IM Board Review

Postoperative delirium in a 64-year-old woman

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Because recent neuroimaging revealed no structural brain lesions and no cause for brain herniation, the patient receives a challenge of 2 mg of intravenous lorazepam to treat potential NCSE. Subsequent improvement is noted in her anisocoria, gaze deviation, and encephalopathy. EEG reveals frequent focal seizures arising from mesial frontal regions with bilateral hemisphere propagation, consistent with bifrontal focal NCSE.

As our patient is being transferred to a room for continuous EEG monitoring, her condition begins to deteriorate, and she again becomes more encephalopathic, with anisocoria and dysconjugate gaze. Additional doses of lorazepam are given (to complete a 0.1-mg/kg load), and additional therapy with intravenous fos­phenytoin (20-mg/kg load) is given. Intubation is done for airway protection.

Continuous EEG monitoring reveals multiple frequent electrographic seizures arising from the bifrontal territories, concerning for persistent focal NCSE. A midazolam drip is initiated for EEG burst suppression of cerebral activity. Over 24 hours, EEG shows resolution of seizure activity. As the patient is weaned from sedation, she awakens and follows commands consistently, tolerating extubation without complications. Her neurologic status remains stable over the next 48 hours, having returned to her neurologic baseline level of functioning. She is able to be transferred out of the ICU in stable condition while continuing on scheduled antiepileptic therapy with phenytoin.

ALTERED MENTAL STATUS IN INPATIENTS

Altered mental status is one of the most frequently encountered reasons for medical consultation from nonmedical services. The workup and management of metabolic, toxic, psychiatric, and neurologic causes requires a deep appreciation for the broad differential diagnosis and a multidisciplinary approach. Physicians caring for these patients should avoid prematurely drawing conclusions when the patient’s clinical condition fails to respond to typical measures.

Delirium is a challenging adverse event in older patients during hospitalization, with a significant national financial burden of $164 billion per year.33 The prevalence of delirium in adults on hospital admission is estimated as 14% to 24%, with an inpatient hospitalization incidence ranging from 6% to 56% in general hospital patients.34 In addition, postoperative delirium has been reported in 15% to 53% of older patients.35

While delirium is preventable in 30% to 40% of cases,36,37 it remains an important independent prognostic determinant of hospital outcomes.38–40

Delirium in hospitalized patients requires a thorough, individualized workup. In our patient’s case, the clinical findings of hypoactive delirium were found to be manifestations of NCSE, a rare life-threatening and potentially reversible neurologic disease.

While establishing seizures as a diagnosis, careful attention must first be directed towards investigating environmental or metabolic triggers that may be inciting the disease. This often involves a similar workup for metabolic derangements, as seen in the approach to delirium.

Magnetic resonance imaging (sagittal view) without contrast reveals significant frontotemporal atrophy (blue arrows) and deep sulci within the frontal lobe, features not as prevalent in occipital and cerebellar territories (red arrows).

Figure 1. Magnetic resonance imaging (sagittal view) without contrast reveals significant frontotemporal atrophy (blue arrows) and deep sulci within the frontal lobe, features not as prevalent in occipital and cerebellar territories (red arrows).

In our patient’s case, an extensive medical evaluation including testing of blood, urine, and cerebrospinal fluid was unable to identify a clear derangement or infectious cause. However, neuroimaging revealed significant atrophy of frontal and parietal regions (Figure 1), and EEG provided evidence of focal seizures with status epilepticus originating in these atrophic territories. It is estimated that 30% of seizures in the elderly present as status epilepticus, with NCSE accounting for 25% to 50% of all cases.41,42 Although NCSE is an underrecognized disease, evidence suggests that the incidence may be between 4 and 43 cases per 100,000 elderly patients per year.42,43

The diagnosis of NCSE, while made in this patient’s case, remains challenging. Careful physical examination should assess for automatisms, “negative” symptoms (staring, aphasia, weakness), and “positive” symptoms (hallucinations, psychosis). Cataplexy, mutism, and other acute psychiatric features have been associated with NCSE,44 highlighting the importance of EEG. A trial of a benzodiazepine in conjunction with clinical and EEG monitoring may help guide clinical decision- making.

As there is no current universally accepted definition for NCSE nor an accepted agreement on required EEG diagnostic features at this time,41 accurate diagnosis is most likely to be obtained in facilities with both subspecialty neurologic consultation and EEG capabilities.

Our patient’s family history of Pick disease is interesting, as this is a progressive form of frontotemporal dementia with both sporadic and genetically linked cases. Recent studies have shown evidence that patients with neurodegenerative disease have increased seizure frequency early in the disease course,31 and efforts are under way to establish the incidence of first unprovoked seizure in patients with frontotemporal dementia. In our patient’s case, resolution of seizure activity yielded a return to her baseline level of neurologic function.

Early use of selective serotonin reuptake inhibitors has been shown to help with the behavioral symptoms of frontotemporal dementia,45 but increasing requirements over time may indicate progression of neurodegeneration and should warrant further appropriate investigation.

In our patient’s case, escalating dose requirements may have reflected worsening frontotemporal atrophy. However, the diagnosis of a neurodegenerative disease such as frontotemporal dementia in a patient such as ours is not definitively established at this time and is being investigated on an outpatient basis.

Given the frequency of delirium and its many risk factors in the inpatient setting, verifying a causative diagnosis can be difficult. Detailed consideration of the patient’s individual clinical circumstances, often in concert with appropriate subspecialty consultations, is essential to the evaluation. Although it is time-intensive, multidisciplinary intervention can lead to safer outcomes and shorter hospital stays.

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Bedside manners: How to deal with delirium

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