I. BE AWARE OF THE NEW BRAIN PARADIGM
Brain research in the last forty-years has culminated in earth shaking changes as to how we understand and describe the brain and brain injury. The old paradigm: you are born with x number of brain cells and as you age you lose them. The new paradigm: the brain is constantly shifting both its structure and efficiency based upon environmental factors that go on during our lives resulting in the fact that “you make your own brain.” Three important concepts are central to these momentous changes in how we understand the brain and are of particular relevance to brain injury litigators. They are as follows:
Neuroplasticity can be defined as the process by which the brain produces more morphological changes in response to environmental stimuli – these changes may be positive or negative. Neuroplasticity occurs during our lifetime and, of course, occurs after injury.
The ability of the human brain to grow new and replace neurons on the brain was only fully proven in 1998. We now know that the hippocampus, as the source of short term memory, continues to send out adult stem cells (called neuronal progenitive cells) throughout the lifetime. We now know that the subventricular zone (SVZ) in the adult brain continues to produce stem cells and new neurons throughout life (Curtis AM et al, 2011).
The concept of cognitive reserve describes how the two concepts above can create either a strong or weak cushion or buffer against the ravages of the brain in old age through poor health, dementia and Alzheimers. Cognitive reserve (hereafter CR) can be built up or lost during our life time. Thus, the protection against early dementia or Alzheimers can ebb and flow according to lifestyle and health.
The brain, we now know, is active, not static and the amount and quality of neuroplasticity and neurogenesis that go on in the brain can be positively or negatively effected by many factors to be discussed below.
II. WHY IS THIS IMPORTANT?
These concepts are extraordinarily important and are integral to the accurate and just assessment of your clients future medical and social needs. To ignore these concepts in a case involving virtually any objective injury seen on MR or DTI, would represent a significant loss to your client. Why do I say this?
- Cognitive reserve or CR represents protection against future senility. There are two types of CR. The first is “passive cognitive reserve”, or brain reserve which simply represents an assessment of the amount of neuronal and other brain tissue a person has when they go into an accident or injury. Large head circumference and larger brains are associated with greater resilience against cognitive impairment (Perneczky R, et al., 2010; Kesler SR, et al. 2003). Remember, for a brain lesion to even show up on MRI indicates the loss of approximately 250 thousand neurons with connections to other neurons totaling one billion. “Active cognitive reserve” is the level at which one has worked out and exercised the brain through their lifetime and lifestyle. Under the simplistic expression, “use it or lose it” we now know that high levels of education, high levels of complex cognitive jobs, social interaction and other factors give rise to higher levels of “active cognitive reserve”. Unfortunately, as we will see, TBI causes a loss of both passive CR and active CR and does so through negative neuroplasticity and negative neurogenesis.
- TBI as a lifelong chronic disease is a concept you should embrace and argue. As I will show below, current research clearly shows that the effects of TBI are ongoing and life altering and thus can be deemed to represent a chronic disease.
- The defense is going to eventually latch onto the concepts of neurogenesis and neuroplasticity to argue that “The patient has rewired around the injury and they are fine”. You must use the arguments below to counter this assertion. You must also realize that a human whose brain has “rewired” around millions of broken wires emerges from that rewiring as a different person. So yes, they have been rewired but no, as spouses and family members will inevitably tell you, the survivor of TBI is not the same person they were.
III. POSITIVE AND NEGATIVE NEUROPLASTICITY AND NEUROGENESIS:
The factors that I will discuss below are now known to affect both neuroplasticity and neurogenesis in approximately the same ways. Thus, cognitive reserve would be likewise affected by the factors that are outlined here. “Negative Neuroplasticity” means that something in the environment of that individual is creating, not in a beneficial environment to the ongoing function and physical structure of the brain, but factors exist that are actually causing atrophy in the brain, a reduced number of dendrites connecting between neurons, and unfavorable level in types of neurotransmitters, and other factors. The result is that the brain over time shrinks, becomes less efficient, is less protected and is essentially older than it otherwise would be.
What are the factors that do this?
FACTORS PROMOTING NEGATIVE NEUROPLASTICITY:
Poor sleep: Poor sleep has been shown to contribute to poor memory consolidation and cognition (Tworoger, SS, et al. 2006 ). Sleep wake cycle disturbance (SWCD) is common in TBI victims (Makley MJ, et al., 2008). In fact, incidences of diabetes in middle aged men have been related to sleep disturbance (Nilsson PM, et al., 2004).
Mood disorders: It has been shown that neuroplasticity is disrupted by mood disorders and chronic stress. Hippocampal atrophy has been repeatedly documented from major depression (Pittenger C, et al., 2008). The increased cortisol levels, anxiety (Bierman EJ, et al. 2008)
Substance abuse: Alcohol use and substance abuse have been shown to result in poor cognitive functioning as well as an increased risk of dementia later in life (Medina KL et al. 2007). Nicotine (Abrous DN et al. 2002), opiates (Eisch AJ, et al. 2006) methamphetamine (Hildebrandt K, et al. 1999) cocaine (Yamaguchi M, et al. 2004) have all been shown to suppress adult hippocampal neurogenesis.
Other factors: Diabetes, lowered socioeconomic status (SES) (Settler C, et al., 2012) was found to reduce the risk of mild cognitive impairment and Alzheimers disease. It is felt that the anxiety provoked by a lowering of socioeconomic status results in higher levels of cortisol in the system chronically, which has adverse effects on the brain and cognitive functioning. High blood pressure, likewise, increases the risk of ischemic vessel disease, micro strokes and loss of brain white matter with aging.
FACTORS PROMOTING POSITIVE NEUROPLASTICITY:
Education levels: The most important factor in all studies points back to the level as the single most protected lifestyle factor of all. Therefore, if you have a client whose future was that of college or graduate school, based upon history, and that is taken away, it is significant. Likewise, any argument that your client who has already completed college or graduate school prior to injury will “carry that protection throughout their life” is misplaced. The change in lifestyle following the injury will wipe out the advantage brought by the earlier, higher education (e.g., Whalley LJ, et al. 2008).
Stimulating environment and vocation: Having a stimulating environment promotes neurogenesis in the dentate gyrus (Brown et al., 2003; van Praag, et al., 2005) environmental enrichment can prevent or slow down the accumulation of Alzheimers pathology (Lazarof O, et al., 2005). Likewise an improvised or monotonous environment is detrimental. Social ties and richness of a persons environment protected against impaired cognition after a stroke (Glymour MM, et al., 2008).
Physical exercise: Many studies have shown that physical exercise greatly promotes neurogenesis and positive neuroplasticity in both humans and animals (Gomez-Pinilla F, and Gomez AG, 2011).
Intellectual pursuits: A study by Grant and Brody, 2004, showed that adults who had musical training and experience, such as former or current orchestra members were significantly less likely to develop dementia and had a later onset of Alzheimers. Even something as simple as learning to juggle has been seen to promote the growth of gray matter in the hippocampus on MRI (Boyke J et al., 2008).
IV. TBI AND NEGATIVE NEUROPLASTICITY/NEUROGENESIS:
How can we talk about TBI as a chronic disease? As the list below will indicate, unfortunately, survivors of TBI will almost all experience a lifetime suppression of neuroplasticity and neurogenesis because of their injuries, resulting in lower lifetime levels of cognitive functioning.How do we show this? Your neuro-psychologist, neurologist, psychiatrist or other experts can point out the following:
Negative personality changes: Frontal lobe injuries, the most common injuries that we see, almost always make the victim less adept socially. Social interactions are extraordinarily complex and we take them for granted. Injury to the frontal lobe creates barriers to successful social integration and success, and often leads to isolation or development of a loner “personality”. This obviously leads to a less enriched environment and negative neuroplasticity. Frontal lobe injury also reduces ones ability to “initiate” activity, resulting in a less rich and varied environment over a lifetime. TBI survivors have an extraordinary increased rate of anxiety and depression, also leading to negative neuroplasticity.
Decreased or nonexistent vocations/education: The inability to complete school or college represents an extraordinarily negative blow to a lifetime of positively shaping your clients brain. It goes hand and hand with reduced vocational enriching opportunities for a lifetime.
Reduced socioeconomic status: TBI always reduces SES. Whether it is from vocational, educational, or personality change issues, TBI victims always move down the socioeconomic ladder. This increases stress and anxiety as it does in hundreds of animal studies as well. Cortisol is destructive and the increased level of anxiety decreases mortality for many known reasons.
Decreased exercise: Many TBI victims are unable to exercise on their own, go outside, or participate in common exercise activities.
Increased rates of abuse: Because of the effects of “disinhibition” TBI victims face reduced resistance to drugs, alcohol, cigarettes, gambling, and any number of other vises. These all lead to negative outcomes for the brain.
V. UTILIZING REDUCED CR IN YOUR CASE:
- If your client has objective lesions of any kind on MRI, then it is indisputable that some cognitive reserve has been lost. How big and what number of lesions does your client have? We know that there are 15 million neurons per square centimeter, so even the smallest area observable on MRI (1mm)would contain between 200,000 and a million neurons. In cases of diffuse axonal injury there could be hundreds of these micro lesions in the brain, then try to calculate the interconnectivity of this loss and dendrites lost and you quickly get into many, many billions of lost connections.
- Your client has lost his or her life raft of CR because of the accident. Your client “earned” the CR through leading a good life full of education and social ties. That protection has been taken away.Your clients previous ability to combat the brain injury through active CR has been taken away. Not only will he be less able to cope with and recover from the brain injury itself (passive CR), but his diminished active CR makes him more susceptible to oncoming dementia or Alzheimer.
- Your neurologist should be able to say as an expert or treater, that reduced CR will more likely than not make your client more susceptible to dementia and Alzheimer in the future. They should also be able to say that because of the injury and reduced CR more likely than not dementia and Alzheimer will strike during the persons 40’s or 50’s rather than late 60’s or 70’s. Neurodegenerative diseases have been described as “advanced aging”. The public is aware of NFL players who have suffered an aging brain because of trauma. Use the empathic argument that your client has been aged involuntarily.
- It has also been established that CR provides protection (e.g., reduced CR) against the onset of psychiatric disorders. There has been a long established association between premorbid IQ and schizophrenia. A lower childhood IQ was associated with an increased risk of developing schizophrenia, adult depression, adult anxiety, all with longer persistence (Koenen KC, et al., 2009). Your client not only has a TBI injury and an ongoing CR deficit, but now has to go into the future wide open to the horrors of mental illness.
- Strangely, many defense doctors do not fully appreciate the ramifications of the loss of CR. Therefore, in your depositions with them you can have them agree to the concept fairly easily. If there are objective signs of injury on MR, the IME doctors will have to agree with you that there have been a loss of passive CR. Then go through the various aspects of active CR which have been and will be diminished in your client, and you should do well.
- Give this information to your life care planner. The loss of CR may require a plan for future medical expenses which includes part time care, followed by years of full time nursing home or nursing care, which will add millions of dollars to your life care plan.
- Another way to look at CR is that the permanent reductions through change of lifestyles for the rest of your clients life represent a form of ongoing brain damage. The brain is now being called the “social brain” by a number of commentators simply because we now know how vastly important social ties and human contact are to the continuing healthy brain. All the factors of TBI represent an ongoing brain injury for your client for his life expectancy.
VI. NO INSURANCE AVAILABLE!
The client has suffered an injury seen on MRI and suffers from memory problems. Right there – no long term (nursing home) health insurance policy will ever be written for them, and, in fact, the first page of all applications states “go no further” if you answer “yes” to having a brain injury. Have your client make multiple applications through a single broker and list the broker as a witness. Those who truly need the insurance, are not able to get it.
Abrous DN, Adriani W, Montaron MF, Aurousseau C, Rougon G, LeMoal M, and Piazza PV. Nicotine Self Administration Impairs Hippocampal Plasticity J. Neurosci. 22, 3656- 3662 (2002).
Bierman EJ, Comijus HC, Rijmen F, Jonker C & Beekman AT. Anxiety Symptoms and Cognitive Performance in Later Life: Results from the Longitudinal Aging Study Amsterdam Aging & Mental Health, 12, 517-523 (2008).
Boyke J, Driemeyer J, Gaser C, Buchel C, & May A. Training-induced Brain Structure Changes in the Elderly Journal of Neuroscience, 28, 7031-7035 (2008).
Brown J, Cooper-Kuhn CM, Kemperman G, van Praag H, Winkler J. Gage FH. Enriched Environment and Physical Activity Stimulate Hippocampal but not Olfactory Bulb Neurogenesis European Journal of Neuroscience 17:2042-2046 (2003).
Curtis MA, Monica Kam and Richard L.M. Faull, Neurogenesis in Humans European Journal of Neuroscience Vol 33, pp. 1170-1174, 2011.
Eisch AJ, and Harburg GC. Opiates, Psychostimulatants, and Adult Hippocampal Neurogenesis: Insights for Addiction and Stem Cell Biology Hippocampus 16, 271- 286 (2006).
Glymour MM, Jennifer Weuve, Martha E. Fay, Thomas Glass, Kisa F. Berkman. Social Ties and Cognitive Recovery after Stroke: Does Social Integration Promote Cognitive Resilience? Neuroepidemiology 31:10-20 (June 2008).
Gomez-Pinilla F, and Gomez AG. The Influence of Dietary Factors in Central Nervous System Plasticity and Injury Recovery PM R. 2011 June; 3(6 Suppl): S111-S116. doi:10.1015/j-pmrj.2011.03.001.
Grant MD & Brody JA. Musical Experience and Dementia Hypothesis Aging Clinical and Experimental Research, 15, 403-405 (2004).
Hildebrandt K, Teuchert-Noodt G, and Dawirs RR. A Single Neonatal Dose of Methamphetamine Suppresses Dentate Granule Cell Proliferation in Adult Gerbils Which is Restored to Control Values by Acute Doses of Haloperidol J. Neural Transm., 106, 549-558 (1999).
Kesler SR, Heather F. Adams, Christine M. Blasey, Erin D. Bigler. Premobid Intellectual Functioning, Education, and Brain Size in Traumatic Brain Injury: An Investigation of the Cognitive Reserve Hypothesis. Applied Neuropsychology Vol. 10, No.3, 153-162 (2003).
Koenen KC, PhD, Terrie E. Moffitt, PhD, Andrea L. Robers, PhD., Laurie T. Martin, ScD, MPH, Laura Kubzansky, PhD, HonaLee Harrington, BA, Richie Poulton, PhD, and Avshalom Caspi, PhD. Childhood IQ and Adult Mental Disorders: A Test of the Cognitive Reserve Hypothesis Am J. Psychiatry 166(1):50-57 (January 2009).
Lazarov O, Robinson J. Tang, YP, Hairston IS, Korade-Mirnics Z, Lee VM, et al. Environmental Enrichment Reduces Abeta Levels and Amyloid Deposition in Transgenic Mice Cell 120:701-13 (2005).
Makley MJ, English JB, Druback DA, Kreuz AJ, Celnik PA, Tarwater PM., Prevalence of Sleep Disturbance in Closed Head Injury Patients in Rehabilitation Unit Neurorehabil Neural Repair, 2008 Jul-Aug; 22(4):341-7.
Medina KL, Schweinsburg AD, Cohen-Zion M, Nagel BJ & Tapert SF. Effects of Alcohol and Combined Marijuana and Alcohol Use During Adolescence on Hippocampal Volume and Asymmetry Neurotoxicology and Teratology, 29, 141-152 (2007).
Nilsson PM, MD, PHD; Mattias Roost, MD; Gunnar Engstron, MD, PHD, Bo Hedblad, MD, PHD; Goran Berglund, MD, PHD. Incidence of Diabetes in Middle Aged Men Is Related to Sleep Disturbances Diabetes Care Volme 27, Number 10, October 2004.
Perneczky R, Wagenpfeil S, Lunetta KL, Cupples LA, Green RC, Decarli C, Farrer LA, Kurz A. Head Circumference, Atrophy, and Cognition: Implications for Brain Reserve in Alzheimer Disease Neurology 75(2):137-42 (July 2010).
Pittenger C and Ronald S. Duman. Stress, Depression and Neuropasticity: A Convergence of Mechanisms Neuropsychopharmacology 33:88-109 (2008).
Settler C, Toro P, Schknecht P, Schrer J. Cognitive Activity, Education, and Socioeconomic Status as Preventive Factors for Mild Cognitive Impairment and Alzheimers Disease Psychiatry Res 2012 Mar 30:196(1):90-5.Epub 2012 Mar 4.
Tworoger, S.S., Lee, S., Schernhammer, ES & Grodstein, F. The Association of Self-Reported Sleep Duration, Difficulty Sleeping and Snoring With Cognitive Function in Older Women Alzheimer Disease & Associated Disorders, 20, 41-48 (2006)
van Praag H, Shubert T, Zhao C, Gage FH. Exercise Enhances Learning and Hippocampal Neurogenesis in Aged Mice Journal of Neuroscience 25:8680-8685 (2005).
Whalley, LJ, Deary, IH, Appleton CL & Starr JM. Cognitive Reserve and the Neurobiology of Cognitive Aging. Ageing Research Reviews, 3, 369-382 (2004).
Yamaguchi M, Suzuki T, Seki T, Namba T, Juan R, Arai H, Hori T, and Asada T. Repetitive Cocaine Administration Decreases Neurogenesis in Adult Rat Hippocampus Ann. N.Y. Acad. Sci., 1025, 351-362 (2004).