BRAIN TRAUMA-How Does Medical Marijuana Help?
Traumatic brain injury (TBI), also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism (closed or penetrating head injury), or other features (e.g. occurring in a specific location or over a widespread area). Head injury usually refers to TBI, but is a broader category because it can involve damage to structures other than the brain, such as the scalp and skull.
BI is a major cause of death and disability worldwide, especially in children and young adults. Causes include falls, vehicle accidents, and violence. Prevention measures include use of technology to protect those who are in accidents, such as seat belts and sports or motorcycle helmets, as well as efforts to reduce the number of accidents, such as safety education programs and enforcement of traffic laws.
Brain trauma can be caused by a direct impact or by acceleration alone. In addition to the damage caused (at the moment) of injury, brain trauma causes secondary injury, a variety of events that take place in the minutes and days following the injury. These processes, which include alterations in cerebral blood flow and the pressure within the skull, contribute substantially to the damage from the initial injury.
TBI can cause a host of physical, cognitive, emotional, and behavioral effects, and outcome can range from complete recovery to permanent disability or death. The 20th century saw critical developments in diagnosis and treatment which decreased death rates and improved outcome. These include imaging techniques such as computed tomography and magnetic resonance imaging. Depending on the injury, treatment required may be minimal or may include interventions such as medications and emergency surgery. Physical therapy, speech therapy, recreation therapy, and occupational therapy for rehabilitation.
Traumatic brain injury is defined as damage to the brain resulting from external mechanical force, such as rapid acceleration or deceleration, impact, blast waves, or penetration by a projectile. Brain function is temporarily or permanently impaired and structural damage may or may not be detectable with current technology.
BI is one of two subsets of acquired brain injury (brain damage that occurs after birth); the other subset is non-traumatic brain injury, which does not involve external mechanical force (examples include stroke and infection). All traumatic brain injuries are head injuries, but the latter term may also refer to injury to other parts of the head. However, the terms head injury and brain injury are often used interchangeably. Similarly, brain injuries fall under the classification of central nervous system injuries and neurotrauma. In neuropsychology research literature, the term "traumatic brain injury" generally is used to refer to non-penetrating traumatic brain injuries.
TBI is usually classified based on severity, anatomical features of the injury, and the mechanism (the causative forces). Mechanism-related classification divides TBI into closed and penetrating head injury. A closed (also called nonpenetrating, or blunt) injury occurs when the brain is not exposed. A penetrating, or open, head injury occurs when an object pierces the skull and breaches the dura mater, the outermost membrane surrounding the brain.
Brain injuries can be classified into mild, moderate, and severe categories. The Glasgow Coma Scale (GCS), the most commonly used system for classifying TBI severity, grades a person's level of consciousness on a scale of ( 3–15) based on verbal, motor, and eye-opening reactions to stimuli. It is generally agreed that a TBI with a GCS of 13 or above is mild, 9–12 is moderate, and 8 or below is severe. Similar systems exist for young children. However, the GCS grading system has limited ability to predict outcomes. Because of this, other classification systems such as the one shown in the table are also used to help determine severity. A current model developed by the Department of Defense and Department of Veterans Affairs uses all three criteria of GCS after resuscitation, duration of post-traumatic amnesia (PTA), and loss of consciousness (LOC). It also has been proposed to use changes which are visible on neuroimaging, such as swelling, focal lesions, or diffuse injury as method of classification. Grading scales also exist to classify the severity of mild TBI, commonly called concussion; these use duration of LOC, PTA, and other concussion symptoms
Systems also exist to classify TBI by its pathological features. Lesions can be extra-axial, (occurring within the skull but outside of the brain) or intra-axial (occurring within the brain tissue). Damage from TBI can be focal or diffuse, confined to specific areas or distributed in a more general manner, respectively. However it is common for both types of injury to exist in a given case
Signs and symptoms
Unequal pupil size is a sign of a serious brain injury. Symptoms are dependent on the type of TBI (diffuse or focal) and the part of the brain that is affected. Unconsciousness tends to last longer for people with injuries on the left side of the brain than for those with injuries on the right. Symptoms are also dependent on the injury's severity. With mild TBI, the patient may remain conscious or may lose consciousness for a few seconds or minutes. Other symptoms of mild TBI include headache, vomiting, nausea, lack of motor coordination, dizziness, difficulty balancing, lightheadedness, blurred vision or tired eyes, ringing in the ears, bad taste in the mouth, fatigue or lethargy, and changes in sleep patterns. Cognitive and emotional symptoms include behavioral or mood changes, confusion, and trouble with memory, concentration, attention, or thinking. Mild TBI symptoms may also be present in moderate and severe injuries
A person with a moderate or severe TBI may have a headache that does not go away, repeated vomiting or nausea, convulsions, an inability to awaken, dilation of one or both pupils, slurred speech, aphasia (word-finding difficulties), dysarthria (muscle weakness that causes disordered speech), weakness or numbness in the limbs, loss of coordination, confusion, restlessness, or agitation. Common long-term symptoms of moderate to severe TBI are changes in appropriate social behavior, deficits in social judgment, and cognitive changes, especially problems with sustained attention, processing speed, and executive functioning. Alexithymia, a deficiency in identifying, understanding, processing, and describing emotions occurs in (60.9%) of individuals with TBI. Cognitive and social deficits have long-term consequences for the daily lives of people with moderate to severe TBI, but can be improved with appropriate rehabilitation. One of two subsets of acquired brain injury (brain damage that occurs after birth); the other subset is non-traumatic brain injury, which does not involve external mechanical force (examples include stroke and infection). All traumatic brain injuries are head injuries, but the latter term may also refer to injury to other parts of the head. However, the terms head injury and brain injury are often used interchangeably. Similarly, brain injuries fall under the classification of central nervous system injuries and neurotrauma. In neuropsychology research literature, the term "traumatic brain injury" generally is used to refer to non-penetrating traumatic brain injuries.
When the pressure within the skull (intracranial pressure, abbreviated ICP) rises too high, it can be deadly. Signs of increased ICP include decreasing level of consciousness, paralysis or weakness on one side of the body, and a blown pupil, one that fails to constrict in response to light or is slow to do so. Cushing's triad, a slow heart rate with high blood pressure and respiratory depression is a classic manifestation of significantly raised ICP. Anisocoria, unequal pupil size, is another sign of serious TBI. Abnormal posturing, a characteristic positioning of the limbs caused by severe diffuse injury or high ICP, is an ominous sign.
Small children with moderate to severe TBI may have some of these symptoms but have difficulty communicating them. Other signs seen in young children include persistent crying, inability to be consoled, listlessness, refusal to nurse or eat, and irritability.
The most common causes of TBI include violence, transportation accidents, construction, and sports. In the US, falls account for( 28%) of TBI, motor vehicle (MV) accidents for (20%), being struck by an object for (19%), violence for ( 11%), and non-MV bicycle accidents for ( 3%). Bicycles and motor bikes are major causes, with the latter increasing in frequency in developing countries. The estimates that between (1.6 and 3.8) million traumatic brain injuries each year are a result of sports and recreation activities in the US. In children aged two to four, falls are the most common cause of TBI, while in older children bicycle and auto accidents compete with falls for this position. TBI is the third most common injury to result from child abuse. Abuse causes (19%) of cases of pediatric brain trauma, and the death rate is higher among these cases. Domestic violence is another cause of TBI, as are work-related and industrial accidents. Firearms and blast injuries from explosions are other causes of TBI, which is the leading cause of death and disability in war zones. According to Representative Bill Pascrell (Democrat, NJ), TBI is "the signature injury of the wars in Iraq and Afghanistan."
Ricochet of the brain within the skull may account for the “coup-contrecoup phenomenon”.
The type, direction, intensity, and duration of forces all contribute to the characteristics and severity of TBI. Even in the absence of an impact, significant acceleration or deceleration of the head can cause TBI, however in most cases a combination of impact and acceleration is probably to blame.
The violent shaking of an infant that causes shaken baby syndrome commonly manifests as diffuse injury. In impact loading, the force sends shock waves through the skull and brain, resulting in tissue damage. Shock waves caused by penetrating injuries can also destroy tissue along the path of a projectile, compounding the damage caused by (the missile) itself.
Damage may occur directly under the site of impact, or it may occur on the side opposite the impact (coup and contrecoup) injury). When a moving object impacts the stationary head, coup injuries are typical Contrecoup injuries are usually produced when the moving head strikes a stationary object.
Forces involving the head striking or being struck by something, termed contact or impact loading, are the cause of most focal injuries, and movement of the brain within the skull, termed noncontact or inertial loading, usually causes diffuse injuries.
Secondary injury events include damage to the blood–brain barrier, release of factors that cause inflammation, free radical overload, excessive release of the neurotransmitter glutamate (excitotoxicity), influx of calcium and sodium ions into neurons, and dysfunction of mitochondria. Injured axons in the brain's white matter may separate from their cell bodies as a result of secondary injury, often killing those neurons. Other factors in secondary injury are changes in the blood flow to the brain;ischemia (insufficient blood flow); cerebral hypoxia (insufficient oxygen in the brain); cerebral edema (swelling of the brain); and raised intracranial pressure (the pressure within the skull). Intracranial pressure may rise due to swelling or a mass effect from a lesion, such as a hemorrhage.
Magnetic resonance imaging (MRI) can show more detail than CT, and can add information about expected outcome in the long term. It is more useful than CT for detecting injury characteristics .
Neuroimaging helps in determining the diagnosis and prognosis and in deciding what treatments to give. Neuropsychological assessment are performed to evaluate the long-term cognitive sequels and to aid in the planning of the rehabilitation
Omega-3 DHA offers protection against the biochemical brain damage that occurs after a traumatic injury. Rats given DHA prior to induced brain injuries suffered smaller increases in two key markers for brain damage (APP and caspase-3), as compared with rats given no DHA.
It is important to begin emergency treatment within the so-called "golden hour" following the injury.
In the acute stage, the primary aim of the medical personnel is to stabilize the patient and focus on preventing further injury because little can be done to reverse the initial damage caused by trauma. Rehabilitation is the main treatment for the subacute and chronic stages of recovery. International clinical guidelines have been proposed with the aim of guiding decisions in TBI treatment, as defined by an authoritative examination of current evidence.
Certain facilities are equipped to handle TBI better than others; initial measures include transporting patients to an appropriate treatment center. Both during transport and in hospital the primary concerns are ensuring proper oxygen supply, maintaining adequate cerebral blood flow, and controlling raised intracranial pressure (ICP), since high ICP deprives the brain of badly needed blood flow and can cause deadly brain herniation. Other methods to prevent damage include management of other injuries and prevention of seizures.
Physical therapy will commonly include muscle strength exercise.
Once medically stable, patients might be transferred to a subacute rehabilitation unit of the medical center or to an independent rehabilitation hospital. Rehabilitation aims to improve independent function at home and in society and to help adapt to disabilities. A multidisciplinary approach is key to optimising outcome.
Pharmacological treatment can help to manage psychiatric or behavioral problems. Medication is also used to control post-traumatic epilepsy; however the preventive use of anti-epileptics is not recommended. In those cases where the person is bedridden due to a reduction of consciousness, has to remain in a wheelchair because of mobility problems, or has any other problem heavily impacting self-caring capacities, care giving and nursing are critical. Improvement of neurological function usually occurs for two or more years after the trauma. For many years it was believed that recovery was fastest during the first six months, but there is no evidence to support this. It may be related to services commonly being withdrawn after this period, rather than any physiological limitation to further progress. Children recover better in the immediate time-frame and improve for longer periods. Complications are distinct medical problems that may arise because of the TBI. The results of traumatic brain injury vary widely in type and duration; they include physical, cognitive, emotional, and behavioral complications. TBI can cause prolonged or permanent effects on consciousness, such as coma, brain death, persistent vegetative state (in which patients are unable to achieve a state of alertness to interact with their surroundings), and minimally conscious state (in which patients show minimal signs of being aware of self or environment). Lying still for long periods can cause complications including pressure sores, pneumonia or other infections, progressive multiple organ failure, and deep venous thrombosis, which can cause pulmonary embolism. Infections that can follow skull fractures and penetrating injuries include meningitis and abscesses. Complications involving the blood vessels include vasospasm, in which vessels constrict and restrict blood flow, the formation of aneurysms, in which the side of a vessel weakens and balloons out, and stroke.. Movement disorders that may develop after TBI include tremor, ataxia (uncoordinated muscle movements), myoclonus (shock-like contractions of muscles), and loss of movement range and control (particularly with a loss of movement repertoire). The risk of post-traumatic seizures increases with severity of trauma (image at right) and is particularly elevated with certain types of brain trauma such as cerebral contusions or hematomas. People with early seizures, those occurring within a week of injury, have an increased risk of post-traumatic epilepsy (recurrent seizures occurring more than a week after the initial trauma). People may lose or experience altered vision, hearing, or smell.
Hormonal disturbances may occur secondary to hypopituitarism, occurring immediately or years after injury in 10 to 15% of TBI patients. Development of diabetes insipidus or an electrolyte abnormality acutely after injury indicate need for endocrinologic work up. Signs and symptoms of hypopituitarism may develop and be screened for in adults with moderate TBI and in mild TBI with imaging abnormalities. Children with moderate to severe head injury may also develop hypopituitarism. Screening should take place 3 to 6 months, and 12 months after injury.
Cognitive deficits that can follow TBI include impaired attention; disrupted insight, judgement, and thought; reduced processing speed; distractibility; and deficits in executive functions such as abstract reasoning, planning, problem-solving, and multitasking. Memory loss, the most common cognitive impairment among head-injured people, occurs in (20–79%) of people with closed head trauma, depending on severity. People who have suffered TBI may also have difficulty with understanding or producing spoken or written language, or with more subtle aspects of communication such as body language. Post-concussion syndrome, a set of lasting symptoms experienced after mild TBI may include physical, cognitive, emotional and behavioral problems such as headaches, dizziness, difficulty concentrating, and depression. Multiple TBIs may have a cumulative effect. A young person who receives a second concussion before symptoms from another one have healed may be at risk for developing a very rare but deadly condition called second-impact syndrome, where the brain swells catastrophically after even a mild blow, with debilitating or deadly results. About one in five career boxers is affected by chronic traumatic brain injury (CTBI), which causes cognitive, behavioral, and physical impairments. Dementia pugilistica, the severe form of CTBI, primarily affects career boxers, years later. It commonly manifests as dementia, memory problems, and parkinsonism (tremors and lack of coordination) . BI may cause emotional or behavioral problems and changes in personality. These may include emotional instability, depression, anxiety, hypomania, mania, apathy, irritability, and anger. TBI appears to predispose a person to psychiatric disorders including obsessive compulsive disorder, alcohol or substance abuse or dependence, dysthymia, clinical depression, bipolar disorder, phobias, panic disorder, and schizophrenia. Behavioral symptoms that can follow TBI include disinhibition, inability to control anger, impulsiveness, lack of initiative, inappropriate sexual activity, and changes in personality. Different behavioral problems are characteristic of the location of injury; for instance, frontal lobe injuries often result in disinhibition and inappropriate or childish behavior, and temporal lobe injuries often cause irritability and aggression. In patients who have depression after TBI, suicidal ideation is not uncommon; the suicide rate among these persons is increased two to three fold.
TBI also has a substantial impact on the functioning of family systems. Caregiving family members and TBI survivors often significantly alter their familial roles and responsibilities following injury, creating significant change and strain on a family system. Typical challenges identified by families recovering from TBI include: frustration and impatience with one another, loss of former lives and relationships, difficulty setting reasonable goals, inability to effectively solve problems as a family, increased level of stress and household tension, changes in emotional dynamics, and overwhelming desire to return to pre-injury status. Additionally, families may exhibit less effective functioning in areas including coping, problem solving and communication. Psychoeducation and counseling models have been demonstrated to be effective in minimizing family disruption.
TBI is a leading cause of death and disability around the globe and presents a major worldwide social, economic, and health problem. It is the number one cause of coma, it plays the leading role in disability due to trauma and is the leading cause of brain damage in children and young adults . In Europe it is responsible for more years of disability than any other cause. It also plays a significant role in half of trauma deaths. A World Health Organization study estimated that between 70 and 90% of head injuries that receive treatment are mild, and a US study found that moderate and severe injuries each account for 10% of TBIs, with the rest mild.
In the US, the mortality (death) rate is estimated to be 21% by 30 days after TBI. A study on Iraq War soldiers found that severe TBI carries a mortality of 30–50%. Deaths have declined due to improved treatments and systems for managing trauma in societies wealthy enough to provide modern emergency and neurosurgical services. The fraction of those who die after being hospitalized with TBI fell from almost half in the 1970s to about a quarter at the beginning of the 21st century. This decline in mortality has led to a concomitant increase in the number of people living with disabilities that result from TBI.
Biological, clinical, and demographic factors contribute to the likelihood that an injury will be fatal. In addition, outcome depends heavily on the cause of head injury. In the US, patients with fall-related TBIs have an 89% survival rate, while only 9% of patients with firearm-related TBIs survive. In the US, firearms are the most common cause of fatal TBI, followed by vehicle accidents and then falls. Of deaths from firearms, 75% are from suicides. The incidence of TBI is increasing globally, largely due to an increase in motor vehicle use in low and middle income countries .
TBI is present in (85%) of traumatically injured children, either alone or with other injuries. The greatest number of TBIs occur in people aged ( 15–24). Because TBI is more common in young people, its costs to society are high, due to the loss of productive years, to death and disability. The age groups most at risk for TBI are children ages (5-9) and adults over age ( 80), and the highest rates of death and hospitalization due to TBI are in people over age ( 65). The incidence of fall-related TBI in First World countries is increasing as the population ages; thus, the median age of people with head injuries has increased.
Regardless of age, TBI rates are higher in males. I n the 1970s , awareness of TBI as a public health problem grew, and a great deal of progress has been made since then in brain trauma research, such as the discovery of primary and secondary brain injury. The 1990s saw the development and dissemination of standardized guidelines for treatment of TBI, with protocols for a range of issues such as drugs and management of intracranial pressure. Research since the early 1990s has improved TBI survival; that decade was known as the "Decade of the Brain" for advances made in brain research. No medication exists to halt the progression of secondary injury, but the variety of pathological events presents opportunities to find treatments that interfere with the “damage processes” .
Hyperbaric oxygen therapy (HBO) for TBI has remained controversial as studies have looked for improvement mechanisms, for the delivery of the oxygen, and further evidence shows that it may have potential as a treatment.
How can Medical Marijuana help TBI patients?
Natural endogenous cannabinoids are produced in the bodies of humans and some animals. Their main function is to bind to cannabinoid receptors in the body of the organism they came from.
A compound the brain manufactures in response to trauma may be useful as a treatment for complications resulting from brain injury, Israeli researchers report.
“``We believe that this compound, that the brain itself produces, may serve as a neuroprotectant agent,'' lead author Esther Shohami, a professor in the School of Pharmacy at the Hebrew University in Jerusalem, told Reuters Health.
The compound, known as 2-arachidonoyl glycerol (2-AG), is a cannabinoid, a substance the body produces with a similar structure to chemicals found in the cannabis plant, the source of marijuana.
In research published in the October 4th issue of Nature, the investigators found 2-AG at 10 times the normal level in the brains of mice 4 hours after a traumatic injury.
The researchers theorize that the compound somehow helps prevent some of the secondary complications associated with brain injury, possibly by reducing the inflammatory response, slowing the production of a toxic brain chemical or boosting the blood supply to the brain immediately after the injury.
However, the natural amounts the brain cells produce following trauma probably do not reach high enough levels to be effective, Shohami noted.
To investigate the effects of the compound, the researchers synthesized 2-AG and injected it an hour after brain injury had been induced in mice. The mice were evaluated 1, 4 and 7 days after injury.
``We found a tremendous improvement in the recovery of the mice,'' Shohami said, noting that there was less excess fluid causing swelling in the brain, better recovery of motor function, and fewer dead brain cells and brain tissue.
However, the drug's protection against neurological damage was short-lived, with significant effects lasting only a day after treatment.
Shohami said she hopes to eventually investigate the compound on humans who have suffered brain injuries and to extend the timeframe in which the substance could be offered.
``Its administration, as a single injection, should be considered as a novel therapeutic modality,'' she said. ``Since the benefit was achieved by a single administration, I do not expect serious side-effects or toxicity to be a major problem.''
Cannabis & Neuroprotection
Not only has modern science refuted the notion that marijuana is neurotoxic, recent scientific discoveries have indicated that cannabinoids are, in fact, neuroprotective, particularly against alcohol-induced brain damage. In a recent preclinical study -- the irony of which is obvious to anyone who reads it -- researchers at the US National Institutes of Mental Health (NIMH) reported that the administration of the non-psychoactive cannabinoid cannabidiol (CBD) reduced ethanol-induced cell death in the brain by up to 60 percent. "This study provides the first demonstration of CBD as an in vivoneuroprotectant ... in preventing binge ethanol-induced brain injury," the study's authors wrote in the May 2005 issue of the Journal of Pharmacology and Experimental Therapeutics. Alcohol poisoning is linked to hundreds of preventable deaths each year in the United States, according to the Centers for Disease Control, while cannabis cannot cause death by overdose.
(Of course), many US neurologists have known about cannabis' neuroprotective ‘”powers” for years. NIMH scientists in 1998 first touted the ability of natural cannabinoids to stave off the brain-damaging effects of stroke and acute head trauma. Similar findings were then replicated by investigators in the Netherlands, then Italy and, most recently, by Japanese research in 2005. However, attempts to measure the potential neuroprotective effects of synthetic cannabinoid-derived medications in humans have so far been inconclusive.
Cannabis & Cognition
What about claims of cannabis' damaging effect of cognition? A review of the scientific literature indicates that rumors regarding the "stoner stupid" stereotype are unfounded. According to clinical trial data published this past spring in the American Journal of Addictions, cannabis use -- including heavy, long-term use of the drug -- has, at most, only a negligible impact on cognition and memory. Researchers at Harvard Medical School performed magnetic resonance imaging on the brains of ( 22) long-term cannabis users (reporting a mean of (20-100) lifetime episodes of smoking) and (26) controls (subjects with no history of cannabis use). Imaging displayed "no significant differences" between heavy cannabis smokers compared to controls.
Previous trials tell a similar tale. An October 2004 study published in the journal Psychological Medicine examining the potential long-term residual effects of cannabis on cognition in monozygotic male twins reported "an absence of marked long-term residual effects of marijuana use on cognitive abilities." A 2003 meta-analysis published in theJournal of the International Neuropsychological Society also "failed to reveal a substantial, systematic effect of long-term, regular cannabis consumption on the neurocognitive functioning of users who were not acutely intoxicated," and a 2002 clinical trial published in the Canadian Medical Association Journal determined, "Marijuana does not have a long-term negative impact on global intelligence."
Finally, a 2001 study published in the journal Archives of General Psychiatry found that long-term cannabis smokers who abstained from the drug for one week "showed virtually no significant differences from control subjects (those who had smoked marijuana less than 50 times in their lives) on a battery of 10 neuropsychological tests.” Investigators further added, "Former heavy users, who had consumed little or no cannabis in the three months before testing, [also] showed no significant differences from control subjects on any of these tests on any of the testing days."
COUNTERING THE ALLEGATION OF MARIJUANA USE IN THE TBI CLIENT (Legal)
As baby boomers age, the percentage of clients who may have used marijuana has increased (or one could simply have a practice in California). In defense of TBI claims, defense attorneys will latch upon any allegations or proof that the client has or does smoke marijuana. This can come up through direct testimony of the Plaintiff, testimony from friends or relatives, a failed drug test or from medical records.
In most jurisdictions the admissibility of this information would be subject to the balancing test of whether the probative value of such information outweighs the prejudicial effect of such information on the jury. The defense will try to establish that the use of marijuana is relevant because of the following:
• (it) had a downward effect on neuropsychological tests battery results;
• (it) adversely affects the recovery of the client from TBI;.
• (it) adversely affects wage and job aspects of the claim.
However, recent medical research can be cited by the Plaintiffs to suggest that the active ingredient in marijuana “cannabinoids” are now thought to play an important role in actually protecting the brain from neuro-trauma following injury. The research cited below should be used to offset the mild amount of research that can be thrown towards the Plaintiff to suggest decreased recovery or test results due to occasional marijuana use. If other (Plaintiff or defense) physicians have the research cited below, they can address the possible protective effects of the marijuana use and thus neutralize or take away the defenses ability to have the whole issue become admissible at trial. The research is as follows:
• “Endocannabinoids and Traumatic Brain Injury” (Mechoulam, R 2007). This study showed that there are various neuro-protective effects of cannabinoids.
• “The Therapeutic Potential of the Cannabinoids in Neuroprotection” (Grundy RI, 2002). The study cites the ability of cannabinoids to modulate neurotransmission and to act as anti-inflammatory and antioxidative agents. Both post : trauma inflamation and post traumatic oxidation are methods of secondary brain injury following the acute phase.
• “Therapeutic Potential of Cannabinoids in CNS Disease” (Croxford JL, 2003). This study found that evidence suggest cannabinoids may prove useful in Parkinson’s disease in that dexanadinol (HU-211), a synthetic cannabinoid, is currently being assessed in clinical trial for traumatic brain injury and stroke.
• “Cannabinoids as Therapeutic Agents for Ablating Neuroinflammatory Disease” (Cabral GA et al. 2008). Studying the early phases of post traumatic brain inflammation they noted that the cannabinoids receptor system may prove therapeutically manageable in reducing neuropathogenic disorders including closed head injuries.
Using some of the above research, a ( Motions in Limine) should be drafted to exclude any reference to marijuana use, arguing that any “adverse” consequence of use, is countered by its possible “benefit” and that the whole issue is based upon criminalizing the plaintiff.
Research has begun to accumulate over the past few years showing that cannabinoids are neuroprotective against brain injury resulting from toxins, hypoxia, and head trauma. Cannabinoids are, loosely, chemicals that are similar in structure to the psychoactive components in cannabis and/or chemicals that activate the cannabinoid receptor system in the body. Researchers have found protective effects not only from the plant-derived cannabinoids such as THC, but also from endogenous cannabinoids (those occurring naturally in the body, such as anandamide) and some synthetic pharmaceutical cannabinoids.
The research with the cannabis-source cannabinoids, conducted in mice, rats, and in vitro, has shown remarkable effectiveness in reducing brain damage from injected toxins, hypoxia, and head trauma. Other research has found that anandamide levels in the brains of rats naturally rise after brain injury or death and the cannabinoid system may play a primary role in limiting brain damage.
Because psychoactivity is considered an unwanted side effect, much of the current research is being done with synthetic cannabinoid system agonists. One synthetic cannabinoid, Dexanabinol (HU-211), is already in (phase 3) trials (medium scale, involving humans) headed towards governmental approval as a neuroprotective pharmaceutical. Research conducted in Israel that gave 67 patients with serious head trauma either Dexanabinol or placebo confirms similar research in rats showing reduced damage and faster recovery among those receiving the cannabinoids. Although other promising head trauma treatments have failed in the demanding and complex (phase 3) research trials, many interested in the field of neuroinjury are excited about the findings to date.
The mechanisms by which the cannabinoids reduce damage from both toxic and traumatic injury to the brain are not fully understood. Although some researchers have suggested that the cannabinoids may offer protection through a strong antioxidant effect, this is now considered unlikely to account for much of the protection, since cannabinoid-receptor antagonists block the beneficial effects and the doses of the cannabinoids given are very low.
Perhaps the current best guess for how these chemicals provide their protective effects is that their general dampening of neural activity reduces excitotoxicity (damage caused by overly excited neurons). One of the
specific ways this happens is through the inhibition of the glutamate system in the brain. The glutamatergic neurons are part of the excitatory system in the brain; inhibiting glutamate reduces the activity of other neurons. At least in some parts of the brain, activation of the CB1 cannabinoid receptor (a specific type of cannabinoid receptor) was shown to block pre-synaptic release of glutamate. CB1 receptor activation is known to inhibit certain calcium channels, directly reducing the production of nitric oxide and other potentially damaging reactive oxygen agents.
1. ^ a b Rehman T, Ali R, Tawil I, Yonas H (2008). "Rapid progression of traumatic bifrontal contusions to transtentorial herniation: A case report".Cases journal 1 (1): 203. doi:10.1186/1757-1626-1-203. PMC 2566562. PMID 18831756.
2. ^ a b c d e f g h i j k l m n o p q r s t u v w x y Maas AI, Stocchetti N, Bullock R (August 2008). "Moderate and severe traumatic brain injury in adults".Lancet Neurology 7 (8): 728–41. doi:10.1016/S1474-4422(08)70164-9. PMID 18635021.
3. ^ a b c d e f g h i j k l m n o Parikh S, Koch M, Narayan RK (2007). "Traumatic brain injury". International Anesthesiology Clinics 45 (3): 119–35.doi:10.1097/AIA.0b013e318078cfe7. PMID 17622833.
4. ^ Chapman SB, Levin HS, Lawyer SL (1999). "Communication problems resulting from brain injury in children: Special issues of assessment and management". In McDonald S, Togher L, Code C. Communication Disorders Following Traumatic Brain Injury. East Sussex: Psychology Press. pp. 235–36. ISBN 0-86377-724-4. Retrieved 2008-11-13.
5. ^ a b Collins C, Dean J (2002). "Acquired brain injury". In Turner A, Foster M, Johnson SE. Occupational Therapy and Physical Dysfunction: Principles, Skills and Practice. Edinburgh: Churchill Livingstone. pp. 395–96. ISBN 0-443-06224-2. Retrieved 2008-11-13.
6. ^ a b Blissitt PA (September 2006). "Care of the critically ill patient with penetrating head injury". Critical Care Nursing Clinics of North America 18 (3): 321–32. doi:10.1016/j.ccell.2006.05.006. PMID 16962454.
7. ^ a b c d e f g h i Hannay HJ, Howieson DB, Loring DW, Fischer JS, Lezak MD (2004). "Neuropathology for neuropsychologists". In Lezak MD, Howieson DB, Loring DW. Neuropsychological Assessment. Oxford [Oxfordshire]: Oxford University Press. pp. 158–62. ISBN 0-19-511121-4.
8. ^ a b c Jennett B (May 1998). "Epidemiology of head injury". Archives of Disease in Childhood 78 (5): 403–06. doi:10.1136/adc.78.5.403.PMC 1717568. PMID 9659083.
9. ^ McCaffrey RJ (1997). "Special issues in the evaluation of mild traumatic brain injury". The Practice of Forensic Neuropsychology: Meeting Challenges in the Courtroom. New York: Plenum Press. pp. 71–75. ISBN 0-306-45256-1.
10. ^ a b LaPlaca et al. (2007). p.16
11. ^ Weber JT, Maas AIR (2007). Weber JT. ed. Neurotrauma: New Insights Into Pathology and Treatment. Amsterdam: Academic Press. p. xi.ISBN 0444530177. Retrieved 2008-11-12.
12. ^ a b c d Saatman KE, Duhaime AC et al. Workshop Scientific Team and Advisory Panel Members (2008). "Classification of traumatic brain injury for targeted therapies". Journal of Neurotrauma 25 (7): 719–38. doi:10.1089/neu.2008.0586. PMC 2721779. PMID 18627252.
13. ^ a b c Department of Defense and Department of Veterans Affairs (2008). "Traumatic Brain Injury Task Force".http://www.cdc.gov/nchs/data/icd9/Sep08TBI.pdf.
14. ^ Marion (1999). p.4.
15. ^ a b c d e f g h i j k l m n o p Valadka AB (2004). "Injury to the cranium". In Moore EJ, Feliciano DV, Mattox KL. Trauma. New York: McGraw-Hill, Medical Pub. Division. pp. 385–406. ISBN 0-07-137069-2. Retrieved 2008–08–15.
16. ^ Hayden MG, Jandial R, Duenas HA, Mahajan R, Levy M (2007). "Pediatric concussions in sports: A simple and rapid assessment tool for concussive injury in children and adults". Child's Nervous System 23 (4): 431–435. doi:10.1007/s00381-006-0277-2. PMID 17219233.
17. ^ Seidenwurm DI (2007). "Introduction to brain imaging". In Brant WE, Helms CA. Fundamentals of Diagnostic Radiology. Philadelphia: Lippincott, Williams & Wilkins. pp. 53–55. ISBN 0-7817-6135-2. Retrieved 2008-11-17.
18. ^ a b c Smith DH, Meaney DF, Shull WH (2003). "Diffuse axonal injury in head trauma". Journal of Head Trauma Rehabilitation 18 (4): 307–16.doi:10.1097/00001199-200307000-00003. PMID 16222127.
19. ^ Granacher (2007). p.32.
20. ^ Kraus, M.F.; Susmaras,T., Caughlin, B.P., Walker, C.J., Sweeney, J.A., & Little, D.M. (2007). "White matter integrity and cognition in chronic traumatic brain injury: A diffusion tensor imaging study.". Brain 130 (10): 2508–2519. doi:10.1093/brain/awm216. PMID 17872928.
21. ^ Kumar, R.; Husain M, Gupta RK, Hasan KM, Haris M, Agarwal AK, Pandey CM, Narayana PA (Feb 2009). "Serial changes in the white matter diffusion tensor imaging metrics in moderate traumatic brain injury and correlation with neuro-cognitive function.". Journal of Neurotrauma 26 (4): 481–495. doi:10.1089/neu.2008.0461. PMID 19196176.
22. ^ a b Melvin JW, Lighthall JW (2002). Nahum AM, Melvin JW. ed. Accidental Injury: Biomechanics and Prevention. Berlin: Springer. pp. 280–81.ISBN 0-387-98820-3. Retrieved 2008-11-15.
23. ^ McCrea, M. (2007). Mild Traumatic Brain Injury and Postconcussion Syndrome: The New Evidence Base for Diagnosis and Treatment (American Academy of Clinical Neuropsychology Workshop Series). New York: Oxford University Press. ISBN 978-0195328295 ISBN 0195328299.
24. ^ a b c Mattson, A. J.; Levin, H.S. (1990). "Frontal lobe dysfunction following closed head injury. A review of the literature.". Journal of Nervous & Mental Disorders 178 (5): 282–291. doi:10.1097/00005053-199005000-00002.
25. ^ Bayly, P.V.; Cohen, T. S., Leister, E. P., Ajo, D., Leuthardt, E. C., & Genin, G. M. (2005). "Deformation of the human brain induced by mild acceleration.". Journal of Neurotrauma 22 (8): 845–856. doi:10.1089/neu.2005.22.845. PMC 2377024. PMID 16083352.
26. ^ a b Cummings, J.L. (1993). "Frontal-subcortical circuits and human behavior.". Archives of Neurology 50 (8): 873–880. PMID 8352676.
27. ^ a b c McDonald, S.; Flanagan, S., Rollins, J., & Kinch, J (2003). "TASIT: A new clinical tool for assessing social perception after traumatic brain injury.". Journal of Head Trauma Rehabilitation 18 (3): 219–238. PMID 12802165.
28. ^ Basso A, Scarpa MT (December 1990). "Traumatic aphasia in children and adults: a comparison of clinical features and evolution". Cortex 26 (4): 501–14. PMID 1706973.
29. ^ Mohr JP, Weiss GH, Caveness WF, et al. (December 1980). "Language and motor disorders after penetrating head injury in Viet Nam". Neurology30 (12): 1273–9. PMID 7192808.
30. ^ a b c d e f g h Hardman JM, Manoukian A (2002). "Pathology of head trauma". Neuroimaging Clinics of North America 12 (2): 175–87, vii.doi:10.1016/S1052-5149(02)00009-6. PMID 12391630. "TBI is highest in young adults aged 15 to 24 years and higher in men than women in all age groups.".
31. ^ a b Barkley JM, Morales D, Hayman LA, Diaz-Marchan PJ (2006). "Static neuroimaging in the evaluation of TBI". In Zasler ND, Katz DI, Zafonte RD.Brain Injury Medicine: Principles and Practice. Demos Medical Publishing. pp. 140–43. ISBN 1-888799-93-5.
32. ^ a b c d e f g h Ghajar J (September 2000). "Traumatic brain injury". Lancet 356 (9233): 923–29. doi:10.1016/S0140-6736(00)02689-1.PMID 11036909.
33. ^ a b Arlinghaus KA, Shoaib AM, Price TRP (2005). "Neuropsychiatric assessment". In Silver JM, McAllister TW, Yudofsky SC. Textbook Of Traumatic Brain Injury. Washington, DC: American Psychiatric Association. pp. 63–65. ISBN 1-58562-105-6.
34. ^ a b c d e "NINDS Traumatic Brain Injury Information Page". National Institute of Neurological Disorders and Stroke. 2008-09-15. Retrieved 2008-10-27.
35. ^ a b Kushner D (1998). "Mild traumatic brain injury: Toward understanding manifestations and treatment". Archives of Internal Medicine 158 (15): 1617–24. doi:10.1001/archinte.158.15.1617. PMID 9701095.
36. ^ a b Stone, V.E.; Baron-Cohen, S., & Knight, R.T. (1998). "Frontal lobe contributions to theory of mind.". Journal of Cognitive Neuroscience 10 (5): 640–656. doi:10.1162/089892998562942. PMID 9802997.
37. ^ a b Kim, E. (2002). "Agitation, aggression, and disinhibition syndromes after traumatic brain injury.". NeuroRehabilitation 17 (4): 297–310.PMID 12547978.
38. ^ Busch, R. M.; McBride, A., Curtiss, G., & Vanderploeg, R. D. (2005). "The components of executive functioning in traumatic brain injury.". Journal of Clinical and Experimental Neuropsychology 27 (8): 1022–1032. doi:10.1080/13803390490919263. PMID 16207623.
39. ^ a b Ponsford, J.; K. Draper, and M. Schonberger (2008). "Functional outcome 10 years after traumatic brain injury: its relationship with demographic, injury severity, and cognitive and emotional status.". Journal of the International Neuropsychological Society 14 (2): 233–242.doi:10.1017/S1355617708080272. PMID 18282321.
40. ^ Williams C, Wood RL (March 2010). "Alexithymia and emotional empathy following traumatic brain injury". J Clin Exp Neuropsychol 32 (3): 259–67.doi:10.1080/13803390902976940. PMID 19548166.
41. ^ a b Milders, M.; Fuchs, S., & Crawford, J. R. (2003). "Neuropsychological impairments and changes in emotional and social behaviour following severe traumatic brain injury.". Journal of Clinical & Experimental Neuropsychology 25 (2): 157–172. doi:10.1076/jcen.22.214.171.12442.
42. ^ Ownsworth, T.; Fleming, J. (2005). "The relative importance of metacognitive skills, emotional status, and executive function in psychosocial adjustment following acquired brain injury.". Journal of Head Trauma Rehabilitation 20 (4): 315–332. doi:10.1097/00001199-200507000-00004.PMID 16030439.
43. ^ Dahlberg, C.A.; Cusick CP, Hawley LA, Newman JK, Morey CE, Harrison-Felix CL, & Whiteneck GG. (2007). "Treatment efficacy of social communication skills training after traumatic brain injury: A randomized treatment and deferred treatment controlled trial.". Archives of Physical Medicine & Rehabilitation 88 (12): 1561–1573. doi:10.1016/j.apmr.2007.07.033. PMID 18047870.
44. ^ a b c d e f g Salomone JP, Frame SB (2004). "Prehospital care". In Moore EJ, Feliciano DV, Mattox KL. Trauma. New York: McGraw-Hill, Medical Pub. Division. pp. 117–8. ISBN 0-07-137069-2. Retrieved 2008-08-15.
45. ^ a b "Signs and Symptoms". Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. 2007-07-07. Retrieved 2008-10-27.
46. ^ Langlois JA, Rutland-Brown W, Wald MM (2006). "The epidemiology and impact of traumatic brain injury: A brief overview". Journal of Head Trauma Rehabilitation 21 (5): 375–8. doi:10.1097/00001199-200609000-00001. PMID 16983222.
47. ^ a b Reilly P (2007). "The impact of neurotrauma on society: An international perspective". In Weber JT. Neurotrauma: New Insights Into Pathology and Treatment. Amsterdam: Academic Press. pp. 5–7. ISBN 0444530177. Retrieved 2008-11-10.
48. ^ a b c d "Traumatic brain injury". Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. 2007. Retrieved 2008-10-28.
49. ^ Granacher (2007). p.16.
50. ^ Hunt JP, Weintraub SL, Wang YZ, Buetcher KJ (2004). "Kinematics of trauma". In Moore EJ, Feliciano DV, Mattox KL. Trauma. New York: McGraw-Hill, Medical Pub. Division. p. 153. ISBN 0-07-137069-2. Retrieved 2008-08-15.
51. ^ a b Elovic E, Zafonte R (2005). "Prevention". In Silver JM, McAllister TW, Yudofsky SC. Textbook of Traumatic Brain Injury. Washington, DC: American Psychiatric Association. p. 740. ISBN 1-58562-105-6.
52. ^ Bay E, McLean SA (February 2007). "Mild traumatic brain injury: An update for advanced practice nurses". Journal of Neuroscience Nursing 39 (1): 43–51. PMID 17396538.
53. ^ a b Comper P, Bisschop SM, Carnide N, et al. (2005). "A systematic review of treatments for mild traumatic brain injury". Brain Injury 19 (11): 863–880. doi:10.1080/02699050400025042. PMID 16296570.
54. ^ The Lancet, (December 2007). "Grappling with traumatic brain injury". Lancet 370 (9603): 1879. doi:10.1016/S0140-6736(07)61785-1.PMID 18068492.
55. ^ a b c d e f g h i j Park E, Bell JD, Baker AJ (April 2008). "Traumatic brain injury: Can the consequences be stopped?". Canadian Medical Association Journal 178 (9): 1163–70. doi:10.1503/cmaj.080282. PMC 2292762. PMID 18427091.
56. ^ "Pentagon Told Congress It’s Studying Brain-Damage Therapy". ProPublica. Retrieved 2011-01-23. "Brave Americans who risked everything for their country and sustained traumatic brain injuries -- the signature injury of the wars in Iraq and Afghanistan -- deserve cognitive rehabilitation therapy to help them secure the best futures possible. It is unacceptable that the United States has been at war for nearly a decade and there is still no plan to treat these soldiers."
57. ^ a b Shaw NA (2002). "The neurophysiology of concussion". Progress in Neurobiology 67 (4): 281–344. doi:10.1016/S0301-0082(02)00018-7.PMID 12207973.
58. ^ American Academy of Pediatrics: Committee on Child Abuse and Neglect (July 2001). "Shaken baby syndrome: Rotational cranial injuries. Technical report". Pediatrics 108 (1): 206–10. doi:10.1542/peds.108.1.206. PMID 11433079.
59. ^ Morrison AL, King TM, Korell MA, Smialek JE, Troncoso JC (1998). "Acceleration-deceleration injuries to the brain in blunt force trauma".American Journal of Forensic Medical Pathology 19 (2): 109–112. doi:10.1097/00000433-199806000-00002. PMID 9662103.
60. ^ Poirier MP (2003). "Concussions: Assessment, management, and recommendations for return to activity (abstract)". Clinical Pediatric Emergency Medicine 4 (3): 179–185. doi:10.1016/S1522-8401(03)00061-2.
61. ^ Sauaia A, Moore FA, Moore EE, et al. (February 1995). "Epidemiology of trauma deaths: A reassessment". The Journal of Trauma 38 (2): 185–93.doi:10.1097/00005373-199502000-00006. PMID 7869433.
62. ^ a b Narayan RK, Michel ME, Ansell B, et al. (May 2002). "Clinical trials in head injury". Journal of Neurotrauma 19 (5): 503–57.doi:10.1089/089771502753754037. PMC 1462953. PMID 12042091.
63. ^ Xiong Y, Lee CP, Peterson PL (2000). "Mitochondrial dysfunction following traumatic brain injury". In Miller LP and Hayes RL, eds. Co-edited by Newcomb JK. Head Trauma: Basic, Preclinical, and Clinical Directions. New York: John Wiley and Sons, Inc.. pp. 257–80. ISBN 0-471-36015-5.
64. ^ Scalea TM (2005). "Does it matter how head injured patients are resuscitated?". In Valadka AB, Andrews BT. Neurotrauma: Evidence-based Answers to Common Questions. Thieme. pp. 3–4. ISBN 3131307811.
65. ^ Morley EJ, Zehtabchi S (September 2008). "Mannitol for traumatic brain injury: Searching for the evidence". Annals of Emergency Medicine 52 (3): 298–300. doi:10.1016/j.annemergmed.2007.10.013. PMID 18763356.
66. ^ a b c d e f g h i j k Zink BJ (March 2001). "Traumatic brain injury outcome: Concepts
67. Aizenstein HJ, Nebes RD, Saxton JA, Price JC, Mathis CA, Tsopelas ND, Ziolko SK, James JA, Snitz BE, Houck, PR, Bi W, Cohen AD, 2008 Frequent Amyloid Deposition Without Significant Impairment Among the Elderly, Arch Neurol, 65 (11) 150.
68. (References: Lack of hippocampal volume change in long-term heavy cannabis users. American Journal of Addictions. 2005 | Neuropsychological consequences of regular marijuana use: a twin study. Psychological Medicine. 2004 | Non-acute (residual) neurocognitive effects of cannabis use: A meta-analytic study. Journal of the International Neuropsychological Society. 2003 | Current and former marijuana use: preliminary findings of a longitudinal study of effects on IQ in young adults. Canadian Medical Association Journal. 2002 | Neuropsychological Performance in Long-term Cannabis Users. Archives of General Psychiatry. 2001)