Anti-neutrophil cytoplasmic antibody associated central nervous system vasculitis with brain and spinal cord subarachnoid hemorrhage: A rare case report and review of the literature.

This case report describes a 48-year old female who presented with altered mental status, lower extremity weakness, low back pain and a recent history of subjective fevers and night sweats found to have posterior parieto-occipital and spinal subarachnoid hemorrhage on imaging. Further work-up revealed vasculitic changes in the intracranial vasculature and the external carotid artery on angiography. She also demonstrated positivity for perinuclear anti-neutrophil cytoplasmic (p-ANCA) antibodies overall consistent with ANCA associated central nervous system vasculitis (AAV). The present case describes a rare and new presentation of AAV that caused both a cerebral and spinal subarachnoid hemorrhage. There has been no documentation of spinal subarachnoid hemorrhage associated with primary or secondary vasculitis in the literature. Ultimately, this case demonstrates the important finding that AAV can have spinal cord manifestations and cervical vasculature involvement along with the more classic intra-cranial vasculitis findings.

Levetiracetam Pharmacokinetics in a Patient with Intracranial Hemorrhage Undergoing Continuous Veno-Venous Hemofiltration.

BACKGROUND Levetiracetam is an antiepileptic drug frequently used in critically ill patients. Levetiracetam is primarily eliminated as a parent compound via glomerular filtration and requires dose adjustment in renal insufficiency, but the literature on patients receiving continuous veno-venous hemofiltration (CVVH) is scant. CASE REPORT We report the levetiracetam pharmacokinetic profile of a patient being treated with levetiracetam 1000 mg intravenously every 12 h who required continuous veno-venous hemofiltration (CVVH). The patient underwent CVVH utilizing a high-flux polyethersulfone membrane filter. The blood flow rate was 250 ml/min, and the predilution replacement therapy fluid flow rate was 2000 ml/h. After achieving presumed steady-state on levetiracetam 1000 mg q12h, serial plasma samples (pre- and post-filter) and effluent samples were drawn at 2, 4, 6, 8, and 10 h. Levetiracetam concentrations were determined utilizing LC-MS/MS. The levetiracetam maximum concentration (Cmax), minimum concentration (Cmin), half-life, area under the concentration-time curve (AUC0-12), clearance (CL), and volume of distribution (Vd) were 30.7 µg/ml, 16.1 µg/ml, 12.9 h, 272 mg·hr/L, 3.68 L/h, and 0.73 L/kg, respectively. The sieving coefficient was 1.03±0.08. CVVH represented 61.3% of the total levetiracetam clearance. The patient was maintained on CVVH for 24 consecutive days and then transitioned to intermittent hemodialysis and remained seizure-free. CONCLUSIONS CVVH is highly effective in removing levetiracetam from circulating plasma. Due to the effective removal, standard doses of levetiracetam are required to maintain adequate plasma concentrations. Dose reductions utilizing HD or estimated creatinine clearance recommendations will likely lead to subtherapeutic levels, especially if higher CVVH flow rates are used.

CLOTBUST-hands free: initial safety testing of a novel operator-independent ultrasound device in stroke-free volunteers.

BACKGROUND AND PURPOSE: We aimed to evaluate safety and tolerability of a novel operator-independent ultrasound device among stroke-free volunteers. METHODS: A headframe containing 18 ultrasound transducers (each operating at 2 MHz, pulsed-wave) was used to expose both temporal windows and the suboccipital window. The transmission characteristics were set to emulate the acoustic characteristics of the exposure levels in the Combined Lysis of Thrombus in Brain Ischemia using Transcranial Ultrasound and Systemic tPA (CLOTBUST) trial and to never exceed Food and Drug Administration mandated diagnostic ultrasound exposure limits. Volunteers underwent 2 hours of insonation with transducer activation one at a time. Safety was captured using serial neurological examinations and pre- and postinsonation MRI for detection of the blood brain barrier permeability. RESULTS: A total of 15 volunteers (40% men; 49 ± 16 years; 27% black; all pre-exposure National Institutes of Health Stroke Scale scores 0) were enrolled. Five volunteers received pulsed-wave ultrasound via the best pair temporal transducers, 5 via sequential activation of the suboccipital transducers, and 5 via sequential activation of all bilateral temporal and suboccipital transducers. All subjects were safely insonated with no adverse effects as indicated by the neurological examinations during, immediately after the exposure, and at 24 hours, and no abnormality of the blood brain barrier was found on any of the MRIs. CONCLUSIONS: Our novel device was well tolerated by stroke-free volunteers and did not cause any neurological dysfunction nor did it affect blood brain barrier integrity. The safety and efficacy of the device are now being tested in stroke patients receiving intravenous tissue-type plasminogen activator in phase II-III clinical trials.

Computed tomography perfusion prognostic maps do not predict reversible and irreversible neurological dysfunction following reperfusion therapies.

BACKGROUND: We aimed to evaluate the ability of commercially available computed tomography perfusion (CTP) prognostic maps software to identify reversibly and irreversibly damaged brain functions in the best case scenario: patients who achieved early and complete tissue reperfusion. METHODS: Consecutive ischemic stroke patients who received reperfusion therapies, those with early (less than two-hours from treatment initiation) and complete Thrombolysis in Myocardial Infarction grade III or equivalent reperfusion were included in the analysis. Computed tomography perfusion prognostic maps were assigned as 'red,' or irreversible if cerebral blood volume declined below 2 ml/100 g and 'green,' or recoverable if the affected/unaffected mean transit time ratio was >1.45. Only patients with middle cerebral artery territory affected were included and subcomponents of the National Institutes of Health Stroke Scale scale pre- and posttreatment were analyzed based on anatomical correlation of the affected CTP areas and corresponding neurological functions. RESULTS: Among 109 consecutive patients who had intra-arterial reperfusion procedures, 16 (age 60 ± 17 years, 56% men, median National Institutes of Health Stroke Scale 13 . 5, interquartile range 7-18) had pretreatment CTP and had early complete reperfusion. We identified 44 affected areas on CTP (red 12 (27%), green 32 (73%)) with corresponding measurable neurological deficits including aphasia, arm, face weakness, and inattention. Red areas correctly identified 5/12 (42%) of functions that did not recover despite early reperfusion. Green areas correctly identified 18/32 (56%) of functions that recover after early reperfusion (OR 0.92, 95% CI 0.25-3.39, P = 1.0). CONCLUSIONS: In-patients achieving early and complete reperfusion, pretreatment CTP prognostic maps were not predictive for irreversibly or reversibly lost neurologic functions.

Velocity criteria for intracranial stenosis revisited: an international multicenter study of transcranial Doppler and digital subtraction angiography.

BACKGROUND AND PURPOSE: Intracranial atherosclerotic disease is associated with a high risk of stroke recurrence. We aimed to determine accuracy of transcranial Doppler screening at laboratories that share the same standardized scanning protocol. METHODS: Patients with symptoms of cerebral ischemia were prospectively studied. Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) criteria were used for identification of ≥50% stenosis. We determined velocity cutoffs for ≥70% stenosis on digital subtraction angiography by Warfarin-Aspirin Symptomatic Intracranial Disease criteria and evaluated novel stenotic/prestenotic ratio and low-velocity criteria. RESULTS: A total of 102 patients with intracranial atherosclerotic disease (age 57±13 years; 72% men; median National Institutes of Health Stroke Scale 3, interquartile range 6) provided 690 transcranial Doppler/digital subtraction angiography vessel pairs. On digital subtraction angiography, ≥50% stenosis was found in 97 and ≥70% stenosis in 62 arteries. Predictive values for transcranial Doppler SONIA criteria were similar (P>0.9) between middle cerebral artery (sensitivity 78%, specificity 93%, positive predictive value 73%, negative predictive value 94%, and overall accuracy 90%) and vertebral artery/basilar artery (69%, 98%, 88%, 93%, and 92%). As a single velocity criterion, most sensitive mean flow velocity thresholds for ≥70% stenosis were: middle cerebral artery>120 cm/s (71%) and vertebral artery/basilar artery>110 cm/s (55%). Optimal combined criteria for ≥70% stenosis were: middle cerebral artery>120 cm/s, or stenotic/prestenotic ratio≥3, or low velocity (sensitivity 91%, specificity 80%, receiver operating characteristic 0.858), and vertebral artery/basilar artery>110 cm/s or stenotic/prestenotic ratio≥3 (60%, 95%, 0.769, respectively). CONCLUSIONS: At laboratories with a standardized scanning protocol, SONIA mean flow velocity criteria remain reliably predictive of ≥50% stenosis. Novel velocity/ratio criteria for ≥70% stenosis increased sensitivity and showed good agreement with invasive angiography.