Chapter 4: Altered Level of Consciousness

Jeffrey Politsky, MD, MSc, FRCP(C) and Neil Morganstein, MD

1. CASE HISTORIES:
   

   CASE 1: A 55-year-old female with a history of Bipolar Disorder presented with agitation and confusion. She was not oriented to place or date and had asterixis on exam. The remainder of her exam was non-focal. Her serum electrolytes were normal.

   1. How would you describe this patient's level of consciousness?
   2. What other historical information is important to help determine the etiology of this patient's problem?
   3. What would be your first step in evaluating this patient?

   CASE 2: A 70-year-old female is brought to the ER in an unresponsive state after being found on the floor. She has a history of hypertension and diabetes. On exam she is not aroused by verbal or physical stimuli. Her gaze is dysconjugate; her pupils are pinpoint, but reactive. She has irregular breathing with sustained inspiration.

   1. What part or parts of the nervous system could be implicated in causing her unresponsiveness?
   2. What would be your first step in managing this patient?
2. DISORDERS:
   

    Both cerebral hemispheres and the brainstem must be intact to maintain a normal level of consciousness. An alteration in ability to respond to the environment may arise from bilateral hemispheric dysfunction or brainstem dysfunction. Unilateral hemispheric pathology does not, in and of itself, usually cause an alteration in the level of consciousness. Some caveats apply, however. A partial seizure, resulting from a focal cerebral pathology, with regional or distant spread of epileptic neuronal hyperactivity could, and often does, produce alteration of consciousness. A unilateral space occupying lesion with significant surrounding edema with or without neuro-imaging evidence of mid-line shift (sub-falcine, transtentorial herniation) could also produce alteration of consciousness. Non-lesional examples of disorders that can produce an altered state of awareness include metabolic and toxic encephalopathies, often associated clinically with agitation, poor concentration, and possibly hallucinations: this is usually a reversible state referred to as delirium. However, if the pathology is irreversible, such as with fulminant hepatic failure, the delirium may not resolve. Meningitis and encephalitis can also lead to a decreased level of consciousness.

   In contrast to delirium, dementia is an irreversible, degenerative neurologic condition characterized by disturbances in memory and cognition, including executive function. As the disorder progresses, and depending on the exact sub-type of dementia (Alzheimer's, fronto-temporal, sub-cortical, multi-infact or vascular), additional signs and symptoms may include speech and language dysfunction, apraxia (loss of knowledge of a previously learned task), hallucinations and paranoia, and slowed mentation. Additionally and importantly, both dementia and delirium can occur in the same patient, especially in the elderly or institutionalized patient. Superimposed infectious illnesses (such as a urinary tract infection or pneumonia), transient metabolic derangements (such as hypoglycemia or hyponatremia), or mild vascular insults (transient ischemic attacks or lacunar infarcts) in a patient with a history of moderate dementia can have a profound effect on that individual's cognitive function and presentation on their own accord or because of additional factors such as seizures or the requirement for additional medications. The foregoing discussion punctuates the necessity of understanding the patient's baseline level of function.

    As in all neurologic disorders the exam is used to localize the problem in the nervous system and the time course is then used to narrow down the possible etiologies. Table 4-1 categorizes etiologies based on localization and time course.

   TABLE 4-1: NEUROLOGICAL DISORDERS
   CAUSING ALTERED LEVEL OF CONSCIOUSNESS

   LOCALIZATION:
   TIME COURSE:	BILATERAL HEMISPHERES	BRAINSTEM
   Acute	— Concussion/Contusion — Subarachnoid Hemorrhage — Bilateral Hemisphere Infarcts — Hemisphere Infarcts/Hemorrhage with herniation — Epidural/Acute Subdural Hematoma with herniation — Tumor with acute hemorrhage/edema & herniation — Anoxic encephalopathy — Status Epilelpticus Postictal state from seizure — Syncope — Drug Toxicity — Acute Disseminated Encephalomylelitis (ADEM) — Fictitious	— Brainstem Infarct/Hemorrhage — Cerebellar Infarct/Hemorrhage with edema — Cerebellar Tumor with hemorrhage/edema
   Subacute	— Metabolic Encephalopathy — Drug Toxicity — Encephalitis — Meningitis — Obstructive Hydrocephalus — Abscess with herniation — Posterior reversible encephalopathy syndrome — Vasculitis	— Central Pontine Myelinolysis — Neoplasm — Inflammatory condition (e.g., sarcoid) — Intracranial hypotension
   Chronic	— Obstructive Hydrocephalus — Chronic Subdural Hematoma	— Brainstem Tumor — Posterior Fossa Tumor

3. HISTORY:
   

   Since the patient has an altered level of consciousness it is imperative that an observer or informed witness (caregiver, relative) be questioned. In addition to determining the rate of symptom onset, important historical points for evaluation of etiology of altered consciousness include medical, psychiatric, and neurologic factors, as listed in Table 4-2.

   TABLE 4-2: IMPORTANT HISTORICAL POINTS

   SYSTEM:	QUESTIONS TO ASK:
   Medical	Current medications, hepatic disease, renal disease, recent infections, recent antibiotics, head trauma, cardiac disease, acute chest pain, systemic cancer
   Psychiatric	Severe depression, possible suicide attempt, drug abuse, alcohol abuse
   Neurologic	Seizure disorder, previous infarct or hemorrhage

4. EXAM:
   

   The goal of the neurologic exam in a patient with altered level of consciousness is to determine if the patient has dysfunction localized to one or both hemispheres or to the brainstem. Sometimes, though this is not often the case, there may be clues on the exam as to whether the cause of altered level of consciousness is reversible, irreversible, or even fictitious. In a patient with a potentially reversible cause, such as metabolic or toxic encephalopathy, the examiner may see negative myoclonus (asterixis), along with confusion or agitation. Reflex blinking to gentle hand movement toward the eyes (threat response) with the eyes passively held open may suggest a fictitious basis for altered level of consciousness. However, additional historical information is often required, such as a pre-morbid psychiatric history, medical history, medication history, laboratory tests, before one can ascertain the underlying basis of an altered level of consciousness.

   The neurologic exam in patients with abnormal levels of consciousness can be categorized into 4 levels or stages: delirium, lethargy, stupor and coma. Since the definitions are not uniformly agreed upon it is preferable to describe the presence or absence or certain key elements on exam, including 1) initial observations; whether the patient is awake, drowsy, or asleep and whether there are any spontaneous movements (eye opening, limb movements, twitching); 2) response to auditory, tactile, and if necessary, noxious stimuli, such as eye movements, facial grimaces, limb movements (limb movement or localization toward stimulus, limb withdrawal from stimulus, decorticate or decerebrate posturing); 3) other exam elements, such as attention span, speech and language pattern and function, level of confusion and/or agitation if the patient is awake, brain stem reflexes (pupillary light responses, corneal reflexes, oculocephalic responses, gag reflex, cold-water caloric responses, if necessary to perform), and tendon reflexes. A delirious patient typically has poor attention span, is agitated, confused and may have asterixis (not specific for hepatic encephalopathy), tremor or myoclonic jerks. A patient who is lethargic appears to be asleep but awakens with verbal stimuli but falls quickly back to sleep. A stuporous patient can be aroused incompletely by noxious stimuli. A comatose patient cannot be aroused by noxious stimuli. (Video 4-1)

   If a patient is comatose or stuporous the goal of the exam is to determine if the dysfunction is in both hemispheres or in the brainstem. Table 4-3 describes the exam findings that often help to localize the affected brain regions.
   

    TABLE 4-3: EXAM OF STUPOROUS OR COMATOSE PATIENTS

   	BREATHING PATTERN	EXTRAOCULAR MOVEMENTS	PUPILLARY REACTION
   LOCATION IN CNS:
   FOREBRAIN	Normal or Cheyne Stokes	Normal, conjugate	Normal, reactive
   MIDBRAIN	Hyperventilation	Dysconjugate or absent	Midposition, fixed
   PONS	End inspiratory cramp (Apneustic)	Dysconjugate or absent	Pinpoint, reactive
   MEDULLA	Apneic	Dysconjugate or absent	Dilated, fixed

5. CLUES TO DIAGNOSIS:
   

   It is helpful to look for asterixis, tremor and myoclonic jerks in patients who are confused and agitated. These are helpful signs that point to a metabolic or toxic cause of altered mental status. In the absence of myoclonus, asterxis, or other definitive localizing neurologic signs on exam, the examiner should consider various conditions that could explain bihemispheric involvement: non-lesional disorders such as metabolic or toxic encephalopathy, a post-ictal state, encephalitis (infectious, inflammatory, paraneoplastic, immune-mediated), extra-axial processes such as subdural hematomas or meningiomas with mass effect, focal or multi-focal intraaxial processes such as para-saggital or midline lesions, intra-cerebral hemorrhage (including sub-arachnoid and intraventricular hemorrhage), abscess, other infection, vasculitis, or neoplastic process. On the other hand patients with brainstem dysfunction often have distinct and localizing clinical signs and are also more likely to have a structural and less reversible cause of their abnormal level of consciousness. Care is required in the interpretation of spontaneous movements such as myoclonic jerks. The etiologic and neuroanatomic basis of myoclonus is varied and diverse; it can occur in a number of pathologic states, appear as focal, segmental, or multifocal, be spontaneous or stimulus-sensitive, and can relate to cortical, subcortical, brainstem, or spinal cord pathology. For example, myoclonus that is frequent, intermittent, spontaneous, and multi-focal, in a comatose patient, may be an ominous prognostic sign, depending, of course, on the underlying pathology (e.g. anoxic-ischemic encephalopathy consequent to a cardio-respiratory arrest).

6. RED FLAGS & WHEN TO REFER:
   

   In general all patients with acute or subacute altered level of consciousness require immediate evaluation. Intravenous access (if not already in place) and administration of thiamine, glucose and an urgent non-contrast head CT are required. Appropriate referrals to neurology or neurosurgery can be obtained following the interpretation of the CT. An electroencephalogram (EEG) and lumbar puncture (LP) may also be useful tests. An EEG may be able to distinguish ongoing seizure activity (status epilepticus) from a post-ictal state, or even rule out the possibility of seizure activity (i.e. non-epileptic events or cause of altered level of consciousness not secondary to seizure phenomena). Results of an LP are often helpful to determine if an infectious or inflammatory central nervous system process is ongoing. Additionally, depending on the time-course, imaging, and lab results, the patient may need to be transferred to and Intensive Care Unit or ICU-step-down setting, either within the same hospital from a hospital ward bed or the emergency room (ER) or to a separate facility that offers a more advanced level of care (usually ER-ER or ER to ICU). Any patient with deterioration in level of consciousness, whether sudden, or progressive over minutes, hours, or days, will likely require the same detailed and extensive work-up once the patient presents. The earlier the process is recognized, the better the chance for recovery, though this is by no means always the case.

7. CASE DISCUSSIONS:
   

   CASE 1: It is very important to note that this patient has Bipolar Disorder and may be on lithium or depakote. Either of these medications can cause a metabolic encephalopathy which is suggested by the agitation, confusion and asterixis. Her level of consciousness would be described as a delirium. The first step in management would be to obtain a metabolic screen, toxicology screen and levels of any drugs that she is on at the time of admission. A CT head scan would also be an important test, to rule out a co-morbid condition or cause of altered consciousness.

   CASE 2: This patient is comatose and has an exam that suggests brainstem involvement, specifically pontine, dysfunction. The first step in evaluation would be to obtain a head CT without contrast to look for obvious pathology such as either a brainstem hemorrhage or infarction.

8. CME QUESTIONS:
   

   1. A metabolic encephalopathy caused by renal failure resulting in agitation, confusion and hallucinations is usually called:
   a. Delusions
   b. Delirium
   c. Dementia
   d. Stupor

   2. Common causes of substantial changes in level of alertness include:
   a. Acute renal failure
   b. Hypocalcaemia
   c. Hypo/hyperglycemia
   d. Transient ischemic attack
   e. Drug toxicity

   3. Physical findings that point to a metabolic cause of mental status changes include:
   a. Asterixis
   b. Fixed, dilated pupils
   c. Extensor plantar responses
   d. Positive Rhomberg's sign
   e. Absence of reflexes

   4. Which one of the following is NOT indicated for most patients presenting with acute mental status changes:
   a. Administer glucose
   b. Administer Thiamine
   c. Administer naloxone
   d. Head CT
   e. Carotid ultrasound

   5. An examination revealing pinpoint but reactive pupils, bilateral extensor plantar responses, disconjugate gaze and a pause or cramp after respirations would be most likely to indicate disease in which part of the nervous system:
   a. Bilateral cerebral cortex,
   b. Thalamus
   c. Midbrain
   d. Pons
   e. Medulla

   CME ANSWERS

   1. b. Delirium
   2. c. hypo/hyperglycemia
   3. a. Asterixis
   4. e. Carotid ultrasound
   5. d. Pons