Andrew R. Pines

Thinking from the Heart: Neurocristopathy, Aortic Abnormalities, and Intracranial Aneurysms.

he formation of intracranial aneurysms (IAs) has been intensively investigated due to its potential for devasT tating consequences. Numerous studies have documented the strong association between aneurysm pathophysiology and “traditional” atherosclerotic risk factors such as smoking, hypertension, and vessel wall inflammation. The presence of multiple aneurysms and familial occurrence, however, raises the valid question of the extent to which genetically determined factors contribute to the phenotype of an innate arteriopathy. Such an association between IAs and several monogenic or polygenic syndromes is well known.

Hypothermia not Supported as a Therapeutic Option for Traumatic Brain Injury in Recent Randomized Trial

Traumatic brain injury (TBI) is a leading cause of permanent disability in people younger than 40 years of age. An increase in intracranial pressure (ICP) during hospitalization for a TBI has been associated with poor long-term neurologic outcomes. On the basis of encouraging research, hypothermia has been embraced by some centers as an innovative way to treat high ICP. More recent trials, however, have hinted that therapeutic hypothermia might contribute to poor neurologic outcomes. In an attempt to define the role of hypothermia in TBI, the Eurotherm 3235 Trial collaborators conducted a randomized controlled trial, which was published October 7, 2015 in the New England Journal of Medicine. The inclusion criteria included patients with closed head injury who sustained an ICP >20 mm Hg for >5 minutes. For the purpose of creating a framework for study analysis, treatments for TBI were divided into stage 1, 2, and 3 therapies (Table 1). Eligible patients were randomized to an experimental arm, hypothermia (32 C 35 C) in addition to best management practice, and a control arm that consisted of best management practices alone. Statistical analysis was performed using ordinal logistic regression to compare the Extended Glasgow Outcome Scale scores between the hypothermia and control groups at 6 months. Only 25.7% of patients from the hypothermia group (49/191) had favorable outcomes at

Defining the Immune Phenotype for Glioblastoma Multiforme: One Step Closer to Understanding Our Enemy.

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Bioresorbable Intracranial Sensors: A New Frontier for Neurosurgeons

The management of brain, spinal cord, and peripheral nerve disorders and injury may benefit from more robust continuous monitoring. Implantation of biosensors is limited by the risk of infection and the need for a second procedure to extract the sensor. Bioresorbable sensors are electronic sensors that can run the required functional course in the body but eliminate via absorption over a reasonable period of time. If properly designed, bioresorbable sensors promise to overcome the limitations of current sensors and reduce the threshold for continuous monitoring.

Managing Post-tPA Intracranial Hemorrhage: Time Is Still Brain

Symptomatic intracerebral hemorrhage (sICH) is the most dreaded complication in ischemic stroke patients treated with recombinant tissue plasminogen activator (rtPA). Symptomatic intracerebral hemorrhage is associated with significant morbidity and a mortality rate of approximately 50%. Yet management of this cohort has been based mostly on anecdotal experience. Since its approval by the U.S. Food and Drug Administration in 1996, rtPA has become the standard of care for select patients with acute ischemic stroke. In the October JAMA Neurology issue, Yaghi et al. reported on a retrospective study examining current treatment paradigms for sICH after rtPA administration at 10 U.S. stroke centers. Patients included in the study had to meet the criteria for the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST). Symptomatic intracerebral hemorrhage was defined as the presence of a parenchymal hematoma accounting for more than one third of the infarct volume (parenchymal hematoma type 2) identified on head computed tomography (CT) with at least a 4point increase from the baseline National Institute of Health Stroke Scale (NIHSS). The primary outcome was in-hospital mortality, and the secondary outcome was hematoma expansion identified on follow-up CT. Other variables were included in the study to examine if there was any association between in-hospital mortality and hematoma expansion. First data on pretreatment factors were reported. These factors included patient demographics, stroke risk factors, antiplatelet or anticoagulant use before thrombolysis, admission NIHSS, and code status change to comfort care measures. Second were laboratory measures, comprising pretreatment blood glucose level, coagulation laboratory values, and fibrinogen level. Third were imaging features including hematoma volume and the time from initiation of rtPA therapy to sICH diagnosis. Fourth was the treatment modality, ranging from fresh frozen plasma, cryoprecipitate, vitamin K, platelet transfusion, recombinant factor VIIa, aminocaproic acid, and surgical decompressive craniotomy or hematoma evacuation.

Cranial dural AV Fistulas: Making sense of who to treat and how

Cranial dural arteriovenous fistulas are aberrant intracranial vascular lesions involving a direct connection between dural arteries on the arterial side and dural sinuses and/or cortical veins on the venous side. DAVFs are classified based on the pattern of venous outflow and the presence of cortical venous reflux (Borden types 1–3 or Cognard types I–V). High-quality imaging with MRI and digital subtraction angiography are crucial to decipher the grade and dynamic flow characteristics of DAVFs. This will subsequently guide the most appropriate next steps in the management of the patient, whether observation or treatment. The treatment modalities for DAVF obliteration are traditionally discussed in terms of three main categories: endovascular, microsurgical, and radiosurgical. Yet it is paramount to recognize that such an approach has the tendency to compartmentalize management, while in reality, patients with DAVF are best served by a multimodal, multidisciplinary approach. Successful DAVF obliteration and follow-up care is ensured with proper patient selection and strategic use of transarterial or transvenous embolization, microsurgery, and/or radiosurgery either alone or in various combinations. This chapter addresses these important issues in diagnosis, grading, patient selection, and treatment of cranial DAVFs.

Aneurysm wall composition may determine rupture risk and endovascular treatment failure.

Although size has emerged as a crude differentiator between high and low risk intracranial aneurysms, it remains an imperfect biomarker of aneurysm behavior (2). Clinicians are increasingly faced with the dilemma of counseling patients with small aneurysm against treatment, yet simultaneously struggling with the difficult care and prognosis of patients with equally small ruptured aneurysms (2). Deflation of aneurysms after rupture has been refuted as an explanation of this paradox (6). Although using aneurysm size may give some insight into individualized risk prediction it is far from the goal of precision medicine of providing patients with an accurate assessment of individualized risk. Vascular dysfunction of the aneurysm wall has been regarded as a potential target for finding more accurate biomarkers for disease behavior. Paucity or absence of smooth muscle cells have been noted in histologic studies of human aneurysm walls (3). Inflammation of the wall has been thought to be a strong potential pathway to eventual aneurysm rupture (4, 7). Although inflammation has been associated with aneurysm rupture, causation has not been clearly established. Furthermore the role of smooth muscle cell dysregulation or absence in this process remains poorly understood.