Mina G. Safain

Repeated Adolescent 3,4-Methylenedioxymethamphetamine (MDMA) Exposure in Rats Attenuates the Effects of a Subsequent Challenge with MDMA or a 5-Hydroxytryptamine 1A Receptor Agonist

Adolescent users of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) may escalate their dose because of the development of tolerance. We examined the influence of intermittent adolescent MDMA exposure on the behavioral, physiological, and neurochemical responses to a subsequent MDMA “binge” or to a 5-hydroxytryptamine1A (5-HT1A) receptor challenge. Male Sprague-Dawley rats were given MDMA (10 mg/kg b.i.d.) or saline every 5th day on postnatal days (PDs) 35 to 60. One week later on PD 67, animals were challenged with either multiple doses of MDMA (four 5 or 10 mg/kg doses) or a single dose of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.1 or 0.5 mg/kg). Adolescent MDMA exposure partially attenuated the hyperthermic effects of the PD 67 MDMA challenge, completely blocked the locomotor hypoactivity otherwise observed on the day after the challenge, and also prevented MDMA-induced serotonin neurotoxicity assessed on PD 74 by measuring regional [3H]citalopram binding to the serotonin transporter (SERT). Adolescent MDMA-treated animals also showed a partial attenuation of the serotonin syndrome but not the hypothermic response to the high dose of 8-OH-DPAT. However, there was no effect of MDMA administration on regional [3H]N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY-100635) binding to 5-HT1A receptors in the brain or spinal cord. These results suggest that chronic, intermittent MDMA exposure during adolescence induces neuroadaptive changes that can protect against the adverse consequences of a subsequent dose escalation. On the other hand, the same exposure pattern appears to produce a partial 5-HT1A receptor desensitization, which may negatively influence the therapeutic responses of chronic MDMA users treated with serotonergic agents for various affective or anxiety disorders.

Arachnoid cyst slit valves: the mechanism for arachnoid cyst enlargement

Arachnoid cysts are common, accounting for approximately 1% of intracranial mass lesions. Most are congenital, clinically silent, and remain static in size. Occasionally, they increase in size and produce symptoms due to mass effect or obstruction. The mechanism of enlargement of arachnoid cysts is controversial. One-way slit valves are often hypothesized as the mechanism for enlargement. The authors present 4 cases of suprasellar prepontine arachnoid cysts in which a slit valve was identified. The patients presented with hydrocephalus due to enlargement of the cyst. The valve was located in the arachnoid wall of the cyst directly over the basilar artery. The authors believe this slit valve was responsible for the net influx of CSF into the cyst and for its enlargement. They also present 1 case of an arachnoid cyst in the middle cranial fossa that had a small circular opening but lacked a slit valve. This cyst did not enlarge but surgery was required because of rupture and the development of a subdural hygroma. One-way slit valves exist and are a possible mechanism of enlargement of suprasellar prepontine arachnoid cysts. The valve was located directly over the basilar artery in each of these cases. Caudad-to-cephalad CSF flow during the cardiac cycle increased the opening of the valve, whereas cephalad-to-caudad CSF flow during the remainder of the cardiac cycle pushed the slit opening against the basilar artery and decreased the size of the opening. Arachnoid cysts that communicate CSF via circular, nonslit valves are probably more likely to remain stable.

Postpartum internal carotid and vertebral arterial dissections.

OBJECTIVE: Headache and neck pain are common postpartum symptoms. However, these symptoms can rarely be associated with internal carotid artery and vertebral artery dissections. We aimed to review five cases of postpartum cervical artery dissection and to review the clinical course of previously reported cases. METHODS: Patients with postpartum dissections diagnosed at our institution since 2005 were identified through a database maintained by the senior author, and their clinical data were reviewed. Additionally, a literature search for previously reported cases was performed, and the clinical data in those reports were reviewed. RESULTS: Five patients presented with cervical artery dissections within 6 weeks postpartum. Four patients had delivered vaginally and one delivered by emergent cesarean. Headache and neck pain were the primary presenting symptoms of all five patients. Four patients demonstrated neurologic symptoms, and one had development of stroke. Two patients had single internal carotid artery dissections, one patient had bilateral dissections of the vertebral artery, and two patients had dissections in the internal carotid artery and vertebral artery. All patients were treated with either anticoagulation therapy or antiplatelet therapy. Two patients required endovascular stenting. Four of five patients returned to neurologic baseline after treatment. A literature search yielded 27 previously reported cases, with similar clinical characteristics of older reproductive age, presentation days to weeks from delivery, and recovery to neurologic baseline in the majority of patients. CONCLUSION: Postpartum cervical dissections are rare occurrences that require prompt diagnosis to prevent long-term neurologic deficits. Individualized management strategies include medical treatment (anticoagulation therapy, antiplatelet therapy, or anticoagulation and antiplatelet therapy) and endovascular recanalization. LEVEL OF EVIDENCE: III

A review of the combined medical and surgical management in patients with herpes simplex encephalitis

BACKGROUND Herpes simplex encephalitis (HSE) is a devastating and severe viral infection of the human central nervous system. This viral encephalitis is well known to cause severe cerebral edema and hemorrhagic necrosis with resultant increases in intracranial pressure (ICP). While medical management has been standardized in the treatment of this disease, the role of aggressive combined medical and surgical management including decompressive craniectomy and/or temporal lobectomy has not been fully evaluated. In addition, while barbiturate coma has been studied for treatment of status epilepticus associated with infectious encephalitis, its use for treatment of encephalitis associated intractable intracranial hypertension has not been fully reported. CASE DESCRIPTION We report the case of a 22 year old female with severe herpetic encephalitis requiring aggressive ICP management utilizing all modalities (both medical and surgical) known to control ICP. She continues to have memory deficits but has made a good recovery with a Glasgow Outcome Scale score of 5. CONCLUSION We provide evidence that aggressive combined medical and surgical therapy is warranted even in cases of severe HSE with transtentorial herniation, as there is evidence for the potential of good recovery. A detailed literature review of the medical and surgical management strategies in this disease is presented.

A single center's experience with the bedside subdural evacuating port system: a useful alternative to traditional methods for chronic subdural hematoma evacuation

Object The traditional methods for managing symptomatic chronic subdural hematoma (SDH) include evacuation via a bur hole or craniotomy, both with or without drain placement. Because chronic SDH frequently occurs in elderly patients with multiple comorbidities, the bedside approach afforded by the subdural evacuating port system (SEPS) is an attractive alternative method that is performed under local anesthesia and conscious sedation. The goal of this study was to evaluate the radiographic and clinical outcomes of SEPS as compared with traditional methods. Methods A prospectively maintained database of 23 chronic SDHs treated by bur hole or craniotomy and of 23 chronic SDHs treated by SEPS drainage at Tufts Medical Center was compiled, and a retrospective chart review was performed. Information regarding demographics, comorbidities, presenting symptoms, and outcome was collected. The volume of SDH before and after treatment was semiautomatically measured using imaging software. Results There was no significant difference in initial SDH volume (94.5 cm(3) vs 112.6 cm(3), respectively; p = 0.25) or final SDH volume (31.9 cm(3) vs 28.2 cm(3), respectively; p = 0.65) between SEPS drainage and traditional methods. In addition, there was no difference in mortality (4.3% vs 9.1%, respectively; p = 0.61), length of stay (11 days vs 9.1 days, respectively; p = 0.48), or stability of subdural evacuation (94.1% vs 83.3%, respectively; p = 0.60) for the SEPS and traditional groups at an average follow-up of 12 and 15 weeks, respectively. Only 2 of 23 SDHs treated by SEPS required further treatment by bur hole or craniotomy due to inadequate evacuation of subdural blood. Conclusions The SEPS is a safe and effective alternative to traditional methods of evacuation of chronic SDHs and should be considered in patients presenting with a symptomatic chronic SDH.

Widening and High Inclination of the Middle Cerebral Artery Bifurcation Are Associated With Presence of Aneurysms

Background and Purpose— The middle cerebral artery (MCA) bifurcation is a preferred site for aneurysm formation. Wider bifurcation angles have been correlated with increased risk of aneurysm formation. We hypothesized a link between the presence of MCA aneurysms and the angle morphology of the bifurcation. Methods— Three-dimensional rotational angiography volumes of 146 MCA bifurcations (62 aneurysmal) were evaluated for angle morphology: parent–daughter angles (larger daughter Ф1, smaller daughter Ф2), bifurcation angle (Ф1+Ф2), and inclination angle (&ggr;) between the parent vessel axis and the plane determined by daughter vessel axes. Statistics were evaluated using Wilcoxon rank-sum analysis and area under the receiver operator characteristic curve. Results— Aneurysmal bifurcations had wider inclination angle &ggr; (median 57.8° versus 15.4°; P<0.0001). Seventy-five percent of aneurysmal MCAs had &ggr; >10°, compared with 25% nonaneurysmal. Ф1 and Ф2, but especially Ф1+Ф2, were significantly larger in aneurysmal bifurcations (median 171.3° versus 98.1°; P<0.0001). Sixty-seven percent of aneurysmal bifurcations had Ф1+Ф2 >161°, compared with 0% nonaneurysmal MCAs. An optimal threshold of 140° was established for Ф1+Ф2 (area under the curve, 0.98). Sixty-eight percent of aneurysms originated off the daughter branches. Seventy-six percent of them originated off the branch with the largest branching angle, specifically if this was the smaller daughter branch. Wider Ф1+Ф2 correlated with aneurysm neck width, but not dome size. Conclusions— MCA bifurcations harboring aneurysms have significantly larger branching angles and more often originate off the branch with the largest angle. Wider inclination angle is strongly correlated with aneurysm presence, a novel finding. The results point to altered wall shear stress regulation as a possible factor in aneurysm development and progression.

Widening of the basilar bifurcation angle: association with presence of intracranial aneurysm, age, and female sex

OBJECT Arterial bifurcations represent preferred locations for aneurysm formation, especially when they are associated with variations in divider geometry. The authors hypothesized a link between basilar apex aneurysms and basilar bifurcation (α) and vertebrobasilar junction (VBJ) angles. METHODS The α and VBJ angles were measured in 3D MR and rotational angiographic volumes using a coplanar 3-point technique. Angle α was compared between age-matched cohorts in 45 patients with basilar artery (BA) aneurysms, 65 patients with aneurysms in other locations (non-BA), and 103 nonaneurysmal controls. Additional analysis was performed in 273 nonaneurysmal controls. Computational fluid dynamics (CFD) simulations were performed on parametric BA models with increasing angles. RESULTS Angle α was significantly wider in patients with BA aneurysms (146.7° ± 20.5°) than in those with non-BA aneurysms (111.7° ± 18°) and in controls (103° ± 20.6°) (p < 0.0001), whereas no difference was observed for the VBJ angle. A wider angle α correlated with BA aneurysm neck width but not dome size, which is consistent with CFD results showing a widening of the impingement zone at the bifurcation apex. BA bifurcations hosting even small aneurysms (< 5 mm) had a significantly larger α angle compared with matched controls (p < 0.0001). In nonaneurysmal controls, α increased with age (p < 0.0001), with a threshold effect above 35 years of age and a steeper dependence in females (p = 0.002) than males (p = 0.04). CONCLUSIONS The α angle widens with age during adulthood, especially in females. This angular widening is associated with basilar bifurcation aneurysms and may predispose individuals to aneurysm initiation by diffusing the flow impingement zone away from the protective medial band region of the flow divider.

Use of concentric Solitaire stent to anchor Pipeline flow diverter constructs in treatment of shallow cervical carotid dissecting pseudoaneurysms

The flow-diverting Pipeline Embolization Device (PED; ev3 Neurovascular, Irvine, CA, USA) provides proven flow diversion for intracranial wide-necked and fusiform aneurysms. The tendency of the PED to migrate and foreshorten when its size is mismatched with the parent vessel makes its use more difficult for cervical carotid pseudoaneurysms, as the parent vessel regains its luminal diameter during the healing phase, and because of its mobility during head movement. We present a novel technique of using a Solitaire detachable stent (ev3 Neurovascular) to anchor PED constructs to mitigate these shortcomings. Two patients with shallow and broad-necked cervical carotid pseudoaneurysms with underlying parent vessel stenosis deemed poor candidates for conventional stent-supported coiling were treated using tandem overlapping PED centered over the neck of the pseudoaneurysm and a Solitaire concentric anchor was deployed to overlap distally and proximally. As predicted, both patients revealed carotid luminal gain after aneurysm thrombosis with attendant migration (3.8 and 2.8mm) and expansion of the PED construct (14% and 7.8%) which remained constrained within the Solitaire anchoring device with persistent luminal patency and no evidence of endoleak at follow-up (3 and 5 months). The use of a concentric anchoring stent can mitigate the inherent tendency of the braided flow-diverting PED to migrate and foreshorten as the target vessel heals upon pseudoaneurysm thrombosis. This novel technique opens the possibility of using PED to treat shallow or fusiform lesions in mobile cervical arteries previously relegated to stent-supported coiling or surgical reconstruction.

High curvature of the internal carotid artery is associated with the presence of intracranial aneurysms

Objective Aneurysm formation in locations not involving vascular bifurcations has not been thoroughly analyzed. This study evaluated the relationship between the degree of vessel curvature and the presence of intracranial sidewall aneurysms of the internal carotid artery (ICA). Methods Catheter-based 3D-rotational angiographic volumes and demographic data were available for 130 ICAs. Mean and peak curvatures were evaluated for the intracranial ICA (50 mm caudal from ICA bifurcation) and for its distal segment (from ICA bifurcation to carotid siphon). Four ICA groups, statistically matched for age, were identified: non-aneurysmal women (n=33) and men (n=25), aneurysmal women (n=58) and men (n=14). Univariate and multivariate analyses were employed to evaluate statistical performance. Results Aneurysmal ICAs had significantly higher mean curvatures than non-aneurysmal ICAs in both the intracranial (p<0.001) and the distal ICA (p<0.001) for both genders. Peak curvature was significantly higher in aneurysmal versus non-aneurysmal men (p=0.008) but not in aneurysmal versus non-aneurysmal women (p=0.12). Mean curvature in non-aneurysmal ICAs was lower in men than in women but higher in aneurysmal ICAs in men than in women. In multivariate analysis, curvature was highly correlated with aneurysm presence but was independent of age, hypertension, hypercholesterolemia and smoking status. Conclusions The presence of a sidewall aneurysm on the ICA is associated with high curvature in both genders. High curvature of the intracranial ICA, as well as of the distal segment, may indicate a higher risk for aneurysm formation. Non-aneurysmal ICAs are less curved in men than in women, which may explain the gender predisposition to aneurysm formation.

Enterprise stenting for intracranial aneurysm treatment induces dynamic and reversible age-dependent stenosis in cerebral arteries

Background Although intracranial stenting has been associated with in-stent stenosis, the vascular response of cerebral vessels to the deployment of the Enterprise vascular reconstruction device is poorly defined. Objective To evaluate the change in parent vessel caliber that ensues after Enterprise stent placement. Methods Seventy-seven patients with 88 aneurysms were treated using Enterprise stent-assisted coil embolization and underwent high-resolution three-dimensional rotational angiography followed by three-dimensional edge-detection filtering to remove windowing-dependence measurement artifact. Orthogonal diameters and cross-sectional areas (CSAs) were measured proximal and distal on either side of the leading stent edge (points A, B), trailing stent edge (points D, E), and at mid-stent (point C). Results Enterprise stent deployment caused an instant increase in the parent artery CSA by 8.98% at D, which was followed 4–6 months later by significant in-stent stenosis (15.78% at A, 27.24% at B, 10.68% at C, 32.12% at D, and 28.28% at E) in the stented artery. This time-dependent phenomenon showed resolution which was complete by 12–24 months after treatment. This target vessel stenosis showed significant age dependence with greater response in the young. No flow-limiting stenosis requiring treatment was observed in this series. Conclusions Use of the Enterprise stent is associated with a significant dynamic and spontaneously resolvable age-dependent in-stent stenosis. Further study is warranted on the clinical impact, if any, of this occurrence.