Urgent considerations

See Differentials for more details

Delirium and acute mental status change

Delirium is characterized by disturbance of attention and awareness, and a fairly rapid change in cognition.[38] Acute change in mental status demands immediate consideration. A careful history and physical exam, in addition to laboratory and radiographic studies, are required to identify the underlying cause(s). The most frequent causes of delirium in HIV-infected patients are infection (including systemic bacterial or local central nervous system [CNS] infections), intoxication, withdrawal from illicit drugs or alcohol, or adverse effects from medications. In people with advanced HIV infection, systemic opportunistic infections such as Pneumocystis jirovecii pneumonia and mycobacterial infections must be considered. Fever, if present, suggests an infectious or inflammatory etiology. Bacterial infections, tuberculosis, syphilis, toxoplasmosis, cryptococcal disease, and other opportunistic infectious causes of encephalitis/meningitis or intracranial abscess should be excluded. An acute or subacute onset also suggests an infectious, inflammatory, or more widespread systemic etiology. Change in mental status could be due to organic disease, such as a stroke. Additionally, comorbid systemic illnesses (such as hypothyroidism) leading to cognitive deficits need to be ruled out.

Therapy-related toxicity

An acute presentation of psychiatric symptoms in patients recently started on combination antiretroviral therapy (ART) could suggest therapy-related toxicities. These patients typically do not have neurologic deficits. Patients who are physically well may have experienced acute adverse effects of therapy. Depression, anxiety, insomnia, and cognitive dysfunction have been reported most frequently in patients receiving efavirenz and, less frequently, in those receiving raltegravir or dolutegravir.[17][18][24][25][26][27][28][29] Patients may develop a persistent dysphoric mood, distress, anxiety, and irritability. Concentration may be poor, with sleep and appetite disturbances, fatigue, and psychomotor retardation.

Rarely, acute mental status changes may be seen with antiretroviral therapy-related adverse effects, such as immune reconstitution inflammatory syndrome (IRIS). Acute systemic symptoms following recent introduction of antiretroviral treatment with fever, night sweats, weight loss, cough, and neurologic deterioration suggest IRIS. This is a paradoxical deterioration in clinical status associated with improved CD4 count and decreased viral load. IRIS develops as a consequence of the reaction of the restored immune system to infectious agents, most commonly Mycobacterium tuberculosis or Mycobacterium avium complex. Immune reconstitution after initiation of ART in the context of underlying cryptococcal infection is well described and is of significant concern.[39]

Delirium

An acute precipitation of a mental status change may occur in HIV-infected patients following recent alcohol or substance misuse.

Given the vast differential of delirium, investigations should be guided by history (including detailed medication history with a focus on recent initiation or changes in ART) and physical exam findings.

Initial treatment should include emergency supportive care, which may include circulatory and electrolyte support. Subsequent management is dependent on underlying etiology.

Encephalitis

An acute or subacute onset of a febrile illness, altered mental status, and seizures raises suspicion for encephalitis. Altered mental state, ranging from subtle alterations in level of arousal and behavioral abnormalities through to coma, is typical. Focal neurologic findings are unusual but possible and may include hemiparesis, ataxia, pyramidal signs (brisk tendon reflexes, extensor plantar responses), cranial nerve deficits, involuntary movements (myoclonus and tremors), and seizures.[40]

Investigations should include blood cultures, neuroimaging (preferably magnetic resonance imaging [MRI]), cerebrospinal fluid (CSF) analysis (for cell count and differential, glucose/protein), and additional diagnostic workup (including polymerase chain reaction for detection of viral etiologies).

Treatment should include standard emergency supportive care, which may include circulatory and electrolyte support, and, potentially, endotracheal intubation and mechanical ventilation, with consideration for deep venous thrombosis and gastrointestinal (ulcer) prophylaxis.

Meningitis and intracranial abscess

Adults with meningitis classically present with features of fever, headache, and nuchal rigidity. In the setting of advanced HIV disease, the presentation may be varied and include focal neurologic deficits or seizures. In nonbacterial cases, the presentation may be subacute in nature. Diagnosis in many patients begins with the evaluation of clinical evidence of increased intracranial pressure, a focal neurologic deficit, or papilledema, which in virtually all cases should prompt neuroimaging with either contrast-enhanced computed tomography (CT) or, preferably, MRI. A decreased level of consciousness should prompt urgent neuroimaging studies to rule out a focal intracranial lesion or increased intracranial pressure.

Standard laboratory tests are helpful but never definitive, and should include, at a minimum, a complete blood count with differential, which may suggest an infectious process. Blood chemistry may reveal an elevated lactate. Blood cultures (two sets) should be drawn prior to initiation of antimicrobial therapy in order to maximize the likelihood of identifying an underlying etiology. Specific diagnostic blood tests can include serum cryptococcal antigen (determined by latex agglutination, enzyme immunoassay, or lateral flow assay), and screening Treponema pallidum enzyme immunoassay or rapid plasma reagin for syphilis.[16][41] Toxoplasma serology (IgG) should be obtained in patients with neuroimaging findings of ring-enhancing lesions. Evaluation of underlying tuberculosis status is important, particularly in patients with risk factors for tuberculosis, and in those with a subacute presentation or where neuroimaging suggests tuberculosis.

Lumbar puncture (LP) with CSF analysis is important in confirming CNS infection and in identifying the etiologic organism. Imaging should always precede the LP in immunocompromised patients to exclude a mass lesion.

The typical radiologic finding in patients with brain abscess (on either CT or MRI) is of 1 or more ring-enhancing lesions. The finding of 1 or more contrast-enhancing lesions in such a patient should be investigated with consideration to the broad spectrum of possible etiologies, and will be influenced by the degree of immunosuppression. Common etiologies include toxoplasmosis, tuberculosis, cryptococcosis, bacterial brain abscess, and lymphoma. In the setting of multiple ring-enhancing lesions, empiric coverage for toxoplasmosis should be considered, while early brain biopsy may be required for single lesions and for patients not responding to empiric therapies.

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