Stupor and Coma PDF

5 Stupor and Coma Joseph R. Berger, Raymond Price OUTLINE Definitions, 34 Differentiating Psychiatric Coma and Pseudocoma from Conditions that May Mimic Coma, 34 Metabolic or Struct...

5 Stupor and Coma Joseph R. Berger, Raymond Price OUTLINE Definitions, 34 Differentiating Psychiatric Coma and Pseudocoma from Conditions that May Mimic Coma, 34 Metabolic or Structural Coma, 48 Approach to the Patient in Coma, 36 Helpful Laboratory Studies, 48 Rapid Initial Examination and Emergency Therapy, 36 Other Useful Studies, 48 Common Presentations, 38 Prognosis, 50 History, 38 Nontraumatic Coma, 50 General Examination, 38 Traumatic Coma, 50 Neurological Examination, 41 Persistent Vegetative State, 51 Coma and Brain Herniation, 47 Brain Death, 51 Differential Diagnosis, 47 Clinical Approach to Brain Death, 51 Differentiating Toxic-Metabolic Coma from Structural Coma, 47 Alterations in arousal, although often referred to as altered levels DEFINITIONS of consciousness, do not actually form discrete levels but rather are Consciousness may be defined as a state of awareness of self and sur- made up of a continuum of subtly changing behavioral states that roundings. Alterations in consciousness are conceptualized into two range from alert to comatose. These states are dynamic and thus may types. The first type affects arousal and is the subject of this chapter. change with time. Four points on the continuum of arousal are often Sleep, the only normal form of altered consciousness, is discussed in used in describing the clinical state of a patient: alert, lethargic, stupor- Chapter 101. The second type involves cognitive and affective mental ous, and comatose. Alert refers to a perfectly normal state of arousal. function, sometimes referred to as the “content” of mental function. Lethargy lies between alertness and stupor. Stupor is a state of baseline Examples of the latter type of alteration in consciousness are dementia unresponsiveness that requires repeated application of vigorous stim- (see Chapter 7), delusions, confusion, and inattention (see Chapter 9). uli to achieve arousal. Coma is a state of complete unresponsiveness These altered states of consciousness, with the exception of advanced to arousal. The terms lethargy and stupor cover a broad area on the dementia, do not affect the level of arousal. continuum of behavioral states and thus are subject to misinterpreta- Delirium is defined by American Psychiatric Association’s tion by subsequent observers of a patient when used without further Diagnostic and Statistical Manual of Mental Disorders, fifth edition qualification. In clinical practice, in which relatively slight changes in (DSM-V), as a disturbance in attention and awareness (European arousal may be significant, only the terms alert and comatose (the end- Delirium Association). Delirium can occur without a reduced level points of the continuum) have enough precision to be used without of consciousness, such as a hyperactive delirium, and in this context further qualification. would be classified as a disorder of the content or mental function. Alternatively, delirium can occur in conjunction with a mildly or mod- erately reduced level of consciousness, such as hypoactive delirium, CONDITIONS THAT MAY MIMIC COMA and would be classified as a disorder of arousal. Delirium is a good Several different states of impaired cognition or consciousness example of a confusional state in which it may be clinically difficult may appear similar to coma or may be confused with it (Table 5.1). to separate decreased arousal from a change in cognitive or affective Moreover, patients who survive the initial coma may progress to certain mental function. In clinical practice, the exact boundary between dif- of these syndromes after varying lengths of time. Once sleep/wake cycles ferent forms of altered consciousness may be vague. Diagnostic criteria become established, true coma is no longer present. Differentiation of for delirium from the American Psychiatric Association’s DSM-V in these states from true coma is important to allow administration of addition to a disturbance in attention and awareness include an addi- appropriate therapy and to help determine prognosis. tional disturbance in cognition (memory, language, visuospatial abil- In the locked-in syndrome (de-efferented state), patients are alert ity, perception) that developed over hours to days as a change from and aware of their environment but are quadriplegic, with lower cra- the patient’s baseline and is not better explained by a neurocognitive nial nerve palsies resulting from bilateral ventral pontine lesions that disorder. Patients with severely reduced levels of arousal such as coma involve the corticospinal, corticopontine, and corticobulbar tracts. cannot also be classified as delirious. The patients are awake and alert but are voluntarily able only to move 34 @ @ @ D D D D @ D1 F CD @ 2C @ C C@ @ ). @ 4 C F  CHAPTER 5 Stupor and Coma 35 TABLE 5.1 Behavioral States Confused with Coma Behavioral State Definition Lesion Comments Locked-in syndrome Alert and aware, quadriplegic with Bilateral ventral pontine A similar state may be seen with severe polyneu- lower cranial nerve palsy ropathies, myasthenia gravis, and neuromuscular blocking agents Persistent vegetative state Absent cognitive function but retained Extensive cortical gray or subcortical Synonyms include apallic syndrome, coma vigile, “vegetative” components white matter with relative preserva- cerebral cortical death tion of brainstem Abulia Severe apathy, patient neither speaks Bilateral frontal medial Severe cases resemble akinetic mutism, but patient nor moves spontaneously is alert and aware Catatonia Mute, with marked decrease in motor Usually psychiatric May be mimicked by frontal lobe dysfunction or activity drugs Pseudocoma Feigned coma their eyes vertically or blink. The locked-in syndrome most often is TABLE 5.2 Criteria for the Diagnosis of a observed as a consequence of pontine infarction due to basilar artery thrombosis. Other causes include central pontine myelinolysis and Persistent Vegetative State brainstem mass lesions. A state similar to the locked-in syndrome also 1. No evidence of awareness of themselves or their environment; they are may be seen with severe polyneuropathy—in particular, acute inflam- incapable of interacting with others matory demyelinating polyradiculoneuropathy, myasthenia gravis, 2. No evidence of sustained, reproducible, purposeful, or voluntary behav- and poisoning with neuromuscular blocking agents. ioral responses to visual, auditory, tactile, or noxious stimuli In the persistent vegetative state (PVS), patients do not demon- 3. No evidence of language comprehension or expression strate clinically the ability to engage in any of the following behaviors: 4. Intermittent wakefulness manifested by the presence of sleep/wake awareness of self and environment, interaction with others, sustained, cycles reproducible, or purposeful voluntary behavioral response to visual, 5. Sufficiently preserved hypothalamic and brainstem autonomic functions to auditory, tactile or noxious stimuli, language comprehension or expres- survive if given medical and nursing care sion, or blink to visual threat. However, these patients do retain vegeta- 6. Bowel and bladder incontinence tive functions such as cardiac action, respiration, maintenance of blood 7. Variably preserved cranial nerve (pupillary, oculocephalic, corneal, vestibulo- pressure, and a sleep/wake cycle. Spontaneous movements may occur ocular, and gag) and spinal reflexe and the eyes may open in response to external stimuli, but the patient Data from The Multi-Society Task Force on PVS. Medical aspects of does not speak or obey commands. Functional magnetic resonance the persistent vegetative state. N Engl J Med 1994;3330, 1499–1508, imaging (MRI) and electroencephalogram (EEG) studies of patients 1572–1579. who meet the aforementioned clinical criteria of PVS have shown that approximately 14% of these patients will activate brain regions similar to healthy subjects when following commands despite not being able to TABLE 5.3 Criteria for the Minimally demonstrate clinically these behaviors. Diagnostic criteria for PVS are provided in Table 5.2. The diagnosis of this condition should be made Conscious State cautiously and only after extended periods of observation. A number To diagnose a minimally conscious state, limited but clearly discernible of poorly defined syndromes have been used synonymously with PVS, evidence of self- or environmental awareness must be demonstrated on a including apallic syndrome or state, akinetic mutism, coma vigil, alpha reproducible or sustained basis by one or more of the following behaviors: coma, neocortical death, and permanent unconsciousness. These terms, 1. Follows simple commands used variously by different authors, probably are best avoided because 2. Gestural or verbal yes/no responses (regardless of accuracy) of their lack of precision. 3. Intelligible verbalization A condition that has been estimated to be 10 times more common 4. Purposeful behavior, including movements or affective behaviors that than PVS is the minimally conscious state, in which severe disability occur in contingent relationship to relevant environmental stimuli and are accompanies minimal awareness. A set of diagnostic criteria for the not due to reflexive activity. minimally conscious state have proposed (Table 5.3). In two separate Data from Giacino, J.T., Ashwal, S., Childs, N., et al., 2002. The mini- studies in Europe, more than 40% of patients in a minimally conscious mally conscious state: definition and diagnostic criteria. Neurology 58, state were misdiagnosed as PVS, most commonly due to lack of appre- 349–353. ciation of eye tracking. Some authors subdivide minimally conscious state into minimally conscious state plus for patients who demon- strated higher-level function such as command following or intelli- minimally conscious state occurs when there is recovery of appropriate gible speech and minimally conscious state minus for patients who yes or no answers to questions or when able to use two familiar objects only rely to environmental stimuli or visually track objects. Similar correctly. Abulia is a severe apathy in which patients have blunting of to PVS patients, functional MRI and EEG studies of patients who feeling, drive, mentation, and behavior such that they neither speak nor meet the clinical criteria minimally conscious state have shown that move spontaneously. Catatonia may result in a state of muteness, with approximately 32% of these patients will activate brain regions sim- dramatically decreased motor activity. The maintenance of body pos- ilar to healthy subjects when following commands despite not being ture, with preserved ability to sit or stand, distinguishes it from organic able to demonstrate clinically these behaviors. Emergence from pathological stupor. It generally is a psychiatric manifestation but may @ @ @ D D D D @ D1 F CD @ 2C @ C C@ @ ). @ 4 C F 36 PART I Common Neurological Problems be mimicked by frontal lobe dysfunction or drug effect. Pseudocoma is may augment local lactic acid production by anaerobic glycolysis and the term for a condition in which the patient appears comatose (i.e., may worsen ischemic or anoxic damage. However, clinically, empiri- unresponsive, unarousable, or both) but has no structural, metabolic, cal glucose administration is recommended when the cause of coma or toxic disorder. is unknown. There are two reasons for this approach: the frequent occurrence of alterations in arousal due to hypoglycemia and the rela- tively good prognosis for coma due to hypoglycemia when it is treated APPROACH TO THE PATIENT IN COMA expeditiously; and the potentially permanent consequences if it is not The initial clinical approach to the patient in a state of stupor or treated. By comparison, the prognosis for anoxic or ischemic coma coma is based on the principle that all alterations in arousal consti- generally is poor and probably will remain poor regardless of glucose tute acute, life-threatening emergencies until vital functions such as supplementation. Thiamine must always be given in conjunction blood pressure and oxygenation are stabilized, potentially reversible with glucose to prevent precipitation of Wernicke encephalopathy. causes of coma are treated, and the underlying cause of the alteration Naloxone hydrochloride may be given parenterally, preferably intrave- in arousal is understood. Urgent steps may be necessary to avoid or nously, in doses of 0.4–2.0 mg if opiate overdose is the suspected cause minimize permanent brain damage from reversible causes. In view of of coma. An abrupt and complete reversal of narcotic effect may pre- the urgency of this situation, every physician should develop a diag- cipitate an acute abstinence syndrome in persons who are physically nostic and therapeutic routine to use with a patient with an alteration dependent on opiates. in consciousness. A basic understanding of the mechanisms that lead An initial examination should include a check of general appear- to impairment in arousal is necessary to develop this routine. The ana- ance, blood pressure, pulse, temperature, respiratory rate and breath tomical and physiological bases for alterations in arousal are discussed sounds, best response to stimulation, pupil size and responsiveness, in Chapter 101. and posturing or adventitious movements. The neck should be stabi- Although it is essential to keep in mind the concept of a spectrum lized in all instances of trauma until cervical spine fracture or sublux- of arousal, for the sake of simplicity and brevity only the term coma is ation can be ruled out. The airway should be protected in all comatose used in the rest of this chapter. Table 5.4 lists many of the common patients and an intravenous line placed. However, in coma, the classic causes of coma. More than half of all cases of coma are due to dif- sign of an acute condition in the abdomen—namely, abdominal rigid- fuse and metabolic brain dysfunction. In Plum and Posner’s landmark ity—may be subtle in degree or absent. In addition, the diagnosis of study (1980, see 2007 revision) of 500 patients initially diagnosed as blunt abdominal trauma is difficult in patients with a change in mental having coma of unknown cause (in whom the diagnosis was ultimately status. Therefore, in unconscious patients with a history of trauma, a established), 326 patients had diffuse and metabolic brain dysfunction. computed tomography (CT) scan of the abdomen or peritoneal lavage Almost half of these had drug poisonings. Of the remaining patients, by an experienced surgeon may be warranted. Hypotension, marked 101 had supratentorial mass lesions, including 77 hemorrhagic lesions hypertension, bradycardia, arrhythmias causing depression of blood and 9 infarctions; 65 had subtentorial lesions, mainly brainstem infarc- pressure, marked hyperthermia, and signs of cerebral herniation man- tions; and 8 had psychiatric coma. A logical decision tree often used in date immediate therapeutic intervention. Hyperthermia or meningis- searching for the cause of coma divides the categories of diseases that mus prompts consideration of urgent lumbar puncture. Examination cause coma into three groups: structural lesions, which may be above of the fundus of the eye for papilledema and a CT scan of the brain or below the tentorium; metabolic and toxic causes; and psychiatric should be performed before lumbar puncture in any comatose patient. causes. The history and physical examination usually provide sufficient Infection at the site of the lumbar puncture, papilledema, decerebrate evidence to determine the presence or absence of a structural lesion posturing, and thrombocytopenia and other bleeding diathesis are and quickly differentiate the general categories to decide what further contraindications to lumbar puncture and, even in their absence, med- diagnostic tests are needed or to allow for immediate intervention if icolegal considerations may render a CT scan of the head preferable necessary. Serial examinations are needed, with precise description before proceeding to lumbar puncture. To avoid a delay in therapy of the behavioral state at different points in time, to determine if the when acute bacterial meningitis is strongly suspected, antibiotics and patient is improving or—a more ominous finding—worsening, and adjunctive corticosteroids should be administered within 1 hour of to decide if a change in therapy or further diagnostic tests is necessary. hospital admission (Brouwer et al., 2010) even if cerebrospinal fluid Subtle declines in the intermediate states of arousal may herald pre- (CSF) collection cannot be obtained in a timely fashion. Corticosteroid cipitous changes in brainstem function, which may affect regulation administration should be avoided in the presence of septic shock. Blood of vital functions such as respiration or blood pressure. The dynamic cultures and throat swabs should be obtained on these patients prior quality of alterations of consciousness and the need for accurate docu- to antibiotic administration. The risk of herniation from a lumbar mentation at different points in time cannot be overemphasized. puncture in patients with evidence of increased intracerebral pressure is difficult to ascertain from the literature; estimates range from 1% to Rapid Initial Examination and Emergency Therapy 12%, depending on the series (Posner et al., 2007). It is important to A relatively quick initial assessment is conducted to ensure that the recognize that both central and tonsillar herniation may increase neck comatose patient is medically and neurologically stable before a more tone. Despite an elevated intracranial pressure (ICP), sufficient CSF detailed investigation is undertaken. This rapid initial examination is should always be obtained to perform the necessary studies. The perfor- essential to rule out the need for immediate medical or surgical inter- mance of bacterial culture and cell count, essential in cases of suspected vention. In addition, various supportive or preventive measures may bacterial meningitis, requires but a few milliliters of fluid. Multiplex be indicated. Urgent and sometimes empirical therapy is given to pre- nucleic acid amplification tests may be helpful in diagnosing a central vent further brain damage. Potential immediate metabolic needs of nervous system (CNS) infection, especially, when caused by fastidious the brain are supplied by empirical use of supplemental oxygen, intra- or noncultivable microorganisms. Intravenous access and intravenous venous thiamine (at least 100 mg), and intravenous 50% dextrose in mannitol or hypertonic saline should be ready in the event that unex- water (25 g). A baseline serum glucose level should be obtained before pected herniation begins after the lumbar puncture. When the CSF glucose administration. The use of intravenous glucose in patients pressure is greater than 500 mm H2O, some authorities recommend with ischemic or anoxic brain damage is controversial. Extra glucose leaving the needle in place to monitor the pressure and administering @ @ @ D D D D @ D1 F CD @ 2C @ C C@ @ ). @ 4 C F  CHAPTER 5 Stupor and Coma 37 TABLE 5.4 Causes of Coma I. Symmetrical—Nonstructural Aminoacidemia Toxins Wernicke encephalopathy Lead Porphyria Thallium Hepatic encephalopathy* Mushrooms Uremia Cyanide Dialysis encephalopathy Methanol Addisonian crisis Ethylene glycol Subarachnoid Hemorrhage Carbon monoxide Thalamic hemorrhage* Drugs Trauma—contusion, concussion* Sedatives Hydrocephalus Barbiturates* Subdural Hemorrhage, Bilateral Other hypnotics Intracerebral bleed Tranquilizers Pituitary apoplexy† Bromides Massive or bilateral supratentorial infarction Alcohol Multifocal leukoencephalopathy Opiates Creutzfeldt-Jakob disease Paraldehyde Adrenal leukodystrophy Salicylate Cerebral vasculitis Psychotropics Cerebral abscess Anticholinergics Infections Amphetamines Bacterial meningitis Lithium Viral encephalitis Phencyclidine Postinfectious encephalomyelitis Monoamine oxidase inhibitors Syphilis II. Symmetrical—Structural Sepsis Supratentorial Typhoid fever Bilateral internal carotid occlusion Malaria Bilateral anterior cerebral artery occlusion Waterhouse-Friderichsen syndrome III. Asymmetrical—Structural Psychiatric Supratentorial Catatonia Thrombotic thrombocytopenic purpura† Other Disseminated intravascular coagulation Postictal Nonbacterial thrombotic endocarditis (marantic endocarditis) Diffuse ischemia (myocardial infarction, congestive heart failure, arrhythmia) Subacute bacterial endocarditis Hypotension Fat emboli Fat embolism Unilateral hemispheric mass (tumor, bleed) with herniation Hypertensive encephalopathy Metabolic Hypothyroidism Hypoxia Infratentorial Hypercapnia Basilar occlusion* Hypernatremia Midline brainstem tumor Hyponatremia* Pontine hemorrhage* Hypoglycemia* Subdural Empyema Hyperglycemic nonketotic coma Thrombophlebitis† Diabetic ketoacidosis Multiple sclerosis Lactic acidosis Leukoencephalopathy associated with hemotherapy Hypercalcemia Acute disseminated encephalomyelitis Hypocalcemia Infratentorial Hypermagnesemia Brainstem infarction Hyperthermia Brainstem hemorrhage Hypothermia Reye encephalopathy *Relatively common asymmetrical presentation. †Relatively symmetrical. Data from Plum, F., & Posner, J.B., 1980. The Diagnosis of Stupor and Coma, third ed. F. A. Davis, Philadelphia; and Fisher, C.M., 1969. The neuro- logical evaluation of the comatose patient. Acta Neurologica Scandinavica 45 (Suppl 36), 5–56. intravenous mannitol or hypertonic saline to lower the pressure. If focal Ecchymosis, petechiae, or evidence of ready bleeding on general signs develop during or after the lumbar puncture, immediate intuba- examination may indicate coagulation abnormality or thrombocy- tion and hyperventilation also may be necessary to reduce intracerebral topenia. This increases the risk of epidural hematoma after a lum- pressure urgently until more definitive therapy is available. bar puncture, which may cause devastating spinal cord compression. @ @ @ D D D D @ D1 F CD @ 2C @ C C@ @ ). @ 4 C F 38 PART I Common Neurological Problems Measurements of prothrombin time, partial thromboplastin time, and infarction, shortness of breath from hypoxia, stiff neck in meningoenceph- platelet count should precede lumbar puncture in these cases, and the alitis, and vertigo in brainstem stroke. Nausea and vomiting are common in coagulation abnormality or thrombocytopenia should be corrected poisonings. Coma also may be secondary to increased ICP. Observers may before proceeding to lumbar puncture. have noted head trauma, drug abuse, seizures, or hemiparesis. Descriptions of falling to one side, dysarthria or aphasia, ptosis, pupillary dilatation, or Common Presentations disconjugate gaze may help to localize structural lesions. The time course of Coma usually manifests in one of three ways. First, and most commonly, the disease, as noted by family or friends, may help to differentiate the often it occurs as an expected or predictable progression of an underlying ill- relatively slow, progressive course of toxic-metabolic or infectious causes ness. Examples are focal brainstem infarction with extension; chronic from abrupt, catastrophic changes that are seen most commonly with obstructive pulmonary disease in a patient who is given too high a con- vascular events. Finally, family members or friends may be invaluable in centration of oxygen, thereby decreasing respiratory drive and resulting identifying psychiatric causes of unresponsiveness. The family may describe in carbon dioxide narcosis; and known barbiturate overdose when the a long history of psychiatric disease, previous similar episodes from which ingested drug cannot be fully removed and begins to cause unresponsive- the patient recovered, current social stresses on the patient, or the patient’s ness. Second, coma occurs as an unpredictable event in a patient whose unusual, idiosyncratic response to stress. Special care must be taken with prior medical conditions are known to the physician. The coma may be psychiatric patients because of the often-biased approach to these patients, a complication of an underlying medical illness, such as in a patient with which may lead to incomplete evaluation. Psychiatric patients are subject to arrhythmia who suffers anoxia after a cardiac arrest. Alternatively, an all of the causes of coma listed in Table 5.4. unrelated event may occur, such as sepsis from an intravenous line in a cardiac patient or a stroke in a hypothyroid patient. Third, coma can General Examination occur in a patient whose medical history is totally unknown to the phy- A systematic, detailed general examination is especially helpful in the sician. Sometimes this type of presentation is associated with a known approach to the comatose patient, who is unable to describe prior or probable cause, such as head trauma incurred in a motor vehicle acci- current medical problems. This examination begins in the initial rapid dent, but often the comatose patient presents to the physician without examination with evaluation of blood pressure, pulse, respiratory rate, an obvious associated cause. Thorough objective systematic assessment and temperature. must be applied in every comatose patient. Special care must be taken not to be lulled or misled by an apparently predictable progression of an Blood Pressure Evaluation underlying illness or other obvious cause of coma. Hypotension. Cerebral hypoperfusion secondary to hypotension may result in coma if the mean arterial pressure decreases to less than History the value for which the brain is able to autoregulate (normally 60 mm Once the patient is relatively stable, clues to the cause of the coma should Hg). This value is substantially higher in chronically hypertensive be sought by briefly interviewing relatives, friends, bystanders, or med- persons, in whom the cerebral blood flow–mean arterial pressure ical personnel who may have observed the patient before or during the curve is shifted to the right. Among the causes of hypotension are decrease in consciousness. Telephone calls to family members may be hypovolemia, massive external or internal hemorrhage, myocardial helpful. The patient’s wallet or purse should be examined for lists of infarction, cardiac tamponade, dissecting aortic aneurysm, medications, a physician’s card, or other information. Attempts should intoxication with alcohol or other drugs (especially barbiturates), be made to ascertain the patient’s social background and prior medical toxins, Wernicke encephalopathy, Addison disease, and sepsis. history and the circumstances in which the patient was found. The pres- Although most patients with hypotension are cold because of ence of drug paraphernalia or empty medicine bottles suggests a drug peripheral vasoconstriction, patients with Addison disease or sepsis overdose. Newer recreational drugs, such as γ-hydroxybutyrate and bath may have warm shock due to peripheral vasodilation. Medullary salts, must be considered in the differential diagnosis. An oral hypogly- damage also may result in hypotension because of damage to the cemic agent or insulin in the medicine cabinet or refrigerator implies pressor center. possible hypoglycemia. Antiarrhythmic agents such as procainamide or Hypertension. Hypertension is the cause of alterations in arousal quinidine suggest existing coronary artery disease with possible myocar- in hypertensive crisis and is seen secondarily as a response to cerebral dial infarction or warn that an unwitnessed arrhythmia may have caused infarction, in subarachnoid hemorrhage, with certain brainstem cerebral hypoperfusion, with resulting anoxic encephalopathy. Oral infarctions, and with increased intracerebral pressure. The Kocher- anticoagulants, including direct thrombin inhibitors, factor Xa inhib- Cushing (or Claude Bernard) reflex is the development of hypertension itors, and warfarin, typically prescribed for patients with deep venous associated with bradycardia and respiratory irregularity due to thrombosis or pulmonary embolism, atrial fibrillation or mechanical increased ICP. This response occurs more commonly in the setting of heart valve, may be responsible for massive intracerebral bleeding. In a posterior fossa lesion and in children. It results from compression patients found to be unresponsive at the scene of an accident, the unre- or ischemia of the pressor area lying beneath the floor of the fourth sponsive state may be due to trauma incurred in the accident, or sudden ventricle. Hypertension is a common condition and thus may be loss of consciousness may have precipitated the accident. present but unrelated to the cause of coma. The neurologist often is called when patients do not awaken after surgery or when coma supervenes following a surgical procedure. Postoperative Heart Rate causes of coma include many of those mentioned in Table 5.4. In addition, In addition to the Kocher-Cushing reflex, bradycardia can result from the physician also must have a high index of suspicion for certain neurologi- myocardial conduction blocks, with certain poisonings, and from effects cal conditions that occur in this setting, including fat embolism, Addisonian of drugs such as the beta-blockers. Tachycardia is a result of hypovo- crisis, and hypothyroid coma (precipitated by acute illness or surgical stress); lemia, hyperthyroidism, fever, anemia, and certain toxins and drugs, Wernicke encephalopathy from carbohydrate loading without adequate including cocaine, atropine, and other anticholinergic medications. thiamine stores; and iatrogenic overdose of a narcotic analgesic. Attempts should be made to ascertain if the patient complained of symptoms before Respiration onset of coma. Common signs and symptoms include headache preceding The most common causes of decreased respiratory rate are meta- subarachnoid hemorrhage, chest pain with aortic dissection or myocardial bolic or toxic, such as carbon dioxide narcosis or drug overdose with @ @ @ D D D D @ D1 F CD @ 2C @ C C@ @ ). @ 4 C F  CHAPTER 5 Stupor and Coma 39 CNS depressants. Increased respiratory rate can result from hypoxia, although this means of evaluation is not very sensitive. Laceration or hypercapnia, acidosis, hyperthermia, hepatic disease, toxins or drugs edema of the scalp is indicative of head trauma. The term raccoon eyes (especially those that produce a metabolic acidosis, such as methanol, refers to orbital ecchymosis due to anterior basal skull fracture. Battle ethylene glycol, paraldehyde, and salicylates), sepsis, and pulmonary sign is a hematoma overlying the mastoid, originating from basilar embolism (including fat embolism), and sometimes is seen in psycho- skull fracture extending into the mastoid portion of the temporal bone. genic unresponsiveness. Brainstem lesions causing hypopnea or hyper- The ecchymotic lesions typically are not apparent until 2–3 days after pnea are discussed later in the chapter. Changes in respiratory rate or the traumatic event. rhythm in a comatose patient may be deceiving, because a metabolic Meningismus, or neck stiffness, may be a sign of infectious or disorder may coexist with a CNS lesion. carcinomatous meningitis, subarachnoid hemorrhage, or central or tonsillar herniation. However, neck stiffness may be absent in Temperature coma from any cause but is likely to be present in less severe alter- Core temperature is best measured with a rectal probe in a comatose ations in arousal. Scars on the neck may be from endarterectomy, patient because oral or axillary temperatures are unreliable. Pyrexia implying vascular disease, or from thyroidectomy or parathyroid- most often is a sign of infection. Accordingly, any evidence of fever ectomy, suggesting concomitant hypothyroidism, hypoparathy- in a comatose patient warrants strong consideration of lumbar punc- roidism, or both. Goiter may be found with hypothyroidism or ture. Absence of an elevated temperature does not rule out infection. hyperthyroidism. Immunosuppressed patients, elderly patients, and patients with met- abolic or endocrine abnormalities such as uremia or hypothyroidism Eye Examination may not experience an increase in temperature in response to over- Examination of the eyes includes observation of the cornea, con- whelming infection. Pure neurogenic hyperthermia is rare and usually junctiva, sclera, iris, lens, and eyelids. Edema of the conjunctiva is due to subarachnoid hemorrhage or diencephalic (hypothalamus) and eyelids may occur in congestive heart failure and nephrotic lesions. A clue to brainstem origin is shivering without sweating. syndrome. Congestion and inflammation of the conjunctiva may Shivering in the absence of sweating, particularly when unilateral in occur in the comatose patient from exposure. Enophthalmos indi- nature, also may be observed with a deep intracerebral hemorrhage. cates dehydration. Scleral icterus is seen with liver disease, and yel- Other causes of increased temperature associated with coma are lowish discoloration of the skin without scleral involvement may heatstroke, thyrotoxic crisis, and drug toxicity. (Atropine and other be due to drugs such as rifampin. Band keratopathy is caused by anticholinergics elevate core temperature but decrease diaphoresis, hypercalcemia, whereas hypocalcemia is associated with cataracts. resulting in a warm, dry patient with dilated pupils and diminished Kayser-Fleischer rings are seen in progressive lenticular degenera- bowel sounds.) tion (Wilson disease). Arcus senilis is seen in normal aging but also Except in heatstroke and malignant hyperthermia, fever does not in hyperlipidemia. Fat embolism may cause petechiae not only in result in stupor or coma by itself. Conversely, hypothermia, regardless skin of the upper body and oral mucosa but also in conjunctiva and of cause, is anticipated to lead to altered consciousness. Hypothermia eye grounds. causes diminished cerebral metabolism and, if the temperature is suf- Funduscopic examination may demonstrate evidence of hyper- ficiently low, may result in an isoelectric EEG. Hypothermia usually tension or diabetes. Grayish deposits surrounding the optic disk have is metabolic or environmental in cause; however, it also is seen with been reported in lead poisoning. The retina is congested and edema- hypotension accompanied by vasoconstriction and may occur with tous in methyl alcohol poisoning, and the disk margin may be blurred. sepsis. Other causes of hypothermia associated with coma are hypothy- Subhyaloid hemorrhage appears occasionally as a consequence of a roid coma, hypopituitarism, Wernicke encephalopathy, cold exposure, rapid increase in ICP due to subarachnoid hemorrhage (Terson syn- drugs (barbiturates), and other poisonings. Central lesions causing drome). Papilledema results from increased ICP and may be indicative hypothermia are found in the posterior hypothalamus. The absence of of an intracranial mass lesion or hypertensive encephalopathy. shivering or vasoconstriction, or the presence of sweating, is a clue to the central origin of these lesions. Otoscopic Examination Otoscopic examination should rule out hemotympanum or CSF otor- General Appearance rhea from a basilar skull fracture involving the petrous ridge, as well as The general appearance of the patient may provide further clues to infection of the middle ear. Infections of the middle ear, mastoid, and the diagnosis. Torn or disheveled clothing may indicate prior assault. paranasal sinuses constitute the most common source of underlying Vomiting may be a sign of increased ICP, drug overdose, or metabolic infection in brain abscess. CSF rhinorrhea, which appears as clear fluid or other toxic cause. Urinary or fecal incontinence suggests an epileptic from the nose, may depend on head position. The presence of glucose seizure or may result from a generalized autonomic discharge resulting in the watery discharge is virtually diagnostic, although false-positive from the same cause as for the coma. Examination of body habitus results are possible. may reveal cushingoid patients at risk for an acute Addisonian crisis with abrupt withdrawal of their medications or additional stress from Oral Examination intercurrent illness. Cachexia suggests cancer, chronic inflammatory Alcohol intoxication, diabetic ketoacidosis (acetone odor), uremia, disorders, Addison disease, hypothyroid coma, or hyperthyroid crisis. and hepatic encephalopathy (musty odor of cholemia or fetor hepati- The cachectic patient also is subject to Wernicke encephalopathy in cus) may be suspected from the odor of the breath. Arsenic poisoning association with carbohydrate loading. Gynecomastia, spider nevi, tes- produces the odor of garlic. Poor oral hygiene or oral abscesses may ticular atrophy, and decreased axillary and pubic hair are common in be a source of sepsis or severe pulmonary infection with associated the alcoholic with cirrhosis. hypoxemia. Pustules on the nose or upper lip may seed the cavern- ous sinus with bacteria by way of the angular vein. Lacerations on the Head and Neck Examination tongue, whether old or new, suggest seizure disorder. Thin, blue-black The head and neck must be carefully examined for signs of trauma. pigmentation along the gingival margin may be seen in certain heavy Palpation for depressed skull fractures and edema should be attempted, metal poisonings (bismuth, mercury, and lead). @ @ @ D D D D @ D1 F CD @ 2C @ C C@ @ ). @ 4 C F 40 PART I Common Neurological Problems Integument Examination the acquired immunodeficiency syndrome (AIDS), with its plethora of Systematic examination of the integument includes inspection of the CNS abnormalities. skin, nails, and mucous membranes. A great deal of information can be gained by a brief examination of the skin (Table 5.5). Hot, dry skin is Examination of Lymph Nodes a feature of heat stroke. Sweaty skin is seen with hypotension or hypo- Generalized lymphadenopathy is nonspecific, because it may be seen glycemia. Drugs may cause macular-papular, vesicular, or petechial-pur- with neoplasm, infection (including AIDS), collagen vascular disease, puric rashes or bullous skin lesions. Bullous skin lesions most often are sarcoid, hyperthyroidism, Addison disease, and drug reaction (espe- a result of barbiturates but also may be caused by imipramine, mep- cially that due to phenytoin). However, local lymph node enlargement robamate, glutethimide, phenothiazine, and carbon monoxide. Kaposi or inflammation may provide clues to a primary tumor site or source sarcoma, anogenital herpetic lesions, or oral candidiasis should suggest of infection. TABLE 5.5 Skin Lesions and Rashes in Coma Lesion or Rash Possible Cause Antecubital needle marks Opiate drug abuse Pale skin Anemia or hemorrhage Sallow, puffy appearance Hypopituitarism Hypermelanosis (increased pigment) Porphyria, Addison disease, chronic nutritional deficiency, disseminated malignant melanoma, chemotherapy Generalized cyanosis Hypoxemia or carbon dioxide poisoning Grayish-blue cyanosis Methemoglobin (aniline or nitrobenzene) intoxication Localized cyanosis Arterial emboli or vasculitis Cherry-red skin Carbon monoxide poisoning Icterus Hepatic dysfunction or hemolytic anemia Petechiae Disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, drugs Ecchymosis Trauma, corticosteroid use, abnormal coagulation from liver disease or anticoagulants Telangiectasia Chronic alcoholism, occasionally vascular malformations of the brain Vesicular rash Herpes simplex Varicella Behçet disease Drugs Petechial-purpuric rash Meningococcemia Other bacterial sepsis (rarely) Gonococcemia Staphylococcemia Pseudomonas subacute bacterial endocarditis Allergic vasculitis Purpura fulminans Rocky Mountain spotted fever Typhus Fat emboli Macular-papular rash Typhus Candida Cryptococcus Toxoplasmosis Subacute bacterial endocarditis Staphylococcal toxic shock Typhoid Leptospirosis Pseudomonas sepsis Immunological disorders Systemic lupus erythematosus Dermatomyositis Serum sickness Other Skin Lesions Ecthyma gangrenosu Necrotic eschar often seen in the anogenital or axillary area Pseudomonas sepsis Splinter hemorrhages Linear hemorrhages under the nail, seen in subacute bacterial endocarditis, anemia, leukemia, and sepsis Osler nodes Purplish or erythematous painful, tender nodules on palms and soles, seen in subacute bacterial endocarditis Gangrene of digits’ extremities Emboli to larger peripheral or arteries Data on diseases associated with rashes from Corey, L., Kirby, P., 1987. Rash and fever. In: Braunwald, E., Isselbacher, K.J., Petersdorf, R.G. (Eds.), Harrison’s Principles of Internal Medicine, eleventh ed. McGraw-Hill, New York, pp. 240–244. @ @ @ D D D D @ D1 F CD @ 2C @ C C@ @ ). @ 4 C F  CHAPTER 5 Stupor and Coma 41 Cardiac Examination TABLE 5.6 Glasgow Coma Scale Cardiac auscultation will confirm the presence of arrhythmias such as atrial fibrillation, with its inherent increased risk of emboli. Changing Best Motor Response M mitral murmurs are heard with atrial myxomas and papillary muscle Obeys 6 ischemia, which is seen with current or impending myocardial infarc- Localizes 5 tion. Constant murmurs indicate valvular heart disease and may be Withdraws 4 heard with the valvular vegetation of bacterial endocarditis. Abnormal flexion 3 Extensor response 2 Abdominal Examination Nil 1 Possibly helpful findings on abdominal examination include abnormal bowel sounds, organomegaly, masses, and ascites. Bowel sounds are Verbal Response V absent in an acute abdominal condition, as well as with anticholin- Oriented 5 ergic poisoning. Hyperactive bowel sounds may be a consequence of Confused conversation 4 increased gastrointestinal motility from exposure to an acetylcholin- Inappropriate words 3 esterase inhibitor (a common pesticide ingredient). The liver may be Incomprehensible sounds 2 enlarged as a result of right heart failure or tumor infiltration. Nodules Nil 1 or a rock-hard liver may be due to hepatoma or metastatic disease. The liver may be small and hard in cirrhosis. Splenomegaly is caused by Eye Opening E portal hypertension, hematological malignancies, infection, and colla- Spontaneous 4 gen vascular diseases. Intraabdominal masses may indicate carcinoma. To speech 3 Ascites occurs with liver disease, right heart failure, neoplasms with To pain 2 metastasis to the liver, or ovarian cancer. Nil 1 Miscellaneous Examinations A positive result on tests for blood in stool obtained at rectal examina- tion is consistent with gastrointestinal bleeding and, possibly, bowel a blink response to visual threat need not indicate consciousness. carcinoma. Large amounts of blood in the gastrointestinal tract may Finally, painful stimuli may be needed to arouse the patient. All be sufficient to precipitate hepatic encephalopathy in the patient with patients in apparent coma should be asked to open or close the eyes cirrhosis. and to look up and down; these voluntary movements are preserved in the locked-in syndrome but cannot be elicited in coma—an important Neurological Examination distinction. Neurological signs may vary depending on the cause of the impaired Supraorbital pressure evokes a response even in patients who may consciousness and its severity, and they may be partial or incomplete. have lost afferent pain pathways as a result of peripheral neuropathy or For example, the patient may have a partial third nerve palsy with spinal cord or some brainstem lesions. Nail bed pressure or pinching pupillary dilation, rather than a complete absence of all third nerve the chest or extremities may help to localize a lesion when it evokes function, or muscle tone may be decreased but not absent. This con- asymmetrical withdrawal responses. Care must be taken to avoid cept is especially important in the examination of the stuporous or soft-tissue damage. Purposeful movements indicate a milder alteration comatose patient because the level of arousal may also influence the in consciousness. Vocalization to pain in the early hours of a coma, expression of neurological signs. In the stuporous or comatose patient, even if only a grunt, indicates relatively light alteration in conscious- even slight deviations from normal should not be dismissed as unim- ness. Later, primitive vocalization may be a feature of the vegetative portant. Such findings should be carefully considered to discover their state. pattern or meaning. The Glasgow Coma Scale (Table 5.6) is used widely to assess the The neurological examination of a comatose patient serves three initial severity of traumatic brain injury. This battery assesses three sep- purposes: (1) to aid in determining the cause of coma, (2) to provide arate aspects of a patient’s behavior: the stimulus required to induce eye a baseline, and (3) to help determine the prognosis. For prognosis and opening, the best motor response, and the best verbal response. Degrees localization of a structural lesion, the following components of the of increasing dysfunction are scored. Its reproducibility and simplic- examination have been found to be most helpful: state of conscious- ity make the Glasgow Coma Scale an ideal method of assessment for ness, respiratory pattern, pupillary size and response to light, sponta- non-neurologists involved in the care of comatose patients. However, neous and reflex eye movements, and skeletal muscle motor response. its failure to assess other essential neurological parameters limits its utility. In addition, in patients who are intubated or who have suffered State of Consciousness facial trauma, assessment of certain components of the Glasgow Coma The importance of a detailed description of the state of consciousness Scale, such as eye opening and speech, may be difficult or impossible. is worth reemphasizing. It is imperative that the exact stimulus and An alternative scale referred to as the Full Outline of UnResponsiveness the patient’s specific response be recorded. Several modes of stimula- (FOUR) score has been proposed (Wijdicks et al., 2005a) and is based tion should be used, including auditory, visual, and noxious. Stimuli on eye response, motor response, brainstem reflexes (pupillary reac- of progressively increasing intensity should be applied, with the maxi- tion, corneal reflex, and cough reflex), and respirations. mal state of arousal noted and the stimuli, the site of stimulation, and the patient’s exact response described. The examiner should start with Respiration verbal stimuli, softly and then more loudly calling the patient’s name Normal breathing is quiet and unlabored. The presence of any respi- or giving simple instructions to open the eyes. If there is no signifi- ratory noise implies airway obstruction, which must be dealt with cant response, more threatening stimuli, such as taking the patient’s immediately to prevent hypoxia. Normal respiration depends on (1) hand and advancing it toward the patient’s face, are applied. However, a brainstem mechanism, located between the midpons and cervical @ @ @ D D D D @ D1 F CD @ 2C @ C C@ @ ). @ 4 C F 42 PART I Common Neurological Problems A B C D E One minute Fig. 5.1 Abnormal respiratory patterns associated with pathological lesions (shaded areas) at various levels of the brain. The tracings were obtained by chest-abdomen pneumograph; inspiration reads up. A, Cheyne- Stokes respiration—diffuse forebrain damage. B, Central neurogenic hyperventilation—lesions of low midbrain ventral to aqueduct of Sylvius and of upper pons ventral to the fourth ventricle. C, Apneusis—dor- solateral tegmental lesion of middle and caudal pons. D, Cluster breathing—lower pontine tegmental lesion. E, Ataxic breathing—lesion of the reticular formation of the dorsomedial part of the medulla. (Reprinted from Plum, F., Posner, J.B., 1995. The Diagnosis of Stupor and Coma, third ed. Oxford University Press, New York. Copyright 1966, 1972, 1980, 1996, Oxford University Press, Inc. Used by permission of Oxford University Press, Inc.) medullary junction, that regulates metabolic needs; and (2) forebrain from Cheyne-Stokes respiration to certain other respiratory patterns, influences that subserve behavioral needs such as speech production. described next, is ominous. The organization and function of brainstem mechanisms responsible Two breathing patterns similar to Cheyne-Stokes respiration for respiratory rhythm generation, as well as forebrain influences, are should not be confused with it. Short-cycle periodic breathing is a respi- complex and beyond the scope of this chapter. Neuropathological cor- ratory pattern with a shorter cycle (faster rhythm) than Cheyne-Stokes relates of respiration are presented in Fig. 5.1. respiration, with one or two waxing breaths, followed by two to four Respiratory patterns that are helpful in localizing levels of involve- rapid breaths, then one or two waning breaths. It is seen with increased ment include Cheyne-Stokes respiration, central neurogenic hyperven- ICP, lower pontine lesions, or expanding lesions in the posterior fossa tilation, apneustic breathing, cluster breathing, and ataxic respiration. (Posner et al., 2007). A similar type of respiration, in which there are Cheyne-Stokes respiration is a respiratory pattern that slowly oscil- short bursts of seven to ten rapid breaths, then apnea without a wan- lates between hyperventilation and hypoventilation. In 1818, Cheyne ing and waxing prodrome, has been erroneously referred to as Biot described his patient as follows: “For several days his breathing was breathing. Biot, in fact, described an ataxic respiratory pattern, which irregular; it would entirely cease for a quarter of a minute, then it is described later. would become perceptible, though very low, then by degrees it became Central neurogenic hyperventilation refers to rapid breathing, from heaving and quick and then it would gradually cease again. This rev- 40 to 70 breaths/min, usually due to central tegmental pontine lesions olution in the state of his breathing occupied about a minute during just ventral to the aqueduct or fourth ventricle (Posner et al., 2007). which there were about 30 acts of respiration.” Cheyne-Stokes respi- This type of breathing is rare and must be differentiated from reactive ration is associated with bilateral hemispheric or diencephalic insults, hyperventilation due to metabolic abnormalities of hypoxemia sec- but it may occur as a result of bilateral damage anywhere along the ondary to pulmonary involvement. Large CNS lesions may cause neu- descending pathway between the forebrain and upper pons. It also is rogenic pulmonary edema, with associated hypoxemia and increased seen with cardiac disorders that prolong circulation time. Alertness, respiratory rate. Increased intracerebral pressure causes spontaneous pupillary size, and heart rhythm may vary during Cheyne-Stokes hyperpnea. Hyperpnea cannot be ascribed to a CNS lesion when arte- respiration (Posner et al., 2007). Patients are more alert during the rial oxygen partial pressure is less than 70–80 mm Hg or carbon diox- waxing portion of breathing. A continuous pattern of Cheyne-Stokes ide partial pressure is greater than 40 mm Hg. respiration is a relatively good prognostic sign, usually implying that Kussmaul breathing is a deep, regular respiration observed with permanent brainstem damage has not occurred. However, the emer- metabolic acidosis. Apneustic breathing is a prolonged inspiratory gasp gence of Cheyne-Stokes respiration in a patient with a unilateral with a pause at full inspiration. It is caused by lesions of the dorso- mass lesion may be an early sign of herniation. A change in pattern lateral lower half of the pons (Posner et al., 2007). Cluster breathing, @ @ @ D D D D @ D1 F CD @ 2C @ C C@ @ ). @ 4 C F  CHAPTER 5 Stupor and Coma 43 Pupillosphincter muscle Hypothalamus Ciliary ganglion Short ciliary nerves Ciliary Internal carotid artery ganglion Pupillodilator muscle Superior cervical sympathetic ganglion Ciliospinal center of Budge Edinger-Westphal nucleus T1 A B Oculomotor nerve Fig. 5.2 A, The parasympathetic pupilloconstrictor pathway. B, The sympathetic pupillodilator pathway. (Reprinted from Plum, F., Posner, J.B., 1995. The Diagnosis of Stupor and Coma, third ed. Oxford University Press, New York. Copyright 1966, 1972, 1980, 1996, Oxford University Press, Inc. Used by permission of Oxford University Press, Inc.) which results from high medullary damage, involves periodic respi- The third-order neuron travels along the internal carotid artery and rations that are irregular in frequency and amplitude, with variable then through the ciliary ganglion to the pupillodilator muscles. The pauses between clusters of breaths. parasympathetic efferent innervation of the pupil arises in the Edinger- Ataxic breathing is irregular in rate and rhythm and usually is due Westphal nucleus and travels in the oculomotor nerve to the ciliary to medullary lesions. The combination of ataxic respiration and bilat- ganglion, from which it innervates the pupillosphincter muscle (Fig. eral sixth nerve palsy may be a warning sign of brainstem compression 5.2). from an expanding lesion in the posterior fossa. This is an important Afferent input to the pupillary reflex depends on the integrity of the sign because brainstem compression due to tonsillar herniation (or optic nerve, optic chiasm, optic tract, and projections into the mid- other causes) may result in abrupt loss of respiration or blood pressure. brain tectum and efferent fibers through the Edinger-Westphal nucleus Ataxic and gasping respirations are signs of lower brainstem damage and oculomotor nerve. Abnormalities in pupil size and reactivity help and often are preterminal respiratory patterns. to delineate structural damage between the thalamus and pons (Fig. 5.3), act as a warning sign heralding brainstem herniation, and help to Pupil Size and Reactivity differentiate structural causes of coma from metabolic causes. Normal pupil size in the comatose patient depends on the level of illu- Thalamic lesions cause small, reactive pupils, which often are mination and the state of autonomic innervation. The sympathetic referred to as diencephalic pupils. Similar pupillary findings are noted efferent innervation consists of a three-neuron arc. The first-order in many toxic-metabolic conditions resulting in coma. Hypothalamic neuron arises in the hypothalamus and travels ipsilaterally through lesions or lesions elsewhere along the sympathetic pathway result in the posterolateral tegmentum to the ciliospinal center of Budge at Horner syndrome. Midbrain lesions produce three types of pupillary the T1 level of the spinal cord. The second-order neuron leaves this abnormality, depending on where the lesion occurs. (1) Dorsal tec- center and synapses in the superior cervical sympathetic ganglion. tal lesions interrupt the pupillary light reflex, resulting in midposition @ @ @ D D D D @ D1 F CD @ 2C @ C C@ @ ). @ 4 C F 44 PART I Common Neurological Problems Metabolic mydriatic agent placed by the patient or a prior observer may wear off unevenly, resulting in pupillary asymmetry. Some common misleading causes of a unilateral dilated pupil include prior mydriatic adminis- Small reactive tration, old ocular trauma or ophthalmic surgery, and, more rarely, carotid artery insufficiency. Ocular Motility Diencephalic Tectal Normal ocular motility (see Chapters 18 and 21) depends on the integ- Small reactive Large “fixed,” hippus rity of a large portion of the cerebrum, cerebellum, and brainstem. Preservation of normal ocular motility implies that a large portion of the brainstem from the vestibular nuclei at the pontomedullary junc- III nerve (uncal) Pons tion to the oculomotor nucleus in the midbrain is intact. Voluntary Dilated, fixed Pinpoint ocular motility cannot be judged in the comatose patient, so the exam- iner must rely on reflex eye movements that allow for assessment of the ocular motor system. The eye movements normally are conjugate, Midbrain and eyes are in the midposition in the alert person. Sleep or obtun- Midposition, fixed dation alone may unmask a latent vertical or horizontal strabismus, Fig. 5.3 Pupils in Comatose Patients. (Reprinted from Plum, F., Posner, J.B., 1995. The Diagnosis of Stupor and Coma, third ed. Oxford Univer- resulting in dysconjugacy; therefore patients must be examined when sity Press, New York. Copyright 1966, 1972, 1980, 1996, Oxford Uni- maximally aroused. The eyes return to the midposition in brain-dead versity Press, Inc. Used by permission of Oxford University Press, Inc.) patients. Evaluation of ocular motility consists of (1) observation of the resting position of the eyes, including eye deviation; (2) nota- tion of spontaneous eye movements; and (3) testing of reflex ocular pupils, which are fixed to light but react to near vision; the latter is movements. impossible to test in the comatose patient. Spontaneous fluctuations in Abnormalities in resting position. Careful attention must be paid size occur, and the ciliospinal reflex is preserved. (2) Nuclear midbrain to the resting position of the eyes. Even a small discrepancy in eye lesions usually affect both sympathetic and parasympathetic pathways, position may represent a partial extraocular nerve palsy. Partial nerve resulting in fixed, irregular midposition pupils, which may be unequal. palsies or combined nerve palsies predictably result in a more complex (3) Lesions of the third nerve fascicle in the brainstem, or after the picture on examination. Unilateral third nerve palsy from either an nerve has exited the brainstem, cause wide pupillary dilation, unre- intramedullary midbrain lesion or extramedullary compression causes sponsive to light. Pontine lesions interrupt sympathetic pathways and the affected eye to be displaced downward and laterally. A sixth nerve cause small, so-called pinpoint pupils, which remain reactive, although palsy produces inward deviation. However, isolated sixth nerve palsy is magnification may be needed to observe this feature. Lesions above the a poor localizer because of the extensive course of the nerve and because thalamus and below the pons should leave pupillary function intact, this palsy may be caused by nonspecific increases in ICP, presumably except for Horner syndrome in medullary or cervical spinal cord from stretching of the extramedullary portion of the nerve. A fourth lesions. The pathophysiology of pupillary response is discussed further nerve palsy is difficult to assess in the comatose patient because of the in Chapter 17. subtle nature of the deficit in ocular motility. Extraocular nerve palsies Asymmetry in pupillary size or reactivity, even of minor degree, is often become more apparent with the “doll’s eye maneuver” or cold important. Asymmetry of pupil size may be due to dilation (mydriasis) caloric testing in the comatose patient. of one pupil, such as with third nerve palsy, or contraction (miosis) Eye deviation. Spontaneous eye deviation may be conjugate of the other, as in Horner syndrome. This may be differentiated by or dysconjugate. Conjugate lateral eye deviation usually is due the pupillary reactivity to light and associated neurological signs. A to an ipsilateral lesion in the frontal eye fields but may be due to a dilated pupil due to a partial third nerve palsy is less reactive and usu- lesion anywhere in the pathway from the ipsilateral eye fields to the ally is associated with extraocular muscle involvement. The pupil in contralateral parapontine reticular formation (see Chapters 18 and 21). Horner syndrome is reactive; if the syndrome results from a lesion in Dysconjugate lateral eye movement may result from a sixth nerve the CNS, it may be associated with anhidrosis of the entire ipsilateral palsy in the abducting eye, a third nerve palsy in the adducting eye, or body. Cervical sympathetic chain lesions produce anhidrosis of only an internuclear ophthalmoplegia. An internuclear ophthalmoplegia face, neck, and arm. A partial or complete third nerve palsy causing may be differentiated from a third nerve palsy by the preservation of a dilated pupil may result from an intramedullary lesion, most com- vertical eye movements. Downward deviation of the eyes below the monly in the midbrain, such as an intramedullary glioma or infarction; horizontal meridian usually is due to brainstem lesions (most often uncal herniation compressing the third nerve; or a posterior commu- from tectal compression); however, it also may be seen in metabolic nicating artery aneurysm. A sluggishly reactive pupil may be one of the disorders such as hepatic coma. Thalamic and subthalamic lesions first signs of uncal herniation, followed soon thereafter by dilation of produce downward and inward deviation of the eyes. Patients with that pupil and, later, complete third nerve paralysis. these lesions appear to be looking at the tip of the nose. Sleep, seizure, Several caveats are important in examining the pupil or assessing syncope, apnea of Cheyne-Stokes respiration, hemorrhage into pupillary reflexes. A common mistake is the use of insufficient illumi- the vermis, and brainstem ischemia or encephalitis cause upward nation. The ophthalmoscope may be useful in this regard because it eye deviation, making this a poor localizing sign. Skew deviation provides both adequate illumination and magnification. Rarely, pre- is a maintained deviation of one eye above the other (hypertropia) existing ocular or neurological injury may fix the pupils or result in that is not due to a peripheral neuromuscular lesion or a local pupillary asymmetry. Seizures may cause transient anisocoria. Local extracranial problem in the orbit. It usually indicates a posterior fossa and systemic medications may affect pupillary function. Topical oph- lesion (brainstem or cerebellar). Dysconjugate vertical eye position thalmological preparations containing an acetylcholinesterase inhibi- sometimes may occur in the absence of a brainstem lesion in the tor, used in the treatment of glaucoma, produce miosis. The effect of a obtunded patient. @ @ @ D D D D @ D1 F CD @ 2C @ C C@ @ ). @ 4 C F  CHAPTER 5 Stupor and Coma 45 Spontaneous eye movements. Spontaneous eye movements (see Vertical nystagmus, due to an abnormal pursuit or vestibular sys- Chapter 18) are of many types. Purposeful-appearing eye movements tem, is slow deviation of the eyes from the primary position, with a in a patient who otherwise seems unresponsive should lead to rapid (saccadic), immediate return to the primary position. It is differ- consideration of the locked-in syndrome, catatonia, pseudocoma, entiated from bobbing by the absence of latency between the correc- or PVS. Roving eye movements are slow, conjugate, lateral to-and-fro tive saccade and the next slow deviation. Ocular-palatal myoclonus (the movements. For roving eye movements to be present, the ocular motor palatal movement also is called palatal tremor) occurs after damage to nuclei and their connections must be intact. In general, when roving the lower brainstem involving the Guillain-Mollaret triangle, which eye movements are present, the brainstem is relatively intact and extends between the cerebellar dentate nucleus, red nucleus, and infe- coma is due to a metabolic or toxic cause or bilateral lesions above the rior olive. It consists of a pendular vertical nystagmus, in synchrony brainstem. Detection of roving eye movements may be complicated by with the palatal movements. Ocular flutter is back-to-back saccades in ocular palsies or internuclear ophthalmoplegia. These superimposed the horizontal plane and usually is a manifestation of cerebellar disease. lesions produce relatively predictable patterns but often obscure Reflex ocular movements. Examination of ocular movement is the essential roving nature of the movement for the inexperienced not complete in the comatose patient without assessment of reflex observer. ocular movements, including the oculocephalic reflex (“doll’s eye Nystagmus occurring in comatose patients suggests an irritative or phenomenon”) and, if necessary, the caloric (thermal) testing. In epileptogenic supratentorial focus. An epileptogenic focus in one fron- practice, the terms doll’s eye phenomenon and doll’s eye maneuver are tal eye field causes contralateral conjugate eye deviation. Nystagmus used synonymously to refer to the oculocephalic reflex, which is the due to an irritative focus may rarely occur alone, without other motor preferred term for the description of the response. This reflex is tested manifestations of seizures. In addition, inconspicuous movements of by observation of the motion of the eyes during sudden rotation of the eye, eyelid, face, jaw, or tongue may be associated with electroen- the head, by the examiner, in both directions laterally and then with cephalographic status epilepticus. An EEG is required to ascertain the flexion and extension of the neck, also performed by the examiner. presence of this condition. When supranuclear influences on the ocular motor nerves are Spontaneous conjugate vertical eye movements are separated into removed, the eyes move in the orbit opposite to the direction of the different types according to the relative velocities of their downward head turn, and maintain their position in space. This maneuver should and upward phases. In ocular bobbing, rapid downward, jerks of both not be performed on any patient until the stability of the neck has been eyes are observed, followed by a brief pause in downgaze, followed by the adequately assessed. If there is any question of neck stability, a neck slow return to the midposition. In the typical form, there is associated brace should be applied and caloric testing substituted. In the normal paralysis of both reflex and spontaneous horizontal eye movements. oculocephalic reflex (normal or positive doll’s eye phenomenon), Monocular or paretic bobbing occurs when a coexisting ocular motor the eyes move conjugately in a direction opposite to the direction palsy alters the appearance of typical bobbing. The term atypical bob- of movement of the head. Cranial nerve palsies predictably alter the bing refers to all other variations of bobbing that cannot be explained response to this maneuver (Table 5.7). by an ocular palsy superimposed on typical bobbing. Most commonly, Clinical caloric testing (as distinct from quantitative calorics, used this term is used to describe ocular bobbing when lateral eye move- to assess vestibular end-organ disorders; see Chapter 22) is commonly ments are preserved. Typical ocular bobbing is specific but not pathog- done by applying cold water to the tympanic membrane. With the nomonic for acute pontine lesions. Atypical ocular bobbing occurs patient supine, the head should be tilted forward 30 degrees to allow with anoxia and is nonlocalizing. In reverse ocular bobbing, there is a maximal stimulation of the lateral semicircular canal, which is most slow initial downward phase, followed by a rapid return that carries the responsible for reflex lateral eye movements. After the ear canal is care- eyes past the midposition into full upward gaze. Then the eyes slowly fully checked to ensure that it is patent and the tympanic membrane return to the midposition. Reverse ocular bobbing is nonlocalizing. is free of defect, 10 mL of ice-cold water is slowly instilled into one ear Ocular dipping, also known as inverse ocular bobbing, refers to spon- canal. For purposes of the neurological examination, irrigation of each taneous eye movements in which an initial slow downward phase is ear with 10 mL of ice water generally is sufficient. followed by a relatively rapid return. Reflex horizontal eye movements Cold water applied to the tympanic membrane causes currents of are preserved. It usually is associated with diffuse cerebral damage. endolymph flow in the semicircular canal, simulating a contralateral TABLE 5.7 Oculocephalic Reflex* Method Response Interpretation Lateral head rotation Eyes remain conjugate, move in direction opposite to head movement, Normal and maintain position in space No movement in either eye on rotating head to left or right Bilateral pontine gaze palsy, bilateral labyrinthine dysfunction, drug intoxication, anesthesia Eyes move appropriately when head is rotated in one direction but do not Unilateral pontine gaze palsy move when head is rotated in opposite direction One eye abducts, the other eye does not adduct Third nerve palsy Internuclear ophthalmoplegia Vertical head flexion and Eyes remain conjugate, move in direction opposite to head movement, Normal extension and maintain position in space No movement in either eye Bilateral midbrain lesions Only one eye moves Third nerve palsy Bilateral symmetrical limitation of upgaze Aging *To be performed only after neck stability has been ascertained. @ @ @ D D D D @ D1 F CD @ 2C @ C C@ @ ). @ 4 C F 46 PART I Common Neurological Problems head turn. This results in a change in the baseline firing of the vestib- whereas ipsilateral paralysis indicates a probable brainstem lesion. ular nerve and slow (tonic) conjugate deviation of the eyes toward the External rotation of the lower limb is a sign of hemiplegia or hip stimulated ear. In an awake person or a patient in pseudocoma, the fracture. eye deviation is corrected with a resulting nystagmoid jerking of the Decerebrate posturing is bilateral extensor posture, with extension eye toward the midline (fast phase). Warm-water irrigation produces of the lower extremities and adduction and internal rotation of the reversal of flow of the endolymph, simulating an ipsilateral head turn, shoulders and extension at the elbows and wrist. Bilateral midbrain which causes conjugate eye deviation with a slow phase away from the or pontine lesions usually are responsible for decerebrate posturing. stimulated ear. In an awake person or a patient in pseudocoma, the Less commonly, deep metabolic encephalopathies or bilateral supra- eye deviation is corrected with a saccadic fast phase toward the ear. By tentorial lesions involving the motor pathways may produce a similar tradition, the nystagmus is named by the direction of the fast phase. pattern. The mnemonic COWS (cold opposite, warm same) refers to the fast Decorticate posturing is bilateral flexion at the elbows and wrists, phases. Simultaneous bilateral cold water application results in slow with shoulder adduction and extension of the lower extremities. It is downward deviation, whereas simultaneous bilateral warm water a much poorer localizing posture, because it may result from lesions application causes upward deviation. in many locations, although usually above the brainstem. Decorticate Oculocephalic or caloric testing may elicit subtle or unsuspected posture is not as ominous a sign as decerebrate posture because the ocular palsies. Abnormal dysconjugate responses occur with cranial former occurs with many relatively reversible lesions. nerve palsies, internuclear ophthalmoplegia, or restrictive eye disease. Unilateral decerebrate or decorticate postures also are less omi- Movements may be sluggish or absent. Sometimes reinforcement of nous. Lesions causing unilateral posturing may be anywhere in the cold caloric testing with superimposed passive head turning after injec- motor system from cortex to brainstem. Unilateral extensor posturing tion of cold water into the ear may reveal eye movement when either is common immediately after a cerebrovascular accident, followed in test alone shows none. time by a flexor response. False-negative or misleading responses on caloric testing occur with Posturing may occur spontaneously or in response to external preexisting inner ear disease, vestibulopathy such as that due to oto- stimuli such as pain or may even be set off by such minimal events as toxic drugs such as streptomycin, vestibular paresis caused by illnesses the patient’s own breathing. These postures, although common, may such as Wernicke encephalopathy, and drug effects. Subtotal labyrin- also be variable in their expression because of other associated brain- thine lesions decrease the response; there is no response when the lab- stem or more rostral brain damage. Special attention should be given yrinth is destroyed. Lesions of the vestibular nerve cause a decreased or to posturing because it often signals a brainstem herniation syndrome. absent response. Drugs that suppress either vestibular or ocular motor Emergency room personnel and inexperienced physicians may mistake function, or both, include sedatives, anticholinergics, anticonvulsants, these abnormal postures for convulsions (seizures) and institute anti- tricyclic antidepressants, and neuromuscular blocking agents. If the convulsant therapy, resulting in an unfortunate delay of appropriate response from one ear is indeterminate, both cold- and warm-water therapy for the patient. stimuli should be applied to the other ear. If the test remains equivo- Adventitious movements in the comatose patient may be help- cal, superimposition of the doll’s eye maneuver is recommended. The ful in separating metabolic from structural lesions. Tonic-clonic or interpretation of abnormal cold caloric responses is summarized in other stereotyped movements signal seizure as the probable cause of Table 5.8. decreased alertness. Myoclonic jerking, consisting of nonrhythmic jerk- An unusual ocular reflex that has been observed in the setting of ing movements in single or multiple muscle groups, is seen with anoxic PVS is reflex opening of both eyes triggered by flexion of an arm at the encephalopathy or other metabolic comas, such as hepatic encepha- elbow. This reflex is distinct from reflex eye opening in the comatose lopathy. Rhythmic myoclonus, which must be differentiated from epi- patient induced by raising the head or turning it from side to side. leptic movements, usually is a sign of brainstem injury. Tetany occurs with hypocalcemia. Cerebellar fits result from intermittent tonsillar Motor System herniation and are characterized by deterioration of level of arousal, Examination of the motor system of a stuporous or comatose patient opisthotonos, respiratory rate slowing and irregularity, and pupillary begins with a description of the resting posture and adventitious dilatation. movements. Purposeful and nonpurposeful movements are noted and The motor response to painful stimuli should be tested, but the pat- the two sides of the body compared. Head and eye deviation to one tern of response may vary depending on the site stimulated. Purposeful side, with contralateral hemiparesis, suggests a supratentorial lesion, responses may be difficult to discriminate from more primitive TABLE 5.8 Caloric Testing Method Response Interpretation Cold water instilled in right ear Slow phase to right, fast (corrective) phase to the left Normal No response (make sure canal is patent, apply warm Obstructed ear canal, “dead” labyrinth, eighth nerve or water stimulus to opposite ear nuclear dysfunction, false-negative result (see text) Slow phase to right, no fast phase Toxic-metabolic disorder, drugs, structural lesion above brainstem Downbeating nystagmus Horizontal gaze palsy Cold water instilled in left ear Responses should be opposite those for right ear Peripheral eighth nerve or labyrinth disorder n right (pro- vided that right canal is patent) Warm water instilled in left ear after no Slow phase to right, fast phase to left response from cold water in right ear @ @ @ D D D D @ D1 F CD @ 2C @ C C@ @ ). @ 4 C F  CHAPTER 5 Stupor and Coma 47 reflexes. Flexion, extension, and adduction may be either voluntary or breathing. These manifestations may occur in a paroxysmal fashion reflex in nature. In general, abduction is most reliably voluntary, with consequent to increases in ICP and have been referred to as the cere- shoulder abduction stated to be the only definite nonreflex reaction. bellar fits of Hughlings Jackson. It is important to suspect herniation This is tested in the comatose patient with noxious stimuli, such as early because, once advanced changes develop, structural injury is pinching the medial aspect of the upper arm. Reflex flexor response to likely to have occurred; sub