3.9.5.1 Focal neurologic changes and deficits suggestive of mass lesions

All patients presenting with a change in mental status, new onset of seizures, or fever and neck stiffness should be urgently evaluated.¹¹³ Clinical examination should determine whether or not the patient has focal neurologic findings or evidence of increased intracranial pressure, either of which may indicate the presence of a mass lesion. If a lumbar puncture (LP) is performed, the presence of mass lesions increases the risk of herniation.

Multiple causes of CNS mass lesions in patients with HIV are known.¹¹⁴ In countries where TB is endemic, tuberculoma may occur at any CD4 count. In patients with relatively preserved CD4 counts (that is, CD4 counts greater than 200 cells/mm³), CNS lymphoma is among the most common AIDS-related mass lesions found in the CNS.¹¹⁵ Lesions may be multiple and produce edema and mass effect.¹¹⁶ In patients with lower CD4 counts, infectious lesions—including toxoplasmosis, tuberculoma, cysticercosis, and cryptococcoma—are more common.¹¹⁷ Therapy should be directed towards the most likely underlying pathogen. (For example, patients with pulmonary TB should be treated for tuberculoma; those without pulmonary TB should be treated for toxoplasmosis.) Provided the risk of overwhelming systemic infection does not outweigh the anti-inflammatory benefits of corticosteroids, these should be carefully prescribed if there is evidence of mass effect. Antiseizure prophylaxis should also be considered.¹¹⁸

3.9.5.2 Meningitis

Once mass effect has been clinically excluded, a lumbar puncture should be performed on any HIV-positive patient experiencing neurologic complications. Meningitis is a common syndrome among HIV patients; as with other opportunistic infections, the pathogen causing meningitis can be classified with respect to the CD4 count at which it occurs (Table 3.6).^119,120

Table 3.6 Differential Diagnosis of Meningitis by CD4 Count

Any CD4 count	CD4 <50 cells/mm3
• Mycobacterium tuberculosis • Bacterial meningitis including Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Listeria monocytogenes • Neurosyphilis	• Mycobacterium tuberculosis • Cryptococcus neoformans, Histoplasma capsulatum

Because TB is the most common OI in resource-poor settings and can occur at any level of immune suppression, TB is also a common cause of meningitis among HIV-positive persons.¹²¹ As tuberculous meningitis can cause basilar meningitis, it may present with abnormalities in the cranial nerve exam; however, tuberculous meningitis can also have a chronic, nonspecific presentation. Tuberculosis is very difficult to diagnose by spinal fluid smear or culture; care should be taken to examine the patient for other findings consistent with TB. Bacterial meningitides—including Streptococcus pneumoniae, Neisseria meningitis, and Haemophilus influenzae—can occur and present acutely at any CD4 count. Meningitis from Cryptococcus neoformans, an endemic fungus in many areas of the world, is common in many heavily HIV-burdened countries.

3.9.5.3 Global mental status changes

If the presentation of a patient experiencing neurologic complications is negative for focal deficit or symptoms of meningitis, global mental status changes or psychiatric issues should be taken into account. After careful consideration of all neoplastic and infectious causes of mental status changes, several further diagnoses must be explored. Table 3.7 presents a helpful conceptual framework developed by the HIV/AIDS Bureau of the Health Resources and Services Administration of the U.S. Department of Health and Human Services.

Table 3.7 Differential Diagnosis of Acute and Chronic Mental Status Changes During the Course of HIV Infection

Direct effect of HIV on brain tissue and function: – AIDS Dementia Complex: Occurs late in AIDS course. Can occur in 20-30% of all AIDS patients with CD4 <100 cells/mm3 Treatment is ART. Imaging shows atrophy and nonspecific white matter changes. – AIDS mania: Seen in late stages. Treatment is ART. Must be differentiated from bipolar disease. Opportunistic infections that cause generalized neurologic symptoms: – Encephalitis: CMV, VZV, HSV, JCV, PML Impact of systemic illness on brain function Endocrine or metabolic disturbances which affect brain function Effects of antiretrovirals and other medical and psychiatric treatments on brain function Pre-existing neurologic or psychiatric disorders Neurologic and psychiatric disorders that arise after HIV infection Persistent or intermittent substance use or withdrawal states

Adapted from: Forstein M. Psychiatric problems. In: O’Neill JF, Selwyn PA, Schietinger H, eds. A clinical guide to supportive and palliative care for HIV/AIDS. United States Department of Health and Human Resources, Health Resources and Services Administration, 2003:207–52.

In the advanced stages of HIV, neuropsychiatric complications often arise in patients who are not receiving ART; these complications include dementia, minor cognitive-motor disorder, and subclinical cognitive-motor impairment.¹²² HIV dementia correlates with the level of HIV in the central nervous system¹²³ and is also related to low body mass index, low CD4 counts, and anemia. Clinical signs of dementia are listed in Table 3.8.¹²⁴

Table 3.8 Clinical Signs and Symptoms of HIV Dementia

Type of impairment	Manifestations
Cognitive	• Impaired concentration and attention • Impaired verbal memory (e.g., word finding) • Mental slowing • Difficulty with calculations • Impairment of visuospatial memory • Lack of visuomotor coordination (e.g., eye movement abnormalities) • Difficulty with complex task sequencing Late: • Global cognitive impairment • Mutism
Motor	• Unsteady gait or ataxia • Loss of balance • Slowed fine motor speed • Tremors • Change in handwriting • Hyperactive DTRs • Weakness Late: • Seizures • Decorticate posturing • Myoclonus • Spastic weakness • Frontal release signs
Behavioral	• Psychomotor retardation (slowed speech or response time) • Personality changes Late: • Hallucinations • Delusions
Affective	• Apathy, loss of interest in friends or others • Irritability • Mania

Source: Forstein M. Psychiatric problems. In: O’Neill JF, Selwyn PA, Schietinger H, eds. A clinical guide to supportive and palliative care for HIV/AIDS. United States Department of Health and Human Resources, Health Resources and Services Administration, 2003:207–52.