Soldiers experience risky environment during their deployment. It ranges from exposure to unique climatic conditions including gases (fire pits with toxic gases or exposure related to chemical and biological weaponry), herbs, temperatures, and frequent sounds coming guns, blasts etc. In addition, they are exposed long term isolation from their loved ones. This unique combination of circumstances and their long-term exposure to them results in a challenging health outcome which presents in the aftermath of the deployment.
Post-Traumatic Stress Disorder (PTSD), Traumatic Brain Injury (TBI) and Chronic Traumatic Encephalopathy (CTE) are some of the most prevalent conditions experienced by the veterans. In addition, ALS and Schizophrenia Both TBI and CTE are the direct result of exposure to serious accidents resulting in head injuries (damage to brain function). Clinically both TBI and CTE are neurological disorders primarily in the form of neurodegeneration. This is an unmet need that BCRI is focused on addressing.
Our ultimate goal is to efficiently develop effective therapies and improve quality-of-life outcomes for patients with autoimmune disorders and neurological diseases.
Traumatic Brain Injury
Traumatic brain injury (TBI) is an acquired brain injury in which sudden trauma causes damage to the brain. TBI is caused by a blow or jolt to the head. Severity of TBI can be mild, moderate, or severe, depending on the degree of impact and subsequent extent of damage to the brain.
Mild TBI typically associated with no or a momentary loss of consciousness, headache, confusion, lightheadedness, dizziness, blurred vision, ringing in the ears, bad taste in the mouth, fatigue or lethargy, a change in sleep patterns, behavioral or mood changes, and trouble with memory, concentration, attention, or thinking.
Moderate and/or severe TBI may be associated with similar symptoms, along with additional signs and symptoms such as worsening headache, nausea and vomiting, seizures, pupillary dilation, slurred speech, weakness or numbness in the extremities, loss of coordination, and amnesia.
Scope of the Problem:
TBI represents a serious public health problem in the United States that can lead to death and permanent disability. According to the Centers for Disease Control (CDC), in the year 2014, there were about 2.87 million TBI-related emergency department visits, hospitalizations, and deaths in the United States. Importantly, more than 837,000 of these health events occurred among children. The eight-year period from 2006–2014 saw a 54% increase in TBI-related emergency room visits but an 8% decrease in hospitalization rates and a 6% decrease in death rates. In addition to the short-term and long-lasting consequences for an individual, TBI has major implications in terms of the burden on the healthcare system and stress on the overall economy.
Moderate and severe TBI requires immediate medical attention. The primary aim of therapy in such patients is to stabilize the individual (maintain adequate oxygenation and blood pressure), and to prevent further injury. In many cases, neuro-imaging (mainly CT scan) helps in the diagnosis of a patient. Recently, a blood test was approved by the U.S. Food and Drug Administration to evaluate mild TBI in adults. Subsequently, depending on the deficit, patients may require physical therapy, occupational therapy, speech therapy, and psychiatric support.
A majority of patients with severe TBI require surgery to repair ruptured blood vessels and/or remove hematomas. The location and severity of the injury can affect short-term and long-term disabilities following TBI, including but not limited to cognitive, motor, sensory, speech/language, and behavioral. More serious head injuries may lead to stupor or coma, or even death.
TBI and Veterans:
For active duty military personnel and reserve service members, blasts as commonly encountered in war zones (for instance due to improvised explosive devices, IEDs) are a leading cause of TBI. According to current scientific evidence, TBI suffered due to blasts is not significantly different from that due to a blunt injury as seen in civilian populations. Hence the management and prognosis of such injuries is similar to those in other TBI.
Chronic Traumatic Encephalopathy
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease resulting from repeated brain trauma or injury. CTE is seen predominantly in professional athletes involved in contact sports that lead to repetitive head trauma (such as football, boxing, etc.) with or without symptomatic concussion. CTE has also been demonstrated in military personnel with histories of repetitive head trauma, specifically in veterans of the wars in Iraq and Afghanistan. Considering the huge numbers of potentially affected individuals – millions of young athletes participating in contact sports, and the large numbers of military personnel, CTE represents an important public health issue.
CTE presents as a progressive decline of memory and cognition, depression, suicidal tendencies, poor impulse control, aggression, Parkinson-like symptoms, and, early-onset dementia. Rarely, CTE may present as a motor neuron disease, that is difficult to distinguish from amyotrophic lateral sclerosis (ALS). CTE is characterized by the accumulation of hyperphosphorylated tau protein (p-tau) in neurons and astrocytes.
Therapy and Future Directions:
Currently, there is no treatment available for CTE. However, reducing mild traumatic brain injuries and preventing additional injury after a concussion may be a way to prevent CTE from developing. More research needs to be carried out to better understand the pathophysiology and molecular pathology of this disease, and to develop therapies to counter this condition.
Amyotrophic Lateral Sclerosis (ALS)
Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by the
progressive loss of motor neurons in the brain and spinal cord. It is a clinically and
genetically heterogeneous, multi-domain neuro-degenerative syndrome of motor and extra-motor systems with multiple underlying pathophysiological mechanisms. ALS is characterized by progressive motor deficits that develop over the course of weeks and sometimes months. It may affect any voluntary muscle, which means the presentation is heterogeneous, ranging from dysarthria to a foot drop. The onset of the disease is focal in most patients, and over time other regions of the body become affected. The mechanisms underlying degeneration in ALS are still not completely understood.
Currently, Riluzole is the only drug that has been shown to prolong survival in ALS. In the absence of effective pharmacological treatments, symptomatic interventions and supportive care remain the cornerstone of ALS management. Owing to the recent demonstration of different pathophysiological mechanisms for ALS, it is likely that the different ALS subtypes respond differently to various therapies. This necessitates applications of the principles of personalized medicine to tailor treatments to different patients based on their disease profiles. Such a modality requires the development of biomarkers for accurately characterizing the disease and targeted therapeutics for the different subtypes.
Schizophrenia is a severe psychiatric disorder with a profound impact on the individual and society. While outcomes may not be as uniformly adverse as is commonly believed, over 50% of those individuals who receive a diagnosis have intermittent but long-term psychiatric problems. Around 20% will experience chronic symptoms and disability. The life expectancy of these individuals is reduced by 10–20 years.
Understanding the etiology and pathogenesis of schizophrenia and developing new, more effective, and acceptable treatments remains a significant unmet medical need. It is also one of the most formidable challenges facing modern medicine. Recent advances in genomics and neurosciences are helping to develop better therapeutics.
Schizophrenia is characterized by positive symptoms such as delusions and hallucinations, and negative symptoms such as impaired motivation, reduction in spontaneous speech, and social withdrawal. In addition, it is associated with cognitive impairment. The positive symptoms tend to relapse and remit, though some patients experience residual long-term psychotic symptoms. The negative and cognitive symptoms tend to be chronic and are associated with long-term effects on social function. Diagnosis is made solely on the clinical basis of history and examination of the mental state. Currently, there are no diagnostic tests or biomarkers for schizophrenia.