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Delirium and Acute Encephalopathies
Clinical Vignette
A 19-year-old woman is brought to the emergency room after she experiences her first ever generalized seizure. An unenhanced brain computed tomography (CT) and basic blood work are normal. She is initially drowsy and disoriented but gradually awakens, becoming increasingly irritable and impulsive. Both the patient and her parents deny that she used alcohol or recreational drugs. She begins pacing the halls and accosting the nurses, who find it difficult to redirect her or to keep her out of other patients’ rooms. Her mental state remains disoriented and inattentive; she is incapable of making her own medical decisions. Over the next 12 hours she becomes aggressive and combative, eventually requiring restraints to protect the safety of hospital staff and other patients. With no explanation for her rapid deterioration and with the consent of her parents acting as her proxies, she is sedated for neurologic testing. After a normal contrast-enhanced magnetic resonance imaging (MRI) scan and lumbar puncture, her parents return home to inspect her room, where they find a stash of stolen clonazepam. She is treated for benzodiazepine withdrawal and makes a full recovery over the next 48 hours.
Delirium is among the most common neuropsychiatric disorders in clinical practice. Virtually every practitioner who treats hospitalized patients will encounter patients suffering from this condition. Various terms are used interchangeably and arbitrarily to describe this diagnosis. Neurologists frequently use the term “toxic metabolic encephalopathy,” whereas psychiatrists prefer “delirium.” Some practitioners reserve the term “delirium” for patients who demonstrate irritability or hypersympathetic activity. “Acute confusional state” and “change in mental status” (abbreviated “Δ MS”) are also frequently used terminologies. The lack of agreement on nomenclature adds a degree of imprecision to the description of these patients. Here, the terms encephalopathy and delirium are used interchangeably.
As encephalopathy often presents within the context of a complex medical or surgical illness, it is often not appreciated as a clinically independent entity. Nevertheless delirium is associated with considerable morbidity and mortality, delaying or interfering with proper care as well as promoting great distress for nursing staff, physicians, and families.
Definition
There are no universally accepted criteria for a diagnosis of encephalopathy. The most often cited criteria are found in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The onset is acute to subacute, within hours or days. It involves a change from baseline that disproportionately affects attention, level of consciousness, and awareness. The state is brought on by a medical condition, intoxication, or withdrawal and follows a fluctuating course. Other elements of cognition may also be affected, including memory, language, visuospatial ability, and/or perception. Patients may experience psychotic features such as delusions or hallucinations.
Causes
The list of conditions that may provoke encephalopathy is seemingly endless. Frequently multiple provocations are present in the same patient and the inciting event becomes impossible to distinguish. Common causes of encephalopathy include central nervous system or systemic infection, single-organ or multiorgan failure, electrolyte disturbances, dysglycemia, nutritional deficiencies, drug intoxication or withdrawal, ischemic or hemorrhagic stroke, and brain trauma.
It is a common misconception that encephalopathy is not caused by structural brain disease. For this reason, patients suffering from stroke, a brain tumor, or intracranial hemorrhage may be treated for a presumed infection or metabolic disturbance until an alternative diagnosis is considered and confirmed with brain imaging. Patients with brain lesions in the nondominant hemisphere are particularly prone to encephalopathy, especially when localized to the parietal lobe or thalamus. Ischemic stroke is a commonly overlooked cause for encephalopathy because it is presumed to be focal. However, embolic stroke may be multifocal or diffuse, as with a “shower of emboli.” Such presentations are more likely to present with encephalopathy. Embolism to the artery of Percheron, causing bilateral thalamic and hypothalamic infarction, may result in a drowsy, inattentive state that is clinically indistinguishable from other, more common encephalopathies. Similarly, spontaneous or traumatic subdural hematoma or “butterfly” glioma (crossing the corpus callosum) may affect both hemispheres, leading to a “nonfocal” syndrome that is most consistent with encephalopathy.
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