Clinical Manual for Management of the HIV-Infected Adult
2006 Edition

Section 5: Complaint-Specific Workups

Neurologic Symptoms

Background

The nervous system may be a site of complications throughout the course of HIV infection, and neurologic complaints are common in people living with HIV/AIDS. Neurologic symptoms may be caused by many factors, including infections (opportunistic and other), central nervous system (CNS) malignancies, medication toxicities, comorbid conditions (eg, diabetes, cerebrovascular disease, chronic hepatitis, mental illness), and nervous system injuries related to HIV itself.

The risk of some conditions, such as CNS infection, malignancy, and dementia, increases with advancing immunosuppression, and the CD4 cell count will help to stratify the patient's risk of opportunistic illnesses (see Table 1 in chapter CD4 Monitoring and Viral Load Testing). This chapter presents a general approach to neurologic symptoms in HIV-infected patients, with reference to other chapters in this manual for more detailed reading. For information on peripheral neuropathy, see chapter Pain Syndrome and Peripheral Neuropathy.

S: Subjective

The patient, or a friend or family member on his or her behalf, reports new neurologic symptoms such as pain, headache, seizures, altered mental status, or weakness.

Ascertain the following during the history:

• Onset and duration: rapid (hours to days), subacute, chronic
• Characteristics of the symptoms (eg, location, quality, timing)
• Progression or stability of symptoms
• Constitutional symptoms: fever, night sweats, unintentional weight loss
• Associated symptoms, including other neurologic, muscular, psychiatric, or behavioral symptoms
• Recent trauma to the head or other area
• Visual changes, photophobia
• Dizziness, vertigo
• Mental status changes (including changes in behavior, personality, or cognition; short-term memory loss; mental slowing; reading comprehension difficulties; changes in personal appearance and grooming habits)
• Seizures (description, duration, number)
• Pain
• Sensory symptoms
• Weakness (distinguish weakness from fatigue or pain; determine whether bilateral or focal, proximal or distal)
• Bowel or bladder changes
• Rash or ulcerations
• Medications: current, past, and recently initiated medications, including antiretroviral therapy (ART)
• Alcohol or drug use; date of last use
• Exposures (sexual, environmental), travel history
• Psychiatric history and past psychiatric care
• Most recent CD4 cell count and HIV viral load, previous AIDS-defining illnesses
• Functional impact of the symptoms: social functioning, ability to work and perform activities of daily living

Differentiate delirium from dementia. Delirium presents as acute onset of clouded sensorium, disturbed and fluctuating level of consciousness, disorientation, cognitive deficits, and reduced attention, sometimes with hallucinations. Delirium is often due to medication toxicities, infections, hypoxia, hypoglycemia, electrolyte imbalances, or mass lesions, and is frequently is correctable. Dementia emerges more gradually and is characterized by cognitive impairment and behavioral, motor, and affective changes. See chapter HIV-Associated Dementia and Minor Cognitive Motor Disorder.

O: Objective

• Check vital signs (temperature, blood pressure, heart rate, and respiratory rate, oxygen saturation) and orthostatic measurements.
• Perform a careful physical examination as guided by the history, with special attention to the following:
  • General appearance: mood, affect, mannerisms
  • Head and neck: signs of trauma, sinus tenderness, lymph node status, neck mobility
  • Eyes, including fundi: lesions, papilledema
  • Lungs, heart: abnormal sounds
  • Extremities: muscle tone and bulk
  • Skin, mucous membranes: rash, lesions
• Conduct a thorough neurologic examination, including cranial nerves, motor function, sensory function, coordination, gait, and deep tendon reflexes.
• Conduct a mental status examination.
• Review recent CD4 measurements, if available, to determine the patient's risk for opportunistic illnesses.

A: Assessment

The differential diagnosis of neurologic abnormalities in patients with HIV infection may be broad, particularly if the CD4 count is low. Both HIV-related and HIV-unrelated causes should be considered; remember that more than one cause of symptoms may be present.

Possible Causes of Neurologic Abnormalities

Causes related to the cerebrum or cranial nerves

• Toxoplasmic encephalitis
• Primary CNS lymphoma
• Cryptococcal meningitis
• Cytomegalovirus (CMV) encephalitis
• Other meningitis (bacterial, tuberculous, fungal, viral)
• Progressive multifocal leukoencephalopathy (PML)
• Neurosyphilis
• CNS coccidioidomycosis, histoplasmosis
• HIV-related dementia
• Alcohol or drug intoxication or withdrawal (medications or illicit drugs); chronic alcohol abuse
• Depression, mania, anxiety, psychosis
• Cerebrovascular accident; stroke
• Metabolic abnormalities, including hypo- or hyperglycemia, electrolyte abnormalities

Causes related to the spinal cord, nerve roots, peripheral nerves, and muscle

• Inflammatory demyelinating polyneuropathy (eg, Guillain-Barré syndrome)
• Polyradiculitis (eg, CMV, herpes simplex virus)
• Vitamin deficiency
• Myositis
• Myopathy (eg, due to zidovudine)
• Myelopathy (HIV vacuolar myelopathy)
• Epidural abscess or mass
• Mononeuritis multiplex
• Lactic acidosis
• Electrolyte abnormality (eg, hypokalemia)
• Peripheral neuropathy
• Distal sensory polyneuropathy
• Antiretroviral toxic neuropathy (especially stavudine, didanosine)
• Other neuropathy (eg, due to diabetes, alcohol, medications [isoniazid, dapsone, many others])

Note that organic causes of neurologic symptoms must be ruled out before concluding that symptoms are psychiatric in nature.

P: Plan

Diagnostic Evaluation

Unstable or seriously ill patients should be hospitalized for evaluation and treatment. Criteria for hospitalization include acutely altered mental status, fever with focal neurologic findings, and new or unstable seizures.

Perform laboratory work and other diagnostic studies as suggested by the history, physical examination, and differential diagnosis. This may include the following:

• Establish the CD4 count (if not done recently) to help with risk stratification for opportunistic illnesses.
• Determine which laboratory tests are appropriate depending on the patient's presentation. The initial evaluation often includes a complete blood count with differential and monitoring of electrolyte and glucose levels.
  • In patients with CNS symptoms or signs and low CD4 counts (<100 cells/µL), check serum levels of toxoplasma antibody (IgG) if not previously checked. Check serum cryptococcal antigen (CrAg) titer.
  • In patients with symptoms of neuropathy or dementia, check serum levels of vitamin B12 and thyroid-stimulating hormone (TSH).
  • In patients with cranial nerve abnormalities, meningoencephalitis, symptoms of dementia, or any symptoms of neurosyphilis, check syphilis serology by rapid plasma reagin (RPR) or Venereal Disease Research Laboratory (VDRL) test.
• When CNS symptoms or signs are present, brain imaging by computed tomography (CT) scan with contrast is usually adequate as the initial test. Magnetic resonance imaging (MRI) is the modality of choice if the neurologic examination is nonfocal or if physical examination suggests a lesion in the posterior fossa.
• For patients with fever and CNS findings, perform lumbar puncture (LP) with cerebrospinal fluid (CSF) sampling. CT or MRI should be performed before the LP, if possible, to rule out a mass lesion that could cause herniation.
• Record the opening pressure, and send CSF for cell count and differential with protein and glucose measurements. Depending on the clinical suspicion, the fluid should also be sent for bacterial culture, India ink stain for fungal organisms (75-85% sensitive), acid-fast bacilli smear and culture, VDRL test, and CrAg titer (95% sensitive).
• If CMV is suspected, perform polymerase chain reaction (PCR) for CMV DNA (62-100% sensitivity; 89-100% specificity).
• If PML is suspected, perform CSF PCR analysis for JC virus DNA (sensitivity approximately 80%; specificity 92-100%).
• For suspected drug or alcohol use, perform urine or serum toxicology screen. (Note that alcohol usually has been metabolized by the time withdrawal symptoms set in, typically 7-48 hours after the last alcohol intake).
• For new-onset seizures, perform an electroencephalogram (EEG)
• Consult with neurology specialists if the workup or the diagnosis is in question.

Treatment

Specific treatment will depend on the cause of neurologic symptoms. Consult relevant chapters in this manual. For complex cases, consult with an HIV-experienced neurologist.

Patient Education

• Inform patients that keeping the CD4 count above 200 cells/µL with ART is the best way to prevent most HIV-associated neurologic diseases.
• Advise patients to take prophylaxis, as appropriate, to prevent opportunistic infections.
• When an antibiotic treatment is prescribed, advise patients to complete the entire regimen to prevent relapse of symptoms. Long-term treatment (prophylaxis) will be needed to prevent recurrence of certain infections.
• Advise patients who have seizures that driving and other potentially dangerous activities will be prohibited until the condition is stable.
• Counsel patients to avoid substances that impair the nervous system, such as alcohol and recreational drugs.
• If a patient is forgetful, educate other members of the household about the medication regimen and help devise a plan for adherence to medications and appointments.

References

• Cantor CR, McCluskey L. CNS Complications. In: Buckley RM, Gluckman SJ, eds. HIV Infection in Primary Care. New York: WB Saunders; 2002.
• McArthur JC, Brew BJ, Nath A. Neurological complications of HIV infection. Lancet Neurol. 2005 Sep;4(9):543-55.
• McGuire D. Neurologic Manifestations of HIV. In: Peiperl L, Coffey S, Volberding PA, eds. HIV InSite Knowledge Base [textbook online]. San Francisco: UCSF Center for HIV Information; 2003. Accessed June 1, 2006.
• Portegies P, Solod L, Cinque P, et al. Guidelines for the diagnosis and management of neurological complications of HIV infection. Eur J Neurol. 2004 May;11(5):297-304.
• Saguil A. Evaluation of the patient with muscle weakness. Am Fam Physician. 2005 Apr 1;71(7):1327-36.