Neuro-psychiatric symptoms in directly and indirectly blast exposed civilian survivors of urban missile attacks.

BACKGROUND: Blast-explosion may cause traumatic brain injury (TBI), leading to post-concussion syndrome (PCS). In studies on military personnel, PCS symptoms are highly similar to those occurring in post-traumatic stress disorder (PTSD), questioning the overlap between these syndromes. In the current study we assessed PCS and PTSD in civilians following exposure to rocket attacks. We hypothesized that PCS symptomatology and brain connectivity will be associated with the objective physical exposure, while PTSD symptomatology will be associated with the subjective mental experience. METHODS: Two hundred eighty nine residents of explosion sites have participated in the current study. Participants completed self-report of PCS and PTSD. The association between objective and subjective factors of blast and clinical outcomes was assessed using multivariate analysis. White-matter (WM) alterations and cognitive abilities were assessed in a sub-group of participants (n = 46) and non-exposed controls (n = 16). Non-parametric analysis was used to compare connectivity and cognition between the groups. RESULTS: Blast-exposed individuals reported higher PTSD and PCS symptomatology. Among exposed individuals, those who were directly exposed to blast, reported higher levels of subjective feeling of danger and presented WM hypoconnectivity. Cognitive abilities did not differ between groups. Several risk factors for the development of PCS and PTSD were identified. CONCLUSIONS: Civilians exposed to blast present higher PCS/PTSD symptomatology as well as WM hypoconnectivity. Although symptoms are sub-clinical, they might lead to the future development of a full-blown syndrome and should be considered carefully. The similarities between PCS and PTSD suggest that despite the different etiology, namely, the physical trauma in PCS and the emotional trauma in PTSD, these are not distinct syndromes, but rather represent a combined biopsychological disorder with a wide spectrum of behavioral, emotional, cognitive and neurological symptoms.

Echoes from the past- changing associations between brain tumors and ethnicity.

BACKGROUND: cranial X radiation therapy was the standard of care for treating dermatological conditions until the 1960s, when its association to cancer and particularly high rates of brain tumors was discovered. This study examines associations found between incidence of brain tumor and ethnicity. METHODS: This study analyzed two cohorts who underwent examination at age 17 and were followed by linkage to the national cancer registry. The first cohort included 376,336 participants born in 1948-1959 (when treatment with cranial X radiation was standard care for treating tinea capitis), and the second 474,923 participants born in 1960-1971. RESULTS: In the first cohort, ethnicity was strongly associated with the incidence of brain tumor (BT), with higher incidence observed among patients with origins in North Africa or the Middle East. This effect was ablated in the second cohort, and a significant decrease in the rate of meningiomas was noted. CONCLUSION: The association of brain tumor with ethnicity was present only during the period when treatment with cranial X radiation was the standard of care for TC in Israel, therefore it is most likely that radiation exposure was a confounding factor, and that ethnic susceptibility for brain cancer was not causative in these cohorts.

Novel SBF1 splice-site null mutation broadens the clinical spectrum of Charcot-Marie-Tooth type 4B3 disease.

Four siblings of consanguineous Bedouin kindred presented at infancy with an autosomal recessive syndrome of congenital microcephaly, facial dysmorphism, strabismus, developmental delay and ataxia with positive pyramidal signs. Toward the end of their first decade, they developed areflexia, multiple cranial neuropathies and severe polyneuropathy with progressive muscle weakness, affecting proximal and distal extremities. Physical assessment exhibited kyphoscoliosis, bilateral syndactyly and distal muscle wasting with drop-foot and pes cavus. Magnetic resonance imaging (MRI) showed profound cerebellar atrophy with highly unique findings at the pontine and mesencephalic levels, previously described as "fork and bracket" signs. Genome-wide linkage analysis identified a single ~1.5 Mbp disease-associated locus on chromosome 22q13.33. Whole exome sequencing identified a single novel homozygous deleterious splice-site mutation within this locus in SET binding factor 1 (SBF1). SBF1 missense mutations were shown to underlie Charcot-Marie-Tooth (CMT) type 4B3 disease, a rare autosomal recessive subtype of CMT4. The novel SBF1 null mutation highlights distinct severe phenotypic manifestations, broadening the clinical spectrum of SBF1-related neuropathies: cerebellar and pyramidal signs evident in the first months of life with peripheral polyneuropathy emerging only toward the end of the first decade, together with unique MRI findings.

Puerperal ventral epidural hematoma after epidural labor analgesia.

Serious complications in obstetric anesthesia are a rare occurrence. High neuraxial block, respiratory arrest in labor and delivery, and an unrecognized spinal catheter are among the most frequently reported serious complications. A serious complication occurs in approximately 1:3000 obstetric patients. Neuraxial hematoma after obstetric epidural analgesia or anesthesia is extremely rare. We present a case of a puerperal spinal epidural hematoma following epidural labor analgesia. The patient presented with foot drop, which resolved after conservative treatment. We reviewed the epidemiology, clinical manifestations and treatment options for this rare complication.

Automated Cross-Sectional Measurement Method of Intracranial Dural Venous Sinuses.

BACKGROUND AND PURPOSE: MRV is an important blood vessel imaging and diagnostic tool for the evaluation of stenosis, occlusions, or aneurysms. However, an accurate image-processing tool for vessel comparison is unavailable. The purpose of this study was to develop and test an automated technique for vessel cross-sectional analysis. MATERIALS AND METHODS: An algorithm for vessel cross-sectional analysis was developed that included 7 main steps: 1) image registration, 2) masking, 3) segmentation, 4) skeletonization, 5) cross-sectional planes, 6) clustering, and 7) cross-sectional analysis. Phantom models were used to validate the technique. The method was also tested on a control subject and a patient with idiopathic intracranial hypertension (4 large sinuses tested: right and left transverse sinuses, superior sagittal sinus, and straight sinus). The cross-sectional area and shape measurements were evaluated before and after lumbar puncture in patients with idiopathic intracranial hypertension. RESULTS: The vessel-analysis algorithm had a high degree of stability with <3% of cross-sections manually corrected. All investigated principal cranial blood sinuses had a significant cross-sectional area increase after lumbar puncture (P ≤ .05). The average triangularity of the transverse sinuses was increased, and the mean circularity of the sinuses was decreased by 6% ± 12% after lumbar puncture. Comparison of phantom and real data showed that all computed errors were <1 voxel unit, which confirmed that the method provided a very accurate solution. CONCLUSIONS: In this article, we present a novel automated imaging method for cross-sectional vessels analysis. The method can provide an efficient quantitative detection of abnormalities in the dural sinuses.

Intracranial nonjugular venous pathways: a possible compensatory drainage mechanism.

BACKGROUND AND PURPOSE: The IJVs are considered to be the main pathway draining the intracranial venous system. There is increasing evidence for the existence of alternative venous pathways. Studies using extracranial sonography techniques have demonstrated a nonjugular venous system. In the current study, we used MR images to investigate the NJV drainage system and its components (vertebral plexus, pterygopalatine plexus). The exact visualization and measurement of the intracranial NJVs could be of diagnostic importance and may have clinical importance. MATERIALS AND METHODS: A total of 64 participants with no history of neurologic disease were included in the study. All participants underwent scanning with a 2D time-of-flight, multisection sequence in the supine position. Image processing software was developed to identify and quantify the size of the IJVs and NJVs in the plane of the internal JF. For evaluation of software accuracy, all images were reviewed by a neuroradiologist experienced in neurovascular imaging preprocessing and postprocessing. RESULTS: The CSA of the NJVs correlated inversely with the CSA of the IJVs (r(2) = 0.25; P < .0001). An inverse correlation was also significant when comparing IJV with NJV components (vertebral plexus: r(2) = 0.19; P = .0004; pterygopalatine plexus: r(2) = 0.11; P = .0069). Furthermore, only NJV cumulative CSA correlated inversely with participant age (r(2) = 0.2; P = .0002). CONCLUSIONS: Our study indicates that the NJVs might serve as a compensatory drainage mechanism in the intracranial compartment. This mechanism appears less significant as the age of the patient progresses.

Post-traumatic anxiety associates with failure of the innate immune receptor TLR9 to evade the pro-inflammatory NFκB pathway.

Post-traumatic anxiety notably involves inflammation, but its causes and functional significance are yet unclear. Here, we report that failure of the innate immune system Toll-like receptor 9 (TLR9) to limit inflammation is causally involved with anxiety-associated inflammation and that peripheral administration of specific oligonucleotide activators of TLR9 may prevent post-traumatic consequences in stressed mice. Suggesting involvement of NFκB-mediated enhancement of inflammatory reactions in the post-traumatic phenotype, we found association of serum interleukin-1ß increases with symptoms severity and volumetric brain changes in post-traumatic stress disorder patients. In predator scent-stressed mice, the moderate NFκB-activating oligonucleotides mEN101 and its human ortholog BL-7040, but not the canonic NFκB activator oligonucleotide ODN1826, induced anxiolytic effects. In stressed mice, peripherally administered mEN101 prevented delayed stress-inducible serum interleukin-1ß increases while limiting stress-characteristic hippocampal transcript modifications and the anxiety-induced EGR1-mediated neuronal activation. Attesting to the TLR9 specificity of this response, BL-7040 suppressed NFκB-mediated luciferase in transfected cells co-expressing TLR9, but not other TLRs. Furthermore, TLR9-/- mice were mEN101 and BL-7040 resistant and presented unprovoked anxiety-like behavior and anxiety-characteristic hippocampal transcripts. Our findings demonstrate functional relevance of TLR9 in protecting stressed mammals from overreacting to traumatic experiences and suggest using oligonucleotide-mediated peripheral TLR9 activation to potentiate the innate immune system and prevent post-traumatic inflammation and anxiety.

Clearance of a status aurae migraenalis in response to thrombendarterectomy in a patient with high grade internal carotid artery stenosis.

We report a patient with high grade internal carotid artery (ICA) stenosis who had frequent migrainous aura-like symptoms for a period of 3 weeks (Latin: status aurae migraenalis). This syndrome has been described previously but it was unclear whether ischaemic damage was associated with it. Using MRI, we demonstrated widely scattered focal laminar cortical infarcts. Importantly, after ICA thrombendarterectomy, the status aurae migraenalis abruptly ceased which supports the concept that high grade ICA stenosis can be the cause of status aurae migraenalis.

Blood-brain barrier disruption in post-traumatic epilepsy.

BACKGROUND: Traumatic brain injury (TBI) is an important cause of focal epilepsy. Animal experiments indicate that disruption of the blood-brain barrier (BBB) plays a critical role in the pathogenesis of post-traumatic epilepsy (PTE). OBJECTIVE: To investigate the frequency, extent and functional correlates of increased BBB permeability in patient with PTE. METHODS: 32 head trauma patients were included in the study, with 17 suffering from PTE. Patients underwent brain MRI (bMRI) and were evaluated for BBB disruption, using a novel semi-quantitative technique. Cortical dysfunction was measured using electroencephalography (EEG), and localised using standardised low-resolution brain electromagnetic tomography (sLORETA). RESULTS: Spectral EEG analyses revealed significant slowing in patients with TBI, with no significant differences between patients with epilepsy and those without. Although bMRI revealed that patients with PTE were more likely to present with intracortical lesions (p = 0.02), no differences in the size of the lesion were found between the groups (p = 0.19). Increased BBB permeability was found in 76.9% of patients with PTE compared with 33.3% of patients without epilepsy (p = 0.047), and could be observed years following the trauma. Cerebral cortex volume with BBB disruption was larger in patients with PTE (p = 0.001). In 70% of patients, slow (delta band) activity was co-localised, by sLORETA, with regions showing BBB disruption. CONCLUSIONS: Lasting BBB pathology is common in patients with mild TBI, with increased frequency and extent being observed in patients with PTE. A correlation between disrupted BBB and abnormal neuronal activity is suggested.

The vein of Labbe masquerading as an epidural abscess.

The occipitotemporal vein (OTV) courses over the temporal lobe, connecting the superficial middle cerebral vein and the transverse sinus. This vein is rarely identifiable on computerized tomography (CT) scans and a large amount of contrast is needed to identify such a relatively small vessel. We present a 12-month-old male with acute coalescent mastoiditis and a subperiosteal abscess. An epidural abscess was suspected on pre-operative CT scan. No abscess was found on surgery. Based on the surgical finding, we determined that this misdiagnosis was due to a vascular variant, the occipitotemporal vein (vein of Labbe) that masqueraded as an abscess on the CT scan. Recognition of the vein of Labbe on CT scan is therefore essential for the appropriate management of otological and neurotological disease.

Early stroke detection and extent: impact of experience and the role of computed tomography angiography source images.

AIM: To test the performance of computed tomography angiography "source images" (CTA-SI) versus unenhanced CT (NCCT) for stroke detection and extent using the Alberta Stroke Programme Early CT Score (ASPECTS), and examine the effect of experience and clinical history. MATERIALS AND METHODS: Studies of 23 consecutive patients presenting within 4.5h were analysed by three reviewers of varying experience. Each reviewer, blinded to clinical information reviewed a random order of NCCT and CTA-SI and documented side of infarct and the ASPECTS. The readings were repeated for CTA-SI with and without clinical information. Performance measures and observer agreement were calculated. Applying an ASPECTS threshold of

Transvenous treatment of cranial dural arteriovenous fistulas with hydrogel coated coils.

SUMMARY: Intracranial dural arteriovenous fistulas (DAVF) with cortical venous reflux may become symptomatic due to venous congestion or intracranial hemorrhage. Venous congestion in the orbit can also occur resulting in proptosis, chemosis, double vision and progressive visual loss. The transvenous approach has been used for selective disconnection of the venous drainage to eliminate the venous congestion and future risk of intracranial bleeding and/or neurological deficit. Hydrogel coated coils (Hydro- Coil(R)) expand after contact with blood causing the coils to swell up to five to 11 times a standard 10-system bare platinum coil. Due to this property, HydroCoils could have an advantage over platinum coils in the transvenous approach to embolization of DAVFs. Ten patients with symptomatic cranial DAVF underwent a transvenous embolization using HydroCoils as the only embolic agent or in a combination with bare platinum coils. The patients' characteristics, symptoms, angioarchitecture of the DAVF, treatment, complications and results were analyzed. All the treated DAVFs were disconnected at the end of the procedure. All the patients with orbital symptoms had complete or significant improvement. There were no periprocedural complications. Nine patients had radiological follow-up showing cure. HydroCoils can be used effectively and safely to treat intracranial DAVFs transvenously. The volume expansion of Hydrocoils may have significant advantage over bare platinum coils given the large venous spaces that need to be filled. The use of HydroCoils may decrease the procedure time and consequently reduce the radiation dose to the patient.

Varix of the vortex vein ampulla: a small case series.

PURPOSE: To report three cases of varix of the vortex vein ampulla. METHODS: Observational small case series. During 2002, three patients were examined for suspected choroidal melanoma. In all cases, the lesions were located at the equator or the periphery. RESULTS: The lesions became more prominent when the eyes were positioned in the direction of the lesion, and disappeared when firm pressure by ultrasound probe was applied on the globe, while the eye was in primary position, or fundus was examined with a three-mirror Goldmann contact lens. These dynamic characteristics were also demonstrated by color Doppler imaging. CONCLUSIONS: Varix of the vortex vein ampulla is an extremely rare condition. This diagnosis should be considered when an elevated choroidal lesion disappears when the fundus is examined with contact lens.

Postmenopausal HRT is not independent risk factor for dural sinus thrombosis.

While a dural sinus thrombosis (DST), is a well-known consequence of the use of oral contraceptives, the role of hormone replacement therapy (HRT) in DST was not previously evaluated. We report two postmenopausal women, presenting with DST under HRT. Antiphospholipid antibodies in one case and borderline protein S deficiency in another were diagnosed. Only five cases of DST under HRT were previously reported and in two of them additional prothrombotic risk factors were found. According to these and previous cases, HRT is not an independent risk factor for DST.

[Management of nasal meningoencephaloceles and cerebrospinal rhinorrhea].

CSF rhinorrhea constitutes a diagnostic challenge. If unrecognized or incompletely managed, it can result in devastating complications. The physician must e aware to this entity and it's management. The conventional neurosurgical management of meningoencephaloceles and cerebrospinal rhinorrhea has been by the intracranial approach. Otolaryngologists have undertaken extracranial approaches for repair of these problems with fair results. In recent years, functional endoscopic sinus surgery has gained popularity and was advocated for the repair of nasal meningoencephaloceles and CSF fistulae. Between 1998 and 1999, five patients were operated by the senior author (M.P) by means of endoscopic sinus surgery. His success rate and lower morbidity make this approach the treatment of choice. The perioperative use of fluoroscein allows us to locate precisely the defect and to confirm complete sealing of the leak. We present our experience in managing 5 cases, 3 of which presented with meningoencephaloceles.

Frequent blood-brain barrier disruption in the human cerebral cortex.

1. The blood-brain barrier (BBB) protects the brain from circulating xenobiotic agents. The pathophysiology, time span, spatial pattern, and pathophysiological consequences of BBB disruptions are not known. 2. Here, we report the quantification of BBB disruption by measuring enhancement levels in computerized tomography brain images. 3. Pathological diffuse enhancement associated with elevated albumin levels in the cerebrospinal fluid (CSF) was observed in the cerebral cortex of 28 out of 43 patients, but not in controls. Four patients displayed weeks-long focal BBB impairment. In 19 other patients, BBB disruption was significantly associated with elevated blood pressure, body temperature, serum cortisol, and stress-associated CSF 'readthrough" acetylcholinesterase. Multielectrode electroencephalography revealed enhanced slow-wave activities in areas of focal BBB disruption. Thus, quantification of BBB disruption using minimally invasive procedures, demonstrated correlations with molecular, clinical, and physiological stress-associated indices. 4. These sequelae accompany a wide range of neurological disorders, suggesting that persistent, detrimental BBB disruption is considerably more frequent than previously assumed.