Ramani Balu

Inflammation and Immune System Activation After Traumatic Brain Injury

Treatment options for managing traumatic brain injury remain limited. Therapies that limit the development of secondary brain injury—the delayed injury that can occur days to weeks after initial presentation—would have a major impact on outcomes and reduce the medical, social, and economic burden of this devastating disease. A growing body of evidence suggests that inflammation and activation of the immune system is a central driver of secondary brain injury. This article reviews the evidence for inflammation mediating secondary injury after head trauma and outlines potential approaches for immunomodulatory therapies after traumatic brain injury.

Dynamic autoregulation of cerebral blood flow measured non-invasively with fast diffuse correlation spectroscopy:

Cerebral autoregulation (CA) maintains cerebral blood flow (CBF) in the presence of systemic blood pressure changes. Brain injury can cause loss of CA and resulting dysregulation of CBF, and the degree of CA impairment is a functional indicator of cerebral tissue health. Here, we demonstrate a new approach to noninvasively estimate cerebral autoregulation in healthy adult volunteers. The approach employs pulsatile CBF measurements obtained using high-speed diffuse correlation spectroscopy (DCS). Rapid thigh-cuff deflation initiates a chain of responses that permits estimation of rates of dynamic autoregulation in the cerebral microvasculature. The regulation rate estimated with DCS in the microvasculature (median: 0.26 s−1, inter quartile range: 0.19 s−1) agrees well (R = 0.81, slope = 0.9) with regulation rates measured by transcranial Doppler ultrasound (TCD) in the proximal vasculature (median: 0.28 s−1, inter quartile range: 0.10 s−1). We also obtained an index of systemic autoregulation in concurrently measured scalp microvasculature. Systemic autoregulation begins later than cerebral autoregulation and exhibited a different rate (0.55 s−1, inter quartile range: 0.72 s−1). Our work demonstrates the potential of diffuse correlation spectroscopy for bedside monitoring of cerebral autoregulation in the microvasculature of patients with brain injury.

Noninvasive optical monitoring of critical closing pressure and arteriole compliance in human subjects

The critical closing pressure (CrCP) of the cerebral circulation depends on both tissue intracranial pressure and vasomotor tone. CrCP defines the arterial blood pressure (ABP) at which cerebral blood flow approaches zero, and their difference (ABP − CrCP) is an accurate estimate of cerebral perfusion pressure. Here we demonstrate a novel non-invasive technique for continuous monitoring of CrCP at the bedside. The methodology combines optical diffuse correlation spectroscopy (DCS) measurements of pulsatile cerebral blood flow in arterioles with concurrent ABP data during the cardiac cycle. Together, the two waveforms permit calculation of CrCP via the two-compartment Windkessel model for flow in the cerebral arterioles. Measurements of CrCP by optics (DCS) and transcranial Doppler ultrasound (TCD) were carried out in 18 healthy adults; they demonstrated good agreement (R = 0.66, slope = 1.14 ± 0.23) with means of 11.1 ± 5.0 and 13.0 ± 7.5 mmHg, respectively. Additionally, a potentially useful and rarely measured arteriole compliance parameter was derived from the phase difference between ABP and DCS arteriole blood flow waveforms. The measurements provide evidence that DCS signals originate predominantly from arteriole blood flow and are well suited for long-term continuous monitoring of CrCP and assessment of arteriole compliance in the clinic.

Cerebrospinal Fluid in Posterior Reversible Encephalopathy Syndrome: Implications of Elevated Protein and Pleocytosis

Background and Purpose: Patients with posterior reversible encephalopathy syndrome (PRES) sometimes undergo analysis of cerebrospinal fluid (CSF) to exclude alternative diagnoses. This study’s objectives were to describe the CSF characteristics in patients with PRES and to identify clinical and radiologic findings associated with distinct CSF abnormalities. Methods: We identified a retrospective cohort of patients with PRES. We compared clinical and radiographic characteristics of those who did versus did not undergo lumbar puncture, described the observed range of CSF findings, and analyzed clinical and radiographic features associated with specific CSF abnormalities. Results: A total of 188 patients were included. Patients with (n = 77) and without (n = 111) CSF analysis had similar clinical and radiographic characteristics. Cerebrospinal fluid protein was elevated in 46 (60%) of 77, with median CSF protein 53 mg/dL (upper limit of normal 45 mg/dL). Protein elevation was significantly associated with radiographic severity (P = .0058) but not with seizure, time from symptom onset, radiographic evidence of diffusion restriction, or contrast enhancement. Five (7%) patients had elevated CSF white blood cells, all of whom had infarction and/or hemorrhage on neuroimaging, and 4 of whom had eclampsia. Conclusion: The CSF of most patients with PRES shows a mild protein elevation commensurate with radiographic severity. Cerebrospinal fluid pleocytosis may mark a distinct subtype of PRES with predisposition toward infarction and/or hemorrhage. These findings help clinicians interpret CSF findings in these patients and generate new hypotheses about the pathophysiology of this syndrome.

Long-term utility and complication profile of open craniotomy for biopsy in patients with idiopathic encephalitis

Neurosurgeons are often asked to perform open biopsy for diagnosis of encephalitis after medical investigations are non-diagnostic. These patients may be critically ill with multiple comorbidities. Patients and their families often request data regarding the success rates and complication profile of biopsy, but minimal literature exists in this area. Retrospective chart review of all patients undergoing open brain biopsy (burr hole or craniotomy) for encephalitis refractory to medical diagnosis between January 2009 and December 2013 was undertaken. Pathology records and outpatient follow-up were reviewed to determine most recent clinical status of each patient. A total of 59 patients were included with mean follow up of 20months. The average age at biopsy was 55years. The most common unconfirmed diagnoses leading to biopsy were vasculitis (44%), neoplasm (27%), infection (12%), autoimmune (12%), amyloidosis (5%). Tissue pathology was diagnostic in 42% of all cases. Overall, biopsy confirmed the preoperative diagnosis in 46% of cases and refuted the preoperative leading diagnosis in 25% of cases. At last follow-up, the tissue pathology resulted in a medical treatment change in 25% of cases. There was a 14% major neurological complication rate (postoperative stroke, hemorrhage, or neurological deficit) and 9% cardiopulmonary complication rate (delayed extubation and re-intubation) attributable to surgical intervention. In this limited series, diagnostic utility of biopsy in patients with idiopathic encephalitis is less than 50% and the major complication rate is 23%. Patients and providers must be counseled accordingly and weigh the risks and benefits of open biopsy for encephalitis cautiously.