Circulating extracellular DNA levels are acutely elevated in ischaemic stroke and associated with innate immune system activation.

OBJECTIVE: The objective of this work was to assess the ability of peripheral blood cell-free DNA (cfDNA) levels to identify ischaemic stroke early in the acute phase of care, as well as to examine the relationship between peripheral blood cfDNA levels and stroke-induced innate immune system activation. METHODS: Upon emergency department admission, peripheral blood samples were obtained from 43 patients experiencing acute ischaemic stroke and 20 patients identified as stroke mimics. Plasma cfDNA levels were measured using quantitative polymerase chain reaction (qPCR), infarct volume and NIH stroke scale (NIHSS) were used to assess injury severity, and peripheral blood neutrophil count was used as a measure of innate immune system status. RESULTS: Peripheral blood cfDNA levels were significantly elevated in patients suffering stroke relative to those diagnosed as stroke mimics, and could differentiate between groups with 86% (95% CI = 72-95%) sensitivity and 75% (95% CI = 51-91%) specificity. Furthermore, cfDNA levels displayed significant positive associations between both infarct volume and peripheral blood neutrophil count within the stroke group. CONCLUSIONS: These findings suggest that assessment of peripheral blood cfDNA levels may be useful for the identification of ischaemic stroke in the acute care setting, and provide associative evidence that cfDNA is a potential activator of the peripheral innate immune system in response to cerebral ischaemia.

Population-based estimates suggest middle meningeal artery embolization for subdural hematomas could significantly expand the scope of neurovascular therapies.

BACKGROUND: This study quantifies the impact of middle meningeal artery embolization (MMAE) for subdural hematomas (SDHs) by estimating a target population. METHODS: A population-based study at a tertiary hospital, the main SDH facility for a four-county population, used primary ICD-10 codes over 3 years to collate SDH hospitalizations. Clinical and imaging data confirmed traumatic versus non-traumatic and acute versus non-acute (mixed or chronic) SDH. The MMAE-eligible population included patients with non-traumatic, non-acute SDH aged ≥18 years plus patients with 'traumatic' but non-acute SDH aged ≥60 years presenting with a fall. This was contrasted with the rate of large vessel strokes in the same population. RESULTS: 1279 hospitalizations with a primary ICD-10 SDH diagnosis were identified, with 389 from the study population. Excluding repeat admissions, 350 patients were analyzed, 233 (67%) traumatic, and 117 (33%) non-traumatic SDH. Regarding etiology, 'fall ≥60 years' was the most common category in the entire cohort (n=156; 45% (95% CI 39% to 50%)). The SDH rate was 52/100 000 persons/year (95% CI 47 to 57). The rate of all non-traumatic, non-acute SDH in patients aged ≥18 years was 17/100 000 persons/year (95% CI 15 to 20), combining with 'traumatic' but non-acute fall-related SDH in patients aged ≥60 years yielded 41/100 000 persons/year (95% CI 36 to 47). This demographic may represent an MMAE-eligible population, exceeding large vessel stroke rates (31/100 000 persons/year) in the same population, estimating 139 387 potential MMAE cases/year (95% CI 121 517 to 158 168) in the USA. CONCLUSION: MMAE could transform non-acute SDH management, especially in the elderly, potentially surpassing the impact of large vessel stroke. Clinical trials are essential for validation of its efficacy and safety compared with standard management.

MR-guided focused ultrasound thalamotomy for lithium-induced tremor: a case report and literature review.

Drug-induced tremor is a common side effect of lithium with an occurrence of approximately 25% of patients. Cessation of the offending drug can be difficult, and many medical treatments for drug-induced tremor are ineffective. Deep brain stimulation (DBS) has been shown in a limited number of case reports to effectively reduce drug-induced tremor, however, which remains an invasive therapeutic option. MR-guided focused ultrasound (MRgFUS) thalamotomy is an FDA-approved non-invasive treatment for essential tremor (ET). To the best of our knowledge, MRgFUS thalamotomy has never been reported to treat drug-induced tremor. Here, we present a case of a left-handed 55-year-old man with a progressive, medically refractory lithium-induced tremor of the bilateral upper extremities. The patient underwent MRgFUS thalamotomy targeting the right ventral intermediate nucleus (VIM) of the thalamus to treat the left hand. There was almost complete resolution of his left-hand tremor immediately following MRgFUS. There were no side effects. The patient continues to show excellent tremor control at 90-day follow-up and remains free from side effects. This case demonstrates MRgFUS thalamotomy as a possible novel treatment option to treat drug-induced tremor.

Acute ischemic optic neuropathy in a case of heroin overdose.

Presence of acute optic disc and optic nerve infarction in a young man is uncommon finding. This is most commonly seen in the setting of vasculitis and infection. Ischemic optic neuropathy has been reported with cocaine use, amlodipine and alcohol use. To our knowledge there is no reported case of ischemic optic neuropathy in the setting of heroin / opioid use. MR imaging findings in the setting of substance use are similar to other etiologies of ischemic optic neuropathy, with high T2/FLAIR signal, diffusion restriction and abnormal gadolinium enhancement. Here we report a case of 23-year-old man with heroin use disorder presenting with optic nerve infarct resulting in acute painless monocular vision loss.

Multiple cerebral cavernous hemangiomas masquerading as hemorrhagic brain metastases.

Intracranial hemorrhagic metastases are a relatively common finding in patients with thyroid carcinoma. Consequently, more unusual vascular lesions may be overlooked in contemplating a differential diagnosis in this patient group. A 50-year-old female with previously treated papillary thyroid carcinoma presented to the emergency department following new onset seizures. Her work up revealed multiple intraparenchymal brain lesions, hyperdense on computed tomography and demonstrating susceptibility effect, T1 shortening and contrast enhancement on magnetic resonance imaging, suggestive of metastases. Subsequent studies revealed lesional architecture consistent with multiple cavernous malformations, made evident by resolution of edema and evolution of blood products. Clinicians should be aware of the possibility of unusual intracranial hemorrhagic lesions in oncology patients which may only become evident on serial imaging evaluation. Cavernous hemangioma has typical MRI characteristic features which includes "mulberry" appearance on T2-weighted and fluid attenuation inversion recovery images with varying internal signal intensity which indicates multiple stages of blood products within the cavernous hamngioma. The lesions commonly have a typical T2-weighted dark hemosiderin rim. Blood sensitive demonstrates prominent surrounding hypointensity representing blooming secondary to internal blood products and/or calcification, if present. Cavernous hemangioma may rarely demonstrate some degree of contrast enhancement. Perfusion imaging may show alteration in capillary permeability involving cavernous malformations which has been previously described in the literature.

The 'bendy' basilar: progressive aneurysm tilting and arterial deformation can be a delayed outcome after coiling of large basilar apex aneurysms.

BACKGROUND: Morphological changes in the basilar artery and the artery-aneurysm relationship following coiling of large basilar apex aneurysms may induce morbidity. METHODS: The basilar artery radius-of-curvature was measured along its center line on volumetrically reconstructed images formatted along the plane of curvature. The aneurysm-tilt-angle was measured between the distal basilar and the vertical long axis of the aneurysm. The measurements were compared between small (<10 mm) and large (≥10 mm) aneurysms on baseline and follow-up studies. The volume (mm3) and mass (g) of the deployed coils was also compared. RESULTS: Among 94 consecutive aneurysms, 62 (66%) were <10 mm and 32 (34%) were ≥10 mm. The mean aneurysm size and volume was 9 mm (±4) and 507 mm3(±1366) respectively. The median aneurysm follow-up was 24 months (IQR 6-59). There was no difference between the groups based on age, gender, or associated comorbidities. The coil mass was 0.4 g (±0.2) for aneurysms <10 mm and 1.9 g (±1.6) for aneurysms ≥10 mm (P<0.0001). The total coil volume was 32 (±20) mm3 for aneurysms <10 mm and 187 (±172) mm3 for aneurysms ≥10 mm (P<0.0001). Aneurysms ≥10 mm tilted 13.5o (±14.4) compared with 1.1o (±2.8) for aneurysms <10 mm (P<0.0001). The basilar artery became more curved by 1.3 (±9.4) mm for aneurysms ≥10 mm and 0.25 (±2.1) mm for aneurysms <10 mm (P=0.0002). Other than size of the coiled aneurysms no other factors correlated with the geometrical changes. CONCLUSION: Large coiled basilar apex aneurysms may be more prone to aneurysm tilting and bending of the basilar artery. Speculative causes include the weight of the coil mass and the biomechanical forces exerted on the coiled aneurysm.

Eustachian Tube Foreign Body with Endoscopic-Assisted Surgical Removal.

OBJECTIVES: Foreign bodies of the external and middle ear are not uncommon; however, foreign bodies in the eustachian tube are rare. Here we describe the presentation, imaging, and endoscopic-assisted surgical management of a case of eustachian tube foreign body. METHODS: A 34-year-old male was seen for evaluation of foreign body of the left eustachian tube while working with metal at a machine shop. Imaging and surgical management are highlighted and review of available literature regarding foreign bodies of the eustachian tube is presented. RESULTS: A CT scan revealed a foreign body present approximately 1 cm into the bony eustachian tube. The patient underwent middle ear exploration which required endoscopic assistance to adequately visualize the foreign body. The foreign body was unable to be removed and required the creation of a bony tunnel lateral to the eustachian tube for visualization and access to the foreign body. CONCLUSIONS: This report presents a rare case of eustachian tube foreign body. Use of the endoscope during the surgical removal greatly enhanced the ease and safety of removal. This report also highlights the importance of ear protection with any machining and welding work.

Intravenous thrombolysis before endovascular therapy for large vessel strokes can lead to significantly higher hospital costs without improving outcomes.

BACKGROUND: Limited efficacy of IV recombinant tissue plasminogen activator (rt-PA) for large vessel occlusions (LVO) raises doubts about its utility prior to endovascular therapy. PURPOSE: To compare outcomes and hospital costs for anterior circulation LVOs (middle cerebral artery, internal carotid artery terminus (ICA-T)) treated with either primary endovascular therapy alone (EV-Only) or bridging therapy (IV+EV)). METHODS: A single-center retrospective analysis was performed. Clinical and demographic data were collected prospectively and relevant cost data were obtained for each patient in the study. RESULTS: 90 consecutive patients were divided into EV-Only (n=52) and IV+EV (n=38) groups. There was no difference in demographics, stroke severity, or clot distribution. The mean (SD) time to presentation was 5:19 (4:30) hours in the EV-Only group and 1:46 (0:52) hours in the IV+EV group (p<0.0001). Recanalization: EV-Only 35 (67%) versus IV+EV 31 (81.6%) (p=0.12). Favorable outcome: EV-Only 26 (50%) versus IV+EV 22 (58%) (p=0.45). For patients presenting within 4.5 hours (n=64): Recanalization: EV-Only 21/26 (81%) versus IV+EV 31/38 (81.6%) (p=0.93). Favorable outcome: EV-Only 14/26 (54%) versus IV+EV 22/38 (58%) (p=0.75). There was no significant difference in rates of hemorrhage, mortality, home discharge, or length of stay. A stent retriever was used in 67 cases (74.4%), with similar recanalization, outcomes, and number of passes in the EV-Only and IV+EV groups. The mean (SD) total hospital cost was $33 810 (13 505) for the EV-Only group and $40 743 (17 177) for the IV+EV group (p=0.02). The direct cost was $23 034 (8786) for the EV-Only group and $28 711 (11 406) for the IV+EV group (p=0.007). These significantly higher costs persisted for the subgroup presenting in <4.5 hours and the stent retriever subgroup. IV rt-PA administration independently predicted higher hospital costs. CONCLUSIONS: IV rt-PA did not improve recanalization, thrombectomy efficacy, functional outcomes, or length of stay. Combined therapy was associated with significantly higher total and direct hospital costs than endovascular therapy alone.

A population-based incidence of M2 strokes indicates potential expansion of large vessel occlusions amenable to endovascular therapy.

BACKGROUND: M2 occlusions may result in poor outcomes and potentially benefit from endovascular therapy. Data on the rate of M2 strokes is lacking. METHODOLOGY: Patients with acute ischemic stroke discharged over a period of 3 years from a tertiary level hospital in the 'stroke belt' were evaluated for M2 occlusions on baseline vascular imaging. Regional and national incidence was calculated from discharge and multicounty data. RESULTS: There were 2739 ICD-9 based AIS discharges. M2 occlusions in 116 (4%, 95% CI 3.5% to 5%) patients constituted the second most common occlusion site. The median National Institute of Health Stroke Scale (NIHSS) score was 12 (IQR 5-18). Good outcomes were observed in 43% (95% CI 34% to 53%), poor outcomes in 57% (95% CI 47% to 66%), and death occurred in 27% (95% CI 19% to 37%) of patients. Receiver operating characteristics curves showed the NIHSS to be predictive of outcomes (area under the curve 0.829, 95% CI 0.745 to 0.913, p<0.0001). An NIHSS score ≥9 was the optimal cut-off point for predicting poor outcomes (sensitivity 85.7%, specificity 67.4%). 71 (61%) patients had an NIHSS score ≥9 and 45 (39%) an NIHSS score <9. The rate of good-outcome was 22.6% for NIHSS score ≥9 versus 78.4% for NIHSSscore <9 (OR=0.08, 95% CI 0.03 to 0.21, p<0.0001). Mortality was 42% for NIHSS score ≥9 versus 2.7% for NIHSS score <9 (OR=26, 95% CI 3.3 to 202, p<0.0001). Infarct volume was 57 (±55.7) cm3 for NIHSS score ≥9 versus 30 (±34)cm3 for NIHSS score <9 (p=0.003). IV recombinant tissue plasminogen activator (rtPA) administered in 28 (24%) patients did not affect outcomes. The rate of M2 occlusions was 7 (95% CI 5 to 9)/100 000 people/year (3%, 95% CI 2% to 4%), giving an incidence of 21 176 (95% CI 15 282 to 29 247)/year. Combined with M1, internal carotid artery terminus and basilar artery, this yields a 'large vessel occlusion (LVO)+M2' rate of 31 (95% CI 26 to 35)/100 000 people/year and a national incidence of 99 227 (95% CI 84 004 to 112 005) LVO+M2 strokes/year. CONCLUSION: M2 occlusions can present with serious neurological deficits and cause significant morbidity and mortality. Patients with M2 occlusions and higher baseline deficits (NIHSS score ≥9) may benefit from endovascular therapy, thus potentially expanding the category of acute ischemic strokes amenable to intervention.

Monocyte-lymphocyte cross-communication via soluble CD163 directly links innate immune system activation and adaptive immune system suppression following ischemic stroke.

CD163 is a scavenger receptor expressed on innate immune cell populations which can be shed from the plasma membrane via the metalloprotease ADAM17 to generate a soluble peptide with lympho-inhibitory properties. The purpose of this study was to investigate CD163 as a possible effector of stroke-induced adaptive immune system suppression. Liquid biopsies were collected from ischemic stroke patients (n = 39), neurologically asymptomatic controls (n = 20), and stroke mimics (n = 20) within 24 hours of symptom onset. Peripheral blood ADAM17 activity and soluble CD163 levels were elevated in stroke patients relative to non-stroke control groups, and negatively associated with post-stroke lymphocyte counts. Subsequent in vitro experiments suggested that this stroke-induced elevation in circulating soluble CD163 likely originates from activated monocytic cells, as serum from stroke patients stimulated ADAM17-dependant CD163 shedding from healthy donor-derived monocytes. Additional in vitro experiments demonstrated that stroke-induced elevations in circulating soluble CD163 can elicit direct suppressive effects on the adaptive immune system, as serum from stroke patients inhibited the proliferation of healthy donor-derived lymphocytes, an effect which was attenuated following serum CD163 depletion. Collectively, these observations provide novel evidence that the innate immune system employs protective mechanisms aimed at mitigating the risk of post-stroke autoimmune complications driven by adaptive immune system overactivation, and that CD163 is key mediator of this phenomenon.

A population-based incidence of acute large vessel occlusions and thrombectomy eligible patients indicates significant potential for growth of endovascular stroke therapy in the USA.

BACKGROUND: Data on large vessel strokes are important for resource allocation and infrastructure development. OBJECTIVE: To determine an annual incidence of large vessel occlusions (LVOs) and a thrombectomy eligible patient population. METHODS: All patients with acute ischemic stroke discharged over 3 years from a tertiary-level hospital serving a large geographic area were evaluated for an LVO (M1, internal carotid artery terminus, basilar artery). The incidence of LVO was determined for the hospital's 4-county primary service area (PSA, population 210 000) based on each county's discharges and extrapolated to the US population. 'Thrombectomy eligibility' for anterior circulation LVOs was based on time (onset <6 hours) and imaging (Alberta Stroke Program Early CT Score (ASPECTS) ≥6). The number of annual thrombectomy procedures was calculated for Medicare and private payer patients using federally available databases. RESULTS: 1157 patients were discharged from the hospital's PSA, of whom 129 (11.1%, 95% CI 9.5% to 13.1%) had an LVO. This translated into an LVO incidence of 24 per 100 000 people per year (95% CI 20 to 28). 20 per 100 000 people per year had anterior circulation LVOs (95% CI 19 to 22), of whom 10/100 000/year (95% CI 8 to 11) were 'thrombectomy eligible'. An additional 5/100 000/year (95% CI 3 to 6) presented with favorable ASPECTS after 6 hours of symptom onset. Basilar occlusion incidence was estimated at 4/100 000/year (95% CI 2 to 5). These rates yield 77 569 (95% CI 65 835 to 91 091) new LVOs per year in the USA. An estimated 10 284 mechanical thrombectomy procedures were performed in 2015. CONCLUSIONS: This study estimates an LVO incidence of 24 per 100 000 person-years (95% CI 20 to 28). A current estimated annual thrombectomy rate of three procedures per 100 000 people indicates significant potential increase in the volume of endovascular procedures and the need to develop systems of care.

The 'pit-crew' model for improving door-to-needle times in endovascular stroke therapy: a Six-Sigma project.

BACKGROUND: Delays in delivering endovascular stroke therapy adversely affect outcomes. Time-sensitive treatments such as stroke interventions benefit from methodically developed protocols. Clearly defined roles in these protocols allow for parallel processing of tasks, resulting in consistent delivery of care. OBJECTIVE: To present the outcomes of a quality-improvement (QI) process directed at reducing stroke treatment times in a tertiary level academic medical center. METHODS: A Six-Sigma-based QI process was developed over a 3-month period. After an initial analysis, procedures were implemented and fine-tuned to identify and address rate-limiting steps in the endovascular care pathway. Prospectively recorded treatment times were then compared in two groups of patients who were treated 'before' (n=64) or 'after' (n=30) the QI process. Three time intervals were measured: emergency room (ER) to arrival for CT scan (ER-CT), CT scan to interventional laboratory arrival (CT-Lab), and interventional laboratory arrival to groin puncture (Lab-puncture). RESULTS: The ER-CT time was 40 (±29) min in the 'before' and 26 (±15) min in the 'after' group (p=0.008). The CT-Lab time was 87 (±47) min in the 'before' and 51 (±33) min in the 'after' group (p=0.0002). The Lab-puncture time was 24 (±11) min in the 'before' and 15 (±4) min in the 'after' group (p<0.0001). The overall ER-arrival to groin-puncture time was reduced from 2 h, 31 min (±51) min in the 'before' to 1 h, 33 min (±37) min in the 'after' group, (p<0.0001). The improved times were seen for both working hours and off-hours interventions. CONCLUSIONS: A protocol-driven process can significantly improve efficiency of care in time-sensitive stroke interventions.