Post-traumatic Amnesia
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Post-traumatic amnesia (PTA) is a state of
confusion In medicine, confusion is the quality or state of being bewildered or unclear. The term "acute mental confusion"
that occurs immediately following a
traumatic brain injury A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic b ...
(TBI) in which the injured person is disoriented and unable to remember events that occur after the
injury An injury is any physiological damage to living tissue caused by immediate physical stress. An injury can occur intentionally or unintentionally and may be caused by blunt trauma, penetrating trauma, burning, toxic exposure, asphyxiation, o ...
. The person may be unable to state their name, where they are, and what time it is. When continuous memory returns, PTA is considered to have resolved. While PTA lasts, new events cannot be stored in the memory. About a third of patients with mild head injury are reported to have "islands of memory", in which the patient can recall only some events. During PTA, the patient's consciousness is "clouded". Because PTA involves confusion in addition to the memory loss typical of amnesia, the term ''"post-traumatic confusional state"'' has been proposed as an alternative. There are two types of
amnesia Amnesia is a deficit in memory caused by brain damage or disease,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be caused temporarily by the use ...
:
retrograde amnesia In neurology, retrograde amnesia (RA) is a loss of memory-access to events that occurred or information that was learned in the past. It is caused by an injury or the onset of a disease. It tends to negatively affect episodic, autobiographical, ...
(loss of memories that were formed shortly before the injury) and
anterograde amnesia In neurology, anterograde amnesia is the inability to create new memories after the event that caused amnesia, leading to a partial or complete inability to recall the recent past, while long-term memories from before the event remain intact. T ...
(problems with creating new memories after the injury has taken place). PTA may refer to only anterograde forms, or to both retrograde and anterograde forms. A common example in sports concussion is the quarterback who was able to conduct the complicated mental tasks of leading a
football team A football team is a group of players selected to play together in the various team sports known as football. Such teams could be selected to play in a match against an opposing team, to represent a football club, group, state or nation, an All-st ...
after a concussion, but has no recollection the next day of the part of the game that took place after the injury. Individuals with retrograde amnesia may partially regain memory later, but memories are not regained with anterograde amnesia because they were not
encoded In communications and information processing, code is a system of rules to convert information—such as a letter, word, sound, image, or gesture—into another form, sometimes shortened or secret, for communication through a communication ...
properly. The term "post-traumatic amnesia" was first used in 1940 in a paper by Symonds to refer to the period between the injury and the return of full, continuous memory, including any time during which the patient was unconscious.


Symptoms

The most prominent symptom of post-traumatic amnesia (PTA) is a loss of
memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembered, ...
of the present time. As a result, patients are often unaware of their condition and may behave as if they are going about their regular lives. This can cause complications if patients are confined to a hospital and may lead to agitation, distress and
anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
. Many patients report feeling as though they were being "held prisoner" and being prevented from carrying on with their daily lives. Other symptoms include agitation,
confusion In medicine, confusion is the quality or state of being bewildered or unclear. The term "acute mental confusion"
,
disorientation Orientation is a function of the mind involving awareness of three dimensions: time, Location (geography), place and person. Problems with orientation lead to ''dis''orientation, and can be due to various conditions, from delirium to Substance int ...
, and restlessness. Patients also often display behavioral disturbances. Patients may shout, swear and behave in a disinhibited fashion. There have been cases in which patients who do not recognize anyone will ask for family members or acquaintances that they have not seen in years. Some patients exhibit childlike behavior. Other patients show uncharacteristically quiet, friendly and loving behavior. Although this behavior may seem less threatening because of its lack of aggressiveness, it may be equally worrisome. PTA patients are often unaware of their surroundings and will ask questions repeatedly. Patients may also have a tendency to wander off, which can be a major concern in those who have sustained additional injuries at the time of trauma, such as injured limbs, as it may lead to the worsening of these secondary injuries.


Attention

Attention Attention is the behavioral and cognitive process of selectively concentrating on a discrete aspect of information, whether considered subjective or objective, while ignoring other perceivable information. William James (1890) wrote that "Atte ...
is a cognitive resource that contributes to many mental functions. The ability to engage attention requires a certain level of conscious awareness, arousal and concentration, all mechanisms that are generally impaired by traumatic brain injury. The involvement of attention in such a vast array of cognitive processes has led to the suggestion that attentional deficit may act as an underlying factor in the range of cognitive deficits observed in patients experiencing post-traumatic amnesia (PTA). Attention has been regarded as an important factor in the healthy functioning of encoding, verbal comprehension and new learning. Automatic attention processes (such as counting forwards) are recovered before simple memory skills (such as a recognition test of verbal material) in individuals with mild to moderate brain injury. This implies that the recovery of attentional ability precedes the progression of memory recovery after injury, helping to pave the way to regain ability for new learning. In terms of more severe brain injuries, this automatic attention task performance recovers before disorientation completely resolves. One of the weaknesses of the method most often used in assessing PTA, the Galveston Orientation and Amnesia Test (GOAT), is that it does not include any assessment of attention, which could help give a better indication of potential for recovery. By omitting attention, the test is omitting some crucial aspects of a person's cognitive capabilities. In addition, assessing attention during the period of PTA may help determine whether the patient is still in a state of PTA or if they are experiencing a more permanent form of memory deficit. In patients with mild TBI, the damage consists primarily of
diffuse axonal injury Diffuse axonal injury (DAI) is a brain injury in which scattered lesions occur over a widespread area in white matter tracts as well as grey matter. DAI is one of the most common and devastating types of traumatic brain injury and is a major cause ...
(widespread damage to white matter) without any focal damage (damage to specific areas). Sometimes, injury of the
brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is cont ...
was also observed. In these cases, there is likely the presence of an attentional deficit without a true amnesiac state. In more severely brain-damaged individuals, the damage to the
temporal lobes The temporal lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The temporal lobe is located beneath the lateral fissure on both cerebral hemispheres of the mammalian brain. The temporal lobe is involved in proc ...
and the
frontal lobes The frontal lobe is the largest of the four major lobes of the brain in mammals, and is located at the front of each cerebral hemisphere (in front of the parietal lobe and the temporal lobe). It is parted from the parietal lobe by a groove betwe ...
serves as good indication that amnesia will result. Patients with more chronic forms of memory impairment showed poor performance when tested with PTA scales, making differentiation between the two types of memory impairment very difficult. PTA patients exhibit poor simple
reaction time Mental chronometry is the scientific study of processing speed or reaction time on cognitive tasks to infer the content, duration, and temporal sequencing of mental operations. Reaction time (RT; sometimes referred to as "response time") is meas ...
, reduced information processing speed and reduced verbal fluency, which are all attentional deficits that could be used to distinguish these patients from those with more severe and permanent memory problems.


Communication skills

The effects of PTA on communication skills were studied using the Revised Edinburgh Functional Communication Profile (REFCP), which measures both linguistic elements (related to speech) and
pragmatic Pragmatism is a philosophical movement. Pragmatism or pragmatic may also refer to: *Pragmaticism, Charles Sanders Peirce's post-1905 branch of philosophy *Pragmatics, a subfield of linguistics and semiotics *''Pragmatics'', an academic journal in ...
elements (related to body language and other non-verbal communication skills). PTA has effects on memory,
perception Perception () is the organization, identification, and interpretation of sensory information in order to represent and understand the presented information or environment. All perception involves signals that go through the nervous system ...
and attention, which are all important for communication. Patients showed mild deficits in verbal communication skills, and moderate to severe deficits in nonverbal communication skills such as maintaining eye contact, initiating greetings, and responding appropriately. Also, a negative correlation was found between the duration of a patient's episode of PTA and his REFCP score; the longer the PTA episode, the more severe the deficit in non-linguistic pragmatic skills. However, the small sample size of this study (only 10 males) means that the results must be interpreted with caution, as they may not generalize to larger samples or to the population at large.


Pathophysiology

Currently, the
pathophysiological Pathophysiology ( physiopathology) – a convergence of pathology with physiology – is the study of the disordered physiological processes that cause, result from, or are otherwise associated with a disease or injury. Pathology is th ...
mechanisms which produce post-traumatic amnesia are not completely known. The most common research strategy to clarify these mechanisms is the examination of the impaired functional capabilities of people with post-traumatic amnesia (PTA) after a traumatic brain injury.


Neurological mechanisms

Research on the effect of emotional trauma on memory retention and amnesic symptoms has shown that exposure to prolonged levels of extreme stress has a direct effect on the
hippocampus The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...
. Elevated
stress Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...
levels can lead to an increase in the production of
enkephalins An enkephalin is a pentapeptide involved in regulating nociception in the body. The enkephalins are termed endogenous ligands, as they are internally derived and bind to the body's opioid receptors. Discovered in 1975, two forms of enkephalin ...
and
corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involve ...
, which can produce abnormal neural activity and disrupt
long-term potentiation In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons ...
(a neural mechanism associated with learning) in the hippocampus. Individuals who have been subjected to repeated sexual abuse during childhood or who have experienced combat show significant impairment and atrophy of the hippocampal region of the brain. The
amygdala The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex verteb ...
, an area of the brain involved in emotional regulation, may be involved in producing remembrance for some aspects of the trauma. Even though the trace of a memory for trauma may be lost from the hippocampus, it may remain partially encoded in the form of an emotional memory in the amygdala where it can be subsequently recalled in the form of a flashback or partially
recovered memory Repressed memory is an inability to recall autobiographical information, usually of a traumatic or stressful nature. The concept originated in psychoanalytic theory where repression is defined as a protective mechanism that excludes memory of ...
.


Diaschisis

Diaschisis refers to the sudden dysfunction of portions of the brain due to lesions in distant but connected
neurons A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
. Diaschisis is implicated as playing an important role in PTA, more particularly in the
declarative memory Explicit memory (or declarative memory) is one of the two main types of long-term human memory, the other of which is implicit memory. Explicit memory is the conscious, intentional recollection of factual information, previous experiences, and con ...
impairments observed in patients experiencing an episode of PTA. The loss of function observed after traumatic brain injuries, as well as the resulting loss of consciousness, was thought to be mediated by the 'neural shock' associated with diaschisis. Diaschisis was originally believed to be a result of disruption to neural tissue, but more recent evidence implicates increased activity levels of
choline acetyltransferase Choline acetyltransferase (commonly abbreviated as ChAT, but sometimes CAT) is a transferase enzyme responsible for the synthesis of the neurotransmitter acetylcholine. ChAT catalyzes the transfer of an acetyl group from the coenzyme acetyl-Co ...
, the enzyme responsible for the production of
acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...
, as a major cause. Based on these findings, diaschisis could be helped through the use of drugs that would reduce cholinergic (acetylcholine) activity, and reduce the levels of acetylcholine in the brain. This idea is supported by the fact that there is an increase in acetylcholine concentrations in the brain after head injury. Animal studies have shown that concussive injuries in rats lead to changes in the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
's cholinergic system. This increase in acetylcholine levels has also been tied to behavioral suppression and unconsciousness, both symptoms of PTA. In long-term recovery, acetylcholine levels associated with diaschisis may continue to play a role in maintaining memory deficits.


Brain-imaging studies

Brain imaging Neuroimaging is the use of quantitative (computational) techniques to study the neuroanatomy, structure and function of the central nervous system, developed as an objective way of scientifically studying the healthy human brain in a non-invasive ...
techniques are useful for examining the changes in the brain that occur as a result of damage. Metting et al. (2001) used
CT scans A computed tomography scan (CT scan; formerly called computed axial tomography scan or CAT scan) is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers ...
to examine the pathophyiological damage in patients currently experiencing an episode of PTA, patients with resolved PTA, and a
control group In the design of experiments, hypotheses are applied to experimental units in a treatment group. In comparative experiments, members of a control group receive a standard treatment, a placebo, or no treatment at all. There may be more than one tr ...
that had not experienced PTA. Bloodflow to the
occipital lobe The occipital lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The name derives from its position at the back of the head, from the Latin ''ob'', "behind", and ''caput'', "head". The occipital lobe is the vi ...
, the
caudate nucleus The caudate nucleus is one of the structures that make up the corpus striatum, which is a component of the basal ganglia in the human brain. While the caudate nucleus has long been associated with motor processes due to its role in Parkinson's di ...
, and the
grey matter Grey matter is a major component of the central nervous system, consisting of neuronal cell bodies, neuropil (dendrites and unmyelinated axons), glial cells (astrocytes and oligodendrocytes), synapses, and capillaries. Grey matter is distingui ...
of the frontal lobe was significantly reduced in patients who were scanned during the episode of PTA. No differences were seen between patients with resolved PTA and the control group. This encouraging finding points to the positive long term prognosis of PTA; most patients return to normal levels of functioning. The frontal lobes are associated with
explicit memory Explicit memory (or declarative memory) is one of the two main types of long-term human memory, the other of which is implicit memory. Explicit memory is the conscious, intentional recollection of factual information, previous experiences, and con ...
retrieval, and deficits on explicit memory tasks are often found with patients experiencing PTA. Working memory deficits are a common symptom in patients with PTA. The duration of an episode of PTA was correlated with reduced bloodflow to the right
hemisphere Hemisphere refers to: * A half of a sphere As half of the Earth * A hemisphere of Earth ** Northern Hemisphere ** Southern Hemisphere ** Eastern Hemisphere ** Western Hemisphere ** Land and water hemispheres * A half of the (geocentric) celestia ...
, a finding which was consistent with
functional MRI Functional magnetic resonance imaging or functional MRI (fMRI) measures brain activity by detecting changes associated with blood flow. This technique relies on the fact that cerebral blood flow and neuronal activation are coupled. When an area o ...
studies that link
working memory Working memory is a cognitive system with a limited capacity that can hold information temporarily. It is important for reasoning and the guidance of decision-making and behavior. Working memory is often used synonymously with short-term memory, ...
with right frontal activity. The
prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA46, ...
, which plays an important role in explicit memory retrieval, was also found to have decreased neural activation in patients scanned during the episode of PTA. Researchers noted that the damage was related to
vascularization Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting ...
and neural functionality, but not to structural injury, suggesting that the resolution of PTA is dependent on functional changes. Memory and new learning involve the
cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of ...
, the subcortical projections, the
hippocampus The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...
, the
diencephalon The diencephalon (or interbrain) is a division of the forebrain (embryonic ''prosencephalon''). It is situated between the telencephalon and the midbrain (embryonic ''mesencephalon''). The diencephalon has also been known as the 'tweenbrain in ol ...
and the
thalamus The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all directions, ...
, areas that often experience damage as a result of TBI. Frontal lobe lesions may also play a role in PTA, as damage to these areas is associated with changes in behavior, including irritability, aggressiveness, disinhibition, and a loss of judgment. Damage to this area may account for the uncharacteristic behavior often exhibited in PTA patients.


Accelerated forgetting

Researchers have also found that individuals experiencing PTA show accelerated forgetting. This contrasts with the normal forgetting observed by patients with normal amnesia related to brain damage. The
temporal lobes The temporal lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The temporal lobe is located beneath the lateral fissure on both cerebral hemispheres of the mammalian brain. The temporal lobe is involved in proc ...
are often the most vulnerable to the diffuse (widely distributed) and focal (more specifically localized) effects of TBI and it is possible that temporal lobe lesions may account for the accelerated forgetting observed in patients with PTA. These predictions were supported by the finding that most of the patients who showed rapid forgetting also had lesions to the temporal lobe. Bilateral damage to the temporal lobes also causes severe anterograde amnesia, making it likely that lesions to this area would be involved in PTA. Patients exhibit a temporal gradient with memory loss, meaning that older memories are preserved at the expense of newer memories. Temporal lobe damage has been linked to a temporal gradient of this sort, because older memories are less dependent on the hippocampus and thus are less influenced by its damage. There is a significant link between individuals currently experiencing PTA and their performance on the
Wechsler Adult Intelligence Scale The Wechsler Adult Intelligence Scale (WAIS) is an IQ test designed to measure intelligence and cognitive ability in adults and older adolescents. The original WAIS (Form I) was published in February 1955 by David Wechsler, as a revision of the ...
(WAIS). The scores of those currently experiencing an episode of PTA were compared to individuals who had previously had a traumatic brain injury resulting in PTA. Those still experiencing PTA performed significantly worse on both the performance and the verbal subscales of the WAIS. Also, people in early stages of PTA have substantial impairment to anterograde memory function. For example, in the
case report In medicine, a case report is a detailed report of the symptoms, signs, diagnosis, treatment, and follow-up of an individual patient. Case reports may contain a demographic profile of the patient, but usually describe an unusual or novel occurrence ...
of a patient referred to as "JL", Demery et al. noted that his memory impairments were so severe following his injury that he had forgotten that he had attended a
Major League Baseball Major League Baseball (MLB) is a professional baseball organization and the oldest major professional sports league in the world. MLB is composed of 30 total teams, divided equally between the National League (NL) and the American League (AL), ...
game less than 30 minutes after returning to the center where he was being treated. The majority of neuropsychological studies available have suggested that the medial temporal lobes are the most important system in the pathophysiology of PTA. However, there is little research done on this topic, and as new research is done, more information should come forth concerning functionality in these areas in PTA patients. One MRI study showed that a long duration of PTA was correlated with damage in the hemispheric and central areas, regardless of whether the duration of the coma was relatively short. In patients who had a longer coma duration, deeper lesions in the central area were observed without extensive damage to the hemispheric area.


Diagnosis


Measure of traumatic brain injury severity

PTA has been proposed to be the best measure of head trauma severity, but it may not be a reliable indicator of outcome. However, PTA duration may be linked to the likelihood that psychiatric and behavioral problems will occur as consequences of TBI. Classification systems for determining the severity of TBI may use duration of PTA alone or with other factors such as
Glasgow Coma Scale The Glasgow Coma Scale (GCS) is a clinical scale used to reliably measure a person's level of consciousness after a brain injury. The GCS assesses a person based on their ability to perform eye movements, speak, and move their body. These thre ...
(GCS) score and duration of
loss of consciousness Loss may refer to: Arts, entertainment, and media Music * ''Loss'' (Bass Communion album) (2006) * ''Loss'' (Mull Historical Society album) (2001) *"Loss", a song by God Is an Astronaut from their self-titled album (2008) * Losses "(Lil Tjay son ...
(LOC) to divide TBI into categories of mild, moderate, and severe. One common system using all three factors and one using PTA alone are shown in the tables at right. Duration of PTA usually correlates well with GCS and usually lasts about four times longer than unconsciousness. PTA is considered a hallmark of
concussion A concussion, also known as a mild traumatic brain injury (mTBI), is a head injury that temporarily affects brain functioning. Symptoms may include loss of consciousness (LOC); memory loss; headaches; difficulty with thinking, concentration, ...
, and is used as a measure of predicting its severity, for example in
concussion grading scales Concussion grading systems are sets of criteria used in sports medicine to determine the severity, or grade, of a concussion, the mildest form of traumatic brain injury. At least 16 such systems exist, and there is little agreement among profe ...
. It may be more reliable for determining severity of concussion than GCS because the latter may not be sensitive enough; individuals with s concussion often quickly regain a GCS score of 15. Longer periods of amnesia or loss of consciousness immediately after the injury may indicate longer recovery times from residual symptoms from concussion. Increased duration of PTA is associated with a heightened risk for TBI complications such as
post-traumatic epilepsy Post-traumatic epilepsy (PTE) is a form of acquired epilepsy that results from brain damage caused by physical trauma to the brain (traumatic brain injury, abbreviated TBI). A person with PTE experiences repeated post-traumatic seizures (PTS, s ...
.


Assessment

Duration of PTA may be difficult to gauge accurately; it may be overestimated (for example, if the patient is asleep or under the influence of drugs or alcohol for part of the time) or underestimated (for example, if some memories come back before continuous memory is regained). Th
Galveston Orientation and Amnesia Test
(GOAT) exists to determine how oriented a patient is and how much material they are able to recall. The GOAT is the most widely used standardized scale for the prospective assessment of PTA in the United States and Canada. The test is made up of 10 items that assess orientation and recollection of the events before and after the injury. It can be used to assess the duration of PTA; this particular GOAT assessment has been found to strongly predict functional outcome as measured by the
Glasgow Outcome Scale The Glasgow Outcome Score (GOS) is a scale of patients with brain injuries, such as cerebral traumas that groups victims by the objective degree of recovery. The first description was in 1975 by Jennett and Bond. __TOC__ Application The Glasgo ...
, return to productivity, psychosocial function and distress. An alternative to the GOAT is the Westmead Post-Traumatic Amnesia Scale (WPTAS) which examines not only orientation to person, place and time, but also crucially the ability to consistently remember new information from one day to the next. It consists of twelve questions (seven orientation questions, and five memory items) and is administered once daily, each and every day, until the patient scores a perfect score of 12/12 on three ''consecutive'' days. It is suitable for patients with moderate to severe traumatic brain injury. The WPTAS is the most common post-traumatic amnesia scale used in Australia and New Zealand. An abbreviated version has been developed to assess patients with mild traumatic brain injury, th
Abbreviated Westmead PTA Scale
(AWPTAS).


Testing

Before the development of the current tests for the assessment of post-traumatic amnesia (PTA), a retrospective method was used to determine the patient's condition, consisting of one or more interviews with the patient after the episode of PTA was judged to be over. The retrospective method, however, fails to account for the apparent lucidity of patients who are still experiencing substantial disorientation, or the finding that the recovery from post-traumatic amnesia is often characterized by the presence of "islands of memory" (short periods of clarity). A failure to take these facts into consideration may have biased retrospective methods towards underestimating the length and severity of an episode of PTA. Also, the retrospective method relies on retrospective memory, one's memory for past events, which is not very reliable in healthy individuals, and even less so in patients who have recently experienced a traumatic brain injury (TBI). Patients may also unconsciously or consciously bias their answers because they want to appear more healthy or more ill than they truly were, or because of poor insight. The retrospective method is also flawed because there is no standard measurement procedure. Although the retrospective method may provide useful subjective data, it is not a useful tool for measurement or categorization.


GOAT

The Galveston Orientation and Amnesia Test (GOAT) is the most frequently used test for assessing PTA in the United States and Canada. The test consists of 10 items that involve the recall of events that occurred right before and after the injury, as well as questions about
disorientation Orientation is a function of the mind involving awareness of three dimensions: time, Location (geography), place and person. Problems with orientation lead to ''dis''orientation, and can be due to various conditions, from delirium to Substance int ...
. Scores of 75 or more on this scale (out of a total possible score of 100) correspond to the termination of the PTA episode. The GOAT typically classifies orientation into three categories: orientation to the person, orientation to the place, and orientation to the time. The idea behind these questions is that each of these classifications places a large demand on the patient's memory and learning abilities.


WPTAS and AWPTAS

The Westmead Post-Traumatic Amnesia Scale (WPTAS) is commonly used in Australia and New Zealand. It questions twelve questions that examine orientation to person, place and time, in addition to the ability to consistently remember new information from one day to the next. The scale is administered once each day, until the patient scores 12/12 on three consecutive days. The WPTAS is suitable for patients with moderate-to-severe traumatic brain injury. An abbreviated version of the WPTAS, th
Abbreviated Westmead PTA Scale
(AWPTAS) assesses patients with mild traumatic brain injury.


=Drawbacks

= Although the GOAT has proved useful in acute care, recent research has called attention to some of its drawbacks. The GOAT's assessment of orientation may put too much of a focus on memory as the main mechanism behind orientation. The range of cognitive and behavioral symptoms associated with PTA seems to indicate that the patient's disorientation is more than just a memory deficit. Consequently, it may be beneficial to incorporate tests of other cognitive functions, such as attention, which relate to both memory and orientation. Another recent study compared the success of the GOAT and the Orientation Log (O-Log) in predicting rehabilitation outcomes, and found that, while the O-Log and the GOAT perform similarly as measures of PTA severity and duration, the O-Log provides a more accurate picture of rehabilitation. While the GOAT is a useful tool, these results suggest that using alternative methods of assessing PTA may increase the amount of information available to physicians and may help in predicting rehabilitative success. The international cognitive (INCOG) expert panel has recommended the use of a validated PTA scale such as the GOAT or WPTAS for assessing PTA duration in patients with moderate-to-severe traumatic brain injury on a daily basis.


Severity

The severity of post-traumatic amnesia (PTA) is directly related to its duration, although a longer duration does not necessarily indicate more severe symptoms. The duration of PTA in brain-injured patients is a useful predictor of the expected long-term effects of the injury, along with the duration of
loss of consciousness Loss may refer to: Arts, entertainment, and media Music * ''Loss'' (Bass Communion album) (2006) * ''Loss'' (Mull Historical Society album) (2001) *"Loss", a song by God Is an Astronaut from their self-titled album (2008) * Losses "(Lil Tjay son ...
(LOC), and scores on the
Glasgow Coma Scale The Glasgow Coma Scale (GCS) is a clinical scale used to reliably measure a person's level of consciousness after a brain injury. The GCS assesses a person based on their ability to perform eye movements, speak, and move their body. These thre ...
(GCS), which measures degrees of consciousness, with higher scores indicating higher levels of functioning. A score of three indicates complete unconsciousness, and a score of 15 indicates normal functioning. In patients experiencing PTA for the duration of: Up to one hour – the injury is very mild in severity and full recovery is expected. The patient may experience a few minor post-concussive symptoms (e.g. headaches, dizziness). 1–24 hours – the injury is moderate in severity and full recovery is expected. The patient may experience some minor post-concussive symptoms (e.g. headaches, dizziness). 1–7 days – the injury is severe, and recovery may take weeks to months. The patient may be able to return to work, but may be less capable than before the injury. 1–2 weeks – the injury is very severe, and recovery is likely to take many months. The patient is likely to experience long-lasting cognitive effects such as decreased verbal and nonverbal intelligence as well as decreased performance on visual tests. Patients should, however, still be able to return to work. 2–12 weeks – the injury is very severe, and recovery is likely to take a year or more. The patient is likely to exhibit permanent deficits in memory and cognitive function, and the patient is unlikely to be able to return to work. 12+ weeks – injury is very severe and accompanied by significant disabilities that will require long-term
rehabilitation Rehabilitation or Rehab may refer to: Health * Rehabilitation (neuropsychology), therapy to regain or improve neurocognitive function that has been lost or diminished * Rehabilitation (wildlife), treatment of injured wildlife so they can be retur ...
and management. The patient is unlikely to be able to return to work.Headway UK. (2008). ''Post-Traumatic Amnesia - Fact Sheet'' act Sheet Retrieved from http://www.headway.org.uk/sitePages.asp?step=4&contentID=1334&navID=115. Note: return to work is meant to indicate a return to a reasonable level of functionality, both in professional and personal arenas. The long-term
prognosis Prognosis (Greek: πρόγνωσις "fore-knowing, foreseeing") is a medical term for predicting the likely or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) or remain stabl ...
of PTA is generally positive. Many patients do recover a great deal of cognitive function, although they may not return to their pre-injury state.


Treatment


Vasopressin


Animal research

Early research pointed to
vasopressin Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travel ...
as a potential treatment for improving the memory of patients living with post-traumatic amnesia (PTA).
Lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...
vasopressin, a modified form of the vasopressin molecule, had positive effects on memory when administered by injection to patients with amnesia resulting from traumatic brain injury and
Korsakoff's syndrome Korsakoff syndrome (KS) is a disorder of the central nervous system characterized by amnesia, deficits in explicit memory, and confabulation. This neurological disorder is caused by a deficiency of thiamine (vitamin B1) in the brain, and it is ...
. Subsequent animal studies with rats found similar results, particularly in aversion and avoidance learning tasks. Rats lacking adequate vasopressin, either due to genetic defect or
hypophysectomy Hypophysectomy is the surgical removal of the hypophysis (pituitary gland). It is most commonly performed to treat tumors, especially craniopharyngioma tumors. Sometimes it is used to treat Cushing's syndrome due to pituitary adenoma or Simmond' ...
(surgical removal of the pituitary gland), exhibited significant improvements in memory and learning functions when
exogenous In a variety of contexts, exogeny or exogeneity () is the fact of an action or object originating externally. It contrasts with endogeneity or endogeny, the fact of being influenced within a system. Economics In an economic model, an exogeno ...
vasopressin was administered. Particularly encouraging was the finding that a short treatment period produced long-lasting improvements, in both humans and rats. However, the animal models of PTA are highly limited, as the dimension of self-awareness and orientation is almost impossible to model adequately. PTA in animals, especially rats, is often observed post-trauma (commonly post-surgery), but it is often only measured in terms of impaired learning or unusual behavior.


Human studies

One subsequent human study found no effects of vasopressin on memory. The nonsignificant results were attributed to the study's many potential flaws, particularly its small sample size, the inability of vasopressin to penetrate the
blood brain barrier Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the Cell (biology), cells, and transports Metabolic waste, metabolic waste products away from th ...
when administered as a nasal spray, inadequate dosing and differences in severity of head injury between the samples. However, Eames et al. (1999) found statistically significant improvements on several tests of memory with the use of a vasopressin nasal spray, with no reported ill effects. Although the degree of improvement was mild, and it could be attributed to numerous other factors of the rehabilitative program, the lack of any ill effects suggests that vasopressin is, at the least, a possible enhancement for a treatment regimen.


Norepinephrine agonists

Diaschisis, as mentioned earlier, has been linked to the mechanism of PTA. The noradrenergic systems may play a role in diaschisis.
Norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
, also known as noradrenalin, is a
catecholamine A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. Catechol can be either a free molecule or a subst ...
neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...
. Administering a norepinephrine receptor
agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
(a substance that initiates a cell response when it binds with a receptor) to patients promoted the recovery of memory and many other cognitive functions after a traumatic brain injury. Conversely, the administration of norepinephrine
antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...
s slowed recovery, and could lead to the reinstatement of deficits when administered after recovery. Noradrenergic antagonists were not prescribed for the purposes of slowing the recovery of memory. Rather, these findings are based on the effects of other commonly prescribed drugs that happen to block noradrenergic receptors. The
alpha-1 adrenergic receptor alpha-1 (α1) adrenergic receptors are G protein-coupled receptors (GPCRs) associated with the Gq heterotrimeric G protein. α1-adrenergic receptors are subdivided into three highly homologous subtypes, i.e., α1A-, α1B-, and α1D-adrenergic ...
is specifically implicated. Although it has not yet been thoroughly investigated, there is potential for
stimulants Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
, which promote catecholamine release, to be an effective treatment in the early stages of recovery from brain trauma, and these positive effects could reduce the symptoms of PTA.


Research


The North Star Project

The North Star Project was developed by researchers at
McGill University McGill University (french: link=no, Université McGill) is an English-language public research university located in Montreal, Quebec, Canada. Founded in 1821 by royal charter granted by King George IV,Frost, Stanley Brice. ''McGill Universit ...
. Researchers developed a "reality orientation", which involved discussing general facts (e.g. date, time, names of family members, etc.) with amnesic patients twice a day in an attempt to lessen their confusion during the early stages of their recovery. Younger patients often had shorter amnesic episodes than older patients, especially those in the North Star group. Although more improvements were noted in the North Star group than in the control group, researchers did not find a statistically significant effect of their intervention.


Findings

A comprehensive analysis of literature based on the effects of early rehabilitation of traumatic brain injury concluded that there is no strong evidence linking any one particular practice of post-injury care to a reduced severity in symptoms. However, even in the absence of a concrete correlation between a specific rehabilitation program and improved outcomes, the evidence and research available can provide many good suggestions for how to proceed with treatment. All rehabilitation strategies reviewed had positive effects on recovery, but none more so than the others. The most accurate measure of determining the length of amnesia is still the a behavioural measure, the duration of the episode of post-traumatic amnesia, rather than a neuroimaging technique or an electrophysiological or biochemical technique. The length of amnesia is also one of the most accurate predictors for determining later cognitive problems, even more so than the duration of either the coma or the period of loss of consciousness. The duration of amnesia after TBI, therefore, can be very useful in the planning the length and intensity of rehabilitation programs for persons affected by PTA.


History


C.P. Symonds

Although Franklin described PTA, it was the British physician C. P. Symonds who first discussed the specific amnesiac symptoms that often follow a
cerebral contusion Cerebral contusion, Latin ''contusio cerebri'', a form of traumatic brain injury, is a bruise of the brain tissue. Like bruises in other tissues, cerebral contusion can be associated with multiple microhemorrhages, small blood vessel leaks into ...
, which is a specific kind of traumatic brain injury. Symonds observed that the patient remains "stuperose, restless and irritable" after recovering consciousness. He also identified a recovery period of days to weeks for this post-concussive state. Presumably, shorter durations of PTA, which are now included in the definition, were not thought to be serious enough for documentation. Most importantly, he identified the amnesia that the patient experiences during this period of recovery, and recommended the use of "formal tests for memory and retention" to assess recovery.


In WWI soldiers

Although there was a general lack of knowledge about its mechanisms, a review of patients seen during WWI combat reveals the symptoms of post-traumatic amnesia (PTA) in many soldiers. The term
shell shock Shell shock is a term coined in World War I by the British psychologist Charles Samuel Myers to describe the type of post-traumatic stress disorder (PTSD) many soldiers were afflicted with during the war (before PTSD was termed). It is a react ...
was used to refer to the acute psychological state that accompanied exposure to exploding shells, and more generally, exposure to combat conditions. There are a number of documented cases of people with shell shock . These soldiers commonly displayed dizziness, varying degrees of consciousness, a loss of non-traumatic personal information, and a lack of normal
self-awareness In philosophy of self, self-awareness is the experience of one's own personality or individuality. It is not to be confused with consciousness in the sense of qualia. While consciousness is being aware of one's environment and body and lifesty ...
lasting anywhere from hours to days. Many of the symptoms of shell shock are highly similar to those of PTA. The following excerpt from a case report illustrates the loss of personal information observed in one patient: Researchers found that physicians had documented reports of combatants where " th central and peripheral details of the traumatic experience were lost." Patients displayed gaps in memory recollection for the period following the trauma, sometimes up to the time of hospitalization, which could be weeks later. An initial assessment supported the role of concussions in causing these symptoms. Concussions could account for the
anterograde amnesia In neurology, anterograde amnesia is the inability to create new memories after the event that caused amnesia, leading to a partial or complete inability to recall the recent past, while long-term memories from before the event remain intact. T ...
and
retrograde amnesia In neurology, retrograde amnesia (RA) is a loss of memory-access to events that occurred or information that was learned in the past. It is caused by an injury or the onset of a disease. It tends to negatively affect episodic, autobiographical, ...
observed in patients, as well as the periods of fluctuating consciousness or delirium that sometimes followed. However, many soldiers who showed these amnesiac effects did not experience injuries that would have led to concussions. As a result, there was controversy over the possible causes of PTA in these non-concussed soldiers, with a separation between proponents of
Freudian Sigmund Freud ( , ; born Sigismund Schlomo Freud; 6 May 1856 – 23 September 1939) was an Austrian neurologist and the founder of psychoanalysis, a clinical method for evaluating and treating pathologies explained as originating in conflicts i ...
repression and those supporting a
dissociative Dissociatives, colloquially dissos, are a subclass of hallucinogens which distort perception of sight and sound and produce feelings of detachment – dissociation – from the environment and/or self. Although many kinds of drugs are capable of ...
view of the condition. This dissociative view was ultimately supported, and accounted for the
fugue state Dissociative fugue (), formerly called a fugue state or psychogenic fugue, is a mental and behavioral disorderDrs; that is classified variously as a dissociative disorder,Dissociative Fugue (formerly Psychogenic Fugue) 'DSM-IV 300.13, Diagnost ...
seen in soldiers who were thought to have dissociated from normal consciousness.


Other psychological disorders

Researchers have investigated the relationship between posttraumatic amnesia (PTA) resulting from traumatic brain injury (TBI) and the development of symptoms of
posttraumatic stress disorder Post-traumatic stress disorder (PTSD) is a mental and behavioral disorder that can develop because of exposure to a traumatic event, such as sexual assault, warfare, traffic collisions, child abuse, domestic violence, or other threats on ...
(PTSD) and acute stress disorder (ASD). 282 outpatients, who were an average of 53 days post-TBI in their recovery, were divided into four groups: PTA episode lasting less than one hour; PTA episode lasting between one hour and 24 hours; PTA episode lasting between 24 hours and one week; and PTA episode lasting for longer than one week. The patients' personal details were used as variables classified for age, gender, marital status, time elapsed between injury and assessment, and type of injury (motor vehicle accident, pedestrian, assault and other). Patients were given two
self-report inventories A self-report inventory is a type of psychological test in which a person fills out a survey or questionnaire with or without the help of an investigator. Self-report inventories often ask direct questions about personal interests, values, sympt ...
: the Impact of Event Scale (IES) and the General Health Questionnaire (GHQ). The IES measures symptoms of PTSD and contains questions regarding the intrusiveness of the traumatic event (ex. nightmares) and avoidant behaviours related to the traumatic event (ex. avoiding a certain location). The GHQ was used as an indicator of overall psychological health. The majority of subjects were in Group 1 (PTA episode lasting less than one hour), injured in motor vehicle accidents, and male. There were no statistical differences found with regards to age, gender, marital status and type of injury. There was an increase in the severity of all indicators of brain damage for the longest durations of PTA; specifically, the GCS scores for this group decreased and the number of patients with an abnormal CT scan increased. There were significant differences in IES scores when comparing the group with the least serious episode of PTA, lasting less than an hour, to all other groups, with the duration of the episode of PTA lasting longer than an hour. The group with an episode of PTA lasting less than an hour had higher IES scores and more intrusive and avoidant symptoms. The fact that GHQ scores were constant throughout all groups, although there were differences in IES scores, suggests that the two scores measure different phenomena.


Aging

Grey and white matter are both found in the many areas of the brain, as well as throughout the central nervous system.
Grey matter Grey matter is a major component of the central nervous system, consisting of neuronal cell bodies, neuropil (dendrites and unmyelinated axons), glial cells (astrocytes and oligodendrocytes), synapses, and capillaries. Grey matter is distingui ...
is more involved in nerve function, and
white matter White matter refers to areas of the central nervous system (CNS) that are mainly made up of myelinated axons, also called tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distribution ...
is more involved in nerve maintenance, as well as the regulation of unconscious functions. However, both are important for memory and learning. The volume of grey and white matter in the brains of aging individuals has been correlated with working memory and retention of cognitive function. Researchers hypothesized that the lesions of both grey and white matter would be larger in older individuals and in those with more severe traumatic brain injuries, and longer episodes of PTA, and the volume of grey and white matter would be smaller in those injured at an older age. A group of 98 participants, predominantly male, were examined using fMRI. The results supported these hypotheses, leading researchers to suggest that the impact of traumatic brain injury gets more severe as age progresses. Although grey and white matter volume was reduced throughout the brain, researchers noted that the grey matter of the
neocortical The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, sp ...
brain regions was particularly affected. This is consistent with the fact that older individuals who had experienced PTA showed greater cognitive impairments than a control group of individuals of the same age who had not experienced PTA. The duration of the episode of PTA was related to the size of the grey matter lesion; longer episodes of PTA correlated with larger grey matter lesions. Advanced age also correlated with reduced
glial Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form mye ...
activity. With less grey matter, the patient is less able to retrieve memories effectively, as neuron function is impaired.


Controversies

On the topic of trauma and memory,
Richard McNally Richard McNally is a Professor and Director of Clinical Training at Harvard University's Department of Psychology. As a clinical psychologist and experimental psycho-pathologist, he studies anxiety disorders and related syndromes, such as post ...
(2005) wrote that memories are not videotapes of our experiences, meaning that they are not unchangeable records. The mechanism that retrieves a memory involves activation of several areas of the brain. Similarly, the mechanism that encodes a memory requires the use of different parts of the brain. Any fault in the encoding-retrieval system will degrade memory, and there are many potential faults, such as distortion by emotion, or focusing on the peripheral details at the expense of central details. An example of the latter is the well-known phenomenon where a person being robbed at gunpoint is so distracted by the gun that they don't have time to encode the robber's face. Misconstruing retrieval failure as traumatic amnesia is not the same phenomenon as post-traumatic amnesia, which describes amnesia for the current elapsing time post-trauma, not amnesia for trauma from the past. Typically, "
repressed memory Repressed memory is an inability to recall autobiographical information, usually of a traumatic or stressful nature. The concept originated in psychoanalytic theory where repression is defined as a protective mechanism that excludes memory of ...
" is the term used to explain this sort of traumatic amnesia; the experience was so horrific that the adult cannot process what occurred years before. The topic of repressed memory is controversial within psychology; many clinicians argue for its importance, while researchers remain skeptical of its existence. A more viable explanation for this forgetting is
childhood amnesia Childhood amnesia, also called infantile amnesia, is the inability of adults to retrieve episodic memories (memories of situations or events) before the age of two to four years, as well as the period before the age of ten of which some older adul ...
, a phenomenon describing the fact that most children do not have recall of events in their lives before the age of three, partially due to the lack of development of cognitive elements such as language.


References

{{memory Amnesia Medical signs Neurotrauma Victimology