Recovery After Cerebral Hemorrhage
Recovery After Cerebral Hemorrhage
Background:

 While the intensive care of patients with life-threatening brain illnesses has advanced
 tremendously, a large number of therapies are still without proper scientific support.

 This can be partly explained by the fact that mechanisms of initial brain injury are still
 not well understood. Why additional neurological injury occurs during a patient's stay in the
 NeuroCritical Care Unit (NCCU) despite current best, evidence-based clinical practices, is
 also not well understood. However, over the past decade, better tools have become available
 to measure and monitor the impact of our clinical care on the rapidly changing physiology and
 chemistry of the injured brain. Some of these tools are CT, MRI, ultrasound, and
 catheter-based technology measuring blood flow and metabolism. These tools have enabled
 earlier detection of injury and complications and newer therapeutic strategies.

 Purpose:

 Examine disease pathways common to all brain injuries seen in the University of Maryland's
 22-bed NCCU. Life-threatening neurological illnesses cared for in the NCCU include massive
 stroke, bleeding in and around the brain (subarachnoid hemorrhage, intracerebral hemorrhage,
 subdural hemorrhage, intraventricular hemorrhage), brain tumors, difficult to control
 seizures, neurologic infections, nerve and muscle diseases (such as myasthenia gravis or
 Guillain-Barre Syndrome), and spinal cord disorders among others. Many NCCU patients are
 comatose or paralyzed and may suffer injuries in other parts of the body as well.

 This effort will require the creation of a robust clinical database for the capture of data
 including patient characteristics (age, sex), clinical characteristics, medical treatments,
 surgical interventions, physiological data (such as vital signs, cerebral blood flow,
 intracranial pressure, cerebral oximetry, etc), laboratory data, and standard-of-care
 diagnostic studies such as electroencephalography (EEG), ultrasound, CT, MRI, and angiograms.
 Similar databases exist at other major centers for neurocritical care and have been
 instrumental to the identification of characteristics both predictive of and associated with
 outcomes of patients long after their stay in the NCCU.

 In addition, the samples collected will be included in the University of Maryland Medicine
 (UMM) Biorepository which is a shared resource to enable biomedical research by University of
 Maryland faculty.
The objective of the proposed minimal-risk, non-interventional retrospective (January 2012
 onwards) as well as prospective, cross-sectional observational study (i.e., NCCU Research
 Repository) is to better understand the common pathophysiological pathways of
 life-threatening neurological illnesses, examine how systemic complications (e.g., fever,
 hyperglycemia, undernutrition, and infections) and our standard-of care management of them
 may exacerbate brain injury, and determine the impact of injury and intervention on
 functionally-relevant outcomes.

 A systematically collected cohort may have an especially important role in the NCCU where
 RCTs are difficult to implement or may lack generalizability, and wherein there are pitfalls
 in research derived solely from administrative databases. This relational database will
 capture all patients admitted to University of Maryland's dedicated 22-bed adult NCCU. The
 investigators will not initially collect all potentially relevant fields unique to specific
 diagnoses. However, future disease-specific studies will allow the addition of data fields in
 this flexible database environment. This approach will include the tiered acquisition of
 patient characteristics (age, sex), clinical characteristics, standard-of-care medical
 treatments and surgical interventions, physiological data (such as vital signs, cerebral
 blood flow, intracranial pressure, cerebral oximetry etc), laboratory data, and diagnostic
 studies--particularly neurophysiology, neuropathology, and neuroimaging. Some data elements
 are inherently less reliable when abstracted from the electronic medical record (e.g., a more
 detailed social history, establishing premorbid functional status, and independent
 confirmation of past medical history), and will require an informed consent process to allow
 the research team to approach subjects or their surrogates.

 Similar databases exist at other centers for neurocritical care and have been central to the
 identification of characteristics, both predictive and associative, of patient outcomes. Done
 properly, this repository can facilitate many NCCU priorities including hypothesis
 generating, determining feasibility of single-site trials or involvement in multi-center
 trials, multimodal monitoring, biomarker research, quality improvement, and resident
 education.

 All data will be collected from the patient medical record, patient bedside monitors,
 radiology PACS, and laboratory systems. The collection of data will not affect nor delay
 patient treatment at any instance.

 Potential subjects will include patients admitted to University of Maryland's 22-bed NCCU for
 treatment of a life-threatening neurological illness. All patients 18 years of age and older
 will be eligible for participation in the study.

 At the time study personnel approach the patient or the patient's surrogate to discuss the
 study, they will be provided with three options: (a) Full Consent, (b) Partial Refusal, or
 (c) Complete Refusal.

 Subject's medical treatment will conform to existing clinical management protocols including
 routine ICU care. Standard ICU protocols call for assessments of mental status several times
 a day. The investigators would like to prospectively record the results of these exams in a
 rigorous, standardized manner. The investigators will attempt to correlate these assessments
 with clinical events and outcome. In addition to standard clinical treatment, details of each
 subject's hospitalization, demographic profile, past medical history, family history will be
 obtained by questionnaire and chart review. At discharge or 2 weeks after admission, a brief
 examination and mental status test will be performed. The subject and a family member or
 caregiver may also be asked to return for follow up evaluations 3 and 12 months after initial
 brain or spinal cord injury, in order to evaluate their longterm neurological status,
 disability, emotional status, cognitive functioning, and overall quality of life. These
 interviews may be conducted in person and will take approximately one hour each. For those
 patients unable to return in person, a shorter telephone interview will be conducted. Outcome
 measures may include the Glasgow Outcome Scale (GOS), the extended Glasgow Outcome Scale
 (eGOS), Modified Rankin Scale, Lawton Activities of Daily Living Index, Barthel Index,
 Sickness Impact Profile (SIP), NIH Stroke Scale, psychosocial assessments, memory and
 cognitive neuropsychometric tests (e.g. the Montreal Cognitive Assessment-MoCA).

 Variables recorded during hospitalization will be examined for statistical correlation with
 neuropsychometric test results. Candidate pathophysiologic variables with independent
 predictive value for cognitive dysfunction, (e.g., including severity of illness upon
 admission, hydrocephalus, ischemia from vasospasm, and laboratory test results) will be
 identified using Pearson correlation and forward stepwise logistic regression. Relationships
 between acute pathology (e.g., lesions on neuroimaging or malignant electrical patterns on
 electroencephalography) and dysfunction within various cognitive domains (memory, attention,
 visuospatial ability, language) will be examined using contingency tables, Pearson
 correlation, linear regression, and the Wilcoxon signed rank test. If necessary, multivariate
 models will be used to confirm that significant independent relationships exist.

 Blood samples will be analyzed to identify the factors causing secondary brain injury (e.g.,
 the narrowing of the blood vessels (vasospasm) after initial hemorrhage).

 For patients requiring an External Ventricular Drain (EVD) as part of their medical
 treatment, the cerebrospinal fluid (CSF) is drained into a collection bag, the amount of
 drainage recorded and the CSF discarded. The investigators may collect a 1 cc sample of the
 CSF daily prior to discard until it is medically warranted to remove the EVD or 14 days
 whichever comes first. NO EVD will be placed for the purposes of clinical research.
Inclusion Criteria:

 -  clinical diagnosis of potentially life-threatening neurological illness

 -  admitted to Neuro ICU within 14 days of initial injury

 Exclusion Criteria:

 -  known pre-existing neurological deficits related to a developmental disorder

 -  prior severe stroke

 -  prior severe dementia

 -  prior severe head injury

 -  prisoners