In-thrombus thrombin secretion: a new diagnostic marker of atrial fibrillation in cryptogenic stroke.

Endovascularly retrieved clots may be a potential resource for diagnosing stroke etiology. This method may influence secondary prevention treatment. We measure thrombin activity eluted by serially washing clots. We concluded that an assay measuring the change in thrombin in clots retrieved during acute stroke endovascular thrombectomy procedures may serve as a diagnostic marker of the origin of the clot. The suggested mechanism for these differences may be the clot location before its retrieval, with high blood flow causing thrombin washout in atherosclerotic clots, in contrast to atrium appendage low blood flow retaining high thrombin levels.

In-thrombus thrombin secretion: a new diagnostic marker of atrial fibrillation in cryptogenic stroke.

BACKGROUND: Endovascularly retrieved clots are a potential resource for diagnosing stroke etiology, which may influence secondary prevention treatment. In this study we measured thrombin activity eluted by serially washing clots. METHODS: Clots were retrieved from 68 patients with acute ischemic stroke, freshly frozen and classified by standard criteria into proven atrial fibrillation (AF, 18 patients), atherosclerotic origin (AS, 15 patients), cryptogenic stroke (Cr, 17 patients) and other known causes (18 patients). Thawed clot samples were washed by transferring them into 1 mL buffer in seven hourly cycles and a fluorescent substrate assay was used to measure secreted thrombin activity. The clots were also examined histologically. Artificial fibrin and red blood cell-rich clots were similarly assayed for wash-eluted thrombin activity as an external control. RESULTS: Thrombin activity eluted from clots of AF origin decreased significantly with time in contrast to steady levels eluted from AS origin thrombi (P<0.0001 by repeated measures ANOVA). The Cr stroke group was indistinguishable from the AF group and differed statistically from the AS group (P=0.017 by repeated measures ANOVA). In artificial clots we found a biphasic activity pattern, with initially decreasing levels of eluted thrombin (AF pattern) and then, with continuing washes, steady eluted thrombin levels (AS pattern). CONCLUSIONS: An assay measuring the change in thrombin in clots retrieved during acute stroke endovascular thrombectomy procedures may serve as a diagnostic marker of the origin of the clot. The suggested mechanism for these differences may be the clot location before its retrieval, with high blood flow causing thrombin washout in atherosclerotic clots, in contrast to atrium appendage low blood flow retaining high thrombin levels.

Modern intraoperative imaging modalities for the vascular neurosurgeon treating intracerebral hemorrhage.

This paper reviews the current intraoperative imaging tools that are available to assist neurosurgeons in the treatment of intracerebral hemorrhage (ICH). This review shares the authors' experience with each modality and discusses the advantages, potential limitations, and disadvantages of each. Surgery for ICH is directed at blood clot removal, reduction of intracranial pressure, and minimization of secondary damage associated with hematoma breakdown products. For effective occlusion and safe obliteration of vascular anomalies associated with ICH, vascular neurosurgeons today require a thorough understanding of the various intraoperative imaging modalities available for obtaining real-time information. Use of one or more of these modalities may improve the surgeon's confidence during the procedure, the patient's safety during surgery, and surgical outcome. The modern techniques discussed include 1) indocyanine green-based video angiography, which provides real-time information based on high-quality images showing the residual filling of vascular pathological entities and the patency of blood vessels of any size in the surgical field; and 2) intraoperative angiography, which remains the gold standard intraoperative diagnostic test in the surgical management of cerebral aneurysms and arteriovenous malformations. Hybrid procedures, providing multimodality image-guided surgeries and combining endovascular with microsurgical strategies within the same surgical session, have become feasible and safe. Microdoppler is a safe, noninvasive, and reliable technique for evaluation of hemodynamics of vessels in the surgical field, with the advantage of ease of use. Intraoperative MRI provides an effective navigation tool for cavernoma surgery, in addition to assessing the extent of resection during the procedure. Intraoperative CT scanning has the advantage of very high sensitivity to acute bleeding, thereby assisting in the confirmation of the extent of hematoma evacuation and the extent of vascular anomaly resection. Intraoperative ultrasound aids navigation and evacuation assessment during intracerebral hematoma evacuation surgeries. It supports the concept of minimally invasive surgery and has undergone extensive development in recent years, with the quality of ultrasound imaging having improved considerably. Image-guided therapy, combined with modern intraoperative imaging modalities, has changed the fundamentals of conventional vascular neurosurgery by presenting real-time visualization of both normal tissue and pathological entities. These imaging techniques are important adjuncts to the surgeon's standard surgical armamentarium. Familiarity with these imaging modalities may help the surgeon complete procedures with improved safety, efficiency, and clinical outcome.

[Neuro-ophthalmology and interventional neuro-radiology--co-treatment for carotid cavernous sinus fistula].

Carotid-cavernous fistulas (CCFs) are abnormal arteriovenous communications in the cavernous sinus. In many cases of CCF's the primary signs are ocular manifestations, which include: pulsatile proptosis, orbital bruit, chemosis and conjunctival injection, elevated intraocular pressure, venous stasis retinopathy, and cranial nerve pareses. Patients in whom the fistula causes arterial drainage into the cerebral veins and sinuses are at risk for intracranial hemorrhage. The most common treatment for CCF's is endovascular occlusion of the lesion. The goal of this procedure is to occlude the fistula but preserve the patency of the internal carotid artery. The CCF itself, as well as its treatment, can be sight- and even life-threatening. We describe 3 case reports of patients with CCF, in order to demonstrate the cooperation between the neuro-opthalmologist and the invasive neuro-radiologist, in the follow-up of the patient and in the treatment timing decision.

[Isolated sixth nerve palsy--presenting sign of multiple myeloma].

Multiple myeloma is a disease caused by neoplastic plasma cells. Initial symptoms in most cases described in the literature include chest and lumbar pain, paresthesia, paraplegia, general weakness and renal failure. We report a case of isolated sixth nerve palsy causing diplopia as the presenting sign of multiple myeloma. Awareness of such a rare clinical presentation - especially when the existence of multiple myeloma is ignored after visualization of a cranial mass with magnetic resonance imaging (MRI) and computerized tomography (CT)--can prevent unnecessary surgical intervention and delay the appropriate treatment.

Long-term response in high-grade optic glioma treated with medically induced hypothyroidism and carboplatin: a case report and review of the literature.

Glioblastoma multiforme (GBM) is the most malignant and frequent brain tumor, with an aggressive growth pattern and poor prognosis despite best treatment modalities. Long-term survival of patients with GBM is rare. Optic glioma represents 0.6-1.2% of all brain tumors. Unlike low-grade optic gliomas in children, optic gliomas in adults are highly aggressive and death usually occurs in less than a year. Prolonged progression-free survival and survival rates have been reported in association with induced hypothyroidism in two clinical trials for recurrent GBM. We present the clinical, radiological, and pathological findings in a patient with inoperable GBM of the optic chiasm. Following failure of initial, standard radiation and temozolomide therapy, chemical hypothyroidism was induced using the antithyroid thioamide, propylthiouracil, followed by carboplatin chemotherapy. Initial thyroid stimulating hormone, free T4, and free T3 analysis was carried out and then monthly. This patient responded rapidly to treatment (clinically and with tumor regression within 4 weeks) on two separate occasions with an extended remission period (2.5 years) and prolonged overall survival (4.5 years). We report the successful long-term tumor response to medically induced chemical hypothyroidism in conjunction with carboplatinum chemotherapy of an adult patient with grade IV GBM of the optic chiasm. These clinical observations find mechanistic support from the recent identification of potent mitogenic actions of the thyroid hormone, L-thyroxine, in malignant glioma through binding to a cognate thyroid hormone receptor on the αvß3 integrin. Approaches to block its activity are now explored in preclinical studies.

Description of the vasospasm phenomena following perimesencephalic nonaneurysmal subarachnoid hemorrhage.

BACKGROUND: Perimesencephalic nonaneurysmal subarachnoid hemorrhage (PM-NASAH) is characterized by a benign course compared with aneurysmal SAH. While vasospasm (VS) after aneurysmal SAH is considered responsible for serious complications, VS post-PM-NASAH is not well documented. Our purpose was to characterize the incidence and course of VS among 63 patients--one of the largest databases of PM-NASAH patients with documented blood flow velocities in the literature. METHODS: Data from 63 patients that were admitted with PM-NASAH from 2000 to 2012 and underwent transcranial Doppler tests to assess cranial vessel flow velocity was analyzed. RESULTS: On average, the maximal flow velocity was measured on the 7th day after hemorrhage. Higher risk for VS was associated with younger age, female sex, and higher Hunt and Hess scores, a lower risk for patients treated with statins (P < 0.05). Using velocity thresholds for diagnosis of VS, 49.2% showed evidence of VS. This is the first description of blood flow velocities in PM-NASAH. VS average onset was on the 4th day, average cessation on day 15 after hemorrhage. No patients showed clinical manifestation of VS. CONCLUSIONS: VS post-PM-NASAH is not as rare as previously believed. However, its lack of clinical significance raises questions regarding the need for diagnosis and may suggest a less intensive treatment protocol.

Neurocysticercosis in travelers: a nation-wide study in Israel.

BACKGROUND: Cysticercosis, a human infestation by Taenia solium is endemic in many resource-limited countries. In developed countries it is mostly encountered among immigrant populations. Only few cases are reported in travelers. This report summarizes a nation-wide study of neurocysticercosis (NCC) diagnosed among Israeli travelers to endemic countries, with an estimation of disease incidence among the traveler population. METHODS: We performed a retrospective, nation-wide survey of travel-related NCC in Israel between the years 1994 and 2009. RESULTS: Nine cases of NCC were diagnosed in Israeli travelers during the study years. Most patients had traveled to South and/or Southeast Asia. The most common symptom at diagnosis was a seizure. The average interval between return from the suspected travel and symptom onset was 3.2 ± 1.8 years. Two patients suffered from multiple lesions, whereas the rest had a single lesion. Antihelminthic treatment was given to most patients with resolution of symptoms. Median duration of antiepileptic treatment was 16 ± 41 months after albendazole was given. Antiepileptic treatment was discontinued without any complications. The estimated attack rate of clinical disease was 1 : 275,000 per travel episode to an endemic region. CONCLUSIONS: NCC in travelers is a rare phenomenon commonly presenting as seizure disorder manifesting months to years post-travel. Antihelminthic therapy followed by 12 to 24 months of antiepileptic therapy resulted in complete resolution of symptoms in our patients.

The application of MRI for depiction of subtle blood brain barrier disruption in stroke.

The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient's propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI at relatively long delays (~15 minutes) after contrast injection and subtracting from them images acquired immediately after contrast administration. In addition, the relatively long delays allow for acquisition of high resolution images resulting in high resolution BBB disruption maps. The sensitivity is further increased by image preprocessing with corrections for intensity variations and with whole body (rigid+elastic) registration. Since only two separate time points are required, the time between the two acquisitions can be used for acquiring routine clinical data, keeping the total imaging time to a minimum. A proof of concept study was performed in 34 patients with ischemic stroke and 2 patients with brain metastases undergoing high resolution T1-weighted MRI acquired at 3 time points after contrast injection. The MR images were pre-processed and subtracted to produce BBB disruption maps. BBB maps of patients with brain metastases and ischemic stroke presented different patterns of BBB opening. The significant advantage of the long extravasation time was demonstrated by a dynamic-contrast-enhancement study performed continuously for 18 min. The high sensitivity of our methodology enabled depiction of clear BBB disruption in 27% of the stroke patients who did not have abnormalities on conventional contrast-enhanced MRI. In 36% of the patients, who had abnormalities detectable by conventional MRI, the BBB disruption volumes were significantly larger in the maps than in conventional MRI. These results demonstrate the advantages of delayed contrast extravasation in increasing the sensitivity to subtle BBB disruption in ischemic stroke patients. The calculated disruption maps provide clear depiction of significant volumes of BBB disruption unattainable by conventional contrast-enhanced MRI.

Ischemic stroke due to acute basilar artery occlusion: proportion and outcomes.

BACKGROUND: Multiple case series, mostly highly selected, have demonstrated a very high mortality following acute basilar artery occlusion. The more widespread availability and use of non-invasive vascular imaging over recent years has increased the rate of ABAO diagnosis. OBJECTIVES: To estimate the proportion of diagnosed ABAO among all-cause ischemic stroke in an era of increasing use of non-invasive vascular imaging and to compare the characteristics and outcomes between these two groups. METHODS: We compared 27 consecutive cases of ABAO identified in a university hospital between 2003 and 2007 with 311 unselected cases of ischemic stroke from two 4 month surveys. RESULTS: ABAO diagnosis increased from 0.3% of all-cause ischemic stroke (2003-2004) to 1.1% (2007), reflecting the increased use of non-invasive vascular imaging. In comparison to all-cause ischemic stroke, ABAO patients were younger (mean age 60 vs. 71 years), were more likely to be male (89% vs. 60%), had less atrial fibrillation (7% vs. 26%), more severe strokes (baseline NIHSS over 20: 52% vs. 12%), higher admission white cell count (12,000 vs. 9000 cells/ mm3), lower admission systolic blood pressure (140 +/- 24 vs. 153 +/- 27 mmHg), higher in-hospital mortality rates (30% vs. 8%) and worse functional outcome (modified Rankin scale < or = 3, 22% vs. 56%) (P< 0.05 for all). Rates of reperfusion therapy for ABAO increased from 0 in 2003-2004 to 60% in 2007. CONCLUSIONS: In this study, ABAO patients represented approximately 1% of all-cause ischemic stroke and were about a decade younger than patients with all-cause ischemic stroke. We report a lower ABAO mortality compared to previous more selected case series; however, most survivors had a poor functional outcome. Given the marked clinical heterogeneity of ABAO, a low threshold for non-invasive vascular imaging with a view to definitive reperfusion treatment is needed.

[Neurocysticercosis in Israel].

BACKGROUND: Neurocysticercosis is the most common cause of adult onset seizures in developing countries. In recent years, with the rise in the number of immigrants to developed countries and travelers to endemic areas, neurocysticercosis is increasingly diagnosed in non-endemic countries. AIMS OF THE STUDY: The authors describe the clinical and epidemiologic characteristics of patients diagnosed with neurocysticercosis acquired in Israel or in immigrants to Israel from endemic countries. METHODS: A retrospective national survey of patients diagnosed with neurocysticercosis during 1994-2009 was conducted. Clinical and epidemiologic data were recorded. Case definition consisted of roentgenologic, serologic and pathologic features. RESULTS: In all, 17 cases of neurocysticercosis were diagnosed in Israel during the study period. Nine (53%) cases were diagnosed in travelers to endemic areas, and six (35%) in immigrants from endemic areas. Two cases were native Israelis who had never traveled to an endemic area. Most immigrants suffered from multiple brain lesions. Two immigrants underwent brain biopsy. CONCLUSIONS: This is the first report of the clinical and epidemiologic characteristics of patients diagnosed with neurocysticercosis acquired in Israel or diagnosed in immigrants to Israel. Neurocysticercosis must be included in the differential diagnosis of seizures, headache or neurologic deficit with single or multiple brain lesions, especially in immigrants from endemic countries. Invasive procedures may be obviated by appropriate clinical diagnosis, imaging and serology.

Trombolysis in acute stroke.

BACKGROUND: Rapid restoration of cerebral blood flow is the principle goal of acute ischemic stroke therapy. Intravenous recombinant tissue plasminogen activator is an effective therapy for acute ischemic stroke. It has been available in the United States for over a decade and was approved for use in Israel at the end of 2004. OBJECTIVES: To assess the implementation of intravenous rt-PA in routine clinical care at our center after its formal approval in Israel, and the therapeutic and logistic implications for reperfusion therapy for acute ischemic stroke in Israel. METHODS: Patients with acute ischemic stroke admitted between January 2005 and June 2006 who were treated with intravenous rt-PA or endovascular-based reperfusion were reviewed. Implementation, timing, safety and clinical outcomes were assessed. RESULTS: Forty-six patients received reperfusion therapy (37 with intravenous rt-PA and 9 with endovascular-based therapy), corresponding to 4.0% of ischemic stroke patients in 2005 and a projection of 6.2% in 2006. The mean age of intravenously treated patients was 67 years (range 22-85 years), median baseline NIHSS score was 14 (25-75%, 10-18) and the median 'onset to drug time' was 150 minutes (25-75%, 120-178). Symptomatic intracerebral hemorrhage and orolingual angioedema each occurred in one patient (2.7%). Significant clinical improvement occurred in 54% of treated patients, and 38% of patients were independent at hospital discharge. CONCLUSIONS: The use of reperfusion therapy for acute ischemic stroke has increased in our center after the formal approval of rt-PA therapy to over 5%, with 'onset to drug time', safety and outcome after intravenous rt-PA treatment comparing favorably with worldwide experience. A prerequisite for the implementation of effective reperfusion therapy and expansion of the proportion of patients treated nationwide is the establishment of a comprehensive infrastructure.

Intravenous recombinant tissue plasminogen activator therapy for acute ischemic stroke: initial Israeli experience.

BACKGROUND: Intravenous recombinant tissue plasminogen activator therapy within 3 hours of stroke onset is a proven effective treatment for acute ischemic stroke. OBJECTIVE: To assess the feasibility and safety of rt-PA therapy for reperfusion in routine clinical practice in Israel, in the setting of a dedicated stroke unit. METHODS: Consecutive patients presenting within less than 3 hours of stroke onset were evaluated by an emergency physician and the neurology stroke team. After brain computerized tomography, eligible patients were treated with intravenous rt-PA (0.9 mg/kg, maximum dose 90 mg) according to an in-hospital protocol corresponding to recommended criteria. Patients were admitted to the acute stroke unit. Safety and clinical outcome were routinely assessed. Recanalization was assessed by serial transcranial Doppler. RESULTS: The study group comprised 16 patients, mean age 61 years (range 47-80 years), male to female ratio 10:6, whose median baseline National Institutes of Health stroke scale was 13 (range 6-24). They were treated within a mean door-to-CT time of 39 minutes (range 17-62 min), door-to-drug time 101 minutes (range 72-150), and stroke onset-to-drug time 151 minutes (range 90-180). There was an early improvement within 24 hours (of > or = 4 points in the NIHSS score) in 7 patients (44%) and no early deteriorations. There were no protocol deviations, no symptomatic intracranial hemorrhages, and no major systemic hemorrhage within 36 hours of rt-PA treatment. Three asymptomatic hemorrhagic transformations of the infarct were noted on routine follow-up brain CT associated with neurologic improvement. Outcome data were comparable to the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study. CONCLUSION: Intravenous rt-PA treatment within 3 hours of stroke onset in routine clinical practice in Israel is feasible and appears safe in the setting of a neurology stroke unit and team. Careful implementation of rt-PA therapy for selected patients in Israel is encouraged.

Rhino-orbital and rhino-orbito-cerebral mucormycosis.

BACKGROUND: Rhino-orbito-cerebral mucormycosis (ROCM) is a devastating infection of immunocompromised hosts. We present our experience with 19 ROCM cases and attempt to define preferred diagnostic and treatment protocols. METHODS: All had tissue biopsies obtained studied by direct smear, histologic studies, and cultures. Imaging was obtained in 14 cases. RESULTS: Sixteen patients presented between August and November. Six had mixed fungal infections. Seven patients had end-stage underlying disease or infection and did not undergo surgery and 4 had an indolent form of disease. Patients were treated by surgery and by amphotericin B. The overall survival was 47%. CONCLUSIONS: ROCM may have seasonal incidence peaking in the fall and early winter. The therapeutic approach should be unchanged in cases of mixed fungal infections. Amphotericin B with aggressive debridement remains the mainstay of treatment. Early recognition and treatment are essential. A presentation and survival-dependent classification of ROCM are offered.