Diagnosis of Coma and Stupor Flashcards
What is ‘lethargy’ defined as?
individual is sleepy but easily aroused with stimulation.
What is ‘hypersomnia’ defined as?
Hypersomnia describes someone who is excessively sleepy and requires vigorous stimulation but shows normal cognition once aroused.
What is ‘obtundation’ defined as?
Obtundation refers to an individual who in addition to severe lethargy shows cognitive dysfunction
What is ‘stupor’ defined as?
Stupor refers to severe obtundation and is distinguished from coma only because the eyes open briefly.
What is ‘coma’ defined as?
. In coma, the eyes fail to open to the most vigorous stimulation
Delirium usually refers to a disoriented, confused patient who fluctuates between lethargy and agitation. These terms are not always used in the same way by all physicians so it is essential that you describe a patient’s response to stimulation.
For example, “eyes again failed to open after nail-bed pinching but the upper limbs moved slightly for the first time” conveys much more useful and precise information than “remains comatose”
What is abulia?
Awake but apathetic, no spontaneity. With vigorous stimulation, cognitive function may be normal. (bilateral frontal lobe disease, lobotomized)
Term describing patients in the aftermath of coma
What is akinetic mutism?
Silent, alert-appearing immobility. No mental activity with vigorous stimulation (disease of frontal lobes and hypothalamus)
Term describing patients in the aftermath of coma
What is a minimally conscious state? vegatative state?
Minimally conscious state: fragments of awareness
Vegetative state: awake, no awareness or meaningful interaction with the environment
Terms describing patients in the aftermath of coma
Overlap & transitions exist between these conditions so you need to describe stimuli for arousal and the patient’s response
Patients in coma generally develop eye-opening and sleep-wake cycles after 2 to 4 weeks regardless of the cause of coma. A number of terms have been used to describe these patients.
A patient is abulic when he has his eyes open but demonstrates no spontaneous interaction with the environment. One sees this after severe bifrontal lobe damage (lobotomy at its worst), but with vigorous stimulation, these patients answer questions correctly.
If no evidence of mental activity can be elicited with vigorous stimulation, the patient may be said to show “akinetic mutism” or be in a “vegetative state.”
The term “vegetative” refers to the so-called “vegetative functions” of the brainstem that include maintaining sleep-wake cycles, respirations, heart rate, blood pressure and visceral autonomic regulation. A patient who appears vegetative but then shows fragments of awareness and meaningful interaction with the environment is said to be in “minimally conscious state” or MCS. Such patients may reach for objects, grunt or gesture in response to a command, visually fixate and track but are unable to do much more. It is important to realize that these conditions may not be static but can undergo transitions over time. That is typically the case when the news media reports on individuals awakening after many years spent in “coma.”
Now that we know the terms used to describe altered consciousness, let us look a little deeper into what constitutes normal consciousness. “How would you describe or define consciousness?”
The idea that the brain was responsible for an individual’s self-awareness, emotions and cognition is an ancient concept. Hippocrates wrote: “And men should know that from nothing else but the brain come joys, delights, laughter and jests, and sorrows, grief, despondency and lamentations. And by this, in an especial manner, we acquire wisdom and knowledge, and see and hear and know what are foul and what are fair, what sweet and what unsavory…”
In the 19th century consciousness was thought to reflect the sum total activity of the cerebral hemispheres and that consciousness disappeared only if both hemisphere were damaged. However, post-mortem exams of unconscious patients dying from Wernicke’s encephalopathy disclosed lesions in the peri-aqueductal grey matter and the caudal part of the third ventricle, while the cerebral hemispheres were left undamaged. This suggested that the anatomy of consciousness was more complicated.
One useful way to address what constitutes consciousness is to recognize that there are actually two components to consciousness. What are they?
One is arousal or wakefulness and the other is the content of consciousness.
Wakefulness is achieved by neural circuits that mediate sleep-wake cycles and involves a specific area of the upper brainstem commonly referred to as the:
“reticular activating system” but more accurately named the “ascending arousal system.”
Disruption of this system causes stupor and coma and is the primary focus of this presentation.
The second component of consciousness involves the content of consciousness. This refers to what?
the cerebral activity responsible for self-awareness, cognition and purposeful interactions with the environment. These behaviors are premeditated and not reflex in nature. The neural networks in the cortex drive this brain activity.
Disease affecting the content of consciousness causes dementia. It should be obvious that a person must be in an awake state in order to engage in any cognitive task.
While the role of the cortex in maintaining consciousness seems obvious, what do we know about the brain’s arousal systems?
In the last century, the anatomy of consciousness became better defined through the work of Baron Constantine von Economo. In 1916, von Economo noticed cases of a new and not previously described type of encephalitis that caused a “sleeping sickness” he termed encephalitis lethargica. This disease became a world-wide epidemic that did not subside until a decade later. This epidemic should not be confused with the huge influenza pandemic of 1918 that killed millions and whose recombinant progeny H1N1 has recently threatened the world.
The virus causing Von Economo’s encephalitis lethargica has never been identified. What did the sleeping sickness look like?
Individuals slept for 20 hours a day, awakening only to eat or go to the toilet. Some patients died, and von Economo’s post-mortem studies revealed lesions in the rostral periaqueductal grey matter and posterior 3rd ventricle.
Some patients with encephalitis would sleep at most only a few hours a day and had lesions in the rostral hypothalamus.
Among the survivors, there was a recovery phase several months after the acute encephalitis when some patients developed sleep attacks and cataplexy. These patients died later from other causes and were found to have lesions in the posterior lateral hypothalamus lying between a sleep promoting area in the rostral hypothalamus and a wakefulness promoting area in the upper midbrain.
What is cataplexy?
Cataplexy refers to the sudden involuntary loss of muscle tone during emotional excitement, such as intense laughter, causing the individual to fall down. These patients had what we now call “narcolepsy.”
Further research has identified the sleep promoting area as:
the ventrolateral preoptic nucleus, whose destruction causes profound insomnia.
What causes narcolepsy?
Narcolepsy is caused by a loss of neurons that can be histochemically stained with antibodies against the neuro-peptide neurotransmitter “orexin”.
The electroencephalogram or EEG was invented in 1929. An array of electrodes on the scalp surface could generate patterns of cortical electrical activity in which wakefulness was readily distinguished from sleep. Soon afterwards, animal studies determined where lesions placed in different parts of the brain disrupted consciousness.
Thus, a brainstem transection at the level of the cervical medulla caused quadriplegia and respiratory arrest requiring mechanical ventilation. While these motionless animals appeared unconscious, the EEG showed a “desynchronized” brain wave pattern characteristic for the awake state. Successive lesions marching upwards (rostrally) toward the midbrain produced the same effect until a cut was made where?
at the level of the posterior colliculi (quadrigeminal plate). At this level, the EEG became “synchronized” showing high voltage slow waves typical of the pattern seen in sleep and in some patients with coma. In other words, lesions of the brainstem did not affect wakefulness, as defined by the EEG pattern, until the lesion reached the upper pontine and midbrain level.
A number of neuropathological lesion have been associated with causing coma. Name them.
The first, represented by A, involves severe sudden bilateral hemispheric disease. It is unusual, however, to have such an extensive global insult without affecting the upper brainstem as well.
The other pictures, B through E, are notable for involving some region of the upper brainstem but always including “reticular grey formation” whether found in the thalamus, hypothalamus, mid-brain peri-aqueductal grey or upper third of the pons.
What is not shown is that often, the damage to these regions are often secondary to a herniation syndrome affecting one or both cerebral hemispheres. In any event, people noticed that the reticular grey formation was affected and that led to the concept of the “reticular activating system” as mediating arousal.
What is the “reticular grey formation”?
Among the cranial nerve nuclei and other clearly demarcated cell groups in the brainstem, anatomists had found diffuse aggregations of neurons of different types and sizes, separated by a wealth of fibers traveling in all directions. When stained to visualize the neuronal processes, a net-like or reticular pattern emerged as shown in this photomicrograph of a section stained to show fibers (myelin) and cell bodies.
The term “reticular formation” was born.
What does the reticular grey formation do?
It was known that sensory pathways on their way to the thalamus would often send a collateral axon to synapse in the reticular formation. It seemed reasonable that sudden major sensory changes might well benefit from a heightened alertness before the sensory information ever got processed by the parietal cortex. A startle response to a sudden noise behind you, or a movement in a nearby brush, or an unexpected nudge to your side, whatever, might mean the difference between life and death in evolutionary terms. It turns out, however, that the reticular formation does much more, and furthermore, it is not a diffuse, undifferentiated structure but quite the contrary.
Cytoarchitectonic differences exist between different areas of the reticular formation and the various cell groups have highly specific connections.
What is the minimal amount of reticular formation that can be damaged in the upper brainstem and still produce coma?
Working at the Mayo Clinic, Parvizi and Damasio performed a combined MRI neuropathological study of comatose individuals with brainstem injury in whom the diencephalon (that is the thalamus and hypothalamus) and most of the midbrain were spared. In other words they excluded patients with so-called “top of the basilar” stroke.
Among 9 patients, the most common lesion site is shown in red and orange. It is the paramedian tegmental area just ventral to the aqueduct of Sylvius from the midbrain to the rostral pons.This study suggests that lesions confined to the upper pons can cause coma in the absence of midbrain and thalamic injury. This explains why some patients with pontine hemorrhage are comatose.
T or F. Lesions below the rostral pons disrupt the corticospinal and corticobulbar tracts bilaterally to leave a patient quadriplegic with a paralyzed lower face, unable to speak, swallow or breathe on his own, yet the patient is conscious, aware, can see and hear, and usually retain some control over vertical eye movements and blinking through which he can communicate with the outside world.
T. Thus other patients with slightly more caudal pontine hemorrhage appear to be in coma but are actually awake and “locked-in”. From a humane aspect, it is essential to make a correct diagnosis and to treat locked-in patients at the bedside as fully conscious and mentally competent individuals.
Thus areas of the reticular formation that produce coma when damaged became known as the reticular activating system or RAS. The RAS extends where?
from the upper third of the pons through the midbrain tegmentum (tegmentum means floor), the floor of the third ventricle and into the thalami as demarcated by the asterisks. These are the areas that injury of any kind, traumatic, ischemic, inflammatory, metabolic, whatever, will suppress wakefulness and cause coma.
The concept of the reticular activating system or RAS underlying arousal is ingrained in medical jargon. Work by Cliff Saper and others, however, has shown that reticular nuclei are not the source of arousal. Damage to these areas destroys axons from specific nearby nuclei that pass through the RAS territory. The nuclei shown in red and yellow are the ones actually responsible for arousal and are more accurately identified as:
the ascending arousal system.
Describe the ascending arousal system
In yellow, two cholinergic nuclei project to the thalamic relay nuclei and inhibit their firing. This inhibition increases wakefulness and places the thalamus “in transmission” mode for filtering and relaying sensory information to the cortex. Without this inhibition, the thalamic relay neurons spontaneously continue their periodic electrical “bursting” and with their widespread connections to the cortex, these thalamic relay neurons synchronize cortical electrical activity and induce sleep.
The monoaminergic systems shown in red (part of the ascending arousal system) also have widespread connections to the cortex, both direct and indirect. What is their role?
Their role is to improve the signal to noise ratio for messages from the thalamus and thereby prevent any misperception of incoming sensory stimuli. When this system fails, sensory hallucinations and confusion result, causing delirium.
Note that different neurotransmitters are responsible for the normal maintenance of consciousness and perturbations in any of them can lead to delirium. Knowledge of these transmitters also offers potential therapeutic targets in the treatment of delirium.
What is the ‘sleep promoting center’?
The ventro-lateral preoptic nucleus or VLPO is the sleep promoting center that von Economo found causes insomnia when destroyed.
How does the VLPO work?
VLPO uses the inhibitory GABA and an inhibitory neuropeptide, galanin, to inhibit the many centers that promote wakefulness in the ascending arousal system.
Notice that one nucleus, the VLPO, singlehandedly counterbalances the influence of multiple arousal nuclei to promote sleep.
What drugs that have GABA-like properties in the brain induce sedation in part by promoting the inhibitory effects of the VLPO on the ascending arousal system?
Ethanol, benzodiazepines and other drugs
Finally, it should be noted that the Ascending Arousal System receives feedback from many sources including:
the thalamus, the limbic system, the frontal and association cortex.
These pathways mediate emotional memories and permit concentrated attention to one sensory modality when necessary. Loss of this feedback from brain injury causes apathy and indifference to sensory stimuli. When the damage is severe, abulia or akinetic mutism can result.
Plum and Posner divided coma into two broad categories, structural and metabolic, that required dramatically different kinds of intervention. How are structural causes handled?
Structural causes typically required neurosurgical intervention such as evacuating a cerebellar hemorrhage or placing a shunt for acute hydrocephalus.
Raised intracranial pressure was common and caused specific signs and symptoms. They included headache made worse with recumbency, nausea, vomiting, transient visual obscurations, papilledema, focal deficits on exam and an abnormal CT or MRI disclosing a mass lesion or other distortions of the brain.
How are metabolic causes of coma handled?
In contrast, metabolic causes of coma typically produced a non-focal exam with no lateralizing signs, normal brain imaging or changes that were diffuse and not amenable to surgery. Here the patient was managed medically in the ICU.
Occasionally, no structural or metabolic cause of coma were found because the unresponsive behavior was entirely psychogenic (make sure to rule out)
Let’s start with a case. A 30 year old man is assaulted and struck on the right head with a bat. The resulting skull fracture lacerates the middle meningeal artery which produces an epidural hematoma as shown in the picture.
The mass effect pushes the right temporal lobe medially and down across the tentorium cerebelli. This is called transtentorial herniation of the medial temporal lobe or the uncus of the temporal lobe. Another term is uncal herniation. What is compressed first?
The oculomotor nerve lies between the herniating uncus and the midbrain and diencephalon. It is therefore compressed first, before pressure on the midbrain and diencephalon produce ischemia and cause increasing lethargy, stupor and coma. In fact the nerve fascicle mediating pupillary constriction lies superficially and may be the first part of the oculomotor nerve to be compressed. At the bedside, the right pupil becomes widened and slower to react to direct and indirect light compared to the left side. This pupillary abnormality may precede the ptosis and weakness of ocular movement caused by ocular motor nerve paresis. It often precedes the increased lethargy and the development of contralateral hemiparesis and a contralateral Babinski sign.
What else commonly accompanies a transtentorial herniation?
The posterior cerebral artery can be trapped against the cerebellar tentorium as well to cause ipsilateral ischemia and stroke in the occipital lobe.
This is a structural and neurosurgical emergency, and the key teaching point is that an early loss of pupil reactivity to light should signal the possibility of imminent herniation, of raised intracranial pressure and impending catastrophe if emergency steps to reduce intracranial pressure are not taken immediately and surgery is not performed in a timely fashion.
Here is another case of herniation. A large malignant tumor caused the medial temporal lobe to herniate around the tentorium and compress the brainstem. You can see the indentation of the tentorium into the temporal lobe as shown by the arrows. The compression of the brainstem often causes small hemorrhages called:
Duret’s hemorrhages as shown by the large arrow.
Here are two more examples of transtentorial herniation leaving a groove in the temporal lobe. What do you think gets caught between the herniating temporal lobe and the upper brainstem?
The oculomotor nerve. It is numbered 6 in the picture and note its proximity to the edge of the tentorium. You should be able to visualize how the temporal lobe traps and compress the oculomotor nerve during the herniation process when examining this picture.
The same point can be made here. Note the proximity of the oculomotor nerve to the tentorium.
Finally, you can see the oculomotor nerve resting on the uncus of the temporal lobe on the right side.
This slide shows an uncal herniation that is unilateral. It also shows that the herniation can involve both hemispheres. How?
The latter can occur when trauma produces bilateral subdural hematomas or the hemispheres are severely and irreversibly damaged by certain metabolic insults such as hypoxia or the cerebral edema that accompanies fulminant liver failure or hydrocephalus. Under such circumstances, there is diffuse and symmetric pressure on the brain both medial and downward to produce central herniation.
Another type of herniation involves a mass effect that pushes the brain under the falx cerebri. This falcine herniation sometimes traps and compresses one or both anterior cerebral arteries against the falx to cause ischemic stroke in the parasagittal cortex on one or both sides.
How does one recognize central herniation at the bedside?
There is a steady progressive failure of the brainstem in a rostral to caudal direction.
It starts with increasing lethargy due to early pressure on the reticular grey in both thalami. The hypothalamus comes under pressure and the central sympathetic tracts originating in the hypothalamus are compromised leading to small but still reactive pupils.
Later, when the pressure extends to the midbrain, the Edinger-Westphal nuclei fail. Constrictive pupillary tone is lost and the pupils become fixed in mid-position.
Decorticate or flexor posturing is followed by decerebrate or extensor posturing and is a late sign of herniation. This posturing will be described and explained later. Cheyne-Stokes respirations, characterized by apneic spells interspersed with hyperventilation periods, also provide an early warning of herniation.
Some lesions cause both a transtentorial and central herniation syndrome. The contribution from the former can be monitored by the accompanying lateral signs and by neuro-imaging.
Structural lesions may also lie below the cerebellar tentorium in the posterior fossa. They can be intrinsic and directly damage the brainstem or extrinsic and indirectly damage the brainstem by compression.
How do you clinically identify a lesion lying in the brainstem?
Firstly, there is often a segmental cranial nerve deficit. This may be an ocular movement abnormality, a deficit of facial sensation, facial droop, hearing loss, etc. Contralateral pain and temperature is reduced with spinothalamic lesions. The medial lemniscus carries fine touch, vibration and proprioceptive information. Descending motor pathways may be affected. One checks for cerebellar deficits.
Case: A 45 year old crack cocaine user suddenly becomes unconscious and displays a flaccid quadriplegia. The eyes show 1 mm pinpoint pupils that do react to bright light when observed with a magnifying glass. There is complete paralysis of horizontal gaze. The eyes can move in the vertical plane and at times show bobbing up and down movements.
This is a classic example of what?
a pontine hemorrhage that caused coma because the upper one-third pontine tegmentum was disrupted. The vertical gaze center in the midbrain, along with cranial nerves 3 and 4 are intact and permit eye movements in the vertical plane.
When this patient awakens (crack cocaine user), he is at risk for what syndrome?
“locked-in syndrome”
Let’s now move on to the other major category of coma. Metabolic abnormalities such as ______, ________, ______, _______, etc. can cause an altered mental status due to metabolic encephalopathy.
hyponatremia, hypoglycemia, hypothermia, hyperglycemia, uremia, hepatic failure, thiamine deficiency, hypoxia, drug intoxication and many more conditions
As a group, this constitutes by far the largest category of coma etiologies. More importantly, many conditions are reversible with timely medical treatment. So it is important to recognize and separate this group from individuals with structural coma who need surgery.
How does one recognize metabolic encephalopathy at the bedside?
Because the metabolic insult is diffuse and global, the neurological deficits are similarly diffuse and global. The neurological exam does not usually disclose any focal or lateralizing deficits.
Occasionally, a compensated deficit from an old stroke becomes unmasked and decompensated by the metabolic derangement, but this does not represent a structurally new neurologic deficit. The CT is typically negative. If there are findings, they are old.
T or F. With a metabolic induced coma, the pupils stay reactive to light even as other brainstem signs disappear with deepening coma.
T. Thus, with metabolic etiologies of coma, the pupils are the last to go, whereas with structural causes of coma, the pupil is often the earliest to become affected.
Pupils can become dilated and fixed in a few metabolic conditions of coma including:
atropine poisoning, botulism and glutethimide intoxication but these are rare.
Clues that you are dealing with a metabolic encephalopathy include:
the presence of asterixes, multifocal myoclonus and tremor.
What is Asterixes, also called negative myoclonus?
refers to sudden, recurrent lapses in muscle tone.
For example if you ask the patient to hold out their hands as if to stop traffic, you will notice a sudden fleeting lapse in tone with wrist drop or even a partial arm drop every 5-10 seconds.
What is Multifocal myoclonus?
refers to muscle twitching in different parts of the body that occurs in a chaotic, unpredictable fashion.
The more common and potentially reversible etiologies for these abnormal movements include liver failure, uremia, hypoxia and drug overdose but you can also see this in the rare Creutzfeldt-Jacob disease in which loss of consciousness, both in wakefulness and content is progressive and irreversible.
There are many metabolic causes of altered mental status but you should be aware that ____, ______, and _______ account for about 90% of delirium in the elderly.
dehydration, drug intoxication and infection
You should also be aware that a post-ictal state can mimic a metabolic encephalopathy but consciousness improves over the next few hours. If the patient has an old and well compensated brain lesion, such as a stroke from which he recovered, a new metabolic encephalopathy may unmask the old lesion and can fool the clinician into thinking there is an acute structural lesion causing new focal weakness. Fortunately, CT and MRI can help date the structural lesion and get the diagnostic thought processes back on track.
What do you do when the patient arrives in the ED?
There are a series of steps that are completed more or less simultaneously.
First secure the airway and check that the patient has a heartbeat and a detectable blood pressure. Otherwise initiate CPR. Remember that if trauma is a possibility, assume the neck is broken until proven otherwise with a CT or plain x-ray films. That means don’t manipulate the neck.
While someone is getting a history from EMS or family members, someone else should be doing the physical. Yet someone else should be putting in an IV line, drawing bloods and giving empirical therapy with thiamine and dextrose 50.
On the chance the patient is hypoglycemic when they present with coma, Dextrose 50 is rapidly infused but always preceded by intravenous thiamine to avoid precipitating what?
Wernicke’s encephalopathy.
New presenting coma patient: History is critical. Ask about the onset of coma, was it sudden, suggesting seizure, top of the basilar artery embolism or massive brain hemorrhage. Any recent complaints of headache, head injury, suicide ideation, stroke-like symptoms or dizziness. Ask about medical illnesses that commonly cause metabolic encephalopathy such as diabetes, renal failure, alcoholism, drug abuse.
Look carefully at the vital signs.
It is very unusual for someone in coma to have normal vital signs. The body temperature, pulse, blood pressure and respiration will typically be high or low. Normal vital signs suggests psychogenic coma.
How might you prove a psychogenic coma?
Recall that ice-water calorics will induce nystagmus in awake patients.
New presenting coma pt.
Look for evidence of trauma, and if you find it, assume the neck is broken. Keep the neck secure in a neutral position and do not manipulate the head until imaging rules out a fractured spine.
Carefully inspect the skin for petechiae, purpura, spider angiomata and jaundice, splinter hemorrhages, needle tracks, etc. The skin rash may offer clues to meningococcal meningitis, Rocky Mountain Spotted Fever, hepatic encephalopathy or bacterial endocarditis.
Check for nuchal rigidity. Is it stiff due subarachnoid hemorrhage or meningitis?
Check eye opening carefully since by definition, the patient is not in coma if he or she opens the eyes spontaneously or to command. Remember that the retina is part of the CNS and it can provide a window on what is going on in the brain. You may see hemorrhages and exudates due to vasculitis, large swings in intracranial pressure and hypertensive emergencies. The presence of retinal venous pulsations means that in that point in time, raised intracranial pressure is unlikely and that eliminates a number of very scary diagnostic possibilities.
Checking pupillary light reactivity is critical. In many structural causes of coma, loss of pupillary reactivity to light is a very early clue to what is going on.
In most metabolic causes of coma, the pupil remains reactive, albeit sluggish, until very late in coma. The light reflex disappears only after all the other brainstem reflexes are gone.
The oculocephalic and oculovestibular responses test the integrity of the vestibular nuclei, the MLF and cranial nerves 3 and 6. If these centrally located structures are preserved, it is likely that the surrounding brainstem is also intact. Thus, these two exams screen the integrity of the brainstem from the midbrain to the pons.
Corneal reflexes attest to the integrity of cranial nerves __ and ___ and their central connections.
5 and 7
Respiratory patterns in coma depend on site of the lesion.
The most important pattern here is the Cheyne-Stokes respirations since this can be an early warning sign of:
transtentorial or central herniation.
If you walk into the rooms and see one of the other patterns, “call a code”. These are essentially patterns that quickly terminate in respiratory arrest. You probably will not see these patterns unless you are the one who calls the code. Most patients will either die, or be placed on a respirator, and the patterns will be obscured by the ventilator.
The motor response is very important in the evaluation of the unconscious patient. When the patient fails to awaken to your voice or to shaking, you apply a noxious stimulus and observe the response. Pressure on the supraorbital nerve, nail bed pinch and sternal rub are relatively painful yet leave no marks. In contrast, nipple pinch or twisting, still used by some physicians, often leaves a bruise and is likely to appear sadistic to any family member who learns of this.
So what are the motor responses. There is a hierarchy of motor responses following brain injury.
For prognosis, the best response is following a complex motor command such as “show me two fingers with your right hand”. With slightly greater brain injury, the patient may follow only the simplest command such as moving a limb when asked to lift it. When there is no motor response to voice command, a painful stimulus is introduced and the highest level of response is localizing the pain and pushing away the offending hand. The next decrement in response involves purposeful withdrawal to pain. That is followed by semi-purposeful withdrawal from pain.
Then come the reflex, stereotypic responses to pain, a definite deterioration.
You first see flexion of the arms or so-called “decorticate posturing.” Prognosis is worse with extensor posturing, also called “decerebrate posturing.”
To appreciate the gravity of the worsening when decorticate becomes decerebrate posturing, you need a little background.
There are multiple motor pathways that influence movement. They can be broadly divided into either flexor facilitatory or extensor facilitatory. In other words, if you stick a DC electrode and stimulate these motor pathways at their origin, the resulting movement is either flexion or extension. It turns out the corticospinal tract, rubrospinal tract, tectospinal tract and the rostral reticulospinal tract are all flexor facilitatory. Their motor tracts start either in the cortex or at the midbrain level.
In contrast, the vestibulospinal tract and caudal reticulospinal tract are extensor facilitatory and take their origin at the pontine level.
There is a balance between extensor and flexor influences in response to pain that favors flexor posturing when the cerebrum loses conscious control of movement. However, once the midbrain becomes compromised, the influence of the flexor facilitatory centers is lost ,and the pontine extensor facilitatory pathways dominate. In other words, a patient who changes from flexor to extensor posturing just lost his midbrain, which is a dire development in structural causes of coma! The worst motor response is none at all. That happens when the insult ,such as hypoxia and hypotension, is so severe that even the spinal cord suffers direct hypoxic damage.
Shown is the Glasgow coma scale in which a patient receives a score for eye opening, motor response and verbal response
The highest score is 15, and patients with head trauma who have an initial score of 12 or better have an excellent prognosis. Scores of 8 or below usually means nursing home care and a score of 3 usually means death.
Lab tests that can be helpful are shown in this slide. Many of the routine metabolic panels actually provide a great deal of useful information that excludes causes of metabolic coma.
Blood testing, for example, can screen for hyperglycemia, hypoglycemia, acid-base and electrolyte abnormalities, uremia, liver failure, thyroid disease, Addison’s disease , sepsis and various kinds of poisoning. CSF studies are especially useful for diagnosing infectious and inflammatory causes of coma.
new coma pt: A CT of the head is obtained as soon as possible since it will often disclose structural etiologies ranging from trauma, ischemic stroke, hemorrhage, other mass lesions, brain herniation and hydrocephalus. What other tests should be ordered?
A chest x-ray is an important screen for pneumonia, heart failure, lung cancer and other disorders that can predispose to coma.
A spinal tap may be indicated if CNS infection is suspected (or subarachnoid hemorrhage).
A urine drug screen is useful to detect sedative or heroin overdose and cocaine that can cause hypertensive encephalopathy, seizures, ischemic and hemorrhagic stroke.
possibly an EEG for status epilepticus, brain death
How do we treat coma?
One starts by maintaining vital signs using oxygen, mechanical ventilation, agents to increase or reduce BP and correct life-threatening acid-base and electrolyte abnormalities.
If intracranial pressure is severely elevated, hyperventilate the patient down to a pCO2 of 25 – 30 mm Hg. That will reduce CSF pressure rapidly but for only about 30 minutes.
Mannitol, hypertonic saline and/or other osmotic agents are given to draw free water out of the brain and into the circulation. These measure buy time to get the OR ready for more definitive intervention such as craniotomy, mass excision, placement of a ventricular drain or shunt.
More on tx of coma
Seizures are aggressively treated with anticonvulsants.
Antibiotics are empirically given if there is a suspicion of CNS infection or sepsis.
Hypothermia may actually benefit some conditions such as ischemia or hypoxia but hyperthermia must be vigorously treated.
Thiamine and multivitamins are given.
If the cause of coma is known and reversible with a specific agent, the antidote is given.Agitation is common and the patient may need sedation with Haldol or Ativan, but be aware that hypoxia is a common cause of an agitated delirium, whose treatment is oxygen. Sedation and tight restraints in such patients can result in a respiratory arrest.
Outcome one year after surviving non-traumatic coma. This included a large number of cardiac arrest patients. As you might expect, the better the neurological response over time, the better the prognosis.
The important finding here, however, is the zero chance of so-called good recovery with moderate disability, if on day 3 of coma, the corneal reflex is absent and the motor response is absent or reflex showing extensor or flexor posturing. In a separate study of cardiac arrest patients, the same group of investigators concluded that there was zero change of a good neurological recovery if the patient was not following motor commands on day seven post-arrest.
Sometimes the injury to brain is so severe that all cerebral and brainstem functions are lost. Because such patients may be candidates for organ donation, criteria have been developed to define brain death as a form of death.
Importantly the criteria have been left intentionally flexible to give the treating physician some latitude in how to make the diagnosis. Thus, a confirmatory test is not necessary in an adult patient in whom apnea testing and brainstem reflexes testing demonstrated no brainstem function whatsoever on two consecutive examinations performed anywhere from 6 hours to 24 hours apart.
Where would you place the lesion?
This was a trick question. There is no organic lesion of the nervous system although there is a psychiatric problem. This is a case of psychogenic unresponsiveness. The clues are everywhere.
The vital signs are normal which would be highly unusual in a bona fide coma of such depth that pain produced no motor response. The neurological exam is negative. Note that the oculocephalic reflex tested by the Doll’s head maneuver shows no movement of the eyes. This happens with visual fixation. If Frenzel lenses had been placed on the patient to suppress visual fixation, then one would have seen movement of the eyes in the direction opposite to the head turn. Finally it doesn’t take a lot of ice water to be placed in the external auditory canal to induce nystagmus. In a deeply comatose patient with the brainstem structurally intact, 50 cc of ice water or more might be necessary to show some modest movement of the eyes.
What is the diagnosis? What ethical concerns might this case raise?
This is a classic case of “locked-in” syndrome. The problem here is that the patient is mentally intact and aware, yet cannot easily communicate with the outside. Typically these patients become terribly depressed and often express the wish “I want to die.” What would you do if your patient asked that he be given morphine and the ventilator be stopped?
In the past, most of these patients would expire in the ICU after a month or two. In the past decade, however, some of these patients have elected to continue life and deal with it as best as possible. One such patient has even written a book about his “locked-in” experience.
More often than not, there is no book contract and there an unfortunate outcome.
He had a left ptosis, enlarged left pupil unreactive to light, and left oculomotor nerve paresis. The remainder of the neuro-exam was negative.
The CT showed subarachnoid blood. There bright substance is blood and in mixing with CSF the blood has obscured the cortical sulci and the Sylvian fissure. What do think may have caused this?
Case 3: On the left side, you can see a posterior communicating artery aneurysm that is unruptured and on the right, you see a ruptured aneurysm with fresh clot on its dome.
Here is a typical circle of Willis. Note the proximity of the oculomotor nerve to the PCOM , the posterior communicating artery, and the relationship to the medial temporal lobe. The point to stress is that structural lesions causing coma such as the rupture of a PCOM aneurysm and transtentorial herniation from other causes often compress the oculomotor nerve, dilate the pupil and do so early in disease.
Here is a diagram of the posterior communicating artery and its relationship with the oculomotor nerve. Note the close approximation between the two so that the oculomotor nerve becomes entrapped and stretched by the physical expansion of the aneurysm. This is yet another instance in which the pupil is affected early by structural disease, here because any subarachnoid hemorrhage has occurred.
The vital signs are all “depressed” including temperature, respirations, heart rate and blood pressure. This was due to a phenobarbital overdose and with ICU supportive care, the patient made a full recovery.
