Savvas Grigoriadis

D-cycloserine improves functional recovery and reinstates long-term potentiation (LTP) in a mouse model of closed head injury

Traumatic brain injury triggers a massive glutamate efflux, activation of NMDA receptor channels, and cell death. Recently, we reported that NMDA receptors in mice are down‐regulated from hours to days following closed head injury (CHI), and treatment with NMDA improved recovery of motor and cognitive functions up to 14 d post‐injury. Here we show that a single injection of a low dose of D‐cycloserine (DCS), a partial NMDA receptor agonist, in CHI mice 24 h post‐injury, resulted in a faster and greater recovery of motor and memory functions as assessed by neurological severity score and object recognition tests, respectively. Moreover, DCS treatment of CHI mice led to a significant improvement of hippocampal long‐term po‐tentiation (LTP) in the CA1 region that was completely blunted in CHI control mice. However, DCS did not improve CHI‐induced impairment in synaptic gluta‐mate release measured by paired pulse facilitation (PPF) ratio in hippocampal CA1 region. Finally, CHI‐induced reduction of brain‐derived neurotrophic factor (BDNF) was fully restored following DCS treatment. Since DCS is in clinical use for other indications, the present study offers a novel approach to treat human brain injury.–Yaka, R., Biegon, A., Grigoriadis, N., Simeonidou, C., Grigoriadis, S., Alexandrovich, A. G., Matzner, H., Schumann, J., Trembovler, V., Tsenter, J., Shohami, E. D‐cycloserine improves functional recovery and reinstates long‐term potentiation (LTP) in a mouse model of closed head injury. FASEB J. 21, 2033–2041 (2007)

Clinically successful late recanalization of basilar artery occlusion in childhood: What are the odds?: Case report and review of the literature

BACKGROUND AND PURPOSE Acute basilar artery occlusion is an infrequent but potentially fatal cause of stroke, both in adults and children. We present our experience with a 6-year-old child and we investigate the rationality for late treatment of acute basilar occlusion in children. METHODS We report the case of a 6-year-old boy with acute basilar artery occlusion presented with a full blown locked-in syndrome, admitted to the endovascular suite 44 h after the stroke onset, and we review all the reported cases of basilar artery occlusions presented with locked-in syndrome in children. RESULTS Six hours following admission the basilar artery was partially recanalized by intra-arterial thrombolysis combined with mechanical clot angioplasty. After 12 h, the patient was awake, oriented, his speech function was fully restored and he had only a mild right hemiparesis that recovered completely after a month. CONCLUSIONS To our knowledge, this is the first report of complete clinical recovery after delayed (50 h) endovascular recanalization of basilar artery in a child. Intra-arterial thrombolysis combined with cerebral angioplasty, can successfully restore the patency of the basilar artery and the neurologic deficit of children with acute basilar artery occlusion, even after a considerable delay.

Spontaneous thrombosis of cerebral aneurysms presenting with ischemic stroke

Complete spontaneous thrombosis of an unruptured cerebral aneurysm is a rare event that can be discovered incidentally on advanced neuroradiologic studies. Occasionally, this phenomenon may be symptomatic and can present as an ischemic stroke. The presumed mechanism is probably due to extension of the thrombi to the parent vessel, embolization of intra-aneurysmatic thrombi to distal arteries or arterial compression due to increased aneurysm mass effect. We present documented cases of this unusual entity and review the literature.

Microglial involvement in neuroprotection following experimental traumatic brain injury in heat-acclimated mice.

Brain-derived neurotrophic factor (BDNF) conveys neuroprotection in various settings of experimental central nervous system injury. Using a model of endogenous neuroprotection, induced in mice by chronic exposure to moderate ambient heat (heat acclimation, HA), we have previously shown that neuroprotection following traumatic brain injury involves reduced post-injury tumor necrosis factor alpha (TNFalpha) expression. As glial cells play a pivotal role in post-injury inflammation on one hand, and are also capable of inducing neuroprotection by harboring trophic factors and BDNF in particular, the effects of injury and HA on overall BDNF content at the trauma area, gliosis and glial BDNF expression were investigated. Western blotting indicated higher overall BDNF levels in HA sham-operated mice. Following injury, a decrease was observed in the HA group only, reaching levels similar to normothermic mice. Immunohistochemical studies demonstrated BDNF-positive resting microglia in non-injured HA but not normothermic animals. Post-injury astrocytosis and microglial immunoreactivity were enhanced in the HA group. Particularly, an increase in the amount of ramified microglia was observed within the penumbra, accompanied by a concomitant decrease in globular microglia, a major source of pro-inflammatory mediators. BDNF labeling on and around microglia and their processes was intensified in HA mice. Furthermore, BDNF immunoreactivity in HA mice was evident in the degenerated edges of axons. These findings, taken together with the growing body of evidence indicating the neuroprotective potential of both BDNF and microglia, suggest a possible role of these cells in HA-induced neuroprotection.

Intra-arterial thrombolysis and stent placement for traumatic carotid dissection with subsequent stroke: a combined, simultaneous endovascular approach.

Traumatic carotid dissection is a well-known cause of ischemic stroke and although the treatment of the dissection itself has received some attention in recent years, the treatment of the concomitant stroke has been less investigated. We present a 43-year-old patient with blunt traumatic internal carotid artery dissection associated with subocclusive stenosis and major cerebral thromboembolic complication. Combined, simultaneous intra-arterial fibrinolysis and carotid stenting through a bilateral approach was successfully performed allowing the complete clinical recovery of the patient. Contralateral carotid artery approach allowed the beginning of intra-arterial thrombolysis without delay, while stent-assisted angioplasty of the injured carotid was simultaneously performed. This approach was proved to be safe and effective and may deserve further evaluation.

Complete and persistent occlusion of arteriovenous malformations of the mandible after endovascular embolization

Abstract Objective: Arteriovenous malformation (AVM) of the mandible is a rare but potentially life-threatening entity. Traditional treatment involved complex surgical procedures that usually failed to completely cure the malformation without disfigurement and functional difficulties. We report our experience in transarterial and transvenous embolizations of mandibular AVMs using different embolization agents and discuss the potential use of Onyx and new detachable-tip microcatheters. Clinical presentation: Patients presented with progressive mandibular swelling, pain, soft-tissues discoloration and dental misalignment with tooth loosening. Intervention: The AVMs were completely and persistently occluded by endovascular transarterial and transvenous approaches. Conclusion: Less invasive endovascular approaches proved to be highly effective in curing certain types of mandibular AVMs. Every malformation requires a tailored endovascular strategy in terms of approach and selection of an embolizing agent.

Urgent endovascular stent-graft placement for traumatic penetrating subclavian artery injuries

Penetrating injuries may infrequently cause pseudoaneurysms, lacerations and arteriovenous fistulas involving the subclavian artery. These injuries present with life-threatening bleedings, associated regional injuries and critical limb ischemia and although surgery has been considered the treatment of choice, subclavian injuries pose a real surgical challenge. We prospectively examined data of six patients presenting with penetrating subclavian artery injuries that were treated by urgent endovascular stent-graft placements. All stent-grafts were deployed successfully achieving complete exclusion of the pseudoaneurysm, control of bleeding and reconstruction of the injured artery. No procedural complications, stent thrombosis or stent infections occurred during hospitalization. One patient developed stenosis at 7 months, which required angioplasty. The series mean clinical and ultrasound-CTA follow-up is 38+/-19.7 months (range 11-60 months) and 28+/-19.1 months (range 6-58 months), respectively. This series shows the feasibility of endovascular repair by means of stent-grafts for selected patients with acute penetrating injuries of the subclavian arteries. This approach proved to be safe and effective in restoring the arterial lumen and patency, excluding the pseudoaneurysms and controlling the bleeding caused by subclavian lacerations. Mid-term follow-up on stent-graft patency rates are encouraging.

Dural Arteriovenous Fistula of the Greater Sphenoid Wing Region in Neurofibromatosis Type 1

Neurofibromatosis type 1 (NF1) has been infrequently associated with different cerebrovascular conditions that may lead to either ischemic or hemorrhagic stroke. Intracranial dural arteriovenous fistulas have not been described in NF1 patients. In this paper we present a unique case of an 8-year-old child with florid NF1 that presented a greater sphenoid wing dural arteriovenous fistula draining directly through the superior ophthalmic vein and causing exophthalmos. The fistula was cured by direct trans-superior ophthalmic vein approach, by means of detachable coils. Only a few cases of dural fistulas in the lesser sphenoidal wing region have been described in the literature but a fistula of the greater sphenoid wing has not been previously described.

Recanalization of symptomatic carotid artery dissections causing occlusion with multiple stents: the use of delayed double-contrast road map.

Abstract Background and Purpose: Internal carotid artery dissections (ICADs) with occlusion present with a high morbidity and mortality. No specific medical treatment has proven to be effective in this setting. In selected cases of ICAD with occlusion, stent-assisted angioplasty has been shown to be effective in restoring the perfusion. Spontaneous ICAD causing occlusion successfully recanalized with multiple telescoped stents extending intracranially has only been reported exceptionally. Methods: We report cases of symptomatic acute carotid occlusion after spontaneous dissection extending from the cervical to the petrocavernous ICA segments. Imaging studies revealed the presence of an extensive penumbra area in every case. Patients were treated by means of multiple stents deployed in a telescoped fashion with the aid of a delayed double-contrast road map. Results: Post-procedural angiography demonstrated restitution of the carotid lumen with no signs of residual dissection or intracranial emboli. The patients improved rapidly, showing no residual neurological deficit after a week. At follow-up, patients are clinically asymptomatic and the vessel is patent with no radiological signs of myointimal hyperplasia. Conclusions: The successful angiographic and clinical results observed in our cases of extraintracranial stenting of a long carotid dissection causing occlusion contribute to the literature of carotid dissection treated with multiple stents.

Prenatal thrombosis of torcular Herophili with spontaneous resolution and normal outcome.

Prenatal thrombosis of torcular Herophili is a rare condition. It may be suspected during the routine ultrasonographic follow‐up of the fetus, but MRI is necessary to establish the diagnosis. There are 7 reported cases with various results.