A 46-year-old man with a history of idiopathic hypoparathyroidism presented to the emergency department with “altered mental status.” His wife described the patient as having been restless and irritable for several days, and then he became quite confused—mumbling words and barely speaking to her. Neurologic examination revealed an alert but restless and inattentive, nonverbal man who was able to follow certain simple commands but required significant encouragement in order to do so. Cranial nerve examination was notable for fine nystagmus that was present nearly continuously, even in primary gaze. The motor examination was nonfocal other than the absence of deep tendon reflexes in the bilateral lower extremities. A computed tomography (CT) scan was performed and did not reveal any acute findings. His laboratory results were primarily notable for a serum calcium of 4.1 mg/dL and an albumin of 3.4 gm/dL. Intravenous (IV) calcium supplementation was initiated, and the patient was admitted; an endocrinologist was called for further recommendations. The patient’s astute admitting physician also ordered an electroencephalogram (EEG), given the patient’s hypocalcemia, severe encephalopathy, and the fine, continuous nystagmus noted on examination. The EEG was suggestive of nonconvulsive status epilepticus. The patient was given 2 mg of IV lorazepam that resulted in a cessation of epileptiform activity on the EEG. Within minutes, he began speaking again, and within hours he was nearly recovered in terms of his encephalopathy.
The term encephalopathy derives from the Greek encephalos (brain) and pathos (suffering or experience). In general, encephalopathy is synonymous with an acute confusional state, eg, “altered mental status.” Patients may present with an alteration in level of consciousness (ranging from agitation to coma), fluctuating levels of attentiveness (delirium), disorientation or perceptual distortions (even hallucinations), and/or disorganized thought processes. These symptoms often wax and wane, both in terms of severity and temporally (“sundowning;” reversal of sleep-wake). Delirium is not infrequent in hospitalized patients and may occur in 5% to 40% of hospitalized patients in general and 11% to 80% of patients in the intensive care unit (ICU).1 Diagnostic tools have been developed to aid in the recognition of encephalopathy and delirium. One such tool—the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) scale2—was specifically developed to identify delirium in the ICU (Table 13-1).
Feature 1: Acute onset and fluctuating course Identify an acute change in mental status from the baseline examination OR Identify fluctuating changes in mental status or behavior over the past 24 hours that may vary in severity AND Feature 2: Inattention Identify an inability to focus attention, easy distractibility, or inability to process components of conversation (eg, count backward, say months backward) AND Feature 3: Disorganized thinking If the patient is verbal: Identify illogical or incoherent thought processes, inability to understand proverbs, or inability to perform simple calculations If the patient is intubated or nonverbal (and not aphasic): Use yes/no questions or a letter board OR Feature 4: Altered level of consciousness Identify if the patient’s level of consciousness is anything other than alert (eg, drowsy, lethargic, stuporous, obtunded, comatose, or agitated and combative) |
The underlying cause of encephalopathy is often a systemic derangement that results in global cerebral dysfunction in the absence of a structural brain lesion (although a structural lesion can present solely as altered mental status in a minority of patients).3 These non-neurologic causes are summarized in Table 13-2, with toxic/metabolic etiologies and infections/sepsis being the most frequent. Patients who are encephalopathic often have an examination described as nonfocal, eg, without a fixed focal neurologic deficit. Focal findings on the neurologic examination suggest instead an underlying structural brain lesion as the cause of encephalopathy and should prompt immediate neuroimaging. That being said, in patients who have had prior focal brain injury (such as a prior stroke or traumatic brain injury) or metabolic or infectious conditions, the examination can unmask prior focal neurologic deficits, resulting in a recrudescence of previous symptoms.
Drugs and Toxins Sedative agents Anticholinergics Benzodiazepines Alcohol Opiates Salicylates Arsenic Lead Ethylene glycol Hyperparathyroid/hypoparathyroid Cyanide Carbon monoxide Organophosphates Withdrawal Systemic infection or sepsis Bacterial Viral Fungal Electrolyte abnormalities Hypernatremia/hyponatremia Hyperglycemia/hypoglycemia Hypercalcemia/hypocalcemia Hypermagnesemia/hypomagnesemia Hypophosphatemia | Organ failure Hepatic encephalopathy Renal failure Pulmonary failure (hypoxemia, hypercapnia) Endocrine abnormalities Hyperthyroid/hypothyroid Adrenal insufficiency Nutritional deficiencies Wernicke’s encephalopathy Vitamin B12 deficiency Niacin deficiency Folate deficiency Refeeding syndrome |
Normal neuronal activity requires a balanced environment of electrolytes, water, amino acids, excitatory and inhibitory neurotransmitters, and metabolic substrates.4 Disruption of the local environmental milieu may manifest as dysfunction of the complex systems mediating arousal and awareness and involving higher cognitive functions. Frequent causes of toxic and metabolic encephalopathy (TME) in hospitalized patients include electrolyte or glucose abnormalities, severe liver or renal dysfunction, nutritional deficiencies such as Wernicke’s encephalopathy (WE), and numerous drugs or toxins, including their withdrawal syndromes. The key to trying to determine the underlying cause of an encephalopathy is often a detailed review of the medical history, including complications that may have arisen during the course of hospitalization, laboratories, toxicology screening, and administering medications.
Recreational drugs and drugs of abuse, high-dose glucocorticoids, anticholinergics, and γ-aminobutyric acid (GABAA) agonists such as alcohol, barbiturates, and benzodiazepines, are key offenders in drug-induced delirium, with elderly patients being particularly susceptible.5 In the ICU, sedatives—continuous infusions of sedative agents or frequent or large-dose boluses—may be a significant contributor to or even the sole cause of altered mental status.6 As such, an appropriate interruption of sedation is often required to assess to what degree sedation may be contributing to TME. If the patient has been receiving high-dose continuous infusions for days to weeks or has liver or renal dysfunction (thereby reducing effective clearance of the sedative agent), the necessary washout period may be hours to even days.
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