Decompressive Craniectomy in Patients with Traumatic Brain Injury: Are the Usual Indications Congruent with Those Evaluated in Clinical Trials?

BACKGROUND: In patients with traumatic brain injury (TBI), multicenter randomized controlled trials have assessed decompressive craniectomy (DC) exclusively as treatment for refractory elevation of intracranial pressure (ICP). DC reliably lowers ICP but does not necessarily improve outcomes. However, some patients undergo DC as treatment for impending or established transtentorial herniation, irrespective of ICP. METHODS: We performed a population-based cohort study assessing consecutive patients with moderate-severe TBI. Indications for DC were compared with enrollment criteria for the DECRA and RESCUE-ICP trials. RESULTS: Of 644 consecutive patients, 51 (8 %) were treated with DC. All patients undergoing DC had compressed basal cisterns, 82 % had at least temporary preoperative loss of ≥1 pupillary light reflex (PLR), and 80 % had >5 mm of midline shift. Most DC procedures (67 %) were "primary," having been performed concomitantly with evacuation of a space-occupying lesion. ICP measurements influenced the decision to perform DC in 18 % of patients. Only 10 and 16 % of patients, respectively, would have been eligible for the DECRA and RESCUE-ICP trials. DC improved basal cistern compression in 76 %, and midline shift in 94 % of patients. Among patients with ≥1 absent PLR at admission, DC was associated with lower mortality (46 vs. 68 %, p = 0.03), especially when the admission Marshall CT score was 3-4 (p = 0.0005). No patients treated with DC progressed to brain death. Variables predictive of poor outcome following DC included loss of PLR(s), poor motor score, midline shift ≥11 mm, and development of perioperative cerebral infarcts. CONCLUSIONS: DC is most often performed for clinical and radiographic evidence of herniation, rather than for refractory ICP elevation. Results of previously completed randomized trials do not directly apply to a large proportion of patients undergoing DC in practice.

Appropriateness of lumbar spine referrals to a neurosurgical service.

BACKGROUND: Patients with lumbar spine complaints are often referred for surgical assessment. Only those with clinical and radiological evidence of nerve root compression are potential candidates for surgery and appropriate for surgical assessment. This study examines the appropriateness of lumbar spine referrals made to neurosurgeons in Edmonton, Alberta. METHODS: Lumbar spine referrals to a group of ten neurosurgeons at the University of Alberta were reviewed over three two month intervals. Clinical criteria for "appropriateness" for surgical assessment were as follows: •"Appropriate" referrals were those that stated leg pain was the chief complaint, or those that described physical exam evidence of neurological deficit, and imaging reports (CT or MRI) were positive for nerve root compression. •"Uncertain" referrals were those that reported both back and leg pain without specifying which was greater, without mention of neurologic deficit, and when at least possible nerve root compression was reported on imaging. •"Inappropriate" referrals contained no mention of leg symptoms or signs of neurological deficit, and/or had no description of nerve root compression on imaging. RESULTS: Of the 303 referrals collected, 80 (26%) were appropriate, 92 (30%) were uncertain and 131 (44%) were inappropriate for surgical assessment. CONCLUSIONS: Physicians seeking specialist consultations for patients with lumbar spine complaints need to be better informed of the criteria which indicate an appropriate referral for surgical treatment, namely clinical and radiological evidence of nerve root compression. Avoiding inappropriate referrals could reduce wait-times for both surgical consultation and lumbar spine surgery for those patients requiring it.

Force, sarcomere shortening velocity and ATPase activity.

UNLABELLED: We have tested the hypothesis that the transition rate (G) of the cardiac XB from the strong force generating state to the weak state is a linear function V of the sarcomere (VSL); furthermore, we tested whether the ATPase rate of the two isoforms of myosin can be held responsible for the difference between V0 of rat cardiac trabeculae containing V1 isomyosin versus those containing V3 isomyosin. METHODS: V1 isomyosin was induced by thyroid hormone treatment of the rats for 2 weeks, V3 isomyosin by PTU treatment for 1 month. Force was measured with a strain gauge in trabeculae from the rat right ventricle in K-H solution ([Ca]o=1.5 mM, 25 degrees C). Sarcomere length (SL) was measured with laser diffraction techniques. Twitch force at constant SL, and the force response to shortening at constant VSL (0-8 microm/s; deltaSL 50-100 nm) were measured at varied time during the twitch. RESULTS: The force response to shortening consisted of a fast initial exponential decline (tau = 2 ms) followed by a slow decrease of F. The instantaneous difference (deltaF) between isometric force (FM) and the declining force depended on shortening duration (deltat), VSL and instantaneous FM: deltaF = G1 x FM x deltat x VSL x (1-VSL/VMAX), where VMAX is the unloaded VSL and G1 was 6.15 +/- 2.12 microm(-1) (mean +/- s.d.; n=6). deltaF/FM was independent of the time onset of shortening. G1 of V1 and V3 trabeculae did not differ. V0 of V1 and V3 trabeculae differed 2-2.5 fold, as did both the ATPase rate and the velocity of actin sliding in a motility assay of the myosin purified from V1 or V3 hearts. The temperature dependence of the ATPase rate (Q10: 4.03 and 4.33, respectively; n.s.) was similar to that of V0 that has previously been reported for predominantly V1 trabeculae. Cross-linking of actin to myosin with the short chain cross linker EDC increased the ATPase rate of the two isomyosins (200-fold and 600-fold respectively) to exactly the same final level and reduced their Q10 by 50%. CONCLUSION: The linear interrelation between deltaF and VSL is consistent with feedback, whereby XB kinetics depends on VSL. This feedback provides an integrated description of cardiac muscle mechanics and energetics. The results, also, suggests that it is unlikely that the hydrolytic domain of the cross bridge determines V0 and warrant ongoing experiments to investigate the role of the actin binding domain of the XB in cardiac sarcomere kinetics. In order to further investigate the role of the actin binding domain, we have expressed chimeric cardiac myosin, co-assembled with MLC, by mutual substitution of actin binding loop on alpha MHC and beta MHC.

Nonuniform activation and the mechanics of myocardial trabeculae with fast or slow myosin.

Left ventricular (LV) wall motion abnormalities reflect regional nonuniform contraction which may be arrhythmogenic. We studied sarcomere mechanics and force development (F) in uniform and nonuniform trabeculae using a model in which half of the muscle can be rendered weak by exposure to low [Ca2+]o. Stretch allowed the weak muscle segment to generate a force that was four-fold higher than force when the whole muscle was exposed to low [Ca2+]o. The sarcomere force-velocity relationships (FSVR) and the force-sarcomere-length relationships (FSLR) explained the force increase in the weak segment and the decrease of force in the strong segment such that both carried the same force. Correction for muscle stiffness converted the FSVR into a [Ca2+]o-independent linear FVRXB for "the single cross-bridge (XB)." Stretch increased XB force<10% above FXB-max, but recruited more XBs by feedback of V to the rate of XB, weakening (g=g0+g1V). The g1 here was indistinguishable from g1 of XBs in slow myosin of aged animals. The mechanics of nonuniform muscle can be explained by a linear FVRXB combined with the effect of V on the XB weakening rate.

Intraventricular hemorrhage volume predicts poor outcomes but not delayed ischemic neurological deficits among patients with ruptured cerebral aneurysms.

BACKGROUND: Intraventricular hemorrhage (IVH) predicts worse outcomes following aneurysmal subarachnoid hemorrhage (SAH). One potential mechanism is that IVH predisposes to the development of delayed ischemic neurological deficits (DINDs). No previous studies have evaluated the association between IVH volume (in milliliters) and subsequent development of DINDs or poor outcomes. OBJECTIVE: To assess the association between the volume of IVH and the subsequent development of DINDs, delayed cerebral infarction, death, and poor neurological outcomes, specifically among patients with concomitant SAH and IVH. METHODS: We performed a cohort study involving 152 consecutive patients with concomitant SAH and IVH. To determine volume of IVH, we used the IVH Score, shown to correlate well with computerized volumetric assessment. To determine the relative quantity of subarachnoid blood, we applied the SAH Sum Score. Multivariate logistic regression was used to adjust for potential confounders. RESULTS: There was no significant association between IVH volume and the development of DINDs or delayed infarction. In contrast, patients with poor neurological outcomes had significantly larger baseline IVH volume (mean, 11.8 mL vs 3.8 mL, P = .001). In the multivariate analysis, IVH volume was an independent predictor of poor outcomes (OR per mL: 1.11 [1.04-1.18]). Patients in the highest quartile for IVH volume were far more likely to progress to poor outcome compared with those in the lowest quartile (OR 4.09 [1.32-12.65]). Interobserver agreement in the determination of IVH Score was moderate to good. CONCLUSIONS: IVH volume is an independent predictor of poor neurological outcomes, even after adjusting for the amount of subarachnoid blood. The pathophysiology of this association does not appear to involve an increased risk of DINDs or delayed infarction. Measures aimed at accelerating IVH clearance, such as intraventricular thrombolysis, merit further evaluation.