Spontaneous otogenic intracerebral pneumocephalus: case report and review of the literature

Pneumocephalus is commonly associated with head and facial trauma, ear infection or surgical interventions. We describe the rare case of a spontaneous pneumocephalus arising from lateral mastoid air cells. A 48-year-old man presented with a 10-day history of sudden, repetitive, ‘hammering-like' acoustic sensations in his left ear that were followed by word-finding difficulties and loss of vision in the right visual field. Imaging revealed a large, left temporal pneumatocele associated with a small acute intracerebral hemorrhage. Left temporal and subtemporal craniotomy and decompression were performed. Further exploration confirmed a dural and osseous defect in the anterolateral surface of the mastoid that was consecutively closed watertight. Although extremely rare, a spontaneous pneumocephalus with mastoidal origin should be considered as a possible diagnosis in patients with suggestive acoustic phenomena and other non-specific neurological symptom

Specialized neurocritical care, severity grade, and outcome of patients with aneurysman subarachnoid hemorrhage

Introduction: To evaluate the impact of specialized neurocritical care on the population admitted to a neurovascular center and on the outcome of patients with severe aneurysmal subarachnoid hemorrhage (aSAH). Methods: After exclusion of patients treated with endovascular techniques, between 1999 and 2003, 198 patients with aSAH treated with early aneurysm clipping were analysed. In 1999, a new standardized protocol for intensive care treatment was established in the Department of Neurosurgery, University Hospital Zurich. The results were compared to the earlier time period (1993-1994) immediately after introduction of early aneurysm clipping. Results: Out of 198 patients with aSAH, 90 patients (45.5%) suffered from mild aSAH World Federation of Neurosurgical Societies (WFNS) grade 1 and 2, 41 (27.3%) from aSAH WFNS grade 3, 36 (18.2%) from grade 4, and 57 (28.8%) from grade 5. From 1999 to 2003, significantly more patients with severe aSAH WFNS grade 4 and 5 underwent (further) treatment (93 out of 198 patients; 47.0%) compared to the former time-period after introduction of early surgery (23 out of 150 patients; 15.3%) (p<0.0001). In the early series, 10 out of 23 patients (43.5%) with WFNS 4 recovered with good outcome Glasgow Outcome Score 4 and 5, whereas in the later series 23 out of 36 (63.9%) with WFNS grade 4 survived in a good functional state. Before 1999, all patients with WFNS grade 5 died or survived in a vegetative state. From 1999 to 2003, 20 out of 57 patients (35.1%) with aSAH WFNS grade 5 survived with good outcome. Conclusions: The availability of extended specialized neurocritical care seems to induce a change within the patient population towards a higher severity grade. Patients with high-grade aSAH might benefit most from highly specialized neurocritical care treatmen

Metastases in Meckel's Cave: A Challenge of Differential Diagnosis

Metastases in Meckel's cave are a rare tumor entity and should be considered as important differential diagnosis, especially if the patient presents with trigeminal neuralgia and suffers from a known primary malignancy. We present three cases of patients with secondary trigeminal neuralgia caused by a metastasis in Meckel's cave, treated by microsurgery and fractionated radiation therapy. Differential diagnoses are discussed on the basis of preoperative neuroradiological imaging. MRI is the preferred diagnostic modality, whereas complementary CT may be needed for evaluation of early bone invasio

Selective changes in GABAA receptor subtypes in white matter neurons of patients with focal epilepsy

Mapping the distribution of GABAA receptor subtypes represents a promising approach to characterize alterations in cortical circuitry associated with neurological disorders. We previously reported subtype-selective changes in GABAA receptor expression in the grey matter of patients with focal epilepsy. In the present follow-up study, we focused on the subcortical white matter in the same tissue specimens obtained at surgery from 9 patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis, 12 patients with TLE associated with neocortical lesions and 5 patients with frontal lobe epilepsy; post-mortem tissue from 4 subjects served as controls. The subunit composition and distribution of three major GABAA receptor subtypes were determined immunohistochemically with subunit-specific antibodies. In all cases, a majority of neurons in the white matter was distinctly labelled, allowing detailed visualization of their dendritic arborization and revealing a differential, cell type-specific expression pattern of α-subunit variants. In controls, α1-subunit staining was most prominent, displaying a gradient that decreased with depth, in parallel with the density of NeuN-positive cells. Subsets of pyramidal cells were α3-subunit-positive, and α2-subunit-labelled neurons were rare. In 19 of the 26 patients with focal epilepsy, no changes were detected as compared with controls. In five patients with TLE, striking changes in the dendritic arborization of a subset of white matter neurons were seen with the α1-subunit antibody. In two further patients with TLE, we observed a disorganized dendritic network immuno-positive for the α1-subunit, cell clusters selectively expressing the α2-subunit and small neuronal aggregates that expressed all subunits and appeared to connect to neighbouring white matter neurons. All seven patients with anomalies in the white matter had a selective reduction in α3-containing GABAA receptors in the superficial layers of the grey matter. These results demonstrate a distinct organization of GABAA receptors in human white matter neurons, consistent with an inhibitory network that is likely to be integrated functionally with the overlying grey matter. The altered dendritic morphology and changes in GABAA receptor expression in the white matter of a subset of patients with focal epilepsy are suggestive for a rewiring of neuronal circuit

Altered expression of α3-containing GABAA receptors in the neocortex of patients with focal epilepsy

Impaired transmission in GABAergic circuits is thought to contribute to the pathogenesis of epilepsy. Although it is well established that major reorganization of GABAA receptor subtypes occurs in the hippocampus of patients with medically refractory temporal lobe epilepsy (TLE), it is unclear whether this disorder is also associated with alterations in GABAA receptor subtypes in the neocortex. Here we have investigated immunohistochemically the subunit composition and neocortical distribution of three major GABAA receptor subtypes using antibodies specifically recognizing the subunits α1, α2, α3, β2/3 and γ2. Cortical tissue was obtained at surgery from patients with TLE and hippocampal sclerosis (HS; n = 9), TLE associated with neocortical lesions (non-HS; n = 12) and frontal lobe epilepsy (FLE; n = 5), with post-mortem samples serving as controls (n = 4). A distinct laminar and neuronal expression pattern of the α-subunit variants was found across the neocortical regions examined in the temporal and frontal lobes in both control and patient tissue samples. In the five patients with FLE, GABAA receptor subunit staining was unchanged as compared to controls. In patients with TLE we observed a marked decrease in α3-subunit staining in the superficial neocortical layers (I-III), but no change in the deep layers (V and VI) or in the expression pattern of the α1 and α2-subunits. Reduced expression in α3-containing GABAA receptors was detected in six out of nine patients of the HS group and four out of twelve patients of the non-HS group. Histopathological changes were present in eight out of the ten patients with decreased α3-subunit staining. The selective reduction in α3-containing GABAA receptors was confirmed using semiquantitative measurements of optical density (OD). The specific changes unique to α3-subunit expression in the superficial neocortical layers of patients with TLE suggest that this subtype is of particular significance in the reorganization of cortical GABAergic systems in focal epileps

ADAMTS13 gene deletion enhances plasma high-mobility group box1 elevation and neuroinflammation in brain ischemia-reperfusion injury

Highly adhesive glycoprotein von Willebrand factor (VWF) multimer induces platelet aggregation and leukocyte tethering or extravasation on the injured vascular wall, contributing to microvascular plugging and inflammation in brain ischemia-reperfusion. A disintegrin and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) cleaves the VWF multimer strand and reduces its prothrombotic and proinflammatory functions. Although ADAMTS13 deficiency is known to amplify post-ischemic cerebral hypoperfusion, there is no report available on the effect of ADAMTS13 on inflammation after brain ischemia. We investigated if ADAMTS13 deficiency intensifies the increase of extracellular HMGB1, a hallmark of post-stroke inflammation, and exacerbates brain injury after ischemia-reperfusion. ADAMTS13 gene knockout (KO) and wild-type (WT) mice were subjected to 30-min middle cerebral artery occlusion (MCAO) and 23.5-h reperfusion under continuous monitoring of regional cerebral blood flow (rCBF). The infarct volume, plasma high-mobility group box1 (HMGB1) level, and immunoreactivity of the ischemic cerebral cortical tissue (double immunofluorescent labeling) against HMGB1/NeuN (neuron-specific nuclear protein) or HMGB1/MPO (myeloperoxidase) were estimated 24h after MCAO. ADAMTS13KO mice had larger brain infarcts compared with WT 24h after MCAO (p<0.05). The rCBF during reperfusion decreased more in ADAMTS13KO mice. The plasma HMGB1 increased more in ADAMTS13KO mice than in WT after ischemia-reperfusion (p<0.05). Brain ischemia induced more prominent activation of inflammatory cells co-expressing HMGB1 and MPO and more marked neuronal death in the cortical ischemic penumbra of ADAMTS13KO mice. ADAMTS13 deficiency may enhance systemic and brain inflammation associated with HMGB1 neurotoxicity, and aggravate brain damage in mice after brief focal ischemia. We hypothesize that ADAMTS13 protects brain from ischemia-reperfusion injury by regulating VWF-dependent inflammation as well as microvascular pluggin