The Neurologic Complications of HIV

1
The Neurologic Complications of HIV

• Stephen Raffanti MD
• Comprehensive Care Center
• Vanderbilt University
• Presentation Prepared for VU Infectious Diseases
  Fellows
• Fall 2002

2
Overview

• Epidemiology of Neurologic Disease
• Neuropathogenesis
• Clinical Manifestations
• Opportunistic Infections
• CNS Lymphoma
• Progressive motor syndromes
• Peripheral Neuropathy
• AIDS Dementia Complex

3
EPIDEMIOLOGY

• Pre-HAART era revealed high incidence of
  neurological disease 7-20 of initial AIDS
  diagnoses, 39-70 prevalence in HIV/AIDS, gt70
  in post mortem studies.
• HAART era shows expected decrease in incidence
  rates of neurologic OIs, CNS lymphoma and AIDS
  Dementia Complex (ADC) (which may be occurring at
  higher CD4 counts).

4
Risk of Neurologic Disease in At-Risk Patients

• Condition Incidence
• PML 4
• Toxoplasmic Encephalitis 5-15
• Cryptococcal Meningitis 6-10
• CNS Lymphoma 7-10
• CMV encephal./radiculopathy 20-40 post
• AIDS Dementia Complex 15-30
• Distal Symmetric Peripheral gt30
• Neuropathy
• What is not known is how prolonged treatment with
  or without immune response will affect the
  incidence and manifestations of these diseases.

5
Neuropathogenesis

• HIV is neurovirulent but not neurotropic
• Virus cannot productively infect primary neuronal
  cell cultures
• In situ hybridization doe not show significant
  amount of free virus in brain tissue.
• HIV can productively infect monocytes,
  macrophages and possibly some glial cells
• In acute infection meningial macrophages are
  most involved
• In later disease perivascular macrophages and
  microglial cells predominate.
• Infection results in a cascade of toxic
  mediators
• Cytokines, arachidonic acid derivatives, IFN,
  interleukins and gp120 are all associated with
  virus induced inflammation.

6
Neuropathology

• Neuronal injury occurs as a result of
  inflammatory process.
• In the brain reactive astrogliosis, myelin
  pallor, neuronal loss, alterations of dendritic
  processes with most severe damage seen in the
  deep gray matter (atrophy).
• In the peripheral neuron degeneration of axons,
  endoneurial perivascular inflammation (Distal
  Symmetric Peripheral Neuropathy) or perivascular
  inflammation with macrophage mediated segmental
  demyelination (Inflammatory Demyelinating
  Neuropathy).

7
Clinical Manifestations

• Opportunistic infections
• Four most common account for over 90 of
  clinically significant CNS infections
  Cryptococcal meningitis, Progressive Multifocal
  Leukoencephalopathy (PML), Toxoplasmic
  encephalitis (TE), CMV encephalitis/radiculopathy.
  
• All four occur at patients identified at risk.
• All four have decreased incidence in HAART
  responders.
• All four may have a different long term course
  with concurrent successful HAART.

8
Clinical Case 1

• 43 year old bakery truck driver, CD4 88
  cells/mm3, VL 16,900 copies/ml, presents with
  headache, fever, nausea and some general malaise
  of three weeks duration. Course has been waxing
  and waning. Yesterday he felt relatively well.
• PE shows uncomfortable patient, no focal
  findings. T100.2.

9
Clinical Case 1

• CT of head with/without contrast negative.
• LP yields OP of 220 mm H2O, WBC of 4 cells/mm3,
  glucose 68 (80) mg/dl, protein 45 mg/dl and
  positive india ink prep.
• Serum reveals cryptococcal antigen 1256.

10
Clinical Case 1

• How uncommon is the duration of his complaints?
  The waxing and waning?
• What predictors of a poor outcome does this case
  have? Of a good outcome?
• How common is the lack of classic meningial
  signs?
• Is it likely that an MRI would have been
  abnormal? If so, would it have changed your
  work-up?

11
Cryptococcal Meningitis

• C. neoformans is an encapsulated yeast, inhaled
  into the small airways where it usually causes
  sub-clinical disease dissemination to the CNS is
  not related to pulmonary response.
• C. neoformans produces no toxins and evokes
  little inflammatory response. The main virulence
  factor is the capsule.

12
Cryptococcal Meningitis

• Clinical manifestations
• headache (70-90), fever (60-80), malaise (76),
  stiff neck (20-30), photophobia (6-18),
  seizures (5-10) nausea.
• Average duration of symptoms is 30 days.
• Predictors of poor outcomes are altered mental
  status, increased opening pressure, WBClt20
  cells/mm3.
• Diagnosis made by CSF examination with india ink
  (74-88), Crypto Ag serum/CSF (99), CSF culture.
  
• Level of Crypto Ag is not indicative of severity
  of disease or a marker of response to therapy.
  Serum Crypto Ag can rule out clinical disease in
  HIV positive but not negative patients.

13
Cryptococcal Meningitis

• Therapy
• Acute Ampho B (0.7-0.8 mg/kg/d) for 14 days with
  or without 5-FC 25 mg/kg QID, then Fluconazole
  400 mg/d for 8-10 weeks.
• Maintenance Fluconazole 200 mg/d. D/C with
  immune reconstitution (?).
• Repeated lumbar puncture for OP gt 250 mm.
• Alternatives with liposomal preparations.
• No controlled trials on stopping maintenance in
  the setting of immune reconstitution.

14
Case 1

• Patient was started on Ampho 5-FU. Received
  total dose of 1 gram ampho, 1 week 5-FU. LP
  performed three times to relieve pressure. Pt
  started on fluconazole 400 mg/day.
• Currently on dual PI-based salvage therapy. 4
  years out from Crypto. VL 3,435 copies/ml, CD4
  468 cells/mm3. Remains on fluconazole.
• No further relapses of cryptococcus.

15
Clinical Case 2

• 31 year old dental hygienist brought to ED with
  new onset seizures. CD4 122 cells/mm3, VL 22,000
  copies/ml. Family reports 10 days of increasing
  fever, some obtundation, social withdrawal.
• PE reveals post-ictal, febrile female with poor
  dentition, questionable LUE weakness.

16
Clinical Case 2

• MRI of head shows multiple ring-enhancing lesions
  in the right basal ganglia and cortico medullary
  junction.
• Toxoplasma IgG serology is positive.
• Patient recovers somewhat in ED with marked LUE
  weakness, slow mentation.

17
Clinical Case 2

• Is the diagnosis made? Would other studies be
  appropriate?
• Is Toxo IgM likely to be positive?
• Would a CT have been as sensitive as an MRI to
  pick up the lesions?
• Is a PET scan warranted?
• Is a brain biopsy warranted?

18
Toxoplasmic Encephalitis

• T. gondii is a ubiquitous intracelluar protozoan,
  definitive host is the cat (millions of oocysts
  are excreted daily in cat feces during acute
  infestation!). AIDS pts can become infested
  either through direct contact with cat feces or
  ingesting tissue cysts in undercooked meat.
• Clinical disease is reactivation disease 30 of
  AIDS patients with baseline serology will
  develop TE if not given prophylaxis.
• Seroprevalence varies greatly nationally and
  internationally (10-40 US, gt70 France,
  developing countries)
• Most clinical disease occurs at below 100 CD4
  cells /mm3 but 20 in 100-200 cell range.
• Pathology ranges from localized granulomatous
  process to diffuse necrotizing encephalitis.

19
Toxoplasmic Encephalitis

• Clinical presentation includes focal neurologic
  deficit (50-89), seizures (15-20), fever (56),
  generalized cerebral dysfunction,
  neuropsychiatric abnormalities.
• Diagnosis is often presumptive based on
  characteristic lesions, clinical course, risk
  strata and positive serology.
• Presumptive diagnosis is considered confirmed by
  tissue sample or response to TOXO therapy in
  appropriate time frame.
• Patients should show clinical response -- neuro
  deficits, not necessarily fever or headache -- by
  day 5 (50), day 7 (70), and day 14 (90). In
  contrast, patients with CNS lymphoma all had
  worsening of signs or symptoms by day 10 of
  therapy.

20
Toxoplasmic Encephalitis

• Treatment (for at least 6 weeks, 80-90
  response)
• Acute Sulfadiazine (4-8 gm/d) or Clindamycin
  (600 mg q6h)
• Plus
• Pyrimethamine (100-200 mg load then 50-75mg/d)
  with folinic acid (10-20 mg/d)
• Less proven regimens macrolides (azithromycin,
  clarithromycin) or atovaquone (750 mg QID) plus
  pyrimeth and folinic acid
• Maintenance Without maintenance therapy relapse
  rate is 50-70 per year. Maintenance dose is
  lower for sulfadiazine therapy, same dose for
  clindamycin
• Maintenance therapy may be discontinued if on
  HAART with CD4gt200 x 3mos for primary and gt6 mos
  for secondary prophylaxis.

21
Case 2

• Patient initially treated empirically for
  toxoplasmic and bacterial encephalitis with sulfa
  and levofloxacin. GI intolerance hampers
  treatment. Undergoes biopsy which confirms
  diagnosis of toxoplasmosis. Patient responds to
  clindamycin-based therapy.
• Starts on HAART and responds clinically,
  virologically, and immunologically. Patient
  gains weight, well-being and is rechallenged with
  sulfa which she tolerates. Remains well on
  maintenance therapy and HAART.

22
Case 3

• 33 year old unemployed substance abusing male is
  brought to the ED after he was found wandering
  near the mission.
• PE reveals cachectic, obtunded male with
  dysarthria. T 100.4, CD4 14 cells/mm3, VL
  648,000 copies/ml.

23
Case 3

• MRI shows single 4 cm enhancing lesion involving
  the corpus callosum. No peri-lesional edema is
  present, no mass effect.
• Patient is stable but obtunded.
• Lumbar puncture is performed.

24
Case 3

• What studies would you perform on the CSF?
• Could a definitive diagnosis be made without
  brain biopsy?

25
Primary CNS Lymphoma

• B-cell malignancies, high-grade (73).
• Occurs in extremely immunocompromised hosts (CD4
  lt 50 cells/mm3), unlike systemic NHL.
• Common signs include focal neuro deficits
  (38-78), altered sensorium (57), seizures
  (21), cranial nerve defects (13).
• 50 of patients will have single lesions, usually
  in the the gray matter. Toxo lesions are usually
  multiple, smaller and associated with basal
  ganglia but the two entities cannot be
  distinguished by imaging alone.

26
Primary CNS Lymphoma

• Diagnosis is based on clinical presentation,
  neuroimaging, CSF studies, and brain biopsy.
• CSF PCR for EBV is sensitive (66-99) and
  specific (60-99).
• Treatment is radiation /- chemotherapy.
• Response is related to stage of disease and
  control of HIV.

27
Case 3

• Toxo serology negative. PCR for EBV negative.
  PET scan hypermetabolic. Neurosurgery confirms
  that lesion is not accessible. Patient does not
  respond to empiric therapy for toxoplasmic and
  bacterial encephalitis.
• Patient becomes more obtunded. Family refuses
  further work-up or treatment.
• Patient is enrolled in Hospice where he dies 2
  weeks later

28
Case 4

• 42 year old mechanic is seen in clinic
  complaining of left side weakness and visual
  disturbance. CD4 98 cells/mm3, VL 234,000.
• PE shows a somewhat slow speaking man, afebrile,
  with left upper and lower extremity weakness and
  homonymous hemianopsia. Disc margins are crisp.

29
Case 4

• MRI of the head shows diffuse white matter
  lesions affecting subcortical area bilaterally.
  Parietal-occipital disease is noted on the left
  side. No enhancement is seen no mass effect.
• CSF shows normal opening pressure, a protein of
  50 mg, glucose of 82, WBC 6.

30
Case 4

• What other test(s) would you order on the CSF?
• How typical was this presentation for PML?

31
Progressive Multifocal Leukoencephalopathy (PML)

• PML is a demyelinating disease of the central
  nervous system caused by infection of
  oligodendrocytes by JCV, a papovavirus.
• JCV does not infect neurons but has been detected
  in urogenital cells, B lymphocytes in the spleen
  and bone marrow, and in peripheral blood
  lymphocytes.
• By age ten, 40-60 of the population have
  antibodies to JCV. Disease occurs only in the
  severely immunocompromised. Acute disease has
  not been documented.
• Pathology shows multifocal demyelination with
  hyperchromatic enlarged oligodendroglial nuclei
  and enlarged bizarre astrocytes.
• Lesions can occur anywhere but typically are
  found in the white matter, most often in the
  parietal-occipital regions. The gray matter may
  be involved as well as the cerebellum, brainstem
  and rarely spinal cord.

32
Progressive Multifocal Leukoencephalopathy (PML)

• Clinical disease occurs in patients with advanced
  disease and onset may be insidious, over several
  weeks.
• Clinical signs and symptoms include hemiparesis
  (43), cognitive defects (22), speech deficits
  (28),visual deficits (16), sensory deficits
  (14), and seizures (5).
• Clinical hallmark of disease is patient with
  focal neurologic defect, white matter disease and
  no mass effect.

33
Progressive Multifocal Leukoencephalopathy (PML)

• Diagnosis rests on clinical picture, neuro
  radiologic findings, CSF findings and tissue
  histopathology.
• PCR for JCV in the CSF is a specific but variably
  sensitive technique for supporting diagnosis.
  Sensitivity ranges from 30-61, specificity 99.
• Distinguishing PML from ADC may be difficult, but
  more rapid onset, lack of cognitive dementia
  findings (slow mental processing), focal
  neurologic deficits and extensive subcortical
  disease suggest PML.
• Treatment efforts have been largely unsuccessful.
  HAART may be beneficial. Ongoing trials
  evaluating cytosine arabinoside (ARA-C) are
  enrolling patients. Scattered reports have
  suggested some response. Approximately 7 of
  patients resolve without any treatment these
  patients generally have less compromised immune
  status.

34
PET/SPECT SCANS and CNS Lesions in AIDS

• 20 patients with AIDS and contrast enhancing
  lesions 7/8 Toxo pts. had PET scans, 7 had
  hypometabolic lesions. 6 pts. with lymphoma had
  hypermetabolic scans. 7 patients had varied
  results (Pierce 1995).
• SPECT scans in 37 AIDS patients with intracranial
  lesions 12 had increased intense focal uptake
  all twelve had Bx proven lymphoma. 25 had no
  uptake 24 had TOXO by clinical , one had MTB
  abscess (Ruiz 1996).
• 24 patients with AIDS and CNS mass lesions by
  MRI were evaluated with SPECT. 8 had lymphoma
  and all had scans, 7/10 Toxo pts had negative
  scans. 1 pt. with Blasto and 3 with PML had
  negative scans. MTB had /- scan. (Barker 1997)

35
Brain Biopsy in CNS Lesions in AIDS

• Brain biopsy should be considered
• In presumptive TE when empiric therapy fails
• In rapidly progressing single lesion disease
• In patients with a clinical picture of TE but a
  reliable history of sulfa-based PCP prophylaxis
• In patients receiving corticosteroid therapy.
• In patients with unexplained potentially
  treatable lesions.
• Other pathogens/conditions to be considered
  lymphoma, bacterial including T. pallidum, BA,
  PML, MTB.

36
Case 4

• LP is performed twice, PCR for EBV is negative x
  2, PCR for JCV is positive in one lab negative in
  other.
• Brian biopsy reveals findings consistent with
  PML.
• Patient is started on new ART regimen with mother
  administering meds. Neurological deterioration
  slows. Patient plateaus at near total care
  status. CD4 increase to 338 cells/mm3, VL lt400
  copies/ml.

37
Case 5

• 41 year old artist from Kentucky presents with
  rapidly progressing bilateral lower extremity
  weakness, urinary retention and lower back pain.
  CD4 33 cells/mm3.
• PE shows wasted male c/o back pain, flaccid
  paralysis of both legs, saddle anesthesia,
  DTRs in both legs are absent.

38
Case 5

• What characteristics of this presentation suggest
  that something relatively rare is occurring?
• What diseases are included in the differential?
• What is your next few studies and how rapidly
  should they be done?

39
Case 5

• Contrasted MRI of the spine shows diffuse
  enhancement of the cauda equina and the conus and
  clumping of nerve roots (ice storm sign).
• CSF reveals 14,000 WBC, 90 PMN, glucose 34mg/dl,
  protein 240 mg/dl.
• Retinal examination shows findings c/w CMV
  retinitis.
• PCR studies are not available.

40
Progressive Motor Syndromes in HIV

• CMV polyradiculomyelitis is a rare (lt2) disease
  presenting in patients with advanced AIDS as
  rapidly progressive flaccid paralysis of lower
  extremities which includes back pain,
  urinary/fecal retention, sensory abnormalities.
• Diagnosis is based on clinical features,
  characteristic CSF and MRI findings and evidence
  of CMV disease (retinal, PCR in blood or CSF).
• Most patients were described in the pre-HAART era
  and survival was poor, with variable response to
  therapy.
• Although there are no large controlled studies,
  scattered reports indicate that treatment with
  ganciclovir plus foscarnet may be superior to one
  agent alone.

41
Progressive Motor Syndromes in HIV

• Inflammatory Demyelinating Neuropathy (IDP) can
  present very early in disease as AIDP (Acute
  IDP), with rapid progressive involvement of
  muscles of two or more limbs. Sensory
  involvement may precede motor. Course may
  resemble GBS.
• Chronic IDP (CIDP) is a slower progressive,
  principally motor, syndrome of the lower
  extremities which may have relapsing course over
  several months.
• Nerve conduction study (NCS) shows slow nerve
  conduction velocities and findings c/w primary
  demyelination. Some axonal degeneration may be
  present. AIDP findings may be less pronounced.
  Sural nerve bx results show perineural edema,
  perivascular infiltrates and macrophage mediated
  segmental demyelination. CMV inclusion in
  Schwann cells have been identified in late stage
  CIDP.
• Treatment options include plasmapheresis, IV Ig,
  prednisone which have all shown efficacy but are
  often of temporary benefit. Up to 15 of
  patients will resolve without specific therapy.

42
Progressive Motor Syndromes in HIV

• HIV associated myelopathy is a rare (lt4)
  manifestation of advanced disease which presents
  with leg stiffness, falling, and slowness of gait
  and slowly progresses to bowel/bladder
  dysfunction, paraplegia.
• Hyperreflexia and spasticity are common.
• Imaging and CSF are normal except for mildly
  elevated protein.
• Pathology shows vacuolar myelopathy with little
  inflammation.
• Treatment is supportive and rehabilitative.

43
Progressive Motor Syndromes in HIV

• Other causes of motor weakness include
• Cord lesions caused by infectious/neoplastic
  processes are usually more fulminant, have
  discrete sensory levels, include back pain, may
  involve thoracic or cervical spine and should
  have imaging or CSF findings c/w diagnosis.
• Patients from endemic areas should be tested for
  HTLV-I co-infection.
• Rarely, mononeuritis multiplex may present as
  motor weakness.

44
Case 5

• Patient is hospitalized and ganciclovir induction
  therapy is started. Severe cytopenia results and
  patient is switched to foscarnet. Neurologic
  decline rapidly progresses to paraplegia and
  coma.
• Patient expires 8 days later.
• Autopsy is refused.

45
Case 6

• 38 year old real estate agent presents
  complaining of numbness, tingling and pain in the
  feet and lower legs progressing over several
  months.
• CD4 424, VLlt400, medications include stavudine,
  didanosine, and nelfinavir.
• PE shows relatively well male, motor strength
  intact, normal light touch perception and
  vibration. Gait normal.

46
Case 6

• What other questions would you ask about the
  pain? What other physical sign might you
  illicit?
• What is the differential for the pain in the
  lower extremities?
• What factors are favoring neuropathy?
• What factors argue against Distal Symmetrical
  Peripheral Neuropathy (DSPN)?
• What other tests would you order?

47
Case 6

• Patient describes pain as burning, starting at
  the soles and involving the dorsum of both feet.
  Walking is impaired at times due to pain. He has
  not bumped into walls or fallen down.
• Achilles DTRs are absent. Patellar reflexes are
  intact. Babinski is absent. Proprioception is
  intact.
• Serum B12 normal, RPR non-reactive.
• EMG/NCS shows mild axonal degeneration. No
  evidence of demyelination.

48
Peripheral Neuropathy

• Two most frequent types DSPN and toxic
  neuropathy.
• Clinical manifestations are similar. Both
  present with sensory symptomatolgy with little
  sensory dysfunction. Both usually involve the
  lower extremities, show absent Achilles DTRs and
  axonal degeneration on NCS. Patients can have
  negative NCS/EMG and abnormal findings on skin
  biopsy and examination of epidermal nerve fibers.
  Differentiating between the two syndromes is
  based on history and concurrent meds.

49
Peripheral Neuropathy

• DSPN is a frequent (30) complication of advanced
  HIV. Course is gradually progressive and may be
  severe enough to disable patient. Factors
  associated with DSPN include low CD4 count, high
  viral load, concurrent ADC.
• Toxic neuropathy is associated with
  antiretrovirals and other medications. Factors
  associated with toxic neuropathy include length
  of time on neurotoxic medications, pre-existing
  neuropathic syndrome, concurrent administration
  of multiple neurotoxic agents.
• Both syndromes are now thought to be part of a
  mitochondrial toxicity phenomenon.

50
Peripheral Neuropathy

• Medications which cause neuropathy include
  zalcitabinegtdidanosinegtstavudine, metronidazole,
  INH, vincristine, dapsone.
• Treatment options include
• d/c of offending agents (sx may worsen
  initially),
• Treatment with amitriptyline, mexilitine,
  carbamazepine, and gabapentin, narcotics,
  acupuncture. Randomized trials have demonstrated
  efficacy for lamotrigine and human nerve growth
  factor.

51
Case 6

• Patients HAART is switched to zidovudine/lamivudi
  ne/ abacavir plus nevirapine. Symptoms worsen
  and patient is started on amitriptyline titrated
  to 150 mg qd. Patient has minimal improvement
  and is switched to gabapentin which he does not
  tolerate. Patient remains on current HAART with
  VLlt400 copies/ml, CD4 544 cells/mm3.
• Neuropathic pain is currently managed with
  amitriptyline 100 mg/day and short acting
  narcotics for exacerbation. Patient also uses
  shoe inserts.

52
Case 7

• 64 year old owner of a construction company is
  seen for first visit after being hospitalized for
  PCP. He was diagnosed with HIV disease during
  this hospitalization. His wife and children
  state that although he had been doing fine
  until he got sick with pneumonia he isnt as
  perky as he used to be.
• CD4 18 cells/mm3, VL gt750k.

53
Case 7

• What questions would you ask to get a sense of
  how well his CNS is functioning?
• What findings on physical exam would you pay
  special attention to?
• If physical exam has no focal findings what other
  tests would be warranted?

54
Case 7

• PE reveals a quiet thin man who lets his wife
  answer most questions. His only complaint is
  soreness at a prior IV site.
• Neuro exam shows no focal defects except for
  absent Achilles reflexes, hyperreflexia
  elsewhere. Fundoscopic exam reveals one cotton
  wool spot O.D.
• Pt is alert but apathetic, short term memory is
  greatly impaired, response time is slow, fine
  motor is impaired, gait is awkward with postural
  difficulty. Rhomberg is negative, cerebellar
  signs are not apparent, slow pursuit eye movement
  is impaired.

55
AIDS Dementia Complex (ADC)

• Extremely common (30) complication of advanced
  disease.
• Characterized by cognitive, motor and behavioral
  changes.
• Spectrum ranges from early mild forgetfulness to
  global amnesia.
• Signs of progressive dementia are not present in
  early asymptomatic individuals.

56
AIDS Dementia Complex

• EARLY LATE
• Cognition
• Inattention Global Dementia
• Reduced Concentration
• Forgetfulness
• Motor
• Slow fine repetitive Paraplegia
• Clumsiness
• Ataxia
• Behavior
• Apathy Mutism
• Altered personality
• (agitation)

57
AIDS Dementia Complex

• CT and MRI typically show cerebral atrophy,
  widened cortical sulci and enlarged ventricles.
• CSF not specific, CSF HIV viral load may
  correlate but high levels also found in pts
  without ADC.
• Differential includes CMV encephalitis, diffuse
  presentations of lymphoma, toxoplasmic
  encephalitis and psychosis.
• Treatment is aggressive treatment of underlying
  HIV, possibly with more CSF penetrating regimens
  (no controlled trials supporting this). Response
  to treatment should be rapid and lack of response
  should warrant re-evaluating diagnosis.

58
CMV Encephalitis

• Rare complication of very advanced HIV disease.
• Differs from ADC by steep slope of neurologic
  decline. May include fever, delirium, somnolence
  and cranial nerve involvement.
• Imaging may reveal meningeal and periventricular
  enhancement.
• Concurrent evidence of CMV disease may be helpful
  in making diagnosis.
• Course is rapidly fatal if not treated.

59
Case 7

• MRI shows cortical atrophy, no enhancement.
  Ophthalmologic evaluation confirms cotton wool
  retinopathy only.
• Patient is started on zidovudine, lamivudine, and
  nevirapine. At 4 week follow up patient has
  gained 21 pounds, is outgoing, and gait has
  improved. Viral load is 4,228.

60
Neurologic Disease in HIV

• Few common syndromes account for majority of
  manifestations.
• A targeted history and physical examination
  usually points to etiology or direction of
  work-up.
• Mild to moderate dementia is often missed by
  superficial exam.
• Few presentations require emergent work-up
• Post-HAART neurologic disease may present
  differently and have different markers of risk
  (nadir CD4 count, peak viral load, host factors).
• Non-HIV related neurologic disease will become
  more important with aging, treated population.