Molecular modeling on GPU is the technique of using a graphics processing unit (GPU) for molecular simulations.
In 2007, NVIDIA
introduced video cards that could be used not only to show graphics but
also for scientific calculations. These cards include many arithmetic
units (as of 2016, up to 3,584 in Tesla P100) working in parallel. Long
before this event, the computational power of video cards was purely
used to accelerate graphics calculations. What was new is that NVIDIA
made it possible to develop parallel programs in a high-level application programming interface (API) named CUDA. This technology substantially simplified programming by enabling programs to be written in C/C++. More recently, OpenCL allows cross-platform GPU acceleration.
Quantum chemistry calculations and molecular mechanics simulations (molecular modeling in terms of classical mechanics)
are among beneficial applications of this technology. The video cards
can accelerate the calculations tens of times, so a PC with such a card
has the power similar to that of a cluster of workstations based on
common processors.
There are two types of murmurs. A functional murmur or "physiologic
murmur" is a heart murmur that is primarily due to physiologic
conditions outside the heart. Other types of murmurs are due to
structural defects in the heart itself. Functional murmurs are benign
(an "innocent murmur").
Murmurs may also be the result of various problems, such as narrowing or leaking of valves,
or the presence of abnormal passages through which blood flows in or
near the heart. Such murmurs, known as pathologic murmurs, should be
evaluated by a cardiologist.
Heart murmurs are most frequently categorized by timing, into systolic heart murmurs and diastolic heart murmurs, differing in the part of the heartbeat on which they can be heard. However, continuous murmurs cannot be directly placed into either category.
Classification
Murmurs can be classified by seven different characteristics: timing, shape, location, radiation, intensity, pitch and quality.
Timing refers to whether the murmur is a systolic or diastolic murmur.
Shape refers to the intensity over time; murmurs can be crescendo, decrescendo
or crescendo-decrescendo. Crescendo murmurs progressively increase in
intensity. Decrescendo murmurs progressively decrease in intensity. With
crescendo—decrescendo murmurs (diamond or kite-shaped murmurs), a
progressive increase in intensity is followed by a progressive decrease
in intensity.
Location refers to where the heart murmur is usually heard
best. There are four places on the anterior chest wall to listen for
heart murmurs; each of the locations roughly corresponds to a specific
part of the heart and should be listened to (through the stethoscope)
with the patient lying down, face up. The four locations are:
Radiation refers to where the sound of the murmur
radiates. The rule of thumb is that the sound radiates in the direction
of the blood flow.
Intensity refers to the loudness of the murmur, and is graded according to the Levine scale, from 1 to 6:
The murmur is only audible on listening carefully for some time.
The murmur is faint but immediately audible on placing the stethoscope on the chest.
A loud murmur readily audible but with no palpable thrill.
A loud murmur with a palpable thrill.
A loud murmur with a palpable thrill. The murmur is so loud that it
is audible with only the rim of the stethoscope touching the chest.
A loud murmur with a palpable thrill. The murmur is audible with the stethoscope not touching the chest but lifted just off it.
Pitch may be low, medium or high and is determined by whether it can be auscultated best with the bell or diaphragm of a stethoscope.
Quality refers to unusual characteristics of a murmur, such as blowing, harsh, rumbling or musical.
Mnemonics
A mnemonic to remember what characteristics to look for when listening to murmurs is SCRIPT: Site, Configuration (shape), Radiation, Intensity, Pitch and quality, and Timing in the cardiac cycle.
The use of two simple mnemonics may help differentiate systolic and diastolic murmurs; PASS and PAID. Pulmonary and aorticstenoses are systolic while pulmonary and aorticinsufficiency (regurgitation) are diastolic. Mitral and tricuspid defects are opposite.
Interventions that change murmur sounds
Inhalation leads to an increase in intrathoracic negative pressure, which increases the capacity of pulmonary circulation, thereby prolonging ejection time. This will affect the closure of the pulmonary valve. This finding, also called Carvallo's maneuver, has been found by studies to have a sensitivity of 100% and a specificity of 80% to 88% in detecting murmurs originating in the right heart. specifically positive Carvallo's sign describes the increase in intensity of a tricuspid regurgitation murmur with inspiration.
Valsalva maneuver. One study found the Valsalva maneuver to have a sensitivity of 65%, specificity of 96% in detecting hypertrophic obstructive cardiomyopathy (HOCM).
Both standing and Valsalva maneuver will decrease venous return and
subsequently decrease left ventricular filling, resulting in an increase
in the loudness of the murmur of hypertrophic cardiomyopathy, since
outflow obstruction is increased by decreasing preload. Alternatively,
squatting increases systemic vascular resistance, increasing afterload
and helping to hold the obstruction in a more open configuration,
decreasing the murmur. Maximum handgrip exercise also results in a
decrease in the loudness of the murmur.
Inhaled amyl nitrite
is a vasodilator that diminishes systolic murmurs in left-to-right
shunts in ventricular septal defects, and reveals right-to left shunts
in the setting of a pulmonic stenosis and a ventricular septal defect.
Positioning of the patient. That is, putting patients in the left lateral position will allow a murmur in the mitral valve area to be more pronounced.
Anatomic sources
Systolic
Aortic valve stenosis
typically is a crescendo/decrescendo systolic murmur best heard at the
right upper sternal border sometimes with radiation to the carotid
arteries. In mild aortic stenosis, the crescendo-decrescendo is early
peaking whereas in severe aortic stenosis, the crescendo is
late-peaking, and the S2 heart sound may be obliterated.
Stenosis of Bicuspid aortic valve
is similar to the aortic valve stenosis heart murmur, but a systolic
ejection click may be heard after S1 in calcified bicuspid aortic
valves. Symptoms tend to present between 40 and 70 years of age.
Mitral regurgitation
typically is a holosystolic (pansystolic) murmur heard best at the
apex, and may radiate to the axilla or precordium. A systolic click may
be heard if there is associated mitral valve prolapse.
Valsalva maneuver in mitral regurgitation associated with mitral valve
prolapse will decrease left ventricular preload and move the murmur
onset closer to S1, and isometric handgrip, which increases left
ventricular afterload, will increase murmur intensity. In acute severe
mitral regurgitation, a holosystolic (pansystolic) murmur may not be
heard.
Pulmonary valve stenosis
typically is a crescendo-decrescendo systolic murmur heard best at the
left upper sternal border, associated with a systolic ejection click
that increases with inspiration (due to increased venous return to the
right side of the heart) and sometimes radiates to the left clavicle.
Tricuspid valve regurgitation
presents as a holosystolic (pansystolic) murmur at the left lower
sternal border with radiation to the left upper sternal border.
Prominent v and c waves may be seen in the JVP (jugular venous
pressure). The murmur will increase with inspiration.
Hypertrophic obstructive cardiomyopathy
(or hypertrophic subaortic stenosis) will be a systolic
crescendo-decrescendo murmur best heard at the left lower sternal
border. Valsalva maneuver will increase the intensity of the murmur, as
will changing positions from squatting to standing.
Atrial septal defect
will present with a systolic crescendo-decrescendo murmur best heard at
the left upper sternal border due to increased volume going through the
pulmonary valve, and is associated with a fixed, split S2 and a right
ventricular heave.
Ventricular septal defect
(VSD) will present as a holosystolic (pansystolic) murmur at the left
lower sternal border, associated with a palpable thrill, and increases
with isometric handgrip. A right to left shunt (Eisenmenger syndrome) may develop with uncorrected VSDs due to worsening pulmonary hypertension, which will increase the murmur intensity and be associated with cyanosis.
Flow murmur may be heard at the right upper sternal border in certain conditions, such as anemia, hyperthyroidism, fever, and pregnancy.
Diastolic
Aortic valve regurgitation
will present as a diastolic decrescendo murmur heard at the left lower
sternal border or right lower sternal border (when associated with a
dilated aorta). This may be associated with bounding carotid and
peripheral pulses (Corrigan's pulse, Watson's water hammer pulse), and a widened pulse pressure.
Mitral stenosis
typically presents as a diastolic low-pitched decrescendo murmur best
heard at the cardiac apex in the left lateral decubitus position. It may
be associated with an opening snap. Increasing severity will shorten
the time between S2(A2) and the opening snap. (i.e. In severe MS the
opening snap will occur earlier after A2)
Pulmonary valve regurgitation
presents as a diastolic decrescendo murmur at the left lower sternal
border. A palpable S2 in the second left intercostal space correlates
with pulmonary hypertension due to mitral stenosis.
Severe coarctation of the aorta
can present with a continuous murmur: a systolic component at the left
infraclavicular region and the back due to the stenosis, and a diastolic
component over the chest wall due to blood flow through collateral
vessels.
Acute severe aortic regurgitation
is associated with a three phase murmur, specifically a midsystolic
murmur followed by S2, followed by a parasternal early diastolic and
mid-diastolic murmur (Austin Flint murmur).
Although the exact cause of an Austin Flint murmur is unknown, it is
hypothesized that the mechanism of murmur is from the severe aortic
regurgitation jet vibrating the anterior mitral valve leaflet, colliding
with the mitral inflow during diastole, with increased mitral inflow
velocity from the narrowed mitral valve orifice leading to the jet
impinging on the myocardial wall.
Another uncommon cause of a continuous murmur is a ruptured sinus of valsalva. Usually the murmur is well heard in the aortic area and along the left sternal border.
Types and disease associations
Continuous machinery murmur, at the left upper sternal border
Classic for a patent ductus arteriosus,
and in serious cases associated with poor feeding, failure to thrive
and respiratory distress. Other examination findings may include widened
pulse pressures and bounding pulses.
Systolic murmur loudest below the left scapula
Classic for a coarctation of the aorta which is often seen in Turner's Syndrome, (gonadal dysgenesis),
an X-linked disorder with a part missing of the X-chromosome. Other
findings of this murmur is radio-femoral delay, and different blood
pressures in the upper and lower extremities.
Harsh holosystolic (pansystolic) murmur at the left lower sternal border
Classic for a ventricular septal defect. It is in these children that the delayed-onset cyanotic heart disease occurs known as Eisenmenger syndrome,
which is a reversal of the left-to-right heart shunt as the right
ventricle hypertrophies, causing a right-to-left shunt and resulting
cyanosis.
Widely split fixed S2 and systolic ejection murmur at the left upper sternal border
Classically due to a patent foramen ovale or atrial septal defect, which is lack of closure of the foramen ovale.
This produces a left-to-right shunt initially, thus does not produce
cyanosis, but causes pulmonary hypertension. Longstanding uncorrected
atrial septal defects can also result in Eisenmenger's syndrome with
resultant cyanosis.
Cooing dove murmur
The
cooing dove murmur is a cardiac murmur with a musical quality (high
pitched - hence the name) and is associated with aortic valve
regurgitation (or mitral regurgitation before rupture of chordae). It is
a diastolic murmur which can be heard over the mid-precordium.
Herniation can also occur in the absence of high ICP when mass lesions such as hematomas
occur at the borders of brain compartments. In such cases local
pressure is increased at the place where the herniation occurs, but this
pressure is not transmitted to the rest of the brain, and therefore
does not register as an increase in ICP.
Because herniation puts extreme pressure on parts of the brain
and thereby cuts off the blood supply to various parts of the brain, it
is often fatal. Therefore, extreme measures are taken in hospital
settings to prevent the condition by reducing intracranial pressure, or
decompressing (draining) a hematoma which is putting local pressure on a
part of the brain.
Signs and symptoms
Brain herniation frequently presents with abnormal posturing, a characteristic positioning of the limbs indicative of severe brain damage. These patients have a lowered level of consciousness, with Glasgow Coma Scores of three to five. One or both pupils may be dilated and fail to constrict in response to light. Vomiting can also occur due to compression of the vomiting center in the medulla oblongata.
Types of brain herniation 1) Uncal 2) Central 3) Cingulate or sub/trans-falcine 4) Transcalvarial 5) Upward 6) Tonsillar
The tentorium is an extension of the dura mater that separates the cerebellum from the cerebrum.
There are two major classes of herniation: supratentorial and
infratentorial. Supratentorial refers to herniation of structures
normally found above the tentorial notch, and infratentorial refers to structures normally found below it.
In uncal herniation, a common subtype of transtentorial herniation, the innermost part of the temporal lobe, the uncus, can be squeezed so much that it moves towards the tentorium and puts pressure on the brainstem, most notably the midbrain. The tentorium is a structure within the skull formed by the dura mater of the meninges. Tissue may be stripped from the cerebral cortex in a process called decortication.
The uncus can squeeze the oculomotor nerve (a.k.a. CN III), which may affect the parasympathetic input to the eye on the side of the affected nerve, causing the pupil of the affected eye to dilate
and fail to constrict in response to light as it should. Pupillary
dilation often precedes the somatic motor effects of CN III compression
called oculomotor nerve palsy
or third nerve palsy. This palsy presents as deviation of the eye to a
"down and out" position due to loss of innervation to all ocular motility muscles except for the lateral rectus (innervated by abducens nerve (a.k.a. CN VI) and the superior oblique (innervated by trochlear nerve
a.k.a. CN IV). The symptoms occur in this order because the
parasympathetic fibers surround the motor fibers of CN III and are hence
compressed first.
Compression of the ipsilateral posterior cerebral artery
will result in ischemia of the ipsilateral primary visual cortex and
contralateral visual field deficits in both eyes (contralateral homonymous hemianopsia).
Another important finding is a false localizing sign, the so-called Kernohan's notch, which results from compression of the contralateral cerebral crus containing descending corticospinal and some corticobulbar tract fibers. This leads to Ipsilateral hemiparesis in reference to the herniation and contralateral hemiparesis with reference to the cerebral crus.
With increasing pressure and progression of the hernia there will be distortion of the brainstem leading to Duret hemorrhages (tearing of small vessels in the parenchyma) in the median and paramedian zones of the mesencephalon and pons. The rupture of these vessels leads to linear or flamed shaped hemorrhages. The disrupted brainstem can lead to decorticate posture, respiratory center depression and death. Other possibilities resulting from brain stem distortion include lethargy, slow heart rate, and pupil dilation.
Uncal herniation may advance to central herniation. The sliding uncus syndrome represents uncal herniation without alteration in the level of consciousness and other sequelae mentioned above.
Central herniation
In central herniation, the diencephalon and parts of the temporal lobes of both of the cerebral hemispheres are squeezed through a notch in the tentorium cerebelli.
Transtentorial herniation can occur when the brain moves either up or
down across the tentorium, called ascending and descending
transtentorial herniation respectively; however descending herniation is
much more common. Downward herniation can stretch branches of the basilar artery (pontine arteries), causing them to tear and bleed, known as a Duret hemorrhage. The result is usually fatal. Other symptoms of this type of herniation include small, fixed pupils with
paralysis of upward eye movement giving the characteristic appearance
of "sunset eyes". Also found in these patients, often as a terminal
complication is the development of diabetes insipidus due to the compression of the pituitary stalk. Radiographically, downward herniation is characterized by obliteration of the suprasellar cistern
from temporal lobe herniation into the tentorial hiatus with associated
compression on the cerebral peduncles. Upwards herniation, on the
other hand, can be radiographically characterized by obliteration of the
quadrigeminal cistern. Intracranial hypotension syndrome has been known
to mimic downwards transtentorial herniation.
Cingulate herniation
Subfalcine herniation on CT
In cingulate or subfalcine herniation, the most common type, the innermost part of the frontal lobe is scraped under part of the falx cerebri, the dura mater at the top of the head between the two hemispheres of the brain. Cingulate herniation can be caused when one hemisphere swells and pushes the cingulate gyrus by the falx cerebri. This does not put as much pressure on the brainstem as the other types of herniation, but it may interfere with blood vessels in the frontal lobes that are close to the site of injury (anterior cerebral artery), or it may progress to central herniation. Interference with the blood supply can cause dangerous increases in ICP that can lead to more dangerous forms of herniation. Symptoms for cingulate herniation are not well defined. Usually occurring in addition to uncal herniation, cingulate herniation may present with abnormal posturing and coma. Cingulate herniation is frequently believed to be a precursor to other types of herniation.
Transcalvarial herniation
In transcalvarial herniation, the brain squeezes through a fracture or a surgical site in the skull. Also called "external herniation", this type of herniation may occur during craniectomy,
surgery in which a flap of skull is removed, the protruding brain
region preventing the piece of skull from being replaced during the
operation.
Upward herniation
Increased pressure in the posterior fossa can cause the cerebellum to move up through the tentorial opening in upward, or cerebellar herniation.[6] The midbrain
is pushed through the tentorial notch. This also pushes the midbrain
down. This is also known as a transtentorial herniation since it occurs
across the tentorium cerebelli.
Tonsillar herniation
Tonsillar herniation of the cerebellum is also known as a Chiari malformation
(CM), or previously an Arnold-Chiari malformation (ACM). There are
four types of Chiari malformation, and they represent very different
disease processes with different symptoms and prognosis. These
conditions can be found in asymptomatic patients as an incidental
finding, or can be so severe as to be life-threatening. This condition
is now being diagnosed more frequently by radiologists, as more patients
undergo MRI scans of their heads, especially upright MRI, which is more
than twice as sensitive for detecting this condition.[13]
Cerebellar tonsillar ectopia (CTE) is a term used by radiologists to
describe cerebellar tonsils that are "low lying" but that do not meet
the radiographic criteria for definition as a Chiari malformation. The
currently accepted radiographic definition for a Chiari malformation is
that cerebellar tonsils lie at least 5mm below the level of the foramen
magnum. Some clinicians have reported that some patients appear to
experience symptoms consistent with a Chiari malformation without
radiographic evidence of tonsillar herniation. Sometimes these patients
are described as having a 'Chiari [type] 0'.
There are many suspected causes of tonsillar herniation
including: decreased or malformed posterior fossa (the lower, back part
of the skull) not providing enough room for the cerebellum;
hydrocephalus or abnormal CSF volume pushing the tonsils out; or dural
tension pulling the brain caudally.
For further evaluation of tonsillar herniation, CINE flow studies
are used. This type of MRI examines flow of CSF at the cranio-cervical
joint. For persons experiencing symptoms but without clear MRI
evidence, especially if the symptoms are better in the supine position
and worse upon standing / upright, an upright MRI may be useful.
Treatment
MRI
showing damage due to herniation. This patient was left with residual
disabilities including those involving movement and speech.
Treatment involves removal of the etiologic mass and decompressive craniectomy. Brain herniation can cause severe disability or death. In fact, when herniation is visible on a CT scan, the prognosis for a meaningful recovery of neurological function is poor.
The patient may become paralyzed on the same side as the lesion causing
the pressure, or damage to parts of the brain caused by herniation may
cause paralysis on the side opposite the lesion. Damage to the midbrain, which contains the reticular activating network which regulates consciousness, will result in coma. Damage to the cardio-respiratory centers in the medulla oblongata will cause respiratory arrest and (secondarily) cardiac arrest.
Investigation is underway regarding the use of neuroprotective agents
during the prolonged post-traumatic period of brain hypersensitivity
associated with the syndrome.
Concussion, also known as mild traumatic brain injury (mTBI), is typically defined as a head injury that temporarily affects brain functioning. Symptoms may include loss of consciousness (LOC); memory loss; headaches; difficulty with thinking, concentration or balance; nausea; blurred vision; sleep disturbances; and mood changes. Any of these symptoms may begin immediately, or appear days after the injury. It is not unusual for symptoms to last 2 weeks in adults and 4 weeks in children. Fewer than 10% of sports-related concussions among children are associated with loss of consciousness.
Common causes include motor vehicle collisions, falls, sports injuries and bicycle accidents. Risk factors include drinking alcohol and a prior history of concussion.
The mechanism of injury involves either a direct blow to the head or
forces elsewhere on the body that are transmitted to the head. This is believed to result in neuron dysfunction, as there is increased glucose requirements but not enough blood supply. Diagnosis requires less than 30 minutes of LOC, memory loss of less than 24 hours, and a Glasgow coma scale score of 13 to 15. Otherwise, it is considered a moderate or severe traumatic brain injury.
Prevention of concussions includes the use of a helmet when bicycling or motorbiking. Treatment generally involves physical and cognitive rest for a day or two, with a gradual return to activities. Prolonged periods of rest may slow recovery and result in greater depression and anxiety. Paracetamol (acetaminophen) or NSAIDs may be recommended to help with a headache. Physiotherapy may be useful for persistent balance problems; cognitive behavioral therapy may be useful for mood changes. Evidence to support the use of hyperbaric oxygen therapy and chiropractic therapy is lacking.
Worldwide, concussions are estimated to affect more than 3.5 per 1,000 people a year. Concussions are classified as mild traumatic brain injuries and are the most common type of TBIs. Males and young adults are most commonly affected. Outcomes are generally good. Another concussion before the symptoms of a prior concussion have resolved is associated with worse outcomes. Repeated concussions may also increase the risk in later life of chronic traumatic encephalopathy, Parkinson's disease and depression.
Concussions are associated with a variety of symptoms, which typically occur rapidly after the injury. Early symptoms usually subside within days or weeks. The number and type of symptoms any one individual has varies. The severity of the initial symptoms is the strongest predictor of recovery time.
Physical
Headaches are the most common mTBI symptom. Others include dizziness, vomiting, nausea, lack of motor coordination, difficulty balancing, or other problems with movement or sensation. Visual symptoms include light sensitivity, seeing bright lights, blurred vision, and double vision. Tinnitus, or a ringing in the ears, is also commonly reported. In one in about seventy concussions, concussive convulsions occur, but seizures that take place during or immediately after a concussion are not "post-traumatic seizures", and, unlike post-traumatic seizures, are not predictive of post-traumatic epilepsy, which requires some form of structural brain damage, not just a momentary disruption in normal brain functioning.
Concussive convulsions are thought to result from temporary loss or
inhibition of motor function and are not associated either with epilepsy
or with more serious structural damage. They are not associated with
any particular sequelae and have the same high rate of favorable outcomes as concussions without convulsions.
Cognitive and emotional
Cognitive symptoms include confusion, disorientation, and difficulty focusing attention. Loss of consciousness may occur, but is not necessarily correlated with the severity of the concussion if it is brief. Post-traumatic amnesia, in which events following the injury cannot be recalled, is a hallmark of concussions. Confusion, another concussion hallmark, may be present immediately or may develop over several minutes. A person may repeat the same questions, be slow to respond to questions or directions, have a vacant stare, or have slurred or incoherent speech. Other mTBI symptoms include changes in sleeping patterns and difficulty with reasoning, concentrating, and performing everyday activities.
A concussion can result in changes in mood including crankiness, loss of interest in favorite activities or items, tearfulness, and displays of emotion that are inappropriate to the situation. Common symptoms in concussed children include restlessness, lethargy, and irritability.
Mechanism
Rotational force is key in a concussion. Punches in boxing can deliver more rotational force to the head than the typical impact in American football.
Forces
The brain is surrounded by cerebrospinal fluid,
which protects it from light trauma. More severe impacts, or the forces
associated with rapid acceleration, may not be absorbed by this
cushion. Concussion may be caused by impact forces,
in which the head strikes or is struck by something, or impulsive
forces, in which the head moves without itself being subject to blunt trauma (for example, when the chest hits something and the head snaps forward).
Forces may cause linear, rotational, or angular movement of the brain or a combination of them.
In rotational movement, the head turns around its center of gravity and
in angular movement, it turns on an axis, not through its center of
gravity. The amount of rotational force is thought to be the major component in concussion and its severity.
Studies with athletes have shown that the amount of force and the
location of the impact are not necessarily correlated with the severity
of the concussion or its symptoms, and have called into question the
threshold for concussion previously thought to exist at around 70–75 g.
The parts of the brain most affected by rotational forces are the midbrain and diencephalon. It is thought that the forces from the injury disrupt the normal cellular activities in the reticular activating system located in these areas and that this disruption produces the loss of consciousness often seen in concussion. Other areas of the brain that may be affected include the upper part of the brain stem, the fornix, the corpus callosum, the temporal lobe, and the frontal lobe. Angular accelerations of 4600, 5900, or 7900 rad/s2 are estimated to have 25, 50, or 80% risk of mTBI respectively.
Pathophysiology
In both animals and humans, mTBI can alter the brain's physiology for hours to years, setting into motion a variety of pathological events.
As one example, in animal models, after an initial increase in glucose
metabolism, there is a subsequent reduced metabolic state which may
persist for up to four weeks after injury. Though these events are thought to interfere with neuronal and brain function, the metabolic processes that follow concussion are reversible in a large majority of affected brain cells; however, a few cells may die after the injury.
Included in the cascade of events unleashed in the brain by concussion is impaired neurotransmission, loss of regulation of ions, deregulation of energy use and cellular metabolism, and a reduction in cerebral blood flow. Excitatory neurotransmitters, chemicals such as glutamate that serve to stimulate nerve cells, are released in excessive amounts. The resulting cellular excitation causes neurons to fire excessively. This creates an imbalance of ions such as potassium and calcium across the cell membranes of neurons (a process like excitotoxicity).
At the same time, cerebral blood flow is relatively reduced for unknown reasons, though the reduction in blood flow is not as severe as it is in ischemia. Thus cells get less glucose than they normally do, which causes an "energy crisis".
Concurrently with these processes, the activity of mitochondria may be reduced, which causes cells to rely on anaerobic metabolism to produce energy, increasing levels of the byproduct lactate.
For a period of minutes to days after a concussion, the brain is especially vulnerable to changes in intracranial pressure, blood flow, and anoxia. According to studies performed on animals
(which are not always applicable to humans), large numbers of neurons
can die during this period in response to slight, normally innocuous
changes in blood flow.
Concussion involves diffuse (as opposed to focal) brain injury, meaning that the dysfunction occurs over a widespread area of the brain rather than in a particular spot. It is thought to be a milder type of diffuse axonal injury, because axons may be injured to a minor extent due to stretching. Animal studies in which rodents were concussed have revealed lifelong neuropathological consequences such as ongoing axonal degeneration and neuroinflammation in subcortical white matter tracts.
Axonal damage has been found in the brains of concussion sufferers who
died from other causes, but inadequate blood flow to the brain due to
other injuries may have contributed.
Findings from a study of the brains of deceased NFL athletes who
received concussions suggest that lasting damage is done by such
injuries. This damage, the severity of which increases with the
cumulative number of concussions sustained, can lead to a variety of
other health issues.
The debate over whether concussion is a functional or structural phenomenon is ongoing.
Structural damage has been found in the mildly traumatically injured
brains of animals, but it is not clear whether these findings would
apply to humans.
Such changes in brain structure could be responsible for certain
symptoms such as visual disturbances, but other sets of symptoms,
especially those of a psychological nature, are more likely to be caused
by reversible pathophysiological changes in cellular function that
occur after concussion, such as alterations in neurons' biochemistry. These reversible changes could also explain why dysfunction is frequently temporary.
A task force of head injury experts called the Concussion In Sport
Group met in 2001 and decided that "concussion may result in
neuropathological changes but the acute clinical symptoms largely
reflect a functional disturbance rather than structural injury."
Using animal studies, the pathology of a concussion seems to start with mechanical shearing and stretching forces disrupting the cell membrane of nerve cells through "mechanoporation".
This results in potassium outflow from within the cell into the
extracellular space with the subsequent release of excitatory
neurotransmitters including glutamate which leads to enhanced potassium
extrusion, in turn resulting in sustained depolarization, impaired nerve
activity and potential nerve damage.
Human studies have failed to identify changes in glutamate
concentration immediately post-mTBI, though disruptions have been seen 3
days to 2 weeks post-injury. In an effort to restore ion balance, the sodium-potassium ion pumps increase activity, which results in excessive ATP (adenosine triphosphate) consumption and glucose utilization, quickly depleting glucose stores within the cells. Simultaneously, inefficient oxidative metabolism leads to anaerobic metabolism of glucose and increased lactate accumulation. There is a resultant local acidosis in the brain and increased cell membrane permeability, leading to local swelling.
After this increase in glucose metabolism, there is a subsequent lower
metabolic state which may persist for up to 4 weeks after injury. A
completely separate pathway involves a large amount of calcium
accumulating in cells, which may impair oxidative metabolism and begin
further biochemical pathways that result in cell death. Again, both of
these main pathways have been established from animal studies and the
extent to which they apply to humans is still somewhat unclear.
Unequal pupil size can be a sign of a brain injury possibly more serious than a concussion.
Head trauma recipients are initially assessed to exclude a more severe emergency
such as an intracranial hemorrhage. This includes the "ABCs" (airway,
breathing, circulation) and stabilization of the cervical spine which is
assumed to be injured in any athlete who is found to be unconscious
after head or neck injury. Indications that screening for more serious
injury is needed include worsening of symptoms such as headaches,
persistent vomiting, increasing disorientation or a deteriorating level of consciousness, seizures, and unequal pupil size. Those with such symptoms, or those who are at higher risk of a more serious brain injury, may undergo brain imaging
to detect lesions and are frequently observed for 24–48 hours. A brain
CT or brain MRI should be avoided unless there are progressive
neurological symptoms, focal neurological findings or concern of skull
fracture on exam.
Diagnosis of mTBI is based on physical and neurological
examination findings, duration of unconsciousness (usually less than
30 minutes) and post-traumatic amnesia (PTA; usually less than
24 hours), and the Glasgow Coma Scale (mTBI sufferers have scores of 13 to 15). Neuropsychological tests exist to measure cognitive function and the international consensus meeting in Zurich recommended the use of the SCAT2 test. Such tests may be administered hours, days, or weeks after the injury, or at different times to demonstrate any trend.
Increasingly, athletes are also being tested pre-season to provide a
baseline for comparison in the event of an injury, though this may not
reduce risk or affect return to play.
If the Glasgow coma scale is less than 15 at two hours or less than 14 at any time, a CT is recommended. In addition, a CT scan is more likely to be performed if observation after discharge is not assured or intoxication is present, there is suspected increased risk for bleeding, age greater than 60, or less than 16. Most concussions, without complication, cannot be detected with MRI or CT scans. However, changes have been reported on MRI and SPECT imaging in those with concussion and normal CT scans, and post-concussion syndrome may be associated with abnormalities visible on SPECT and PET scans. Mild head injury may or may not produce abnormal EEG readings.
A blood test known as the Brain Trauma Indicator was approved in the
United States in 2018 and may be able to rule out the risk of
intracranial bleeding and thus the need for a CT scan for adults.
Concussion may be under-diagnosed because of the lack of the
highly noticeable signs and symptoms while athletes may minimize their
injuries to remain in the competition. A retrospective survey in 2005 suggested that more than 88% of concussions are unrecognized.
Diagnosis can be complex because concussion shares symptoms with
other conditions. For example, post-concussion symptoms such as
cognitive problems may be misattributed to brain injury when, in fact,
due to post-traumatic stress disorder (PTSD).
Classification
No single definition of concussion, minor head injury, or mild traumatic brain injury is universally accepted. In 2001, the expert Concussion in Sport Group of the first International Symposium on Concussion in Sport defined concussion as "a complex pathophysiological process affecting the brain, induced by traumatic biomechanical forces."
It was agreed that concussion typically involves temporary impairment
of neurological function that heals by itself within time, and that neuroimaging normally shows no gross structural changes to the brain as the result of the condition.
However, although no structural brain damage occurs according to the classic definition, some researchers have included injuries in which structural damage has occurred and the National Institute for Health and Clinical Excellence definition includes physiological or physical disruption in the brain's synapses.
Also, by definition, concussion has historically involved a loss of
consciousness. However, the definition has evolved over time to include a
change in consciousness, such as amnesia, although controversy continues about whether the definition should include only those injuries in which loss of consciousness occurs.
This debate resurfaces in some of the best-known concussion grading
scales, in which those episodes involving loss of consciousness are
graded as being more severe than those without.
Concussion falls under the classification of mild TBI, but it is not clear whether concussion is implied in mild brain injury or mild head injury. "mTBI" and "concussion" are often treated as synonyms in medical literature but other injuries such as intracranial hemorrhages (e.g. intra-axial hematoma, epidural hematoma, and subdural hematoma) are not necessarily precluded in mTBI or mild head injury, as they are in concussion. mTBI associated with abnormal neuroimaging may be considered "complicated mTBI". "Concussion" can be considered to imply a state in which brain function is temporarily impaired and "mTBI" to imply a pathophysiological state, but in practice, few researchers and clinicians distinguish between the terms.
Descriptions of the condition, including the severity and the area of
the brain affected, are now used more often than "concussion" in
clinical neurology.
Grading systems
At least 41 systems measure the severity, or grade, of a mild head injury, and there is little agreement about which is best.
In an effort to simplify, the 2nd International Conference on
Concussion in Sport, meeting in Prague in 2004, decided that these
systems should be abandoned in favor of a 'simple' or 'complex'
classification.
However, the 2008 meeting in Zurich abandoned the simple versus complex
terminology, although the participants did agree to keep the concept
that most (80–90%) concussions resolve in a short period (7–10 days) and
although the recovery time frame may be longer in children and
adolescents.
In the past, the decision to allow athletes to return to participation was frequently based on the grade of concussion. However, current research and recommendations by professional organizations including the National Athletic Trainers' Association recommend against such use of these grading systems.
Currently, injured athletes are prohibited from returning to play
before they are symptom-free during both rest and exertion and until
results of the neuropsychological tests have returned to pre-injury levels.
Symptoms last >15 minutes, no loss of consciousness
Loss of consciousness (IIIa, coma lasts seconds, IIIb for minutes)
Prevention
Prevention of mTBI involves general measures such as wearing seat belts, using airbags in cars, and protective equipment such as helmets for high-risk sports.
Older people are encouraged to reduce fall risk by keeping floors free
of clutter and wearing thin, flat, shoes with hard soles that do not
interfere with balance.
Protective equipment such as helmets and other headgear and
policy changes such as the banning of body checking in youth hockey
leagues have been found to reduce the number and severity of concussions
in athletes. Secondary prevention such as a Return to Play Protocol for an athlete may reduce the risk of repeat concussions.
New "Head Impact Telemetry System" technology is being placed in
helmets to study injury mechanisms and may generate knowledge that will
potentially help reduce the risk of concussions among American Football
players.
Educational interventions, such as handouts, videos, workshops,
and lectures, can improve concussion knowledge of diverse groups,
particularly youth athletes and coaches.
Strong concussion knowledge may be associated with greater recognition
of concussion symptoms, higher rates of concussion reporting behaviors,
and reduced body checking-related penalties and injuries, thereby
lowering risk of mTBI.
Self-reported concussion rates among U-20 and elite rugby union players in Ireland are 45–48%.
Half of these injuries go unreported. Changes to the rules or enforcing
existing rules in sports, such as those against "head-down tackling",
or "spearing", which is associated with a high injury rate, may also
prevent concussions.
Treatment
After exclusion of neck or head injury, observation should be
continued for several hours. If repeated vomiting, worsening headache,
dizziness, seizure activity, excessive drowsiness, double vision,
slurred speech, unsteady walk, or weakness or numbness in arms or legs,
or signs of basilar skull fracture develop, immediate assessment in an emergency department is needed.
After this initial period has passed, there is debate as to whether it
is necessary to awaken the person several times during the first night,
as has traditionally been done, or whether there is more benefit from
uninterrupted sleep.
Physical and cognitive rest should be continued until all
symptoms have resolved with most (80–90%) concussions resolving in seven
to ten days, although the recovery time may be longer in children and
adolescents.
Cognitive rest includes reducing activities which require concentration
and attention such as school work, video games, and text messaging.
It has been suggested that even leisure reading can commonly worsen
symptoms in children and adolescents and proposals include time off from
school and attending partial days. Since students may appear 'normal', continuing education of relevant school personnel may be needed.
Those with concussion are generally prescribed rest, including adequate nighttime sleep as well as daytime rest. Rest includes both physical and cognitive rest until symptoms clear and a gradual return to normal activities at a pace that does not cause symptoms to worsen is recommended. Education about symptoms, their management, and their normal time course, can lead to an improved outcome.
For persons participating in athletics, the 2008 Zurich Consensus
Statement on Concussion in Sport recommends that participants be
symptom-free before restarting and then progress through a series of
graded steps. These steps include:
complete physical and cognitive rest
light aerobic activity (less than 70% of maximum heart rate)
sport-specific activities such as running drills and skating drills
non-contact training drills (exercise, coordination, and cognitive load)
full-contact practice
full-contact games.
Only when symptom-free for 24 hours, should progression to the next
step occur. If symptoms occur, the person should drop back to the
previous asymptomatic level for at least another 24 hours. The emphasis is on remaining symptom-free and taking it in medium steps, not on the steps themselves.
Medications may be prescribed to treat sleep problems and depression. Analgesics such as ibuprofen can be taken for headaches, but paracetamol (acetaminophen) is preferred to minimize the risk of intracranial hemorrhage. Concussed individuals are advised not to use alcohol or other drugs that have not been approved by a doctor as they can impede healing.
Activation database-guided EEG biofeedback has been shown to return the
memory abilities of the concussed individual to levels better than the
control group.
About one percent of people who receive treatment for mTBI need surgery for a brain injury. Observation to monitor for worsening condition is an important part of treatment. Health care
providers recommend that those suffering from concussion return for
further medical care and evaluation 24 to 72 hours after the concussive
event if the symptoms worsen. Athletes, especially intercollegiate or professional,
are typically followed closely by team athletic trainers during this
period but others may not have access to this level of health care and
may be sent home with minimal monitoring.
People may be released after assessment from hospital or
emergency room to the care of a trusted person with instructions to
return if they display worsening symptoms
or those that might indicate an emergent condition such as change in
consciousness, convulsions, severe headache, extremity weakness,
vomiting, new bleeding or deafness in either or both ears.
Prognosis
People who have had a concussion seem more susceptible to another
one, particularly if the new injury occurs before symptoms from the
previous concussion have completely gone away. It is also a negative process if smaller impacts cause the same symptom severity. Repeated concussions may increase a person's risk in later life for dementia, Parkinson's disease, and depression.
mTBI has a mortality rate of almost zero. The symptoms of most concussions resolve within weeks, but problems may persist. These are seldom permanent, and the outcome is usually excellent. About 75% of children recover within three months.
The overall prognosis for recovery may be influenced by a variety
of factors that include age at the
time of injury, intellectual
abilities, family environment, social support system, occupational
status, coping strategies, and financial circumstances. People over age 55 may take longer to heal from mTBI or may heal incompletely.
Similarly, factors such as a previous head injury or a coexisting
medical condition have been found to predict longer-lasting
post-concussion symptoms. Other factors that may lengthen recovery time after mTBI include psychological problems such as substance abuse or clinical depression, poor health before the injury or additional injuries sustained during it, and life stress.
Longer periods of amnesia or loss of consciousness immediately after
the injury may indicate longer recovery times from residual symptoms. For unknown reasons, having had one concussion significantly increases a person's risk of having another.
Having previously sustained a sports concussion has been found to be a
strong factor increasing the likelihood of a concussion in the future.
Other strong factors include participation in a contact sport and body
mass size. The prognosis may differ between concussed adults and children; little research has been done on concussion in the pediatric population, but concern exists that severe concussions could interfere with brain development in children.
A 2009 study found that individuals with a history of concussions
might demonstrate a decline in both physical and mental performance for
longer than 30 years. Compared to their peers with no history of brain
trauma, sufferers of concussion exhibited effects including loss of episodic memory and reduced muscle speed.
Post-concussion syndrome
In post-concussion syndrome, symptoms do not resolve for weeks,
months, or years after a concussion, and may occasionally be permanent. About 10% to 20% of people have post-concussion syndrome for more than a month. Symptoms may include headaches, dizziness, fatigue, anxiety, memory and attention problems, sleep problems, and irritability. There is no established treatment, and rest, a recommended recovery technique, has limited effectiveness. Symptoms usually go away on their own within months but may last for years.
The question of whether the syndrome is due to structural damage or
other factors such as psychological ones, or a combination of these, has
long been the subject of debate.
Cumulative effects
Cumulative effects of concussions are poorly understood, especially
the effects on children. The severity of concussions and their symptoms
may worsen with successive injuries, even if a subsequent injury occurs
months or years after an initial one. Symptoms may be more severe and changes in neurophysiology can occur with the third and subsequent concussions.
Studies have had conflicting findings on whether athletes have longer
recovery times after repeat concussions and whether cumulative effects
such as impairment in cognition and memory occur.
Cumulative effects may include psychiatric disorders and loss of long-term memory. For example, the risk of developing clinical depression has been found to be significantly greater for retired American football players with a history of three or more concussions than for those with no concussion history. Three or more concussions is also associated with a fivefold greater chance of developing Alzheimer's disease earlier and a threefold greater chance of developing memory deficits.
CTE
Chronic traumatic encephalopathy, or "CTE", is an example of the
cumulative damage that can occur as the result of multiple concussions
or less severe blows to the head. The condition was previously referred
to as "dementia pugilistica", or "punch drunk" syndrome, as it was first noted in boxers. The disease can lead to cognitive and physical handicaps such as parkinsonism, speech and memory problems, slowed mental processing, tremor, depression, and inappropriate behavior. It shares features with Alzheimer's disease.
Second-impact syndrome
Second-impact syndrome, in which the brain swells dangerously after a minor blow, may occur in very rare cases.
The condition may develop in people who receive second blow days or
weeks after an initial concussion before its symptoms have gone away.
No one is certain of the cause of this often fatal complication, but it
is commonly thought that the swelling occurs because the brain's arterioles lose the ability to regulate their diameter, causing a loss of control over cerebral blood flow. As the brain swells, intracranial pressure rapidly rises. The brain can herniate, and the brain stem can fail within five minutes. Except in boxing, all cases have occurred in athletes under age 20. Due to the very small number of documented cases, the diagnosis is controversial, and doubt exists about its validity. A 2010 Pediatrics
review article stated that there is debate whether the brain swelling
is due to two separate hits or to just one hit, but in either case,
catastrophic football head injuries are three times more likely in high
school athletes than in college athletes.
Epidemiology
Annual incidence of MTBI by age group in Canada
Most cases of traumatic brain injury are concussions. A World Health
Organization (WHO) study estimated that between 70 and 90% of head
injuries that receive treatment are mild.
However, due to under reporting and to the widely varying definitions
of concussion and mTBI, it is difficult to estimate how common the
condition is.
Estimates of the incidence of concussion may be artificially low, for
example, due to under reporting. At least 25% of mTBI sufferers fail to
get assessed by a medical professional.
The WHO group reviewed studies on the epidemiology of mTBI and found a
hospital treatment rate of 1–3 per 1000 people, but since not all
concussions are treated in hospitals, they estimated that the rate per
year in the general population is over 6 per 1000 people.
Age
Young children have the highest concussion rate among all age groups. However, most people who suffer a concussion are young adults. A Canadian study found that the yearly incidence of mTBI is lower in older age groups (graph at right). Studies suggest males suffer mTBI at about twice the rate of their female counterparts. However, female athletes may be at a higher risk of suffering a concussion than their male counterparts.
Sports
Up to five percent of sports injuries are concussions. The U.S. Centers for Disease Control and Prevention
estimates that 300,000 sports-related concussions occur yearly in the
U.S., but that number includes only athletes who lost consciousness. Since loss of consciousness is thought to occur in less than 10% of concussions, the CDC estimate is likely lower than the real number. Sports in which concussion is particularly common include football and boxing (a boxer aims to "knock out",
i.e. give a mild traumatic brain injury to, the opponent). The injury
is so common in the latter that several medical groups have called for a
ban on the sport, including the American Academy of Neurology, the World Medical Association, and the medical associations of the UK, the US, Australia, and Canada.
The Hippocratic Corpus, a collection of medical works from ancient Greece, mentions concussion, later translated to commotio cerebri, and discusses loss of speech, hearing and sight that can result from "commotion of the brain".
This idea of disruption of mental function by "shaking of the brain"
remained the widely accepted understanding of concussion until the
19th century. In the 10th century, the Persian physician Muhammad ibn Zakarīya Rāzi was the first to write about concussion as distinct from other types of head injury.
He may have been the first to use the term "cerebral concussion", and
his definition of the condition, a transient loss of function with no
physical damage, set the stage for the medical understanding of the
condition for centuries.
In the 13th century, the physician Lanfranc of Milan's Chiurgia Magna
described concussion as brain "commotion", also recognizing a
difference between concussion and other types of traumatic brain injury
(though many of his contemporaries did not), and discussing the
transience of post-concussion symptoms as a result of temporary loss of
function from the injury. In the 14th century, the surgeon Guy de Chauliac pointed out the relatively good prognosis of concussion as compared to more severe types of head trauma such as skull fractures and penetrating head trauma.
In the 16th-century, the term "concussion" came into use, and symptoms
such as confusion, lethargy, and memory problems were described. The 16th century physician Ambroise Paré used the term commotio cerebri, as well as "shaking of the brain", "commotion", and "concussion".
Until the 17th century, a concussion was usually described by its
clinical features, but after the invention of the microscope, more
physicians began exploring underlying physical and structural
mechanisms.
However, the prevailing view in the 17th century was that the injury
did not result from physical damage, and this view continued to be
widely held throughout the 18th century.
The word "concussion" was used at the time to describe the state of
unconsciousness and other functional problems that resulted from the
impact, rather than a physiological condition. In 1839, Guillaume Dupuytren described brain contusions, which involve many small hemorrhages, as contusio cerebri and showed the difference between unconsciousness associated with damage to the brain parenchyma and that due to concussion, without such injury. In 1941, animal experiments showed that no macroscopic damage occurs in concussion.
Society and culture
Costs
Due to the lack of a consistent definition, the economic costs of mTBI are not known, but they are estimated to be very high.
These high costs are due in part to the large percentage of hospital
admissions for head injury that is due to mild head trauma, but indirect costs such as lost work time and early retirement account for the bulk of the costs. These direct and indirect costs cause the expense of mild brain trauma to rival that of moderate and severe head injuries.
Terminology
The terms mild brain injury, mild traumatic brain injury (mTBI), mild
head injury (MHI), and concussion may be used interchangeably;
although the term "concussion" is still used in sports literature as
interchangeable with "MHI" or "mTBI", the general clinical medical
literature uses "mTBI" instead, since a 2003 CDC report outlined it as an important strategy. In this article, "concussion" and "mTBI" are used interchangeably.
The term "concussion" is from Latinconcutere, "to shake violently" or concussus, "action of striking together".
Measurement of predictive visual tracking is being studied as a screening technique to identify mild traumatic brain injury. A head-mounted display unit with eye-tracking
capability shows a moving object in a predictive pattern for the person
to follow with their eyes. People without brain injury will be able to
track the moving object with smooth pursuit eye movements and correct trajectory while it is hypothesized that those with mild traumatic brain injury cannot.
