Brad E. Zacharia

The surgical management of chronic subdural hematoma

Chronic subdural hematoma (cSDH) is an increasingly common neurological disease process. Despite the wide prevalence of cSDH, there remains a lack of consensus regarding numerous aspects of its clinical management. We provide an overview of the epidemiology and pathophysiology of cSDH and discuss several controversial management issues, including the timing of post-operative resumption of anticoagulant medications, the effectiveness of anti-epileptic prophylaxis, protocols for mobilization following evacuation of cSDH, as well as the comparative effectiveness of the various techniques of surgical evacuation. A PubMed search was carried out through October 19, 2010 using the following keywords: “subdural hematoma”, “craniotomy”, “burr-hole”, “management”, “anticoagulation”, “seizure prophylaxis”, “antiplatelet”, “mobilization”, and “surgical evacuation”, alone and in combination. Relevant articles were identified and back-referenced to yield additional papers. A meta-analysis was then performed comparing the efficacy and complications associated with the various methods of cSDH evacuation. There is general agreement that significant coagulopathy should be reversed expeditiously in patients presenting with cSDH. Although protocols for gradual resumption of anti-coagulation for prophylaxis of venous thrombosis may be derived from guidelines for other neurosurgical procedures, further prospective study is necessary to determine the optimal time to restart full-dose anti-coagulation in the setting of recently drained cSDH. There is also conflicting evidence to support seizure prophylaxis in patients with cSDH, although the existing literature supports prophylaxis in patients who are at a higher risk for seizures. The published data regarding surgical technique for cSDH supports primary twist drill craniostomy (TDC) drainage at the bedside for patients who are high-risk surgical candidates with non-septated cSDH and craniotomy as a first-line evacuation technique for cSDH with significant membranes. Larger prospective studies addressing these aspects of cSDH management are necessary to establish definitive recommendations.

Smart wearable body sensors for patient self-assessment and monitoring

BackgroundInnovations in mobile and electronic healthcare are revolutionizing the involvement of both doctors and patients in the modern healthcare system by extending the capabilities of physiological monitoring devices. Despite significant progress within the monitoring device industry, the widespread integration of this technology into medical practice remains limited. The purpose of this review is to summarize the developments and clinical utility of smart wearable body sensors.MethodsWe reviewed the literature for connected device, sensor, trackers, telemonitoring, wireless technology and real time home tracking devices and their application for clinicians.ResultsSmart wearable sensors are effective and reliable for preventative methods in many different facets of medicine such as, cardiopulmonary, vascular, endocrine, neurological function and rehabilitation medicine. These sensors have also been shown to be accurate and useful for perioperative monitoring and rehabilitation medicine.ConclusionAlthough these devices have been shown to be accurate and have clinical utility, they continue to be underutilized in the healthcare industry. Incorporating smart wearable sensors into routine care of patients could augment physician-patient relationships, increase the autonomy and involvement of patients in regards to their healthcare and will provide for novel remote monitoring techniques which will revolutionize healthcare management and spending.

Intracranial infectious aneurysms: a comprehensive review

Intracranial infectious aneurysms, or mycotic aneurysms, are rare infectious cerebrovascular lesions which arise through microbial infection of the cerebral arterial wall. Due to the rarity of these lesions, the variability in their clinical presentations, and the lack of population-based epidemiological data, there is no widely accepted management methodology. We undertook a comprehensive literature search using the OVID gateway of the MEDLINE database (1950–2009) using the following keywords (singly and in combination): “infectious,” “mycotic,” “cerebral aneurysm,” and “intracranial aneurysm.” We identified 27 published clinical series describing a total of 287 patients in the English literature that presented demographic and clinical data regarding presentation, treatment, and outcome of patients with mycotic aneurysms. We then synthesized the available data into a combined cohort to more closely estimate the true demographic and clinical characteristics of this disease. We follow by presenting a comprehensive review of mycotic aneurysms, highlighting current treatment paradigms. The literature supports the administration of antibiotics in conjunction with surgical or endovascular intervention depending on the character and location of the aneurysm, as well as the clinical status of the patient. Mycotic aneurysms comprise an important subtype of potentially life-threatening cerebrovascular lesions, and further prospective studies are warranted to define outcome following both conservative and surgical or endovascular treatment.

Epidemiology of Aneurysmal Subarachnoid Hemorrhage

Aneurysmal subarachnoid hemorrhage (aSAH) is a form of hemorrhagic stroke that affects up to 30,000 individuals per year in the United States. The incidence of aSAH has been shown to be associated with numerous nonmodifiable (age, gender, ethnicity, family history, aneurysm location, size) and modifiable (hypertension, body mass index, tobacco and illicit drug use) risk factors. Although early repair of ruptured aneurysms and aggressive postoperative management has improved overall outcomes, it remains a devastating disease, with mortality approaching 50% and less than 60% of survivors returning to functional independence. As treatment modalities change and the percentage of minority and elderly populations increase, it is critical to maintain an up-to-date understanding of the epidemiology of SAH.

A mouse model of intracerebral hemorrhage using autologous blood infusion

The development of controllable and reproducible animal models of intracerebral hemorrhage (ICH) is essential for the systematic study of the pathophysiology and treatment of hemorrhagic stroke. In recent years, we have used a modified version of a murine ICH model to inject blood into mouse basal ganglia. According to our protocol, autologous blood is stereotactically infused in two stages into the right striatum to mimic the natural events of hemorrhagic stroke. Following ICH induction, animals demonstrate reproducible hematomas, brain edema formation and marked neurological deficits. Our technique has proven to be a reliable and reproducible means of creating ICH in mice in a number of acute and chronic studies. We believe that our model will serve as an ideal paradigm for investigating the complex pathophysiology of hemorrhagic stroke. The protocol for establishing this model takes about 2 h.

Intranasal delivery of caspase-9 inhibitor reduces caspase-6-dependent axon/neuron loss and improves neurological function after stroke.

Despite extensive research to develop an effective neuroprotective strategy for the treatment of ischemic stroke, therapeutic options remain limited. Although caspase-dependent death is thought to play a prominent role in neuronal injury, direct evidence of active initiator caspases in stroke and the functional relevance of this activity have not previously been shown. Using an unbiased caspase-trapping technique in vivo, we isolated active caspase-9 from ischemic rat brain within 1 h of reperfusion. Pathogenic relevance of active caspase-9 was shown by intranasal delivery of a novel cell membrane-penetrating highly specific inhibitor for active caspase-9 at 4 h postreperfusion (hpr). Caspase-9 inhibition provided neurofunctional protection and established caspase-6 as its downstream target. The temporal and spatial pattern of expression demonstrates that neuronal caspase-9 activity induces caspase-6 activation, mediating axonal loss by 12 hpr followed by neuronal death within 24 hpr. Collectively, these results support selective inhibition of these specific caspases as an effective therapeutic strategy for stroke.

The complement cascade as a therapeutic target in intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is the second most common and deadliest form of stroke. Currently, no pharmacologic treatment strategies exist for this devastating disease. Following the initial mechanical injury suffered at hemorrhage onset, secondary brain injury proceeds through both direct cellular injury and inflammatory cascades, which trigger infiltration of granulocytes and monocytes, activation of microglia, and disruption of the blood-brain barrier with resulting cerebral edema. The complement cascade has been shown to play a central role in the pathogenesis of secondary injury following ICH, although the specific mechanisms responsible for the proximal activation of complement remain incompletely understood. Cerebral injury following cleavage of complement component 3 (C3) proceeds through parallel but interrelated pathways of anaphylatoxin-mediated inflammation and direct toxicity secondary to membrane attack complex-driven erythrocyte lysis. Complement activation also likely plays an important physiologic role in recovery following ICH. As such, a detailed understanding of the variation in functional effects of complement activation over time is critical to exploiting this target as an exciting translational strategy for intracerebral hemorrhage.

Herniation Secondary to Critical Postcraniotomy Cerebrospinal Fluid Hypovolemia

OBJECTIVE:Cerebrospinal fluid hypovolemia resulting in postural headaches is a well-known clinical entity, but severe forms of cerebrospinal fluid hypovolemia with altered mental status and signs of transtentorial herniation (“brain sag”) have rarely been reported. This article describes the clinical features of brain sag after craniotomy in an attempt to increase recognition of this syndrome. METHODS:Between April 2001 and January 2003, 220 consecutive patients with subarachnoid hemorrhage were prospectively enrolled in the Columbia Subarachnoid Hemorrhage Outcomes Project; 137 underwent craniotomy for aneurysm clipping. Among these patients, the diagnosis of brain sag was made when all three of the following criteria were present: clinical signs of transtentorial herniation, head computed tomographic scans revealing effacement of the basal cisterns with an oblong brainstem, and improvement of symptoms after placement of the patient in the Trendelenburg position (–15 to –30 degrees). For each patient, the symptoms, clinical course, and subsequent response to treatment were characterized. In addition, brainstem dimensions were measured on computed tomographic scans taken before, during, and after resolution of brain sag. A “sag ratio” was generated for these time points by dividing the maximum anteroposterior distance by the maximum bipeduncular distance. RESULTS:Eleven (8.0%) of 137 aneurysmal subarachnoid hemorrhage patients treated by craniotomy and an intraoperative spinal drain met the criteria for brain sag. Signs of transtentorial herniation developed most commonly between 2 and 4 days postoperatively. Pupillary asymmetry was noted in 10 (91.0%) of 11 patients, whereas the other patient demonstrated extensor posturing. The Trendelenburg position reversed the symptoms in all patients. The mean sag ratios before, during, and after resolution of brain sag were 0.91 ± 0.03 (mean ± standard error), 1.18 ± 0.03, and 0.91 ± 0.03, respectively. This represented a 30.9% elongation of the brainstem during sag (P < 0.001) and a 23.6% change back to baseline after resolution of the syndrome (P < 0.002). There was no significant difference between the presag and postsag ratios. CONCLUSION:Severe cerebrospinal fluid hypovolemia after craniotomy may produce a dramatic herniation syndrome that is completely reversed by the Trendelenburg position. Brain sag should be included in the differential diagnosis for acute postoperative clinical deterioration in this patient population.

Renal Dysfunction as an Independent Predictor of Outcome After Aneurysmal Subarachnoid Hemorrhage A Single-Center Cohort Study

Background and Purpose— Acute kidney injury occurs in 1% to 25% of critically ill patients with small increases in creatinine adversely affecting outcome. We sought to determine the burden of acute kidney injury in patients with aneurysmal subarachnoid hemorrhage and whether this dysfunction affects outcome. Methods— Between 1996 and 2008, 787 consecutive patients with aneurysmal subarachnoid hemorrhage were enrolled in our prospective database. Demographics, serum creatinine levels, and discharge modified Rankin scores were recorded, and changes in creatinine clearance were calculated. A multiple logistic regression was performed using known predictors for poor outcome after aneurysmal subarachnoid hemorrhage in addition to burden of contrast-enhanced imaging and change in creatinine clearance. Results— One hundred seventy-nine (23.1%) patients were at risk for renal failure during their hospitalization. In a multivariate model, those patients who developed risk for renal failure were twice as likely to have a poor 3-month outcome (OR, 2.01; P=0.021). Survival curves comparing those not at risk, those at risk (increasing severity classes Risk, Injury, and Failure, and the 2 outcome classes Loss and End-Stage Kidney Disease [RIFLE] R), and those with renal injury or failure (RIFLE I and F) demonstrated that risk of death increases significantly as one progresses through the RIFLE classes (log rank, P<0.0001). Conclusions— In a large, consecutive series of prospectively enrolled patients with aneurysmal subarachnoid hemorrhage, we demonstrate, using the newly defined RIFLE classification for risk of renal failure, that even seemingly insignificant decreases in creatinine clearance are associated with significantly worse 3-month outcomes. This study highlights the importance of close surveillance of renal function and stresses the value of renal hygiene in the aneurysmal subarachnoid hemorrhage population.

Impact of platelet transfusion on hematoma expansion in patients receiving antiplatelet agents before intracerebral hemorrhage

Abstract Objectives: Patients receiving antiplatelet medications are reported to be at increased risk for hematoma enlargement and worse clinical outcomes following intracerebral hemorrhage (ICH). While platelet transfusions are frequently administered to counteract qualitative platelet defects in the setting of ICH, conclusive evidence in support of this therapeutic strategy is lacking. In fact, platelet transfusions may be associated with adverse effects, and represent a finite resource. We sought to determine the clinical efficacy of platelet transfusion and its impact on systemic complications following ICH in a cohort of patients receiving antiplatelet medications. Methods: We retrospectively analysed the medical records of 66 patients admitted to our institution from June 2003 to July 2008 who suffered a primary ICH while receiving antiplatelet (acetylsalicylic acid and/or clopidogrel) therapy. The primary outcome was the rate of significant (>25% increase from admission) hematoma expansion in transfused (n=35) versus non-transfused (n=31) patients. Discharge modified-Rankin score (mRS) and the rates of systemic complications were also assessed. Results: There were no statistically significant differences in rates of hematoma expansion between cohorts, nor were there differences in demographic variables, systemic complications or discharge mRS. Subgroup analysis revealed that there was a higher rate of hematoma expansion in the clopidogrel cohort (p=0.034) than in the cohort of patients receiving aspirin alone. Discussion: This study suggests that platelet administration does not reduce the frequency of hematoma expansion in ICH patients receiving antiplatelet medications. This lack of efficacy may relate to transfusion timing, as a significant proportion of hematoma expansion occurs within 6 hours post-ictus. Additionally, the increased rates of hematoma expansion in the clopidogrel cohort may relate to its prolonged half-life. A larger, prospective study is warranted.