Friday, October 24, 2014

1. CHADS2 score for risk of stroke in patients with a-fib:
-CHF +1
-Hypertension +1
-Age >=75 +1
-Diabetes +1
-History of stroke/TIA/thromboembolism +2
2. CHADS2 score- annual stroke risk correlation. Based on this data in {JAMA} (n=1733, national a-fib registry)
0 points: 2% risk
1 point: 3% risk
2 points: 4% risk
3 points: 6% riks
4 points: 8%
5 points: 12%
6 points: 18%
3. Really good editorial/review in {circulation} of the evidence of discontinuation of warfarin in favor of antiplatelets (aspirin +/- plavix) after ablation:
-Bunch et al describe the safety of discharging selected low-risk patients (CHADS2 0-1; n=123) undergoing AF ablation with aspirin in a retrospective single-center study. Over 1 year, no strokes occurred in the aspirin group, but 4 strokes (CHADS2 scores: 2, 2, 3, and 4) occurred in the warfarin group (n=507).
-Oral et al reported a similar stroke risk in patients after catheter ablation compared with a matched population without history of AF. In this retrospective analysis of 755 patients (82% CHADS2 score 0-1), OAC was discontinued and replaced with aspirin in the case of freedom from AF. None of these patients had thromboembolism during a follow-up of 25±8 months, whereas 2 late thromboembolic events occurred in patients adequately anticoagulated (CHADS2 scores, 0 and 2).
-Themistoclakis et al published a retrospective study (n=3,355, most with CHADS2 0-1). OAC was discontinued irrespective of CHADS2 score. At 2 years, 2 patients on aspirin (CHADS2 scores, 0 and 1) and 3 on warfarin (CHADS2 scores, 1, 2, and 2) had an ischemic stroke. None of the patients with discontinued OAC and a CHADS2 risk score of ≥2 (n=347) had an ischemic stroke. Major hemorrhage was observed in 1 patient off warfarin and 13 patients on warfarin.
Although most neurosurgeons hate antiplatelets just as much if not more than coumadin.
4. Treatment of agitation in older adults with dementia/alzheimer's: 
-Risk of dementia at 65 is 10%, at 85 is 33%.
-Antipsychotics - associated with an increased risk of death (potentially due to QT prolongation)
-{Double blinded, placebo controlled RCT, n=196, JAMA} of citalopram for the management of agitation in dementia; 40% had significant improvement on citalopram, 26% placebo. However, risk of complications (QT prolongation by 18 ms, slight decline in cognitive function) were higher in citalopram group.
5. The ARUBA trial: Management of unruptured AVMs.
-Multicenter, multi-national RCT (n=226), 33 months of follow up, published in the Lancet
-Inclusion criteria: adults with an AVM diagnosed by imaging without any evidence of previous hemorrhage/rupture or any previous intervention for AVM.
-Randomized to medical management (hypertension control, correction of coagulopathy, etc) vs intervention (5% neurosurgery only, 30% endovascular embolization only, 30% stereotactic radiosurgery only, 12% embolization + neurosurgery, 15% embolization + SRS)
-Primary outcome: stroke/hemorrhage
-Results: 10% incidence of death or hemorrhagic/ischemic stroke in medical management group, 31% in intervention group. 12% risk of focal neurological deficit (mostly reversible) in intervention group, <1% in medical management group.
-Study aborted early due to loss of equipoise.
-Overall annual spontaneous hemorrhage rate found at 2.2%
-Looking at the below study, the increased risk of bleeding from intervention is likely entirely due to endovascular embolization or streotactic radiosurgery. Neurosurgical intervention is much, much less likely to lead to hemorrhage than either of those two.
6. Treatment of AVMs: a meta-analysis {JAMA, 2011}
-137 observational studies including 142 cohorts, totaling 13,698 patients and 46,314 patient-years of follow-up.
-Case fatality was 0.68 (95% CI, 0.61-0.76) per 100 person-years overall, 1.1 (95% CI, 0.87-1.3; n = 2549) after microsurgery, 0.50 (95% CI, 0.43-0.58; n = 9436) after SRS, and 0.96 (95% CI, 0.67-1.4; n = 1019) after embolization.
-Intracranial hemorrhage rates were 1.4 (95% CI, 1.3-1.5) per 100 person-years overall, 0.18 (95% CI, 0.10-0.30) after microsurgery, 1.7 (95% CI, 1.5-1.8) after SRS, and 1.7 (95% CI, 1.3-2.3) after embolization.
-More recent studies were associated with lower case-fatality rates (rate ratio [RR], 0.972; 95% CI, 0.955-0.989) but increased rates of hemorrhage (RR, 1.02; 95% CI, 1.00-1.03).
-Predictors of lower fatality: Male sex (RR, 0.964; 95% CI, 0.945-0.984), small brain AVMs (RR, 0.988; 95% CI, 0.981-0.995), strictly deep venous drainage (RR, 0.975; 95% CI, 0.960-0.990).
-Predictors of lower hemorrhage rates: male sex (RR, 0.976, 95% CI, 0.964-0.988), small brain AVMs (RR, 0.988, 95% CI, 0.980-0.996), and brain AVMs with deep venous drainage (0.982, 95% CI, 0.969-0.996).
-Complications leading to permanent neurological deficits or death occurred in a median 7.4% (range, 0%-40%) of patients after microsurgery, 5.1% (range, 0%-21%) after SRS, and 6.6% (range, 0%-28%) after embolization.
-Successful brain AVM obliteration was achieved in 96% (range, 0%-100%) of patients after microsurgery, 38% (range, 0%-75%) after SRS, and 13% (range, 0%-94%) after embolization.
-Conclusion: compared to embolization or SRS, neurosurgery is much more effective for the treatment of AVM, and carries a much lower risk of hemorrhage, but a slightly higher risk of complications/death (presumably from factors unrelated to the AVM and related to the fact that you're getting brain surgery).
7. Risk of rupture in AVMs: 
-Stapf et al, n=622, retrospective review of AVMs all at Columbia, "The mean pretreatment follow-up was 829 days (median: 102 days), during which 39 (6%) patients experienced AVM hemorrhage. Increasing age (hazard ratio [HR] 1.05, 95% CI 1.03 to 1.08), initial hemorrhagic AVM presentation (HR 5.38, 95% CI 2.64 to 10.96), deep brain location (HR 3.25, 95% CI 1.30 to 8.16), and exclusive deep venous drainage (HR 3.25, 95% CI 1.01 to 5.67) were independent predictors of subsequent hemorrhage. Annual hemorrhage rates on follow-up ranged from 0.9% for patients without hemorrhagic AVM presentation, deep AVM location, or deep venous drainage to as high as 34.4% for those harboring all three risk factors."
8. Rationale for Spetzler-Martin Grading scale: from Martin's original 1986 paper in JNS
"Size of the AVM. The size of the AVM is determined by measuring on angiograms the largest diameter of the nidus of the malformation. When magnified angiographic views are considered, a correction for the magnification factor is required. The size of the AVM is determined to be small (< 3 cm), medium (3 to 6 cm), or large (> 6 cm), and the AVM is scored appropriately.
The size of the malformation is responsible for much of the technical difficulty in removing AVM's. The larger an AVM, the larger the amount of normal adjacent neural tissue that is exposed to injury during microsurgical resection of the nidus. Large AVM's mandate longer operating time, thereby increasing the risk of anesthesia-related complications. Furthermore, the criterion of size encompasses several of the other important factors that determine the degree of surgical difficulty. In general the size of an AVM determines, or is closely related to, the number of feeding arteries, the amount of flow, and the degree of [vascular] steal."
"Pattern of Venous Drainage. The course of the draining veins is determined from the angiogram. The venous pattern is considered superficial if all the drainage from the AVM is through the cortical venous system. The venous pattern is considered deep if any or all of the drainage is through deep veins (such as internal cerebral veins, basal veins, or precentral cerebellar vein). In the posterior fossa, only cerebellar hemispheric veins that drain directly into the straight sinus or transverse sinus are considered to be superficial veins.Clearly, the pattern of venous drainage is closely related to the surgical accessibility of an AVM. Deep venous drainage, no matter how small, further complicates AVM excision. Often the vast majority of an AVM will have been separated from the surrounding brain when the small arterialized subependymal veins of the deep component are encountered. These veins are friable, resist bipolar coagulation, and have the dangerous propensity to retract and bleed into the parenchyma or ventricle when disrupted."
"Eloquence of Adjacent Brain. Eloquent brain regions are defined as those that speak to readily identifiable neurological function and, if injured, result in a disabling neurological deficit. For the purpose of this grading scheme, the following are considered eloquent areas (Fig. 1): the sensorimotor, language, and visual cortex; the hypothalamus and thalamus; the internal capsule; the brain stem; the cerebellar peduncles; and the deep cerebellar nuclei. Areas with much more subtle neurological function, or areas in which injury does not cause permanent disabling deficit (such as the anterior portion of the frontal or temporal lobes, or the cerebellar cortex) are considered non-eloquent. To preserve simplicity, it is assumed that eloquent cortical regions occupy their normal anatomic location. For the purpose of grading, Wada testing or electrophysiological mapping techniques designed to precisely localize eloquent cortex are not required. Data from these techniques, if available, can easily be used for grading brain eloquence in this scheme. The removal of AVM's adjacent to eloquent areas carries a much greater risk of disabling neurological morbidity than does excision of these lesions from less critical regions. The brain that is adjacent to the AVM is liable to experience damage during surgery from AVM dissection and retraction, and after surgery from postoperative hemorrhage or edema."
9. Spetzler Martin Grading Scale (from above paper)
-Size: 0 points for <3 cm, 1 point for 3-6 cm, 2 points for >6cm
-Venous drainage: 0 points for superficial drainage, 1 point for deep drainage
-Eloquence: 0 points for presence in a non-eloquent region, 1 point for presence in an eloquent region
-Sum the points to determine the grade. The more points, the higher the difficulty of the surgical excision and the higher the risk of postoperative morbidity and mortality.
-"A Grade V lesion is associated with significant risk of surgical morbidity and mortality. These large, critically located malformations require extensive dissection in close proximity to important brain regions; their removal may be complicated by difficulties with controlling fragile deep veins. Obliteration of the large AVM shunt presents surrounding normal vessels with a sudden increase in perfusion that may result in vasogenic edema or even hemorrhage-a phenomenon that has been termed normal perfusion pressure breakthrough"
-There is a grade VI, describing an inoperable lesion- "extremely large diffuse AVM's that are dispersed through critical neurologically eloquent areas, or malformations with a diffuse nidus that encompasses critical structures such as the hypothalamus or brain stem... surgical resection of such lesions would almost unavoidably be associated with a totally disabling deficit or death."
10. Correlation of grading scale with outcomes, from 100 surgeries, all done by spetzler before 1986:

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