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.



































