers. RESULTS: The FA values varied considerably between different regions. The highest values were found in the genu and splenium of the corpus callosum and the lowest in the corona radiata, respectively. In general, ADC values showed less variation; the highest values were found in the body of the corpus callosum and the lowest in the corona radiata. The reproducibility of both inter- and intra-observer measurements also varied regionally. The highest agreement was found for the corpus callosum and the lowest for the corona radiata and centrum semiovale. CONCLUSION: In a normal adult population FA and ADC values of the brain white matter show regional variation. The repeatability of the ROI measurements also varies regionally. This regional variability must be acknowledged when these measurements are interpreted in clinical patients.

Alexander disease as a cause of nocturnal vomiting in a 7-year-old girl.

Alexander disease is a rare form of leukodystrophy with a highly variable clinical course. Occasionally night-time nausea and vomiting are the first symptoms of juvenile Alexander disease. A 7-year-old girl had recurrent night-time vomiting and her growth and weight gain had deteriorated after her sixth birthday. Cranial MRI demonstrated two small, symmetrical focal areas of abnormally high signal intensity in the dorsal medulla oblongata on T2-W and FLAIR images. These were suggestive of juvenile Alexander disease, and subsequent sequencing of the glial fibrillary acidic protein (GFAP) gene revealed a heterogeneous missense mutation in the GFAP gene in exon 6. Alexander disease should be considered in young patients with atypical anorexia nervosa-type symptoms.

Diffusion tensor imaging and disability progression in multiple sclerosis: A 4-year follow-up study.

OBJECTIVES: Diffusion tensor imaging (DTI) is sensitive technique to detect widespread changes in water diffusivity in the normal-appearing white matter (NAWM) that appears unaffected in conventional magnetic resonance imaging. We aimed to investigate the prognostic value and stability of DTI indices in the NAWM of the brain in an assessment of disability progression in patients with a relapsing-onset multiple sclerosis (MS). METHODS: Forty-six MS patients were studied for DTI indices (fractional anisotropy (FA), mean diffusivity (MD), radial (RD), and axial (AD) diffusivity) in the NAWM of the corpus callosum (CC) and the internal capsule at baseline and at 1 year after. DTI analysis for 10 healthy controls was also performed at baseline. Simultaneously, focal brain lesion volume and atrophy measurements were done at baseline for MS patients. Associations between DTI indices, volumetric measurements, and disability progression over 4 years were studied by multivariate logistic regression analysis. RESULTS: At baseline, most DTI metrics differed significantly between MS patients and healthy controls. There was tendency for associations between baseline DTI indices in the CC and disability progression (p < 0.05). Changes in DTI indices over 1 year were observed only in the CC (p < 0.008), and those changes were not found to predict clinical worsening over 4 years. Clear-cut association with disability progression was not detected for baseline volumetric measurements. CONCLUSION: Aberrant diffusivity measures in the NAWM of the CC may provide additional information for individual disability progression over 4 years in MS with the relapsing-onset disease. CC may be a good target for DTI measurements in monitoring disease activity in MS, and more studies are needed to assess the related prognostic potential.

Clinical Management of Epilepsy With Glutamic Acid Decarboxylase Antibody Positivity: The Interplay Between Immunotherapy and Anti-epileptic Drugs.

Background: There is scanty guidance in the literature on the management of patients with glutamic acid decarboxylase (GAD65) antibody associated autoimmune epilepsy (GAD-epilepsy). GAD-epilepsy is a rare distinct neurological syndrome with a wide clinical spectrum. We describe six GAD-epilepsy patients with special emphasis on the treatment timing and the relationship between immunologic and anti-epileptic therapy. Methods: Six patients diagnosed with GAD-epilepsy in Tampere University Hospital who had received immunotherapy from 2013 to 2017 were retrospectively analyzed from patient records. Data about symptom onset, including antibody levels, magnetic resonance imaging (MRI), electroencephalograms, immunotherapy and anti-epileptic treatment timing and treatment responses were collected and analyzed. Kruskall-Wallis test was used in the statistical evaluation. Results: All patients were female aged 9-54 at symptom onset. Three had hypothyroidism, none had diabetes, two had migraine. Five patients had very high (>2,000 IU/ml) and one had high (52-251 IU/ml) GAD65 antibody titers. All patients presented with seizure disorders. Patients who received early initiation of immunotherapy (3-10 months) responded well to treatment; patients in whom the immunotherapy was started later (15-87 months) did not respond (p = 0.0495). The first patient was seizure-free after 1 year of regular intravenous immunoglobulin and one antiepileptic drug (AED). The second patient developed unilateral temporal lobe T2 signal changes in MRI; she responded well to immunotherapy, experiencing a significant reduction in seizure frequency and resolution of MRI abnormalities. However, seizures continued despite trials with several AEDs. The third patient responded well to immunoadsorption and rituximab with one AED, with lowering of GAD65 titers (from >2,000 to 300). There was a long delay in the diagnosis of GAD-epilepsy in the three patients who had developed refractory epilepsy, one with hippocampal sclerosis. They all received immunotherapy but none responded. However, AED modification or vagus nerve stimulation reduced the seizure frequency in two patients. Epilepsy surgery was ineffective. Conclusions: These results highlight the importance of early detection of GAD65 antibodies in refractory epilepsy as immunotherapy can be effective if administered in the early stages of the disease when it can prevent permanent brain tissue damage.

Characterizing the type and location of intracranial abnormalities in mild traumatic brain injury.

OBJECTIVEThe incidence of intracranial abnormalities after mild traumatic brain injury (TBI) varies widely across studies. This study describes the characteristics of intracranial abnormalities (acute/preexisting) in a large representative sample of head-injured patients who underwent CT imaging in an emergency department.METHODSCT scans were systematically analyzed/coded in the TBI Common Data Elements framework. Logistic regression modeling was used to quantify risk factors for traumatic intracranial abnormalities in patients with mild TBIs. This cohort included all patients who were treated at the emergency department of the Tampere University Hospital (between 2010 and 2012) and who had undergone head CT imaging after suffering a suspected TBI (n = 3023), including 2766 with mild TBI and a reference group with moderate to severe TBI.RESULTSThe most common traumatic lesions seen on CT scans obtained in patients with mild TBIs and those with moderate to severe TBIs were subdural hematomas, subarachnoid hemorrhages, and contusions. Every sixth patient (16.1%) with mild TBI had an intracranial lesion compared with 5 of 6 patients (85.6%) in the group with moderate to severe TBI. The distribution of different types of acute traumatic lesions was similar among mild and moderate/severe TBI groups. Preexisting brain lesions were a more common CT finding among patients with mild TBIs than those with moderate to severe TBIs. Having a past traumatic lesion was associated with increased risk for an acute traumatic lesion but neurodegenerative and ischemic lesions were not. A lower Glasgow Coma Scale score, male sex, older age, falls, and chronic alcohol abuse were associated with higher risk of acute intracranial lesion in patients with mild TBI.CONCLUSIONSThese findings underscore the heterogeneity of neuropathology associated with the mild TBI classification. Preexisting brain lesions are common in patients with mild TBI, and the incidence of preexisting lesions increases with age. Acute traumatic lesions are fairly common in patients with mild TBI; every sixth patient had a positive CT scan. Older adults (especially men) who fall represent a susceptible group for acute CT-positive TBI.

Skeletal dysplasia presenting as a neuromuscular disorder - report of three children.

Three pediatric patients were investigated because of suspected muscle disorder. They were clumsy with an awkward looking waddling gait and had increasing muscle weakness and pain in the legs. Serum CK-values, electroneuromyography (ENMG) and muscle biopsy were all normal. A post-traumatic X-ray of the ankle of one of them showed epiphyseal changes and his condition was diagnosed as Camurati-Engelmann disease. Because of similarities in the clinical presentation of these boys, bone changes were looked for in the two other patients and a diagnosis of multiple epiphyseal dysplasia was made. Skeletal dysplasia should be considered as a diagnostic alternative when a child presents with an unexplained muscle weakness accompanied with pain in the limbs. Specific treatment for bone dysplasias can alleviate symptoms and prevent fractures.

Greater Attention to Task-Relevant Threat Due to Orbitofrontal Lesion.

Injury to the orbitofrontal cortex (OFC) is a frequent consequence of head injury and may lead to dysfunctional regulation of emotional and social behavior. Dysfunctional emotional behavior may partly be related to the role of the OFC in emotion-attention interaction, as reported previously. In order to better understand its role in emotion-attention and emotion-cognitive control interactions, we investigated attention allocation to task-relevant and task-irrelevant threat-related emotional stimuli during a task requiring cognitive control in patients with lesion to the OFC. We measured the behavioral performance and event-related potentials (ERP) of 13 patients with OFC lesion and 11 control subjects during a Go/NoGo visual discrimination task. In the task, line drawings of threatening (spider) and neutral (flower) figures served as either task-relevant Go or NoGo signals, or as task-irrelevant distractors. Overall performance did not differ between the groups. In contrast to the control group performance, the orbitofrontal group performance was improved by relevant threat signal in comparison with neutral signal. Further, task-relevant threat signals evoked larger frontocentral N2-P3 amplitude in the orbitofrontal group. Taken together, behavioral and electrophysiological results suggest that patients with OFC injury allocated more attentional and cognitive control resources in the context of task-relevant emotional stimuli. This study provides new evidence for the role of the OFC in emotion-attention and emotion-cognitive control interactions. Further, the OFC seems to contribute to the balance between voluntary and involuntary attention networks in context of emotional stimuli. Better understanding of alterations in emotion-attention interaction offers insight into affective dysfunction due to OFC lesion.