Neurology_Adams

Neurology_Adams. A coma-causing lesion in a cerebral hemisphere can be detected by careful observation of spontaneous movements, responses to stimulation, prevailing postures, and by examination of the cranial nerves. Hemiplegia is revealed by a lack of restless movements of the limbs on one side and by inadequate protective movements in response to painful stimuli. The weakened limbs are usually slack and, if lifted from the bed, they “fall flail.” The hemiplegic leg lies in a position of external rotation (this may also be caused by a fractured femur), and the affected thigh appears wider and flatter than the nonhemiplegic one. In expiration, the cheek and lips puff out on the paralyzed side of the face. A lesion in one cerebral hemisphere causes the eyes to be turned away from the paralyzed side (toward the lesion, as described below); the opposite occurs with brainstem lesions. In most cases, a hemiplegia and an accompanying Babinski sign are indicative of a contralateral hemispheral lesion; but


Neurology_Adams

Neurology_Adams. the lesion, as described below); the opposite occurs with brainstem lesions. In most cases, a hemiplegia and an accompanying Babinski sign are indicative of a contralateral hemispheral lesion; but with lateral mass effect and compression of the opposite cerebral peduncle against the tentorium, extensor posturing, a Babinski sign, and weakness of arm and leg may appear ipsilateral to the lesion (the earlier-mentioned Kernohan-Woltman sign). A moan or grimace may be provoked by painful stimuli applied to one side but not to the other, reflecting hemianesthesia. During grimacing in response to stimuli, facial weakness may be noted.


Neurology_Adams

Neurology_Adams. Of the various indicators of brainstem function, the most useful are pupillary size and reactivity, ocular movements, vestibulo-ocular reflexes and, to a lesser extent, the pattern of breathing. These functions, like consciousness itself, are dependent on the integrity of structures in the midbrain and rostral pons.


Neurology_Adams

Neurology_Adams. These are of great diagnostic importance in the comatose patient. A unilaterally enlarged (“Huthcinson”) pupil is an early indicator of stretching or compression of the third nerve and reflects the presence of an overlying ipsilateral hemispheral mass as described earlier in the section on herniations. A loss of light reaction usually precedes enlargement of the pupil. As a transitional phenomenon, the pupil may become oval or pear-shaped or appear to be off center (corectopia) because of a differential loss of innervation of a portion of the pupillary sphincter. The light-unreactive pupil continues to enlarge to a size of 6 to 9 mm diameter and is soon joined by a slight outward deviation of the eye. In unusual instances, the pupil contralateral to the mass may enlarge first; this has reportedly been the case in 10 percent of subdural hematomas but has been far less frequent in our experience. As midbrain displacement continues, both pupils dilate and become unreactive to light,


Neurology_Adams

Neurology_Adams. reportedly been the case in 10 percent of subdural hematomas but has been far less frequent in our experience. As midbrain displacement continues, both pupils dilate and become unreactive to light, probably as a result of compression of the oculomotor nuclei in the rostral midbrain (Ropper, 1990). The last step in the evolution of brainstem compression tends to be a slight reduction in pupillary size on both sides, to 5 mm or smaller. Normal pupillary size, shape, and light reflexes indicate integrity of midbrain structures and direct attention to a cause of coma other than a mass.


Neurology_Adams

Neurology_Adams. Pontine tegmental lesions cause extremely miotic pupils (<1 mm in diameter) with barely perceptible reaction to strong light; this is characteristic of the early phase of pontine hemorrhage. The ipsilateral pupillary dilatation from pinching the side of the neck (the ciliospinal reflex) is usually lost in brainstem lesions. The Horner syndrome (miosis, ptosis, and reduced facial sweating) may be observed ipsilateral to a lesion of the brainstem or hypothalamus or as a sign of dissection of the internal carotid artery.


Neurology_Adams

Neurology_Adams. With coma caused by drug intoxications and intrinsic metabolic disorders, pupillary reactions are usually spared, but there are notable exceptions. Serum concentrations of opiates that are high enough to cause coma have as a consistent sign pinpoint pupils, with constriction to light that may be so slight that it is detectable only with a magnifying glass. High-dose barbiturates may act similarly, but the pupillary diameter tends to be 1 mm or more. Systemic poisoning with atropine or with drugs that have atropinic qualities, especially the tricyclic antidepressants, but also, through another mechanism the selective serotonin reuptake inhibitors is characterized by dilatation and relative unresponsiveness to light of the pupils. Hippus, or fluctuating pupillary size, is a characteristic but not invariant sign of metabolic encephalopathy. Movements of Eyes and Eyelids and Corneal Responses


Neurology_Adams

Neurology_Adams. Movements of Eyes and Eyelids and Corneal Responses These are altered in a variety of ways in coma. In stupor or light coma of metabolic origin, the eyes rove conjugately from side to side in seemingly random fashion, sometimes resting briefly in an eccentric position. These movements disappear as coma deepens, and the eyes then remain motionless and slightly exotropic. In bihemispheral coma, the eyes may rove smoothly from side-to-side (windshield wiper” eyes).


Neurology_Adams

Neurology_Adams. A lateral and slight downward deviation of one eye suggests the presence of third-nerve palsy on that side, and a medial deviation, of sixth-nerve palsy. There is persistent conjugate deviation of the eyes to one side—away from the side of the paralysis with a large cerebral lesion (looking toward the lesion) and toward the side of the paralysis with a unilateral pontine lesion (looking away from the lesion). “Wrong-way eyes” a paradoxical conjugate deviation to the side opposite a large hemispherical lesion may occur with thalamic and upper brainstem lesions. During a focal seizure the eyes turn or jerk toward the convulsing side (opposite to the irritative focus). The globes turn down and inward (looking at the nose) with hematomas or ischemic lesions of the thalamus and upper midbrain (a variant of Parinaud syndrome). Retraction and convergence nystagmus and “ocular bobbing,” described in Chap. 13, occur with lesions in the tegmentum of the mid-brain and pons, respectively. “Ocular


Neurology_Adams

Neurology_Adams. variant of Parinaud syndrome). Retraction and convergence nystagmus and “ocular bobbing,” described in Chap. 13, occur with lesions in the tegmentum of the mid-brain and pons, respectively. “Ocular dipping,” in which the eyes move down slowly and return rapidly to the meridian, is observed with coma caused by anoxia and drug intoxications; horizontal eye movements are preserved with ocular dipping but obliterated in cases of ocular bobbing as a result of destruction of pontine gaze centers. Coma-producing structural lesions of the brainstem abolish most if not all conjugate ocular movements, whereas metabolic disorders generally do not (except for instances of deep hepatic coma and antiepileptic drug overdose).


Neurology_Adams

Neurology_Adams. Vestibulo-ocular reflexes (doll’s-eye movements) are elicited by turning or tilting the head and observing the movement of the globes by holding open the lids. The response in coma of metabolic origin or that caused by bihemispheric structural lesions consists of conjugate movement of the eyes in the opposite direction. Elicitation of these ocular reflexes in a comatose patient provides three invaluable pieces of information: (1) evidence of unimpeded function of the midbrain and pontine tegmental structures that integrate biocular eye movements; (2) the intactness of the oculomotor nerves (III, IV, and VI) on both sides, but also (3) loss of the cortical inhibition that normally holds these movements in check. In other words, the presence of unimpaired reflex eye movements implies that coma is not caused by compression or destruction of the upper midbrain. In reference to the last of these, coma from bihemispheral damage or metabolic suppression, the eyes appear to rock easily from


Neurology_Adams

Neurology_Adams. coma is not caused by compression or destruction of the upper midbrain. In reference to the last of these, coma from bihemispheral damage or metabolic suppression, the eyes appear to rock easily from side to side and vertically as the head is moved in the opposite direction. In fact, the eyes are stationary with respect to the three dimensions of space but give the impression of moving because the head is in motion. It is as if the globes are under gyroscopic control, and in fact they are through their connections to the vestibular apparatus. In an awake patient, for example, one who is feigning coma, the eyes move with the head as it is turned because the parietal lobes inhibit the oculocephalic reflexes in order to allow for visual tracking of objects. Also, in brain death the destruction of brainstem pathways and oculomotor nuclei cause the yes to move with the head as it is turned. Similarly, sedative or antiepileptic intoxication profound enough to cause coma may often the


Neurology_Adams

Neurology_Adams. of brainstem pathways and oculomotor nuclei cause the yes to move with the head as it is turned. Similarly, sedative or antiepileptic intoxication profound enough to cause coma may often the brainstem mechanisms for oculocephalic reactions and, in extreme cases, even the vestibular-ocular (caloric) responses as noted below.


Neurology_Adams

Neurology_Adams. Asymmetry of the elicited eye movements is a sign of focal brainstem disease. In instances of coma caused by a large mass in one cerebral hemisphere that secondarily compresses the upper brainstem, the oculocephalic reflexes are usually present, but the movement of the eye on the side of the mass may be impeded in adduction as a result of a compressive third-nerve paresis.


Neurology_Adams

Neurology_Adams. A more vigorous stimulus for ocular movements in coma is accomplished by irrigation of one ear with 10 mL of cold water (or room-temperature water if the patient is still arousable). This causes slow conjugate deviation of the eyes toward the irrigated ear, followed in a few seconds by compensatory nystagmus (fast component away from the stimulated side). This is the vestibulo-ocular (oculovestibular), or caloric test. The ears are irrigated separately several minutes apart. In comatose patients, the fast “corrective” phase of nystagmus that is mediated by the frontal lobes is lost and the eyes are tonically deflected to the side irrigated with cold water, or away from the side irrigated with warm water; this position may be held for 2 to 3 min. Brainstem lesions disrupt these oculovestibular reflexes; if one eye abducts and the other fails to adduct, one can conclude that the medial longitudinal fasciculus has been interrupted (an internuclear ophthalmoplegia on the side of adductor


Neurology_Adams

Neurology_Adams. reflexes; if one eye abducts and the other fails to adduct, one can conclude that the medial longitudinal fasciculus has been interrupted (an internuclear ophthalmoplegia on the side of adductor paralysis) or that the third nerve nucleus has been damaged. Abducens palsy is indicated by an esotropic resting position and a lack of outward deviation of one eye with the reflex maneuvers. The complete absence of ocular movement in response to oculovestibular testing indicates a severe disruption of brainstem tegmental systems in the pons and midbrain or, as already mentioned, a profound overdose of sedative, anesthetic, or anticonvulsant drugs.


Neurology_Adams

Neurology_Adams. A reduction in the frequency and eventual loss of spontaneous blinking, then a loss of response to touching the eyelashes, and, finally, a lack of response to corneal touch (the corneal reflex afferent limb travels in the trigeminal nerve and efferent limb, facial nerve) are among the most dependable signs of deepening coma. A marked asymmetry in corneal responses indicates either an acute lesion of the opposite hemisphere or, less often, an ipsilateral lesion in the brainstem.


Neurology_Adams

Neurology_Adams. Restless movements of both arms and both legs and grasping and picking movements signify that the corticospinal tracts are more or less intact. Oppositional resistance to passive movement (paratonic rigidity), complex avoidance movements, and discrete protective movements have the same meaning; especially if they are bilateral and they suggest the coma is not deep. Abduction movements (away from the midline) to escape a noxious stimulus have the same significance and differentiate a motor response from posturing, described below. Focal motor epilepsy indicates that the corticospinal pathway to the convulsing side is intact. With massive destruction of a cerebral hemisphere, as occurs in hypertensive hemorrhage or internal carotid–middle cerebral artery occlusion, seizure activity may be manifest solely in the ipsilateral limbs, the contralateral limbs being prevented from participating by the hemiplegia. Elaborate forms of semivoluntary movement may be manifest on the nonhemiparetic


Neurology_Adams

Neurology_Adams. manifest solely in the ipsilateral limbs, the contralateral limbs being prevented from participating by the hemiplegia. Elaborate forms of semivoluntary movement may be manifest on the nonhemiparetic side in patients with extensive disease in one hemisphere; they probably represent some type of disinhibition of cortical and subcortical movement patterns. Choreic, athetotic, or hemiballistic movements indicate a disorder of the basal ganglionic and subthalamic structures, just as they do in the alert patient, but are not helpful in localizing the cause of coma.


Neurology_Adams

Posturing in the Comatose Patient

Neurology_Adams. Posturing in the Comatose Patient


Neurology_Adams

Neurology_Adams. An abnormal posture of some consequence is decerebrate rigidity, which in its fully developed form consists of opisthotonos, clenching of the jaws, and stiff extension of the limbs, with internal rotation of the arms and plantar flexion of the feet (see Chap. 3). It is most often manifest as brief tonic extension of the limbs. This postural pattern was first described by Sherrington, who produced it in cats and monkeys by transecting the brainstem at the intercollicular level. Decerebrate posture was noted in animals to be ipsilateral to a one-sided lesion, hence not a result of involvement of the corticospinal tracts; the opposite is true in humans. A precise anatomic correlation between posturing and the level of the lesion is rarely possible in patients who develop stereotyped extensor posturing as it arises in a variety of settings—with midbrain compression caused by a hemispheral mass; with cerebellar or other posterior fossa lesions; in certain metabolic disorders such as anoxia


Neurology_Adams

Neurology_Adams. posturing as it arises in a variety of settings—with midbrain compression caused by a hemispheral mass; with cerebellar or other posterior fossa lesions; in certain metabolic disorders such as anoxia and hypoglycemia; and, rarely, with hepatic coma and profound drug or alcohol intoxication. Patients with an acute lesion of one cerebral hemisphere may show a similar type of extensor posturing of the contralateral and sometimes ipsilateral limbs, and this may coexist with the ability to make purposeful movements of the same limb. Extensor postures, unilateral or bilateral, occur spontaneously, but more often they are in response to manipulation of the limbs or a tactile or noxious stimulus. Another related pattern consists of extensor posturing of an arm and leg on one side, and flexion and abduction of the opposite arm.


Neurology_Adams

Neurology_Adams. In some patients with the extensor postural changes the lesion is clearly in the cerebral white matter or basal ganglia, which is difficult to reconcile with the classic physiologic explanation for decerebrate posturing. Decerebrate posturing, either in experimental preparations or in humans, is usually not a persistent state. Hence, the term decerebrate state, as suggested by Feldman and Sahrmann, is preferable to decerebrate rigidity, which implies a fixed, tonic extensor attitude.


Neurology_Adams

Neurology_Adams. Decorticate posturing, usually, with arm or arms in flexion and adduction and leg(s) extended, signifies lesions at a more rostral level of the nervous system—in the cerebral white matter or internal capsule and thalamus. Bilateral decorticate rigidity is essentially a bilateral spastic hemiplegia. Diagonal postures, for example, flexion of one arm and extension of the opposite arm and leg, usually indicate a supratentorial lesion. Forceful extensor postures of the arms and weak flexor responses of the legs are usually seen with lesions at about the level of the vestibular nuclei. Lesions below this level lead to flaccidity and abolition of all postures and movements. If preceded by decorticate or decerebrate postures, the coma is profound and usually progresses to brain death.


Neurology_Adams

Neurology_Adams. Only in the most advanced forms of intoxication and metabolic coma, as might occur with anoxic necrosis of neurons throughout the entire brain, are coughing, swallowing, hiccoughing, and spontaneous respiration all abolished. Further, the tendon and plantar reflexes may give little indication of what is happening. Tendon reflexes are preserved until the late stages of coma that is due to metabolic disturbances and intoxications. In coma caused by a large cerebral infarct or hemorrhage, the tendon reflexes may be normal or only reduced on the hemiplegic side and the plantar reflexes may initially be absent before becoming extensor. Plantar flexor responses, succeeding extensor responses, signify either a return to normalcy or, in the context of deepening coma, a transition to brain death. Patterns of Breathing


Neurology_Adams

Neurology_Adams. Massive supratentorial lesions, bilateral deep-seated cerebral lesions, and mild metabolic disturbances give rise to altered patterns of breathing, particularly periods of waxing and waning hyperpnea alternating with a shorter period of apnea (Cheyne-Stokes respiration). This phenomenon has been attributed, on uncertain grounds, to isolation of the brainstem respiratory centers from the cerebrum, rendering them more sensitive than usual to carbon dioxide (hyperventilation drive). It is postulated that as a result of overbreathing, the blood carbon dioxide drops below the concentration required to stimulate the centers, and breathing gradually stops. Carbon dioxide then reaccumulates until it exceeds the respiratory threshold, and the cycle then repeats itself. Alternatively, the periodicity has been attributed to the stimulating effect of a low arterial PO2 on a depressed respiratory center. In either case, the presence of Cheyne-Stokes breathing signifies bilateral dysfunction of


Neurology_Adams

Neurology_Adams. has been attributed to the stimulating effect of a low arterial PO2 on a depressed respiratory center. In either case, the presence of Cheyne-Stokes breathing signifies bilateral dysfunction of cerebral structures, usually deep in the hemispheres or diencephalon, usually from intoxication or a metabolic derangement or from bilateral structural lesions such as subdural hematomas. Careful observation will disclose that the apneic part of the cycle corresponds to a diminished level of arousal. In itself, Cheyne-Stokes breathing is not a grave sign. It may occur during sleep in elderly individuals and can be a manifestation of a variety of cardiopulmonary disorders in awake patients. Only when it gives way to more irregular respiratory patterns that reflect structural damage of the brainstem is the patient in imminent danger, as discussed below.


Neurology_Adams

Neurology_Adams. A number of other aberrant breathing rhythms occur from brainstem lesions (these are reviewed in Chap. 25), but few are specifically localizing. The more conspicuous respiratory arrhythmias are associated with lesions below the level of the reticular-activating system and are therefore found in the late stages of brainstem compression or with destructive brainstem lesions such as infarction, hemorrhage, or infiltrating tumor.


Neurology_Adams

Neurology_Adams. Lesions of the lower midbrain-upper pontine tegmentum, either primary or secondary to transtentorial herniation, may give rise to central neurogenic hyperventilation (CNH). This disorder is characterized by an increase in the rate and depth of respiration to an extent that produces advanced respiratory alkalosis. The pattern must be distinguished from compensatory overbreathing caused by systemic acidosis, particularly diabetic ketoacidosis (Kussmaul breathing). In addition, mild degrees of hyperventilation are common after a number of acute neurologic events, notably head injury. The neurologic basis of central neurogenic hyperventilation is uncertain. It is theorized to represent a release of the reflex mechanisms for respiratory control in the lower brainstem. It has been observed with tumors of the medulla, lower pons, and midbrain. However, North and Jennett, in a study of respiratory abnormalities in neurosurgical patients, found no consistent correlation between tachypnea and


Neurology_Adams

Neurology_Adams. tumors of the medulla, lower pons, and midbrain. However, North and Jennett, in a study of respiratory abnormalities in neurosurgical patients, found no consistent correlation between tachypnea and the site of the lesion. A rare but noteworthy cause of central hyperventilation is primary brain lymphoma without brainstem involvement (Pauzner et al).


Neurology_Adams

Neurology_Adams. Low pontine lesions, usually caused by basilar artery occlusion, sometimes cause apneustic breathing (a pause of 2 to 3 s in full inspiration) or so-called short-cycle Cheyne-Stokes respiration, in which a few rapid deep breaths alternate with apneic cycles. With lesions of the dorsomedial part of the medulla, the rhythm of breathing is chaotic, being irregularly interrupted and each breath varying in rate and depth (Biot breathing; also called “ataxia of breathing”). This pattern progresses to one of intermittent prolonged inspiratory gasps that are recognized by all physicians as agonal in nature, and finally to apnea. In fact, respiratory arrest is the mode of death of most patients with serious central nervous system (CNS) disease.


Neurology_Adams

Neurology_Adams. Probably all of these erratic patterns of breathing are interrelated in some manner. Webber and Speck have shown that apnea, Biot breathing, and gasping could be produced in the same animal with lesions in the dorsolateral pontine tegmentum by altering the depth of anesthesia. As pointed out by Fisher and by Plum and Posner, when certain supratentorial lesions progress to the point of temporal lobe and cerebellar herniation, one may observe a succession of respiratory patterns (Cheyne-Stokes, then hyperventilation, then Biot breathing), indicating an extension of the functional disorder from upper to lower brainstem; but again, such a sequence is not always observed. Rapidly evolving lesions of the posterior fossa, mainly masses in the cerebellum, more often cause sudden respiratory arrest without any of the aforementioned abnormalities of breathing as intermediaries; presumably apnea results from fulminant medullary compression by the cerebellar tonsils.


Neurology_Adams

Neurology_Adams. Clinical Signs of Increased Intracranial Pressure


Neurology_Adams

Neurology_Adams. A history of headache before the onset of coma, vomiting, severe hypertension beyond the patient’s static level, unexplained bradycardia, or subhyaloid retinal hemorrhages (Terson syndrome) are immediate clues to the presence of increased intracranial pressure, usually from one of the types of intracranial hemorrhage. Papilledema develops within 12 to 24 h in cases of brain trauma and hemorrhage, and if it is apparent when coma supervenes, it usually signifies brain tumor or abscess, that is, a lesion of longer duration. Increased intracranial pressure produces coma by impeding global cerebral blood flow; but this occurs only at extremely high levels of pressure. Increased pressure within one compartment displaces central structures and produces a series of “false localizing” signs because of lateral distortion of deep brain tissue and herniations, as noted in the earlier discussion of this type. However, the absence of papilledema does not exclude the presence of increased


Neurology_Adams

Neurology_Adams. because of lateral distortion of deep brain tissue and herniations, as noted in the earlier discussion of this type. However, the absence of papilledema does not exclude the presence of increased intracranial pressure, particularly in the elderly.


Neurology_Adams

Neurology_Adams. The syndrome of acute hydrocephalus, most often from subarachnoid hemorrhage or from obstruction of the ventricular system by a tumor in the posterior fossa, induces a state of abulia (slowed responsivity), followed by stupor, and then coma with bilateral Babinski signs. The pupils are small and the tone in the legs is usually increased or there may be extensor posturing. The signs of hydrocephalus may be accompanied by headache and systemic hypertension, mediated through raised intracranial pressure. Chapter 29 discusses this subject further. Laboratory Procedures for the Diagnosis


Neurology_Adams

Neurology_Adams. Laboratory Procedures for the Diagnosis Unless the cause of coma is established at once by history and physical examination, it becomes necessary to carry out a number of laboratory procedures. In patients with signs of raised intracranial pressure or indications of brain displacements, CT scan or MRI should be obtained as the primary procedure. As discussed in Chap. 2, lumbar puncture, although carrying a small risk of promoting further herniation, is nevertheless necessary in some instances to exclude bacterial meningitis or encephalitis.


Neurology_Adams

Neurology_Adams. If poisoning or drug overdosage is suspected, aspiration and analysis of the gastric contents are sometimes helpful, but greater reliance should be placed on chromatographic analysis of the blood and urine (“toxic screen”). Accurate means are available for measuring the blood concentrations of most antiepileptic drugs, opiates, diazepines, barbiturates, alcohol, and a wide range of other toxic substances. These screening procedures vary widely between hospitals and certain toxins must be specifically sought. A specimen of urine is obtained by catheter for determination of specific gravity and for glucose, acetone, and protein content. Proteinuria may also be found for 2 or 3 days after a subarachnoid hemorrhage or with high fever. Urine of high specific gravity, glycosuria, and acetonuria occurs almost invariably in diabetic coma; but transient glycosuria and hyperglycemia may be precipitated solely by a massive cerebral lesion. Blood counts should be obtained and in malarial


Neurology_Adams

Neurology_Adams. occurs almost invariably in diabetic coma; but transient glycosuria and hyperglycemia may be precipitated solely by a massive cerebral lesion. Blood counts should be obtained and in malarial districts, a blood smear should be examined for parasites. Neutrophilic leukocytosis occurs in bacterial infections and mild elevations of the white blood cell counts also with brain hemorrhage and infarction, although rarely exceeding 12,000/mm3. Venous blood should be examined for the concentrations of glucose, urea, carbon dioxide, bicarbonate, ammonia, sodium, potassium, chloride, calcium, and AST (aspartate serum transaminase); analysis of blood gases and carboxyhemoglobin should be obtained in appropriate cases of anoxia or exposure to carbon monoxide by smoke inhalation or faulty heating systems. Determination of ammonia level may be added in instances where hepatic failure is a possible cause of stupor or coma.


Neurology_Adams

Neurology_Adams. It should be kept in mind that disorders of water and sodium balance, reflected in hyperor hyponatremia, may be the result of cerebral disease (excess antidiuretic hormone [ADH] secretion, diabetes insipidus, atrial natriuretic factor release), as well as being the proximate cause of coma. An EEG is informative if no adequate explanation for coma is forthcoming from the initial examinations. At times, this is the only way to reveal nonconvulsive status epilepticus as the cause of stupor. Classification of Coma and Differential Diagnosis The demonstration of focal brain disease by hemiparesis, and meningeal irritation with abnormalities of the CSF serve to divide the diseases that cause coma into three classes, as follows: I. Diseases that cause no focal or lateralizing neurologic signs, usually with normal brainstem functions. CT scan and cellular content of the CSF are normal. A. Exogenous intoxications: alcohols, barbiturates and other sedative drugs, opiates (Chaps. 41


Neurology_Adams

Neurology_Adams. A. Exogenous intoxications: alcohols, barbiturates and other sedative drugs, opiates (Chaps. 41 B. Endogenous metabolic disturbances: anoxia, diabetic acidosis, uremia, hepatic failure, nonketotic hyperosmolar hyperglycemia, hypoand hypernatremia, hypoglycemia, addisonian crisis, profound nutritional deficiency, carbon monoxide poisoning, thyroid states, hypercalcemia (Chaps. 39 and 40) C. Severe systemic infections: pneumonia, peritonitis, typhoid fever, malaria, septicemia, Waterhouse-Friderichsen syndrome D. Circulatory collapse (shock) from any cause E. Postseizure states and convulsive and nonconvulsive status epilepticus (Chap. 15) F. Hypertensive encephalopathy and eclampsia (Chap. 33) G. Hyperthermia and hypothermia (Chap. 39) H. Concussion (Chap. 34) I. Acute hydrocephalus (Chap. 29) J. Late stages of certain degenerative diseases (Chap. 38) and of Creutzfeldt-Jakob disease (Chap. 31)


Neurology_Adams

Neurology_Adams. H. Concussion (Chap. 34) I. Acute hydrocephalus (Chap. 29) J. Late stages of certain degenerative diseases (Chap. 38) and of Creutzfeldt-Jakob disease (Chap. 31) II. Diseases that cause meningeal irritation and an excess of white blood cells (WBCs) or red blood cells (RBCs) in the CSF, usually without focal or lateralizing cerebral or brainstem signs. CT scanning or MRI (which preferably should precede lumbar puncture) may be normal or abnormal. A. Subarachnoid hemorrhage from ruptured aneurysm, arteriovenous malformation, and cerebral trauma (Chaps. 33 and 34) B. Acute bacterial meningitis (Chap. 31) C. Viral meningoencephalitis (Chap. 32) D. Neoplastic meningeal infiltration (Chap. 30) E. Parasitic meningitis (Chap. 31) F. Pituitary apoplexy (Chap. 30) III. Diseases that cause focal brainstem or lateralizing cerebral signs, with or without changes in the CSF. CT scan and MRI are abnormal. A. Hemispheral hemorrhage or massive cerebral infarction (Chap. 33)


Neurology_Adams

Neurology_Adams. A. Hemispheral hemorrhage or massive cerebral infarction (Chap. 33) B. Brainstem infarction caused by basilar artery thrombosis or embolism (Chap. 33) C. Brain abscess, subdural empyema, herpes encephalitis (Chap. 31) D. Epidural and subdural hemorrhage and brain contusion (Chap. 34) E. Brain tumor (Chap. 30) F. Cerebellar and pontine hemorrhage (Chap. 33) G. Multiple focal cerebral lesions that cumulate to cause generalized brain dysfunction: multiple embolic infarction caused by bacterial endocarditis, acute disseminated (postinfectious) encephalomyelitis, intravascular lymphoma, TTP, sagittal sinus thrombosis diffuse fat embolism, and others Problems in Differential Diagnosis of Coma (Table 16-3)


Neurology_Adams

Neurology_Adams. Using the clinical criteria outlined previously, one can usually ascertain whether a given case of coma falls into one of these three categories. Concerning the group without focal or lateralizing or meningeal signs (which includes most of the metabolic encephalopathies, intoxications, concussion, and postseizure states), it must be kept in mind that residua from previous neurologic disease may confuse the clinical picture. Thus, an earlier hemiparesis from vascular disease or trauma may reassert itself in the course of uremic or hepatic coma with hypotension, hypoglycemia, diabetic acidosis, or following a seizure. In hypertensive encephalopathy, focal signs may also be present. Occasionally, for no understandable reason, one leg may seem to move less, one plantar reflex may be extensor, or seizures may be predominantly or entirely unilateral in a metabolic coma, particularly in the hyperglycemic–hyperosmolar states. Babinski signs and extensor rigidity, conventionally considered to


Neurology_Adams

Neurology_Adams. or seizures may be predominantly or entirely unilateral in a metabolic coma, particularly in the hyperglycemic–hyperosmolar states. Babinski signs and extensor rigidity, conventionally considered to be indicators of structural disease, do sometimes occur in profound intoxications with a number of agents or with hepatic encephalopathy.


Neurology_Adams

Neurology_Adams. The diagnosis of concussion or of postictal coma depends on observation of the precipitating event or indirect evidence, as discussed in Chap. 34. Usually, a convulsive seizure is marked by a bitten tongue, urinary incontinence, and an elevated creatine kinase–skeletal muscle fraction; it may be followed by another seizure or burst of seizures. The presence of small clonic or myoclonic convulsive movements of a hand or foot or fluttering of the eyelids or eyes makes an EEG useful to determine whether underlying status epilepticus is the cause of coma. This state, nonconvulsive status epilepticus, described in Chap. 15, must be considered in the diagnosis of unexplained coma, especially in known epileptics (see Table 16-3).


Neurology_Adams

Neurology_Adams. With respect to the second group with signs primarily of meningeal irritation (head retraction, stiffness of neck on forward bending, Kernig and Brudzinski signs), bacterial meningitis and subarachnoid hemorrhage are the usual causes. However, if the coma is profound, stiff neck may be absent in both infants and adults. In such cases the spinal fluid must be examined in order to establish the diagnosis. In most cases of bacterial meningitis, the CSF pressure is elevated but is not exceptionally high (usually <400 mm H2O). However, in cases associated with brain swelling, the CSF pressure is greatly elevated; the pupils become fixed and dilated, and there may be signs of compression of the brainstem with arrest of respiration. Patients in coma from ruptured aneurysms also have high CSF pressure; the CSF is overtly bloody and the blood is invariably visible in the CT scan throughout the basal cisterns and ventricles if the bleeding has been severe enough to cause coma.


Neurology_Adams

Neurology_Adams. In the third group of patients, it is the focality of sensorimotor signs and the abnormal pupillary and ocular reflexes, postural states, and breathing patterns that provide the clues to serious structural lesions in the cerebral hemispheres and their pressure effects upon segmental brainstem functions. As the brainstem features become more prominent, they may obscure earlier signs of cerebral disease.


Neurology_Adams

Neurology_Adams. It is worth emphasizing once more that profound hepatic, hypoglycemic, hyperglycemic, and hypoxic states may resemble the coma due to a brainstem lesion in that asymmetrical motor signs, focal seizures, and decerebrate postures arise and deep coma from drug intoxication may obliterate reflex eye movements. Conversely, certain structural lesions of the cerebral hemispheres are so diffuse as to produce a picture that simulates a metabolic disturbance; TTP, fat embolism, vasculitis, intravascular lymphoma, acute disseminated encephalomyelitis, and the late effects of global ischemia–anoxia are examples of such states. At other times, they cause a diffuse encephalopathy with superimposed focal signs. The multifocal cerebral lesions, typified by TTP, are among the most difficult to detect as causes of coma, particularly because the structural damage may be combined with seizures.


Neurology_Adams

Neurology_Adams. Unilateral cerebral infarction because of anterior, middle, or posterior cerebral artery occlusion produces no more than drowsiness, as a rule; however, with massive unilateral infarction as a result of carotid artery occlusion, coma can occur if extensive brain edema and secondary tissue shift develop. There are exceptional cases wherein stupor results from massive infarction of the dominant (left) hemisphere. Edema of a degree serious enough to compress the brainstem and cause coma seldom develops before 12 or 24 h. Rapidly evolving hydrocephalus causes smallness of the pupils, rapid respiration, extensor rigidity of the legs, Babinski signs, and sometimes a loss of eye movements.


Neurology_Adams

Neurology_Adams. Of course, diagnosis has as its prime purpose the direction of therapy. The treatable causes of coma are drug and alcohol intoxications, shock from infection, cardiac failure, or systemic bleeding, uremia, epidural and subdural hematomas, brain abscess, bacterial and fungal meningitis, diabetic acidosis or hyperosmolar state, hypoglycemia, hypoor hypernatremia, hepatic coma, hypercalcemia, uremia, status epilepticus, Wernicke disease, Hashimoto encephalopathy, and hypertensive encephalopathy. Also treatable to a varying degree are cerebellar hemorrhages, which can be removed successfully; edema from massive stroke, which may be ameliorated by hemicraniectomy; and hydrocephalus from any cause, which may respond to ventricular drainage. Management of the Acutely Comatose Patient


Neurology_Adams

Neurology_Adams. Seriously impaired states of consciousness, regardless of their cause, are often fatal not only because they represent an advanced stage of many diseases but also because they add their own particular burdens to the primary disease. The physician’s main objective, of course, is to find the cause of the coma and to treat it appropriately. It often happens, however, that the disease process is one for which there is no specific therapy; or, as in hypoxia or hypoglycemia, the acute, irreversible effects have already occurred before the patient comes to the attention of the physician. Again, the problem may be highly complex, for the disturbance may be attributable not to a single cause but to several factors acting in unison, no one of which could account for the total clinical picture. In certain circumstances two processes contribute to depressing consciousness, particularly head injury combined with drug or alcohol intoxication, and focal lesion(s) combined with inevident seizures. In


Neurology_Adams

Neurology_Adams. circumstances two processes contribute to depressing consciousness, particularly head injury combined with drug or alcohol intoxication, and focal lesion(s) combined with inevident seizures. In lieu of specific therapy, supportive measures must be used; indeed, the patient’s chances of surviving the original disease often depend on the effectiveness of these general medical measures.


Neurology_Adams

Neurology_Adams. The successful management of the insensate patient requires the participation of a well-coordinated team of nurses and a physician. Necessary treatments must be instituted rapidly, even before all the diagnostic steps have been completed; diagnosis and treatment may have to proceed concurrently. The following is a brief outline of the principles involved in the treatment of such patients. The details of management of shock, fluid and electrolyte imbalance, and other complications that threaten the comatose patient (pneumonia, urinary tract infections, deep venous thrombosis, etc.) can be found in Harrison’s Principles of Internal Medicine.


Neurology_Adams

Neurology_Adams. 1. Shallow and irregular respirations, stertorous breathing (indicating obstruction to inspiration), and cyanosis require the establishment of a clear airway and delivery of oxygen. The patient should initially be placed in a lateral position so that secretions and vomitus do not enter the tracheobronchial tree. Secretions and vomitus should be removed by suctioning as soon as they accumulate; otherwise they will lead to atelectasis and bronchopneumonia. Arterial blood gases should be measured and further observed by monitoring of oxygen saturation. A patient’s inability to protect against aspiration and the presence of either hypoxia or hypoventilation dictate the use of endotracheal intubation and a positive-pressure respirator. 2. The management of shock, if present, takes precedence over all other diagnostic and therapeutic measures.


Neurology_Adams

Neurology_Adams. 2. The management of shock, if present, takes precedence over all other diagnostic and therapeutic measures. 3. Concurrently, an intravenous line is established and blood samples are drawn for determination of glucose, intoxicating drugs, and electrolytes and for tests of liver and kidney function. Naloxone, 0.5 mg, should be given intravenously if a narcotic overdose is a possibility. Hypoglycemia that has produced stupor or coma requires the infusion of glucose, usually 25 to 50 mL of a 50 percent solution followed by a 5 percent infusion; this must be supplemented with thiamine. A urine sample is obtained for drug and glucose testing. If the diagnosis is uncertain, both naloxone and the glucose-thiamine combination should be administered.


Neurology_Adams

Neurology_Adams. 4. With the development of elevated intracranial pressure from a mass lesion, mannitol, 25 to 50 g in a 20 percent solution, should be given intravenously over 10 to 20 min and hyperventilation instituted if deterioration occurs, as judged by pupillary enlargement or deepening coma. Repeated CT scanning allows the physician to follow the size of the lesion and degree of localized edema and to detect displacements of cerebral tissue. With massive cerebral lesions, it may be appropriate to place a pressure-measuring device in the cranium of selected patients (see Chap. 35 for details of intracranial pressure monitoring and treatment).


Neurology_Adams

Neurology_Adams. 5. A lumbar puncture should be performed if meningitis or subarachnoid hemorrhage is suspected on the basis of headache and meningismus (and fever in the case of infectious meningitis), keeping in mind the risks of this procedure and the means of dealing with them. A CT scan may have disclosed a primary subarachnoid hemorrhage, in which case lumbar puncture is not necessary. In the case of meningitis, broad-spectrum antibiotics that penetrate the meninges should be instituted immediately, independent of the timing of the lumbar puncture. The choice of drug is then determined by the principles set forth in Chap. 31. If CSF pressure is greatly elevated when measured from a lumbar puncture that has been performed to diagnose bacterial meningitis, it has been recommended that the stylette should be left in the lumen of the needle, as little CSF should be withdrawn as is necessary for diagnostic purposes, and mannitol or hypertonic saline should be administered to lower the pressure.


Neurology_Adams

Neurology_Adams. 6. Convulsions should be controlled by measures outlined in Chap. 15, usually by intravenous diazepines. 7. As indicated earlier, gastric aspiration and lavage with normal saline may be diagnostically and therapeutically useful in some instances of coma due to drug ingestion. Salicylates, opiates, and anticholinergic drugs (tricyclic antidepressants, phenothiazines, scopolamine), all of which induce gastric atony, may be recovered many hours after ingestion. Caustic materials should not be lavaged because of the danger of gastrointestinal perforation. The administration of activated charcoal is indicated in certain drug poisonings. Measures to prevent gastric hemorrhage and excessive gastric acid secretion are usually advisable. 8. The temperature-regulating mechanisms may be disturbed and extreme hypothermia or hyperthermia should be corrected. In severe hyperthermia, evaporative-cooling measures are indicated in addition to antipyretics.


Neurology_Adams

Neurology_Adams. 9. The bladder should not be permitted to become distended; if the patient does not void, decompression should be carried out with an indwelling catheter. Needless to say, the patient should not be permitted to lie in a wet or soiled bed.


Neurology_Adams

Neurology_Adams. 10. Diseases of the CNS may disrupt the control of water, glucose, and sodium. The unconscious patient can no longer adjust the intake of food and fluids by hunger and thirst. Both salt-losing and salt-retaining syndromes have been described with brain disease (see Chap. 26). Water intoxication and severe hyponatremia may of themselves prove damaging. If coma is prolonged, the insertion of a nasogastric tube will ease the problems of feeding the patient and maintaining fluid and electrolyte balance. It is quite acceptable to leave the tube in place for long periods. Otherwise, approximately 35 mL/kg of isotonic fluid should be administered per 24 h (5 percent dextrose in 0.45 percent saline with potassium supplementation unless there is brain edema, in which case the use of hypertonic normal saline is indicated).


Neurology_Adams

Neurology_Adams. 11. Aspiration pneumonia is avoided by prevention of vomiting (gastric tube and endotracheal intubation), proper positioning of the patient, and restriction of oral fluids. Should aspiration pneumonia occur, it requires treatment with appropriate antibiotics and aggressive pulmonary physical therapy. Oral decontamination with chlorhexidine is advised to reduce the incidence of ventilator-associated pneumonia. 12. Leg vein thrombosis, a common occurrence in comatose and hemiplegic patients, often does not manifest itself by obvious clinical signs. An attempt may be made to prevent it by the subcutaneous administration of heparin, 5,000 U q12h, or of low-molecular-weight heparin, and by the use of intermittent pneumatic compression boots. There are few absolute contraindications to the prophylactic use of low-dose anticoagulants such as heparin and enoxaparin.


Neurology_Adams

Neurology_Adams. 13. If the patient is capable of moving, suitable restraints should be used to prevent him from falling out of bed and to avert self-injury from convulsions. 14. Regular conjunctival lubrication and oral cleansing should be instituted. Prognosis of Coma (See Also “Prognosis of Hypoxic-Ischemic Brain Injury” in Chap. 39.)


Neurology_Adams

Neurology_Adams. As a general rule, recovery from coma of metabolic and toxic causes is far better than from anoxic coma, with head injury occupying an intermediate prognostic position. Most patients who are initially comatose as a result of a stroke will die; subarachnoid hemorrhage in which coma is a result of hydrocephalus is an exception and those cases in which brain shift is relieved by craniectomy are also exceptions. In regard to all forms of coma, but particularly after cardiac arrest, if there are no pupillary, corneal, or oculovestibular responses within 1 day of the onset of coma, the chances of regaining independent function are practically nil (Levy et al). Other signs that predict a poor outcome according to an analysis of various studies by Booth and colleagues are absence of corneal reflexes, eye-opening responses, atonia of the limbs at 1 and 3 days after the onset of coma, and absence of the cortical component of the somatosensory-evoked responses on both sides. A consecutive series


Neurology_Adams

Neurology_Adams. eye-opening responses, atonia of the limbs at 1 and 3 days after the onset of coma, and absence of the cortical component of the somatosensory-evoked responses on both sides. A consecutive series of comatose patients followed by Kowalski and colleagues found that predictors of awakening from coma included younger age, a nontraumatic etiology as alluded to above, an higher Glasgow Coma Score and lesser amounts of pineal shift (see Chap. 39 for further details).


Neurology_Adams

Neurology_Adams. The frequency of vegetative state after head injury and the negligible chances of improvement if the condition persists for several months have already been discussed, and a discussion of the outcome of anoxic–ischemic coma can be found in Chap. 39. The novel perspectives that have been introduced by demonstrating residual and willful cognitive activity in survivors of traumatic brain injury have been discussed in an earlier section. In all other cases, the nature of the underlying disease and to some extent, the patient’s age, determines outcome; the reader should refer to the appropriate sections of this book for details. Adams JH, Graham DI, Jennet B: The neuropathology of the vegetative state after an acute brain insult. Brain 125:1327, 2000. Andrews BT, Chiles BW, Olsen WL, et al: The effects of intracerebral hematoma location on the risk of brainstem compression and outcome. J Neurosurg 69:518, 1988.


Neurology_Adams

Neurology_Adams. Andrews BT, Chiles BW, Olsen WL, et al: The effects of intracerebral hematoma location on the risk of brainstem compression and outcome. J Neurosurg 69:518, 1988. Andrews K: Recovery of patients after four months or more in the persistent vegetative state. BMJ 306:1597, 1993. Beecher HK, Adams RD, Sweet WH: A definition of irreversible coma: Report of the Committee of Harvard Medical School to examine the definition of brain death. JAMA 205:85, 1968. Bernat JL: Chronic disorders of consciousness. Lancet 367:1181, 2006. Booth CM, Boone RH, Tomlinson G, Detsky AS: Is this patient dead, vegetative, or severely impaired? JAMA 291:870, 2004. Braakman R, Jennett WB, Minderhound JM: Prognosis of the post-traumatic vegetative state. Acta Neurochir (Wien) 95:49, 1988. Bremer F: L’activité cerebralé au cours du sommeil et de la narcose. Bull Acad R Soc Belg 2:68, 1937. Brown N, Lydic R, Schiff ND: General anesthesia, sleep, and coma. N Engl J Med 363:2638, 2010.


Neurology_Adams

Neurology_Adams. Bremer F: L’activité cerebralé au cours du sommeil et de la narcose. Bull Acad R Soc Belg 2:68, 1937. Brown N, Lydic R, Schiff ND: General anesthesia, sleep, and coma. N Engl J Med 363:2638, 2010. Cairns H, Oldfield RC, Pennybacker JB, et al: Akinetic mutism with an epidermoid cyst of the third ventricle. Brain 64:273, 1941. Campagna JA, Miller KW, Forman SA: Mechanisms of actions of inhaled anesthetics. N Engl J Med 348:2210, 2003. Childs NL, Mercer WN: Late improvement in consciousness after post-traumatic vegetative state. N Engl J Med 334:24, 1996. Crick FA, Koch C. Framework for consciousness. Nat Neurosci 6:119, 2003. Di HB, Yu SM, Wend XC, et al: Cerebral response to patient’s own name in the vegetative and minimally conscious states. Neurology 68:895, 2007. Estraneo A, Moretta P, Loreto V, et al: Late recovery after traumatic, anoxic, or hemorrhagic long-lasting vegetative state. Neurology 75:239, 2010.


Neurology_Adams

Neurology_Adams. Estraneo A, Moretta P, Loreto V, et al: Late recovery after traumatic, anoxic, or hemorrhagic long-lasting vegetative state. Neurology 75:239, 2010. Feldman MH, Sahrmann S: The decerebrate state in the primate: II. Studies in man. Arch Neurol 25:517, 1971. Fisher CM: The neurological examination of the comatose patient. Acta Neurol Scand 45 (Suppl 36):1, 1969. Fitzsimmons RB, Wolfenden WH: Migraine coma: meningitic migraine with cerebral oedema associated with a new form of autosomal dominant cerebellar ataxia. Brain 108:555, 1985. Giacino JT, Ashwal S, Childs N, et al: The minimally conscious state. Definition and diagnostic criteria. Neurology 58:349, 2002. Haimovic IC, Beresford HR: Transient unresponsiveness in the elderly. Report of five cases. Arch Neurol 49:35, 1992. Hansotia PL: Persistent vegetative state: review and report of electrodiagnostic studies in eight cases. Arch Neurol 42:1048, 1985.


Neurology_Adams

Neurology_Adams. Hansotia PL: Persistent vegetative state: review and report of electrodiagnostic studies in eight cases. Arch Neurol 42:1048, 1985. Higashi K, Sakata Y, Hatano M, et al: Epidemiologic studies on patients with a persistent vegetative state. J Neurol Neurosurg Psychiatry 40:876, 1977. Huberfeld G, Dupont S, Hazemann P, et al: Stupeur recurrente idiopathique ches un patient: imputabilite benzodiazepines endogenes ou exogenes? Rev Neurol 158:824, 2002. Iragui VJ, McCutchen CB: Physiologic and prognostic significance of “alpha coma.” J Neurol Neurosurg Psychiatry 46:632, 1983. Jennett B, Plum F: Persistent vegetative state after brain damage. Lancet 1:734, 1972. Joffe AR, Lequier L, Cave D: Specificity of radionuclide brain blood flow testing in brain death—case report and review. J Int Care Med 25:53, 2010. Kernohan JW, Woltman HW: Incisura of the crus due to contralateral brain tumor. Arch Neurol Psychiatry 21:274, 1929.


Neurology_Adams

Neurology_Adams. Kernohan JW, Woltman HW: Incisura of the crus due to contralateral brain tumor. Arch Neurol Psychiatry 21:274, 1929. Kinney HC, Korein J, Panigraphy A, et al: Neuropathological findings in the brain of Karen Ann Quinlan—the role of thalamus in the persistent vegetative state. N Engl J Med 330:1469, 1994. Kowalski RG, Buitrageo MM, Duckworth J, et al: Neuroanatomical predictors of awakening in acutely comatose patients. Ann Neurol 77:804, 2015. Laureys S, Lemaire C, Maquet P, et al: Cerebral metabolism during vegetative state and after recovery of consciousness. J Neurol Neurosurg Psychiatry 67:121, 1999. Levy DE, Bates D, Caronna JJ: Prognosis in nontraumatic coma. Ann Intern Med 94:293, 1981. Luaté J, Maucort-Boulch D, Tell L, et al: Long-term outcomes of chronic minimally conscious and vegetative states. Neurology 75:246, 2010.


Neurology_Adams

Neurology_Adams. Luaté J, Maucort-Boulch D, Tell L, et al: Long-term outcomes of chronic minimally conscious and vegetative states. Neurology 75:246, 2010. Lugaresi E, Montagna P, Tinuper P, et al: Suspected covert lorazepam administration misdiagnosed as recurrent endozepine stupor. Brain 121:2201, 1998. Lustbader D, O’Hara D, Wijdicks EF, et al: Second brain death examination may negatively affect organ donation. Neurology 76:119, 2011. Lutkenhoff ES, Chiang J, Tshibanda L, et al: Thalamic and extrathalamic mechanisms of consciousness after severe brain injury. Ann Neurol 78:68, 2015. Magnus DC, Wilford BS, Caplan AL: Accepting brain death. N Engl J Med 370:891, 2014. McNealy DE, Plum FP: Brainstem dysfunction with supratentorial mass lesions. Arch Neurol 7:10, 1962. Meador KJ, Ray PG, Echauz JR, et al: Gamma coherence and conscious perception. Neurology 59:847, 2002. Mollaret P, Goulon M: Le coma dépassé. Rev Neurol 101:3, 1959.


Neurology_Adams

Neurology_Adams. Meador KJ, Ray PG, Echauz JR, et al: Gamma coherence and conscious perception. Neurology 59:847, 2002. Mollaret P, Goulon M: Le coma dépassé. Rev Neurol 101:3, 1959. Monti MM, Vanhaudenhuyse A, Coleman M, et al: Willful modulation of brain activity in disorders of consciousness. N Engl J Med 362:579, 2010. Moruzzi G, Magoun H: Brain stem reticular formation and activation of EEG. Electroencephalogr Clin Neurophysiol 1:455, 1949. Multi-Society Task Force on PVS. Medical aspects of the persistent vegetative state: Parts I and II. N Engl J Med 330:1499, 1572, 1994. Nakagawa TA, Ashwal S, Mathur M, et al: Guidelines for the determination of brain death in infants and children: an update of the 18987n task force recommendations-executive summary. Ann Neurol 71:573, 2012. North JB, Jennett B: Abnormal breathing patterns associated with acute brain damage. Arch Neurol 32:338, 1974.


Neurology_Adams

Neurology_Adams. North JB, Jennett B: Abnormal breathing patterns associated with acute brain damage. Arch Neurol 32:338, 1974. Owen AM, Coleman MR, Boly M, et al: Detecting awareness in the vegetative state. Science 313:1402, 2006. Parvizi J, Damasio JR: Neuroanatomical correlates of brainstem coma. Brain 126:1524, 2003. Pauzner R, Mouallem M, Sadeh M, et al: High incidence of primary cerebral lymphoma in tumor-induced central neurogenic hyper-ventilation. Arch Neurol 46:510, 1989. Pleasure SJ, Abosch A, Friedman J, et al: Spontaneous intracranial hypotension resulting in stupor caused by diencephalic compression. Neurology 50:1854, 1998. Plum F: Coma and related global disturbances of the human conscious state. In: Peters A (ed): Cerebral Cortex. Vol 9. New York, Plenum Press, 1991, pp 359–425. Plum F, Posner JB: Diagnosis of Stupor and Coma, 3rd ed. Philadelphia, Davis, 1980. Qin P, Wu X, Huang Z, et al: How are different neural networks related to consciousness? Ann Neurol 78:594, 2015.


Neurology_Adams

Neurology_Adams. Philadelphia, Davis, 1980. Qin P, Wu X, Huang Z, et al: How are different neural networks related to consciousness? Ann Neurol 78:594, 2015. Reich JB, Sierra J, Camp W, et al: Magnetic resonance imaging measurement and clinical changes accompanying transtentorial and foramen magnum brain herniation. Ann Neurol 33:159, 1993. Reptinger S, Fitzgibbons WP, Omojoia MF, et al: Long survival following bacterial meningitis associated brain destruction. J Child Neurol 21:591, 2006. Ropper AH: Cogito ergo sum by MRI. N Engl J Med 362:648, 2010. Ropper AH: Lateral displacement of the brain and level of consciousness in patients with an acute hemispheral mass. N Engl J Med 314:953, 1986. Ropper AH: The opposite pupil in herniation. Neurology 40:1707, 1990. Ropper AH: Unusual spontaneous movements in brain-dead patients. Neurology 34:1089, 1984. Ropper AH, Shafran B: Brain edema after stroke: Clinical syndrome and intracranial pressure. Arch Neurol 41:26, 1984.


Neurology_Adams

Neurology_Adams. Ropper AH, Shafran B: Brain edema after stroke: Clinical syndrome and intracranial pressure. Arch Neurol 41:26, 1984. Rosenberg GA, Johnson SF, Brenner RP: Recovery of cognition after prolonged vegetative state. Ann Neurol 2:167, 1977. Rosenberg H, Clofine R, Bialik O: Neurologic changes during awakening from anesthesia. Anesthesiology 54:125, 1981. Scheibel AB: On detailed connections of the medullary and pontine reticular formation. Anat Rec 109:345, 1951. Schiff ND, Giacino JT, Kalmar K, et al: Behavioural improvement with thalamic stimulation after severe traumatic brain injury. Nature 448:600, 2007. Scott S, Ahmed I: Modafinil in endozepine stupor. A case report. Can J Neurol Sci 31:409, 2004. Sherrington CS: Decerebrate rigidity and reflex coordination of movements. J Physiol 22:319, 1898. Shewmon DA: Chronic “brain death”: meta-analysis and conceptual consequences. Neurology 51:1538, 1998.


Neurology_Adams

Neurology_Adams. Shewmon DA: Chronic “brain death”: meta-analysis and conceptual consequences. Neurology 51:1538, 1998. Solomon P, Aring CD: Causes of coma in patients entering a general hospital. Am J Med Sci 188:805, 1934. Steriade M: Arousal: revisiting the reticular activating system. Science 272:225, 1996. Voss HU, Ulug AM, Dyke JP, et al: Possible axonal regrowth in late recovery from the minimally conscious state. J Clin Invest 116:2005, 2006. Webber CL Jr, Speck DF: Experimental Biot periodic breathing in cats: effects of changes in PiO2 and PiCO2. Respir Physiol 46:327, 1981. Wijdicks EFM: Brain Death. Lippincott Williams & Wilkins, Philadelphia, 2001. Wijdicks EFM, Bamlet WR, Maramattom BV, et al: Validation of a new coma scale: The FOUR score. Ann Neurol 58:585, 2005. Young GB: Consciousness, in Young GB, Ropper AH, Bolton CG: Coma and Impaired Consciousness: A Clinical Perspective. New York, McGraw Hill, 1998, pp 3–38. Zeman A: Consciousness. Brain 124:1263, 2001.


Neurology_Adams

Neurology_Adams. Zeman A: Consciousness. Brain 124:1263, 2001. Zeman A: Persistent vegetative state. Lancet 350:795, 1997. Figure 16-1. Schematic depiction of brain herniations between dural compartments. Transfalcial (1), transtentorial uncal-parahippocampal (2), cerebellar tonsillar (3), and horizontal (4), causing Kernohan-Woltman notch phenomenon. Herniations are shown in pink. M = mass. Chapter 16 Coma and Related Disorders of Consciousness


Neurology_Adams

Neurology_Adams. Chapter 16 Coma and Related Disorders of Consciousness The term syncope (Greek: synkope) literally means a “cessation,” a “cutting short,” or “pause.” Medically, it refers to an episodic loss of consciousness and postural tone and an inability to stand because of a diminished flow of blood to the brain. It is synonymous in everyday language with fainting. Feeling faint and a feeling of faintness are also commonly used terms to describe the loss of strength and other symptoms that characterize the impending or incomplete fainting spell. This latter state is referred to as presyncope. Relatively abrupt onset, brief duration, and spontaneous and complete recovery not requiring specific resuscitative measures are other typical features.


Neurology_Adams

Neurology_Adams. Faintness and syncope are among the most common of all medical problems. Practically every adult has experienced some presyncopal symptoms, if not a fully developed syncopal attack, or has observed such attacks in others. Description of these symptoms, as with other predominantly subjective states, is often ambiguous. The patient may refer to the experience as light-headedness, dizziness, a “drunk feeling,” a weak spell, or, if consciousness was lost, a “blackout.” Careful questioning may be necessary to ascertain the exact meaning the patient has given to these words. In many instances the nature of the symptoms is clarified by the fact that they include a sensation of faintness and then a momentary loss of consciousness, which is easily recognized as a faint, or syncope. This sequence also informs us that under certain conditions any difference between faintness and syncope is only one of degree. These symptoms must be clearly set apart from certain types of epilepsy, the other


Neurology_Adams

Neurology_Adams. also informs us that under certain conditions any difference between faintness and syncope is only one of degree. These symptoms must be clearly set apart from certain types of epilepsy, the other major cause of episodic unconsciousness, and from disorders such as cataplexy, transient ischemic attacks (TIAs), “drop attacks,” and vertigo, which are also characterized by episodic attacks of generalized weakness or inability to stand upright, but not by a loss of consciousness.


Neurology_Adams

Neurology_Adams. From a clinical perspective, syncope is essentially of three main types, all ultimately causing hypotension and each of which may lead to a temporary reduction in the flow of blood to the brain. The first, reflex withdrawal of vascular sympathetic tone (vasodepressor effect), triggered by centrally mediated inhibition of the normal tonic sympathetic influences, is often associated with excessive vagal effect and bradycardia (vagal effect). The type associated with bradycardia is called vasovagal syncope, a special form of neurogenic, or neurocardiogenic syncope, by which is meant the withdrawal of sympathetic tone through a reflex neural mechanism. Neurocardiogenic syncope usually signifies that the inciting stimulus originates in neural receptors within the heart.


Neurology_Adams

Neurology_Adams. The second is a failure of sympathetic innervation of blood vessels and of autonomically activated compensatory responses (reflex tachycardia and vasoconstriction), which occurs with assumption of the upright body position and leads to pooling of blood in the lower parts of the body—causing orthostatic hypotension and syncope. Typically, in individuals with these first two forms of syncope, there is no evidence of underlying cardiac disease. Syncope of a third type is caused by a primary diminished cardiac output because of disease of the heart itself as in the Stokes-Adams bradyarrhythmia attack, severe aortic or subaortic stenosis, or ischemic heart disease. Greatly reduced blood volume from dehydration or blood loss usually causes only near syncope, but complete loss of consciousness may certainly occur in severe circumstances.


Neurology_Adams

Neurology_Adams. As a rough guide to the relative frequency of the various causes of syncope, the large amount of information from the Framingham Heart Study accumulated by Soteriades and colleagues can be taken as representative: the leading cause was vasovagal, a cardiac cause was established in about 10 percent; and orthostatic hypotension in another 10 percent. Also, 7 percent of cases were attributed to medications, mainly those that interfered with sympathetic tone, and remaining 40 percent could not be categorized. The three main types of syncope as well as several others that cannot readily be classified within these categories can be further subdivided by their pathophysiologic mechanism, as follows: I. Neurogenic vasodepressor reactions A. Elicited by extrinsic signals to the medulla from baroreceptors 1. Vasodepressor (vasovagal) 2. Neurocardiogenic 3. Carotid sinus hypersensitivity 4. Vagoglossopharyngeal 5. Severe pain, especially if arising in a viscera (bowel, ovary, testicle, etc.)


Neurology_Adams

Neurology_Adams. B. Coupled with diminished venous return to the heart 1. Micturitional 2. Tussive 3. Valsalva, straining, breathholding, weight lifting 4. Postprandial C. Intrinsic and extrinsic psychic stimuli 1. Fear, anxiety (presyncope is more common) 2. Sight of blood 3. Hysterical II. Failure of sympathetic nervous system innervation (postural–orthostatic hypotension) A. Peripheral nervous system autonomic failure (peripheral neuropathy, autonomic neuropathy 1. Diabetes 2. Pandysautonomia 3. Guillain-Barré syndrome 4. Amyloid neuropathy 5. Surgical sympathectomy 6. Antihypertensive medications and other blockers of vascular sympathetic innervation and presynaptic α-agonsits 7. Pheochromocytoma


Neurology_Adams

Neurology_Adams. B. Central nervous system (CNS) autonomic failure 1. Primary autonomic failure (idiopathic orthostatic hypotension) 2. Multiple system atrophy (parkinsonism, ataxia, orthostatic hypotension) 3. Lewy-body and Parkinson diseases 4. Spinal cord trauma, infarction, and necrosis 5. Centrally acting antihypertensive and other medications III. Reduced cardiac output or inadequate intravascular volume (hypovolemia)


Neurology_Adams

Neurology_Adams. III. Reduced cardiac output or inadequate intravascular volume (hypovolemia) A. Reduced cardiac output 1. Cardiac arrhythmias a. Bradyarrhythmias i. Atrioventricular (AV) block (second and third degree) with Stokes-Adams attacks ii. Ventricular asystole iii. Sinus bradycardia, sinoatrial block, sinus arrest, sick sinus syndrome b. Tachyarrhythmias i. Episodic ventricular tachycardia ii. Supraventricular tachycardia (infrequently causes syncope) 2. Myocardial: angina, infarction, or severe congestive heart failure with reduced cardiac output 3. Obstruction to left ventricular or aortic outflow: aortic stenosis, hypertrophic subaortic stenosis, Takayasu arteritis 4. Obstruction to pulmonary flow: pulmonic stenosis, tetralogy of Fallot, primary pulmonary hypertension, pulmonary embolism 5. Pericardial tamponade B. Inadequate intravascular volume (hemorrhage); dehydration IV. Other causes of episodic faintness and syncope A. Hypoxia B. Severe anemia


Neurology_Adams

Neurology_Adams. B. Inadequate intravascular volume (hemorrhage); dehydration IV. Other causes of episodic faintness and syncope A. Hypoxia B. Severe anemia C. Cerebral vasoconstriction caused by diminished CO2 as a result of hyperventilation 1. Without Valsalva (faintness common, syncope rare) 2. With Valsalva: purposeful (“mess trick”) or induced by crying in children D. Hypoglycemia (faintness frequent, syncope rare) E. Anxiety (panic) attacks F. Environmental overheating This list of conditions causing faintness and syncope is deceptively long and involved, but the usual types are reducible to a few well-established mechanisms. So as not to obscure these mechanisms by too many details, only the varieties of fainting commonly encountered in clinical practice and those of particular neurologic interest are discussed in the following text. The Common Faint (Vasodepressor Syncope)


Neurology_Adams

Neurology_Adams. The Common Faint (Vasodepressor Syncope) This is the common faint, seen mainly in young individuals. A familial predisposition is well known (Mathias et al). The evocative factors are usually strong emotion, physical injury—particularly to viscera (testicles, gut)—or other factors (see in the following text). As described earlier, the vasodilatation of adrenergically innervated “resistance vessels” is postulated to lead to a reduction in peripheral vascular resistance, but cardiac output fails to exhibit the compensatory rise that normally occurs in hypotension. Some physiologic studies suggest that the dilatation of intramuscular vessels, innervated by β-adrenergic fibers, may be more important than dilatation of the splanchnic ones.


Neurology_Adams

Neurology_Adams. Skin vessels, in contrast, are constricted. Vagal activation may be superimposed either as a primary or a reactive phenomenon (hence the term vasovagal) causing bradycardia and leading possibly to a slight further drop in blood pressure. Other vagal effects are perspiration, increased peristaltic activity, nausea, and salivation. However, bradycardia probably contributes little to the hypotension and syncope. The term vasovagal was used originally by Thomas Lewis. As Lewis himself pointed out, atropine, “while raising the pulse rate up to and beyond normal levels during the attack, leaves the blood pressure below normal and the patient still pale and not fully conscious.”


Neurology_Adams

Neurology_Adams. The vasodepressor faint occurs (1) in normal health under the influence of strong emotion, particularly in some susceptible individuals (sight of blood or an accident) or in conditions that favor peripheral vasodilatation, for example, hot, crowded rooms (“heat syncope”), especially if the person is hungry or tired or has had alcoholic drinks; (2) during a painful illness or after bodily injury (especially of the abdomen or genitalia), as a consequence of fright, pain, and other factors (where pain is involved, the vagal element tends to be more prominent in the genesis of the faint); and (3) after standing immobile for prolonged periods, particularly in warm environments (military at attention, marching bands) (4) during exercise in some sensitive persons (see further on).


Neurology_Adams

Neurology_Adams. The clinical manifestations of fainting attacks vary to some extent, depending on their mechanisms and the settings in which they occur. The most common types of faint—namely, vasodepressor and vasovagal syncope, conform more or less to the following pattern. In these types, which are taken in this section as one characteristic manifestation, the patient is usually in the upright position at the beginning of the attack, either sitting or standing. Certain subjective symptoms, the prodrome, mark the onset of the faint. The person feels queasy, is assailed by a sense of giddiness and apprehension, may sway, and sometimes develops a headache. What is most noticeable at the beginning of the attack is pallor or an ashen-gray color of the face; often the face and body become bathed in cool perspiration. Salivation, epigastric distress, nausea, and sometimes vomiting may accompany these symptoms, and the patient tries to suppress them by yawning, sighing, or breathing deeply. Vision may dim


Neurology_Adams

Neurology_Adams. Salivation, epigastric distress, nausea, and sometimes vomiting may accompany these symptoms, and the patient tries to suppress them by yawning, sighing, or breathing deeply. Vision may dim or close in concentrically, the ears may ring, and it may be impossible to think clearly (“grayout”). This serves to introduce the common faint that is known to all physicians and most laypersons.


Neurology_Adams

Neurology_Adams. The duration of the prodromal symptoms is variable from a few minutes to only a few seconds. If, during the prodromal period, the person is able to lie down promptly, the attack may be averted before complete loss of consciousness occurs; otherwise, consciousness is lost and the patient falls to the ground. The more or less deliberate onset of this type of syncope enables patients to lie down or at least to protect themselves as they slump. A hurtful fall is exceptional in the young, although an elderly person may be injured.


Neurology_Adams

Neurology_Adams. The depth and duration of unconsciousness vary. Sometimes the person is not completely oblivious to his surroundings; he may still hear voices or see the blurred outlines of people. More often there is a complete lack of awareness and responsiveness. The patient lies motionless, with skeletal muscles fully relaxed. Sphincteric control is maintained in nearly all cases. The pupils are dilated. The pulse is thin and slow or cannot be felt; or they may be tachycardic, the systolic blood pressure is reduced (to 60 mm Hg or less as a rule), and breathing may be almost imperceptible. It is the brief period of hypotension and cerebral hypoperfusion that is the unifying feature of the various forms of syncope. The depressed vital functions, striking facial pallor, and unconsciousness almost simulate death.


Neurology_Adams

Neurology_Adams. Once the patient is horizontal, the flow of blood to the brain is restored. The strength of the pulse soon improves and color begins to return to the face. Breathing becomes quicker and deeper. Then the eyelids flutter and consciousness is quickly regained. However, should unconsciousness persist for 15 to 20 s, some motor activity is commonly observed. The term convulsive syncope has been used to describe this phenomenon, but it has also been used for an authentic seizure caused by a prolonged period of brain hypoxia. These movements, which are often mistaken for a seizure, usually take the form of brief clonic jerks of the limbs and trunk and twitchings of the face or a tonic extension of the trunk, clenching of the jaw or turning of the eyes to either direction or upward. Occasionally, the extensor rigidity and jerking flexor movements are more severe, but very rarely is there urinary incontinence or biting of the tongue, features that characterize a generalized tonic-clonic


Neurology_Adams

Neurology_Adams. the extensor rigidity and jerking flexor movements are more severe, but very rarely is there urinary incontinence or biting of the tongue, features that characterize a generalized tonic-clonic convulsion. These movements are displayed in the exercise carried out with medical students, who induced syncope by hyperventilation followed by the Valsalva maneuver. Nearly all had myoclonic jerks and ocular deviation as syncope commenced as demonstrated in a video (Bauer, Lempert, and Schmidt; https://www.youtube.com/watch?v=KPewaYFWsrE&feature=youtu.be).


Neurology_Adams

Neurology_Adams. Gastaut and Fischer-Williams used the oculocardiac inhibitory reflex to study the pattern of electroencephalographic (EEG) changes in syncope. They found that the heightened vagal discharge produced by compression of the eyeballs (oculovagal reflex, a cause of syncope in acute glaucoma) could produce brief periods of cardiac arrest and syncope. This effect was produced in 20 of 100 patients who had a history of syncopal attacks. These investigators found that after a 7to 13-s period of cardiac arrest, there was a loss of consciousness, pallor, and muscle relaxation and changes in EEG activity. Toward the end of this period, runs of bilaterally synchronous theta and delta waves appeared in the EEG, predominantly in the frontal lobes; in some patients there were one or more myoclonic jerks, synchronous with the slow waves. If the hypotension persisted beyond 14 or 15 s, the EEG became flat. This period of electrical silence lasted for 10 to 20 s and was sometimes accompanied by a


Neurology_Adams

Neurology_Adams. jerks, synchronous with the slow waves. If the hypotension persisted beyond 14 or 15 s, the EEG became flat. This period of electrical silence lasted for 10 to 20 s and was sometimes accompanied by a generalized tonic spasm with incontinence. Following the spasm, heartbeats and large-amplitude delta waves reappeared, and after another 20 to 30 s, the EEG reverted to normal. It is noteworthy that rhythmic clonic seizures or epileptiform EEG activity was not observed at any time during the periods of cardiac arrest, syncope, and tonic spasm.


Neurology_Adams

Neurology_Adams. From the moment that consciousness is regained, there is a correct perception of the environment. Confusion, headache, and drowsiness, the common sequelae of a convulsive seizure, do not follow a syncopal attack. Nevertheless, the patient often feels weak and groggy after a vasodepressor faint and, by arising too soon, may precipitate another faint. The clinical features of cardiac and carotid sinus syncope are in some ways the same as those described above except that the onset may be absolutely abrupt, without any warning symptoms, and is independent of the patient being in an upright posture. The clinical particulars of these and other forms of syncope are described further on.


Neurology_Adams

Neurology_Adams. This term refers to all forms of syncope that result directly from the vascular effects of neural signals coming from the central nervous system. In essence, all the types of syncope in this category are “vasovagal,” meaning a combination of vasodepressor and vagal effects in varying proportions; the only differences are in the stimuli that elicit the reflex response. A number of stimuli, mostly from the viscera but some of psychologic or emotional origin, are capable of eliciting this response, which consists of a reduction or loss of sympathetic vascular tone coupled with a heightened vagal activity. The nucleus of the tractus solitarius (NTS) in the medulla integrates these afferent stimuli and normal baroreceptor signals with the efferent sympathetic mechanisms that maintain vascular tone (see further on and Chap. 25).


Neurology_Adams

Neurology_Adams. Several lines of study suggest that there are disturbances of both sympathetic control of vascular tone and also of the responsiveness of baroreceptors in neurogenic syncope, but the precise mechanisms are unclear. By the use of microneurography, Wallin and Sundlof have demonstrated an increase in sympathetic outflow in peripheral nerves just prior to syncope, as would be expected; however, this activity then ceases at the onset of fainting. Unmyelinated (postganglionic sympathetic) fibers cease firing during vasovagal fainting at a point when the blood pressure falls below 80/40 mm Hg and the pulse, below 60. This would signify that there is an initial attempt to compensate for the falling blood pressure, following which there is a centrally mediated withdrawal of sympathetic activity. Which one of these mechanisms (perhaps both) is responsible for syncope is not clear. More recently, Bechir and colleagues showed that muscle sympathetic activity as assessed using microneurography is


Neurology_Adams

Neurology_Adams. one of these mechanisms (perhaps both) is responsible for syncope is not clear. More recently, Bechir and colleagues showed that muscle sympathetic activity as assessed using microneurography is increased in the resting state in patients with orthostatic hypotension and, importantly, does not increase further with venous pooling (induced by lower-body negative pressure). Moreover, in the same patients, the response of the cardiac baroreceptors to pooling was significantly diminished. These data are only partially in agreement with those of Wallin and Sundlof, and they are not in accord with an initial increase in sympathetic activity prior to syncope.


Neurology_Adams

Neurology_Adams. There is agreement that peripheral vascular resistance is greatly reduced just prior to and at the onset of fainting. This drop in resistance has been attributed to an initial adrenergic discharge that, at high levels, causes a vasodilatation (rather than constriction) in intramuscular blood vessels. High levels of epinephrine and the vasodilating effects of nitric oxide acting on vascular endothelium, as well as greatly augmented levels of circulating acetylcholine during syncope, also have been invoked as additional or intermediary factors, but all remain speculative. In the current view, the drop in blood pressure is the result of a transient but excessive activity of sympathetic nerves that paradoxically leads to vascular dilatation in muscle and viscera from an imbalance between β-adrenergic and α-adrenergic activity peripherally.


Neurology_Adams

Neurology_Adams. It has been further suggested, on the basis of reasonable physiologic evidence, that the early sympathotonic attempt to maintain blood pressure leads to overly vigorous contractions of the cardiac chambers and that this, in turn, acts as the afferent stimulus for withdrawal of sympathetic tone in common fainting (see “Neurocardiogenic Syncope,” later). Also of interest are abnormalities in the response to hypocarbia of patients who are prone to syncope. Norcliffe-Kaufmann and colleagues recorded a greater-than-normal reduction in cerebral blood flow velocity (gauged by transcranial Doppler) and an excessively reduced vascular resistance in the forearm in response to hypocarbia, and the opposite reactions to hypercarbia. They relate the degree of these changes to variations in orthostatic tolerance among patients and suggest that the two aforementioned changes relate to decreased cerebral blood flow that may engender syncope.


Neurology_Adams

Neurology_Adams. This entity, a component or perhaps a subtype of vasodepressor syncope, has received attention as a cause of otherwise unexplained fainting in healthy and athletic children and young adults. As mentioned earlier, it may be the final precipitant in the common vasodepressor faint, and the term is used synonymously with vasovagal or vasodepressor syncope by some authors.


Neurology_Adams

Neurology_Adams. Oberg and Thoren were the first to observe that the left ventricle itself can be the source of neurally mediated syncope in much the same way as the carotid sinus when stimulated, produces vasodilatation and bradycardia. During acute blood loss in cats, they noted a paradoxical bradycardia that was preceded by increased afferent activity in autonomic fibers arising from the ventricles of the heart, a reaction that was eliminated by sectioning these nerves. This concept of the heart as the afferent source of vasodepressor reflexes had been suggested by Bezold, as well as by Jarisch and Zoterman, and came to be known as the Bezold-Jarisch reflex (see Mark). The inferoposterior wall of the left ventricle is the site of most of the subendocardial mechanoreceptors that are responsible for afferent impulses to the nucleus tractus solitarius.


Neurology_Adams

Neurology_Adams. For this mechanism to become active, very vigorous cardiac contractions must occur in the presence of deficient filling of the cardiac chambers (hence “neurocardiogenic”). In the simple faint, an initial burst of sympathetic activity is thought to precipitate physiologic circumstances of excessive cardiac contraction. Echocardiographic findings of a diminished ventricular chamber size and vigorous contractions just prior to syncope support this notion (the “empty-heart syndrome”). The remaining baroreceptors in the aorta may be responsible for the increased afferent activity.


Neurology_Adams

Neurology_Adams. According to Kaufmann, a proclivity to primary neurocardiogenic syncope can be identified by the finding of delayed fainting when the patient is placed at a 60-degree upright position on a tilt table. After approximately 10 min of upright posture, the blood pressure drops below 100 mm Hg; soon thereafter, the patient complains of dizziness and sweating and subsequently faints. In contrast, patients with primary sympathetic failure will faint soon after upward tilting. Half of patients with unexplained syncope display a delayed tilt-table reaction, but it is also seen in 5 percent of controls (see “Tilt-Table Testing” further on). The value of isoproterenol as a cardiac stimulant and peripheral vasodilator to enhance the effect of upright posture and expose neurocardiogenic syncope during the tilt-table test is controversial. The subject has been reviewed by Abboud.


Neurology_Adams

Neurology_Adams. Aerobic exercise, particularly running, is known to induce fainting in some persons, a trait that may become apparent in late childhood or later and may be familial. There is nausea as well as other presyncopal symptoms; the faint can be avoided by discontinuing exercise or not exceeding a threshold of effort set by the patient himself. Such persons do not seem unduly sensitive to nonaerobic exercise and have no recognizable electrocardiographic or structural heart problems. They have a predilection to faint with prolonged tilt-table testing and with isoproterenol infusion, suggesting that this represents a form of neurocardiogenic syncope. For this reason, these patients may benefit from β-adrenergic-blocking drugs if given under careful supervision. As discussed further on, exercise can also precipitate syncope in patients with a number of underlying cardiac conditions (myocardial ischemia, long QT syndrome, aortic outflow obstruction, cardiomyopathy, structural chamber anomalies,


Neurology_Adams

Neurology_Adams. also precipitate syncope in patients with a number of underlying cardiac conditions (myocardial ischemia, long QT syndrome, aortic outflow obstruction, cardiomyopathy, structural chamber anomalies, exercise-induced ventricular tachycardia, and, less often, supraventricular tachycardias).


Neurology_Adams

Neurology_Adams. Athletes who faint unpredictably during exercise pose a particularly difficult problem. Obviously those found to have serious heart disease should give up competitive sports, but the majority has no demonstrable cardiac abnormality. Subjecting these patients to intense exercise and other testing sometimes fails to elicit the faints, but many have varying degrees of hypotension when subjected to prolonged head-up tilt, again suggesting that the cause of fainting is essentially neurocardiogenic (see above). Implanted cardiac pacemakers are not curative in these vasodepressor faints, as the main deficiency is in vascular resistance. Unless the results of tilt-table testing are unequivocal and reproducible, it is best to consider the more serious causes of exercise-induced syncope due, for example, to ischemic heart disease or aortic valve disease, and to treat the patient appropriately.


Neurology_Adams

Neurology_Adams. The carotid sinus is normally sensitive to stretch and gives rise to sensory impulses carried via the nerve of Hering, a tributary of the glossopharyngeal nerve, to the medulla. Massage of one of the carotid sinuses or of both alternately, particularly in elderly persons, causes (1) a reflex cardiac slowing (sinus bradycardia, sinus arrest, or even atrioventricular block)—the vagal type of response, or (2) a fall of arterial pressure without cardiac slowing—the vasodepressor type of response. Another (“central”) type of carotid sinus syncope was in the past ascribed to cerebral arteriolar constriction, but such an entity has never been validated.


Neurology_Adams

Neurology_Adams. Faintness or syncope because of carotid sinus sensitivity reportedly has been initiated by turning of the head to one side while wearing a tight collar or even by shaving over the region of the sinus. However, the absence of a history of such an association does not exclude the diagnosis. The attack nearly always occurs when the patient is upright, usually standing. The onset is sudden, often with falling. Small convulsive movements occur quite frequently in both the vagal and vasodepressor types of carotid sinus syncope. The period of unconsciousness in carotid sinus syncope seldom lasts longer than 30 s, and the sensorium is immediately clear when consciousness is regained. The majority of the reported cases have been in men.


Neurology_Adams

Neurology_Adams. In some circumstances, it is important to avoid compression of the carotid artery as an evocative test, particularly if a carotid bruit is heard over either carotid vessel. Moreover, carotid sinus compression for syncope testing should be conducted in controlled circumstances. A number of other types of purely reflexive cardiac slowing can be traced to direct irritation of the vagus nerves (from esophageal diverticula, mediastinal tumors, gallbladder stones, carotid sinus disease, bronchoscopy, and needling of body cavities). Here, the reflex bradycardia is more often of sinoatrial than atrioventricular type. Weiss and Ferris called such faints vagovagal.


Neurology_Adams

Neurology_Adams. Through a similar mechanism, tumors or lymph node enlargements at the base of the skull or in the neck that impinge on the carotid artery, as well as postradiation fibrosis, are capable of causing dramatic syncopal attacks, sometimes preceded by unilateral head or neck pain. Often the episodes are unpredictable, but some patients find that turning the head stimulates an attack. The mechanism in one of our patients with cervical adenopathy was primarily a vasodepressor response; patients with prominent bradycardia have generally had tumors that directly surrounded or infiltrated the glossopharyngeal and vagus nerves (Frank et al; see also MacDonald et al). If the tumor can be safely removed from the carotid region, the syncope often abates; in many cases, however, intracranial section of the ninth and upper rootlets of the tenth nerves on the side of the mass is necessary.


Neurology_Adams

Neurology_Adams. Glossopharyngeal neuralgia typically begins in the sixth decade with paroxysms of pain localized to the base of the tongue, pharynx or larynx, tonsillar area, or an ear (see discussion in Chaps. 10 and 47). In only a small proportion of cases (estimated at 2 percent) are the paroxysms of pain complicated by syncope. Always the sequence is pain, then bradycardia, and, finally, syncope. Presumably the pain gives rise to a massive volley of afferent impulses along the ninth cranial nerve, activating the medullary vasomotor centers via collateral fibers from the nucleus of the tractus solitarius. An increase in parasympathetic (vagal) activity slows the heart. Wallin and colleagues demonstrated that, in addition to bradycardia, there is an element of hypotension caused by inhibition of peripheral sympathetic activity. Here, the effects of the bradycardia exceed those of the vasodepressor hypotension, sometimes to the point of asystole, reflecting the opposite relationship from that seen


Neurology_Adams

Neurology_Adams. sympathetic activity. Here, the effects of the bradycardia exceed those of the vasodepressor hypotension, sometimes to the point of asystole, reflecting the opposite relationship from that seen in most other types of syncope.


Neurology_Adams

Neurology_Adams. The medical treatment of this type of syncope parallels that of trigeminal neuralgia (which is associated in approximately 10 percent of cases, usually on the same side). Antiepileptic drugs and baclofen are helpful in reducing both the pain and syncope in some patients. Intracranial vascular decompression procedures involving small branches of the basilar artery or venous loops that impinge on the ninth nerve are said to be useful, but such patients have not been extensively studied. Conventional surgical treatment, which consists of sectioning the ninth cranial nerve and upper rootlets of the tenth, has proved to be effective in intractable cases. The same mechanism is probably operative in so-called deglutitional syncope, in which consciousness is lost during or immediately after a forceful swallow. The administration of anticholinergic drugs (propantheline 15 mg tid) has abolished these attacks (Levin and Posner).


Neurology_Adams

Neurology_Adams. This infrequent condition is usually seen in men, sometimes in young adults but more often in the elderly, who arise from bed at night to urinate. The syncope occurs at the end of micturition or soon thereafter, and the loss of consciousness is abrupt, with rapid and complete recovery. Several factors are probably operative. A full bladder causes reflex vasoconstriction; as the bladder empties, this gives way to vasodilatation, which, combined with an element of postural hypotension, might be sufficient to cause fainting in some individuals. Vagally mediated bradycardia and, in some cases, a mild Valsalva effect may also be factors, and alcohol ingestion, hunger, fatigue, and upper respiratory infection are common predisposing factors. Moreover, the use of α-adrenergic blockers for bladder outlet obstruction in men may contribute to the situation. In some instances, especially in the elderly, the nocturnal faint has caused serious injury.


Neurology_Adams

Neurology_Adams. Syncope as a result of a severe paroxysm of coughing was first described by Charcot in 1876. Affected patients are usually heavyset males who smoke and have chronic bronchitis. Occasionally, the problem occurs in children, particularly following paroxysmal coughing spells of pertussis and laryngitis. After sustained hard coughing, the patient suddenly becomes weak and may lose consciousness momentarily. This is mainly attributable to the greatly elevated intrathoracic pressure, which interferes with venous return to the heart. Increased cerebrospinal fluid pressure and diminished PCO2, with resultant cerebral vasoconstriction, are possibly contributing factors. Powerful efforts to exhale against a closed glottis (as occurs in tussive syncope) are referred to as the


Neurology_Adams

Neurology_Adams. Powerful efforts to exhale against a closed glottis (as occurs in tussive syncope) are referred to as the Valsalva maneuver. The unconsciousness that results from breathholding spells in infants is probably based on this mechanism as well; the so-called pallid attacks in infants probably represent reflex vasodepression. Also, the loss of consciousness that occurs during competitive weight lifting (“weight lifters’ blackout”) is mainly the effect of a Valsalva maneuver, added to which are the effects of vascular dilatation produced by squatting and hyperventilation. Lesser degrees of this phenomenon (faintness and light-headedness) often follow other kinds of strenuous activity, such as unrestrained laughing, straining at stool, heavy lifting, underwater diving, or effortful playing of a wind instrument (e.g., trumpet). Rarely, a brief faint may occur in each of these circumstances.


Neurology_Adams

Neurology_Adams. Syncope may occur occasionally in the course of prostatic or rectal examination, but there is only pallor and bradycardia unless the patient stands immediately (prostatic syncope). A Valsalva effect and reflex vagal stimulation appear to be contributing factors. Postprandial hypotension may occasionally lead to syncope in elderly persons, in whom impaired baroreflex function cannot compensate for pooling of blood in splanchnic vessels.


Neurology_Adams

Neurology_Adams. This type of syncope is the result of an orthostatic drop in of blood pressure. It affects persons whose adrenergic innervation to the blood vessels is defective or, of course, those who are hypovolemic. The patient with autonomic failure, on assuming an upright position, shows a steady decline in blood pressure that begins almost immediately and, if not checked, declines to a level at which the cerebral circulation cannot be supported. This rapid effect and the slow decline in pressure are quite different from the situation in neurocardiogenic syncope, in which there is a delayed but then rapid onset of hypotension.


Neurology_Adams

Neurology_Adams. These conditions are easily understood if one keeps in mind that, on assuming the erect posture, the pooling of blood in the lower parts of the body is normally prevented by (1) reflex arteriolar and arterial constriction, through αand β-adrenergic effector mechanisms; (2) reflex acceleration of the heart by means of aortic and carotid reflexes, as described earlier; and (3) muscular activity, which improves venous return. Lipsitz has pointed out that aging is associated with a progressive impairment of these compensatory mechanisms, thus rendering the older person especially vulnerable to syncope. However, even in some younger persons, after the blood pressure has fallen slightly and stabilized at a lower level, the compensatory reflexes may also fail suddenly, with a precipitant drop in blood pressure.


Neurology_Adams

Neurology_Adams. With few exceptions (see Chap. 25), peripheral autonomic failure includes an element of vagal dysfunction that precludes the development of a compensatory tachycardia because vagal tone has already been maximally reduced, and also contrary to what happens in vasodepressor syncope, there tend to be no autonomic responses such as pallor, sweating, nausea, or release of norepinephrine.


Neurology_Adams

Neurology_Adams. Postural syncope occurs under a wide variety of clinical conditions: (1) in otherwise normal individuals who, in certain circumstances, experience an excess centrally mediated sympathetic discharge, as described earlier under vasodepressor syncope, or the simple faint; (2) as part of a chronic, probably degenerative central nervous system syndrome known as idiopathic orthostatic hypotension or primary autonomic insufficiency and with a variety of central nervous system degenerations that have autonomic failure as an accompanying feature (multiple system atrophy, Parkinson disease, Lewy-body disease); (3) after a period of prolonged illness with recumbency, especially in elderly individuals with poor muscle tone; (4) in association with diseases of the peripheral nerves that involve autonomic nerve fibers—diabetes, tabes dorsalis, amyloidosis, Guillain-Barré syndrome, a primary idiopathic autonomic neuropathy, pandysautonomia, and several other polyneuropathies, all of which interrupt


Neurology_Adams

Neurology_Adams. nerve fibers—diabetes, tabes dorsalis, amyloidosis, Guillain-Barré syndrome, a primary idiopathic autonomic neuropathy, pandysautonomia, and several other polyneuropathies, all of which interrupt vasomotor reflexes; (5) in patients receiving L-dopa, dopamine agonists, antihypertensive agents, and certain sedative and antidepressant drugs; (6) in spinal cord transection above the T6 level, particularly in the acute stage; (7) in patients with hypovolemia, (8) in pheochromocytoma, in which repeated exposure to catecholamines leads to desensitization of α-receptors on resistance blood vessels.