Sensitivity of frequency-domain optical measurements to brain hemodynamics: simulations and human study of cerebral blood flow during hypercapnia

This study characterizes the sensitivity of noninvasive measurements of cerebral blood flow (CBF) by using frequency-domain near-infrared spectroscopy (FD-NIRS) and coherent hemodynamics spectroscopy (CHS). We considered six FD-NIRS methods: single-distance intensity and phase (SDI and SDϕ), single-slope intensity and phase (SSI and SSϕ), and dual-slope intensity and phase (DSI and DSϕ). Cerebrovascular reactivity (CVR) was obtained from the relative change in measured CBF during a step hypercapnic challenge. Greater measured values of CVR are assigned to a greater sensitivity to cerebral hemodynamics. In a first experiment with eight subjects, CVR_SDϕ was greater than CVR_SDI (p < 0.01), whereas CVR_DSI and CVR_DSϕ showed no significant difference (p > 0.5). In a second experiment with four subjects, a 5 mm scattering layer was added between the optical probe and the scalp tissue to increase the extracerebral layer thickness (L_ec), which caused CVR_DSϕ to become significantly greater than CVR_DSI (p < 0.05). CVR_SS measurements yielded similar results as CVR_DS measurements but with a greater variability, possibly resulting from instrumental artifacts in SS measurements. Theoretical simulations with two-layered media confirmed that, if the top (extracerebral) layer is more scattering than the bottom (brain) layer, the relative values of CVR_DSI and CVR_DSϕ depend on L_ec. Specifically, the sensitivity to the brain is greater for DSI than DSϕ for a thin extracerebral layer (L_ec < 13 mm), whereas it is greater for DSϕ than DSI for a thicker extracerebral layer.     

The FRED Flow-Diverter Stent for Intracranial Aneurysms: Clinical Study to Assess Safety and Efficacy

BACKGROUND AND PURPOSE:Flow-diverter stents are emerging for the endovascular treatment of difficult-to-treat or otherwise untreatable cerebral aneurysms (wide-neck, fusiform, dissecting, blisterlike, or giant). We assessed the clinical safety and efficacy of the Flow-Redirection Endoluminal Device.MATERIALS AND METHODS:This was an institutional review board–approved single-center observational clinical study in 29 patients with 34 aneurysms elected to be treated by endovascular intervention. After providing informed consent, patients were included according to the following criteria: aneurysm fundus-to-neck ratio <2 or neck diameter >4 mm, fusiform, dissecting, or giant aneurysms. The primary end point for clinical safety was the absence of death, absence of major or minor stroke, and absence of transient ischemic attack. The primary end point for treatment efficacy was complete angiographic occlusion according to the O''Kelly Marotta grading scale immediately after the procedure and at follow-up after 3 and 6 months (O''Kelly Marotta D: complete occlusion).RESULTS:The Flow-Redirection Intraluminal Device deployment was technically successful in all cases. In 26/29 (89%) of patients, the primary end point of safety was reached; in the 3 remaining patients, 1 disabling ischemic stroke and 2 minor strokes with complete recovery at follow-up were observed. Angiographic (DSA and MRA) and clinical follow-up were available after 3 months in 29/29 (100%) and after 6 months in 25/29 (86%) patients (after 6 months, only MRA follow-up was performed according to our study protocol and institutional standard). At 3-month follow-up, complete occlusion was reached in 19/34 aneurysms (O''Kelly Marotta D: 19/34; 56%). At 6-month follow-up, aneurysm occlusion was complete in 22/30 aneurysms (O''Kelly Marotta D: 22/30; 73%).CONCLUSIONS:Deployment of the Flow-Redirection Intraluminal Device flow-diverter stent is safe and effective in the treatment of difficult-to-treat or otherwise untreatable intracranial aneurysms.

Endovascular treatment of intracranial aneurysms by coiling has become an accepted alternative to surgical clipping, with increasing evidence for lower morbidity and mortality rates, especially in clinical equipoise.^1–3 However, especially in wide-neck, fusiform, dissecting, and giant aneurysms, incomplete coiling and reperfusion are still a major limitation preventing stable long-term occlusion. Aneurysm recanalization and/or neck remnants may be observed despite further refinement in coil technology such as coated platinum coils⁴ and/or procedural modification such as the balloon-remodeling technique⁵ or stent-assisted coil embolization.⁶The development of flow-diverter (FD) stents has offered the potential of aneurysm occlusion through thrombosis triggered by the disruption of flow into the aneurysm sac.^7–16 As a key element of construction, these stents have a braided mesh with a densely covered surface. Once the FD is expanded to cover the aneurysm neck, thrombosis is induced by stasis of flow within the aneurysmal sac. The porosity of the FD mesh and the pressure gradient between parent and smaller adjacent branch vessels preserve flow and patency of the latter even if covered. The Flow-Redirection Endoluminal Device (FRED; MicroVention, Tustin, California) is a new generation of FDs for reconstruction of the parent artery and aneurysm occlusion. Its unique dual-layer design composed of a low-porosity inner mesh and a high-porosity outer stent may provide potential advantages over other available FDs in safe deliverability and effective occlusion of the target lesion. We report our analysis of the clinical safety and efficacy of the FRED in 29 patients with 34 aneurysms.     

Purpura fulminans and anticardiolipin antibodies in a patient with Grave's disease

We describe a patient with Grave's discase who developed purpura fulminans and who was found to have anticardiolipin antibodies after being started on propylthiouracil (PTU). We discuss the potential role of the antiphospholipid antibody in this woman's presentation, and its association to both PTU and autoimmune thyroid disease.     

Cell cycle progression of B-chronic lymphocytic leukemia cells induced to differentiate by TPA

The cell cycle transition and differentiation-associated surface antigen expression was studied in a clone of B cell chronic lymphocytic leukemia (B-CLL) with phenotypic properties similar to those of resting B lymphocytes. Differentiation was induced with TPA (12-O-tetradecanoyl- phorbol-13-acetate) and defined and quantitated by morphological and functional markers. Changes in the cell cycle position were determined by flow cytometry of acridine orange-stained cells. The uninduced B-CLL cells represented a homogeneous population with the same cell cycle position (GO) as resting normal peripheral blood lymphocytes. After five days of TPA stimulation, 56% of the B-CLL cells were found in G1A, 9% in G1B, and 3% in the S + G2/M phase, of which 2% was accounted to proliferating T cells. The cell cycle transition of the differentiating B-CLL cells was also examined using cell cycle-associated surface antigens as markers. HLA-DR and CD23 antigens were present already on noninduced cells. The former had a high constant expression, while the amount of CD23 increased upon induction. The 4F2 antigen was absent on noninduced cells but present on 86% of the induced cells. HH1 (CD37) was expressed by the majority of the cells before TPA treatment and decreased to almost undetectable levels within 24 hours. Two antigens related to late stages of the cell cycle, the interleukin 2 (IL 2; CD25) and the transferrin receptor, were present on about 20% of the induced cells. Experiments with enriched T cells showed that T but not B cells incorporated 3H-thymidine. Taken together these results and previous work on the induction of the protooncogene c-myc and c-fos suggest that this B-CLL clone represents GO cells that undergo differentiation without concomitant proliferation when exposed to TPA.     

Effect of antituberculosis drug resistance on response to treatment and outcome in adults with tuberculous meningitis

BACKGROUND: Tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis resistant to 1 or more antituberculosis drugs is an increasingly common clinical problem, although the impact on outcome is uncertain. METHODS: We performed a prospective study of 180 Vietnamese adults admitted consecutively for TBM. M. tuberculosis was cultured from the cerebrospinal fluid (CSF) of all patients and was tested for susceptibility to first-line antituberculosis drugs. Presenting clinical features, time to CSF bacterial clearance, clinical response to treatment, and 9-month morbidity and mortality were compared between adults infected with susceptible and those infected with drug-resistant organisms. RESULTS: Of 180 isolates, 72 (40.0%) were resistant to at least 1 antituberculosis drug, and 10 (5.6%) were resistant to at least isoniazid and rifampicin. Isoniazid and/or streptomycin resistance was associated with slower CSF bacterial clearance but not with any differences in clinical response or outcome. Combined isoniazid and rifampicin resistance was strongly predictive of death (relative risk of death, 11.63 [95% confidence interval, 5.21-26.32]) and was independently associated with human immunodeficiency virus infection. CONCLUSIONS: Isoniazid and/or streptomycin resistance probably has no detrimental effect on the outcome of TBM when patients are treated with first-line antituberculosis drugs, but combined isoniazid and rifampicin resistance is strongly predictive of death.