Aluminium Chloride instead of Ferric chloride for inducing superior sagittal sinus thrombosis to reduce ferromagnetic artifacts on MRI-imaging in experimental models.

Using ferric chloride (FeCl3) to induce experimental superior sagittal sinus (SSS) thrombosis might interfere with magnetic resonance imaging (MRI)-assisted visualization and evaluation of the thrombus, the brain parenchyma, and the quality of the occlusion. The aim of this study was to investigate whether aluminum chloride (AlCl3)-induced thrombosis of the SSS has comparable properties to those of FeCl3 without causing artifacts in MRI. SSS thrombosis was induced in 14 male Wistar rats by exposure of the SSS and subsequent topical application of a filter paper strip soaked in AlCl3 (n = 7) or FeCl3 (n = 7) over a period of 15 min. The animals with AlCl3-induced SSS thrombosis showed a constant and complete occlusion with in histological analysis large thrombi. Blood flow measurements indicated a significant reduction on the first and seventh postoperative day compared to preoperative measurements. MRI enabled visualization and subsequent evaluation of the thrombus and the surrounding parenchyma. In comparison, FeCl3-induced SSS thrombosis could not be evaluated by MRI due to artifacts caused by the paramagnetic properties and increased susceptibility of FeCl3. The occluded sinus and the surrounding area appeared hypointense. The quality of SSS occlusion by AlCl3 was comparable to that of FeCl3. AlCl3 therefore represents a significant alternative substance in experimental SSS thrombosis ideally suited for studies using MRI.

Multiple Dural and Pial Arteriovenous Fistulae in a Twenty-Four-Year-Old Woman in the Setting of Superior Sagittal Sinus Thrombosis: Case Report and Review of Literature.

CASE: A 24-year-old woman presented with headache, nausea, and vomiting, and was found to have chronic superior sagittal sinus (SSS) thrombosis and multiple dural arteriovenous fistulae (dAVFs). Despite anticoagulant therapy and successful recanalization of her sinus, her fistulae persisted, and she developed additional separate pial arteriovenous fistulae (pAVFs). Her fistulae were treated with staged endovascular embolization, open clipping, and gamma knife radiosurgery over the course of 10 months. Complete resolution of SSS thrombosis and all arteriovenous fistulae (AVFs) was noted on cerebral angiogram performed 18 months from initial presentation. DISCUSSION: dAVFs have frequently been associated with venous sinus thrombosis. Sinus thrombosis resulting after endovascular or surgical treatment of dural arteriovenous fistulous connections has been reported in literature and is considered a possible complication of treatment. Multiple dAVFs and pAVFs are rare and often require multimodal staged approaches for definitive treatment. CONCLUSION: We report a case of chronic sagittal sinus thrombosis resulting in multiple AVFs requiring staged multimodal treatment with successful resolution of the fistulous connections. Furthermore, upon reviewing the literature addressing multiple dAVFs and the treatment of such lesions using endovascular, microsurgical, and stereotactic radiosurgery techniques, we elucidate the success a multimodal approach to therapy can afford for the unique challenges associated with multiple lesions.

Post-Traumatic Bifrontoparietal Extradural Hematoma with Superior Sagittal Sinus Detachment: A Case Report and Review of the Literature.

OBJECTIVE: To present, to our knowledge, the first case of a single bilateral extradural hematoma due to superior sagittal sinus detachment that was treated conservatively with an excellent outcome. METHODS: Bilateral extradural hematomas are a rare condition, accounting for only 2%-5% of all extradural hematomas. They can be either 2 distinct hematomas on either side or 1 single bilateral hematoma mostly due to sagittal sinus injury, with the latter being the most rare owing to the firm attachment of the sinus to its subperiosteal loggia. These hematomas usually require immediate surgical evacuation, as patients present with decreased level of consciousness, and have good postoperative outcomes. We present a bilateral extradural hematoma due to superior sagittal sinus injury, which was treated conservatively. RESULTS: The patient had an excellent recovery, with no residual neurological deficits and a Glasgow outcome scale of 5 on discharge. CONCLUSION: Bilateral extradural hematomas due to superior sagittal sinus injury almost always require surgical intervention. We present a patient who was treated conservatively with an excellent outcome and we also perform a review of the current literature.

White-matter connectivity related to paliperidone treatment response in patients with schizophrenia.

The objective of this study was to examine whether white-matter (WM) connectivity of patients with schizophrenia at early stage of treatment is related to treatment response after paliperidone extended-release (ER) treatment. Forty-one patients with schizophrenia and 17 age- and sex-matched healthy control subjects were included in this study. Brain magnetic resonance scans at 3 Tesla were conducted at early stage of treatment. Voxel-wise statistical analysis of the fractional anisotropy (FA) data was performed using Tract-Based Spatial Statistics. At baseline and eight weeks after paliperidone treatment, patients were assessed using the Positive and Negative Syndrome Scale, the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms. Among the patients with schizophrenia, the FA values of the corpus callosum, corona radiata, internal capsule, external capsule, superior longitudinal fasciculus and fronto-temporal WM regions showed significant negative correlations with scores of the treatment response. The current study suggests that the treatment response after paliperidone ER treatment may be associated with the fronto-temporo-limbic WM connectivity at early stage of treatment in patients with schizophrenia, and it could be used as a predictor of treatment response to paliperidone ER treatment after studies with large samples verify these results.

Photothrombosis combined with thrombin injection establishes a rat model of cerebral venous sinus thrombosis.

OBJECTIVE: Cerebral venous sinus thrombosis (CVST) is a rare but life-threatening disease and an animal model for in-depth study of CVST is needed. This study aimed to develop a rat model suitable for studying clinically relevant aspects of CVST and investigating its dynamic pathophysiological changes during a 7-day period. METHOD: A photothrombosis method was used to create a rat sinus-vein thrombosis model. A spot size-adjustable Diode Pumped Solid State laser (DPSS) combined with thrombin injection occluded the rostral and caudal superior sagittal sinus (SSS). The model was used to evaluate pathophysiological changes at different time points over 7 days. Evans Blue dye injection was used to detect alterations in blood-brain barrier (BBB) permeability. Brain water content was also measured. Moreover, we examined changes in brain infarct volume, neurological function, as well as histology after induction of CVST. RESULT: CVST in rats significantly altered BBB permeability, consistent with the development of brain edema. It was accompanied by an increase in brain infarct volume and deficits in neurological function that began on day 1, peaked on day 2, and typically improved by day 7 due to the neuroprotective effects of angiogenesis and gliocyte proliferation. CONCLUSION: In this study, we describe a rat model that produces clinically relevant pathophysiology and pathology that will facilitate evaluation of therapeutic regimens for CVST. Furthermore, our results indicate a period of optimal clinical intervention for patients with CVST, which may reduce the probability of dependency and death.

Histopathological effects of different therapy strategies in experimental sinus thrombosis.

The optimal treatment for cerebral venous thrombosis is still under debate. The histological consequences of different treatments have not been systematically studied and may be of value in this debate. Thrombosis of the superior sagittal sinus was induced in rats by topical application of ferric chloride. Animals were treated 6 h after operation with subcutaneous injection of 450 IU/kg enoxaparin twice daily (n = 10), with 10 mg recombinant tissue plasminogen activator (rt-PA)/kg (n = 12), and with 6 mg abciximab/kg (n = 10). Eleven animals were treated with saline (controls), and four animals were sham-operated without thrombosis induction. Animals were killed on day 7. Coronal brain slices were stained with hematoxylin-eosin (HE) and against glial fibrillary acidic protein (GFAP), and factor VIII. Histology was quantified in parasagittal and temporal regions of interest. Compared with controls, counts of pyknotic neurons on HE stain were significantly lower in the enoxaparin group. Counts for GFAP-expressing astrocytes were highest in the enoxaparin (p < 0.001) and rt-PA (p < 0.05)-treated groups. Angiogenesis defined as factor VIII-expressing vessels was significantly (p < 0.01) higher in the enoxaparin and significantly lower (p < 0.01) in the rt-PA group compared with controls. In this animal model, we found histological differences related to the different treatments, which cannot be explained by recanalization and its speed alone.

Differential trigeminovascular nociceptive responses in the thalamus in the familial hemiplegic migraine 1 knock-in mouse: a Fos protein study.

Familial hemiplegic migraine type 1 (FHM-1) is a monogenic subtype of migraine with aura caused by missense mutations in the CACNA1A gene, which encodes the pore-forming α1 subunit of voltage-gated neuronal CaV2.1 (P/Q-type) calcium channels. Transgenic knock-in mice expressing the CACNA1A R192Q mutation that causes FHM-1 in patients show a greater susceptibility to cortical spreading depression, the likely underlying mechanism of typical human migraine aura. The aim of this study was to compare neuronal activation within the trigeminal pain pathways in response to nociceptive trigeminovascular stimulation in wild-type and R192Q knock-in mice. After sham surgery or electrical stimulation of the superior sagittal sinus for 2h, or stimulation preceded by treatment with naratriptan, mice underwent intracardiac perfusion, and the brain, including the brainstem, was removed. Fos expression was measured in the trigeminocervical complex (TCC) and the lateral (ventroposteromedial, ventrolateral), medial (parafascicular, centromedian) and posterior thalamic nuclei. In the TCC of wild-type animals, the number of Fos-positive cells increased significantly following dural stimulation compared to the sham control group (P<0.001) and decreased after naratriptan treatment (P<0.05). In R192Q knock-in mice, there was no significant difference between the stimulated and sham (P=0.10) or naratriptan pre-treated groups (P=0.15). The number of Fos-positive cells in the R192Q stimulated group was significantly lower compared to the wild-type stimulated mice (P<0.05). In the thalamus, R192Q mice tended to be more sensitive to stimulation compared to the sham control in the medial and posterior nuclei, and between the two strains of stimulated animals there was a significant difference in the centromedian (P<0.005), and posterior nuclei (P<0.05). The present study suggests that the FHM-1 mutation affects more rostral brain structures in this experimental paradigm, which offers a novel perspective on possible differential effects of mutations causing migraine in terms of phenotype-genotype correlations.