Neurologic Infectious Diseases



Neurologic Infectious Diseases


Tamara B. Kaplan

Nagagopal Venna



NERVOUS SYSTEM LYME DZ

Definition: Tick-borne spirochete infxn caused by Borrelia burgdorferi (Borrelia garinii or afzelii in Europe/Asia).

Epidemiology:



  • Most common vector-borne illness in the United States; peak incidence in summer (May-Aug)


  • Majority of cases in NY, NJ, CT, RI, WI, PA, MA, ME, NH, MI, MD, DE, northern CA
























Clinical Manifestations


Stage

Manifestation


Stage 1: Early localized: Wks after infxn

General: flu-like illness. Derm (˜80%): Erythema migrans (EM)


Stage 2: Early disseminated: Wks to mos after infxn

General: Fatigue, malaise, LAN, HA; fever uncommon. Derm: Multiple (1-100) annular lesions ±EM. Rheum (˜10%) migratory arthralgias (knee & hip) & myalgias. Neuro (˜15%): Cranial neuropathies (esp, CN VII), aseptic meningitis, mononeuritis multiplex (±pain), transverse myelitis. Cardiac: (˜8%): Heart block, myopericarditis


Stage 3: Late persistent: Mos to yrs after infection

Derm: Acrodermatitis chronica atrophicans, panniculitis. Rheum (60%): Joint pain, recurrent mono- or oligoarthritis of large joints (classically knee), synovitis. Neuro: Subacute encephalomyelitis, polyneuropathy, dementia


Lancet 2003;362:1639; CID 2006;43:1089; NEJM 2007;357:1422.



Neurologic presentations of Lyme dz: (Neurology 1996;46:619). Neuro involvement in ˜15% untreated cases, typically in stages II-III. Even untreated, most cases of acute CNS Lyme improve or completely resolve in weeks-months; ˜5% untreated pts → chronic neurologic dz

































Neurologic Presentations

Comments


Meningitis

± Cranial neuritis or acute radiculoneuritis: Up to 15% cases (si/sx: HA, neck stiffness, cranial neuropathies (esp CN VII palsy), painful radiculoneuritis w/motor & sensory involvement). Thoracic radiculitis w/segmental weakness of the abdominal wall. CSF antibodies almost always positive. CSF PCR unreliable


Peripheral neuropathy/chronic radiculoneuropathy

˜30% cases. Mononeuritis multiplex. Unlike early radiculoneuritis, not a/w meningitis, cranial neuropathy, or CSF abs


Chronic axonal polyneuropathy

With radicular pain, distal paresthesias


Encephalomyelitis

Rare, 0.1%-5% most commonly involves the spinal cord at the level of a radiculopathy and is usually apparent on MRI scans; assoc w/inflammatory CSF


Encephalopathy

Mild cog. dysfxn. Brain MRI & CSF usually nml likely 2/2 systemic infxn. Similar to “toxic metabolic” encephalopathy a/w chronic UTI, PNA


Optic neuritis

In pedi population 2/2 infl. or ↑ ICP


Chronic encephalomyelitis

W/spastic paraparesis, CN palsy, cognitive Δs, persistent CSF abs (seen in Europe w/B. garinii infxn). Subtle cognitive dysfxn w/o inflammatory Δs in CSF but w/+ CSF abs.


Diagnostic eval: CLINICAL dx w/lab data as supportive. High suspicion if h/o tick exposure & typical skin lesion. LP: Do if e/o CNS involvement, incl severe, prolonged HA, nuchal rigidity, AMS, or subacute meningoradiculitis, multiple cranial neuropathies. Pts w/isolated neuropathy (e.g., Bell palsy) do not automatically require LP.

Diagnosis of CNS Lyme: Need (1) & (2) & one of (3): (1) One of the neurologic entities described above & (2) Possible tick exposure in endemic area & (3a) EM (or histopathologically proven Borrelia lymphocytoma or acrodermatitis) OR (3b) +immunologic e/o exposure in serum OR (3c) +isolation of B. burgdorferi from cx, histology or PCR. Ideally also find immunologic e/o exposure in CSF (unless strictly PNS involvement or chronic dz). Definite dx of CNS Lyme difficult (low Se of cx from specimens other than skin lesions).


Diagnostic studies



  • Serology (in right clinical setting): Screen w/ELISA, but false+ due to other spirochetal diseases, SLE, RA, EBV, HIV, etc.; false- due to early abx therapy or w/in 6 wk of infxn. IgM response first, then declines. IgG+ after ˜1 mo. Confirm ELISA results w/Western blot Se 20%-30% in first weeks (IgM) but >80% after 6 wk; Sp > 95%


  • CSF if suspected neuro disease: Intrathecal Ab if (IgGCSF/IgGserum)/(albCSF/albserum) >1 (Compare CSF and serum specific Abs, correcting for total IgG concentration in both compartments).


  • If only PNS involvement, there is no reason to expect CSF Ab to be positive


  • Active CNS infection—CSF pleocytosis ± increased prt, should improve w/Abx.

































Other Laboratory Dx of Lyme Dz

Comments Sensitivity/Specificity


Western blot

Confirmatory, usu not helpful if seroneg; IgG blot + if 5/10 bands present; IgM blot + if 2/3 bands present

CDC recs: “Two tier” test w/ELISA & Western blot 56%-100% Se, 100% Sp; Se lower during acute period (<6 wk)


CSF ab detection

Less useful in nonacute presentation of CNS Lyme

Sensitivity ranges from 50%-100%, often near 90% for meningitis; up to 95% specific


Culture

Difficult to cx; low sensitivity of specimens other than skin

Skin cx: Se 80%, Sp 100% CSF cx: Se 10%, Sp 100%


PCR (serum, CSF or synovial fluid)

High rate of false +; useful mainly if classic clinical presentation in endemic area & serum Lyme ab is neg

Se, Sp not well established; may be ˜100% but clinical signif. +PCR unclear; may detect DNA from dead bacteria


Cell-mediated immunoassay

Useful if suspicion high in seroneg pt (due to antibiotic use around time of exposure)


Treatment: Approp abx can → dramatic improvements even w/severe forms of meningoradiculitis. Consider repeat LP after 2 wk to eval response of pleocytosis, protein, & antibodies to Rx. IgG ab in CSF often persists for years after Rx. No known benefit of concurrent steroid administration. Vaccine 76% effective in preventing Lyme infxn.

Prophylactic doxycycline 200 mg recommended if able to give w/in 72 h of removing tick that can be identified as Ixodes scapularis & is attached for >36 h (NEJM 2001;345:79).

Prognosis: Good Rx response in 90% of appropriate pts. No proven benefit of additional abx for “post-Lyme syndrome” (chronic fatigue, diffuse pain, cognitive impairment).










































Treatment of Lyme Dz

Antibiotic

Dose

Side effects


Parenchymal CNS Lyme (e/o infxn crossing blood-brain barriera)

IV ceftriaxone (first line)


IV cefotaxime IV PCN G

2 g/day × 2-4 wk. 2 g/day q8h


18-24 MU/day q4h

Rash, n/v/d, pseudomemb. colitis, ↑ LFTs


Rash, n/v/d, HA, pseudomembranous colitis


GI upset, n/v/d, black or hairy tongue


Peripheral neuropathy, isolated cranial neuropathies

Oral doxycycline (children >8 yo, nonpregnant F


Oral amoxicillin (children <8 yr & pregnant F)

200 mg/day × 14-21 days


500 mg tid × 14-21 days

Photosensitivity rash in sun, pseudomembranous colitis


Rash, diarrhea, pseudomembranous colitis, hemolytic anemia


CNS Lyme w/e/o infxn crossing blood-brain barriera

IV ceftriaxone (first line)


IV cefotaxime


IV PCN G

2 g/day × 2-4 wk 6 g/day


18-24 MU/day div q4h

Rash, n/v/d, pseudomemb. colitis, ↑ LFTs.


Rash, n/v/d, HA, pseudomembranous colitis


GI upset, n/v/d, black or hairy tongue


Early localized or disseminated infxn

Same as for periph. neuropathy/isolated cranial neuropathy, Alt: cefuroxime 500 mg bid × 14-21 days

Same as above


Serious cardiac or joint involvement

Same as for CNS Lyme

Same as above


a In Europe, oral doxycycline may be sufficient for CNS Lyme (Lancet Neurol 2008;7:690.)


Oral Abx are probably effective for meningitis and other neuro involvement, w/the exception of parenchymal CNS infection




EHRLICHIOSIS

Presentation (J Vector Borne Dis 2008;45:273): 1-2 wk post-tick exposure, develop malaise, low back pain, fever, HA, N/V, myalgias/arthralgias. Can also p/w pharyngitis, lymphadenopathy, encephalopathy.

Etiology: Ehrlichia chaffeensis = Obligatory intracellular tick-transmitted bacterium. Vector: Most commonly A. americanum (lone star tick); can be other ticks (e.g., Ixodes). Reservoirs: White-tailed deer. Most infxns occur in S. central, SE, & mid-Atlantic states.

Dx: IFA ab titer to E. Chaffeensis, or + PCR (blood, CSF) & confirmation of E. chaffeensis DNA, or immunostain + for E. chaffeensis Ag in bx, or +Cx (blood, CSF).

Rx: Doxycycline 100 mg bid PO or IV × 7-14 days; tetracycline 500 mg PO qid × 7-14 days.


NEUROSYPHILIS

Definition: Spirochete, Treponema pallidum, infxn. Varied presentation: “Great imitator.”

Epidemiology: Historically highest rates in southern states & in blacks. After decades of decline, rates of 1° & 2° syphilis on the rise, esp in HIV+ MSM.

Special considerations in HIV (Clin Infect Dis 2007;44:1222): (1) 1° syphilis infxn facilitates transmission & acquisition of HIV. (2) May see multiple, more persistent, or larger/deeper chancres, concurrent 1° & 2° stages at presentation, earlier development of gummas & more frequent CSF abnlities w/higher cell count, higher elevation of protein, lower glucose. (3) Transient ↑ in viral load & ↓ CD4 count w/syphilis infxn. (4) Neurologic dz seen earlier—HIV pts may be at ↑ risk for developing neurosyphilis. (5) Risk of neurosyphilis in HIV pts after adequate Rx for syphilis unknown. (6) More likely to have persistently + serologic & CSF tests despite Rx (unclear clin. significance). (7) If CD4 count ≤350 cells/mL or RPR titer ≥1:32 → need LP (Clin Infect Dis 2009;48:816).





































Clinical Presentation

Manifestations

Comments


1° (weeks after exposure)

Chancre: painless, indurated, nonpurulent ulcer

Resolves in 2-6 wk w/or w/o Rx.


2° (4-8 wk after chancre)

3-10 mm macular rash (flanks, shoulders, arms, chest, back); w/o Rx → maculopap. rash (esp palms/soles); malaise, fatigue, HA, lymphadenopathy, sore throat; ± fever, wt ↓, myalgias/arthralgias, condyloma lata

Resolves w/o Rx but 25% recur, usu in first year. Rash is most common presenting sx in syphilis (˜90% pts).


Latent (early L:<1 yr post-infxn, late L: >1 yr post-infxn)

Seroreactivity w/o other e/o dz

Infectious only via mother → child transmission


Early neurosyphilis (w/in weeks-years)

Meningitis (aseptic meningitis); cranial neuropathy; ocular dz (anterior uveitis, choroiditis, interstitial keratitis, retinitis, scleritis, optic neuritis); meningovascular dz w/strokes: typically brainstem & cerebral lacunar syndromes, 2/2 propensity for small arterioles; also ACA branch strokes.

25%-60% pts during 1° or 2° syphilis → early neurosyphilis; <5% symptomatic. Enters CNS early (→ CSF pleocytosis, ↑ protein, +CSF-VDRL or PCR). W/o Rx ˜25% do not clear organisms. W/Rx, most immunocompetent pts clear CSF infxn. BUT Rx does not preclude → neurosyphilis.


Tertiary syphilis, incl late neurosyphilis, usu years-decades after infxn

Cardiovascular syphilis (10%, ˜20-30 yr after exposure); Gummatous dz (15%, 1-46 yr); General paresis (˜5%, 2-30 yr): chronic dementia w/prominent behavioral ↓, delusions; Tabes dorsalis (˜5%, 3-50 yr): chronic spinal cord d/o, sensory gait & limb ataxia & ↓ bowel/bladder fxn; Rapidly progressive dementia w/psychosis (esp HIV pts).

Pts w/tertiary syphilis are not infectious. 1/3 untreated pts develop late sequelae.


JAMA 2003;290:1510.





































Diagnostic Evaluation of Syphilis


Syphilis cannot be cultured. Direct e/o infxn requires dark-field microscopic exam or fluorescent ab stains of genital or mucosal lesions; neither test is sensitive.


Test

Nontreponemal serologic lipid antigen tests

Treponemal serologic tests

CSF tests (non-TP & TP)

RPR, VDRL

TPPA, FTA-abs

RPR, VDRL, FTA-abs


Se, Sp

Se: 1°: 78%-86%, 2°: 100%, latent: ˜95%; false+ 1%-2% (IVDU, TB, vaccinations, pregnancy, HIV, rickettsial infxn mononucleosis, endocarditis, other spirochetal infxns (titers usu <1:8 in false+’s); false- in HIV; VDRL→ +1-2 wk after chancre; rare false- w/↑ ↑ ↑ titers (prozone phenomenon)

False+ from other spirochetal infxns, malaria, leprosy; false-in HIV

CSF-VDRL Se 30%-70%, Sp 99%


CSF-FTA-abs ˜100% Se, but low Sp


Note

Usu → neg after Rx, although up to 28% w/1° syphilis & 44% w/2° syphilis still + at 36 mo (Ann Intern Med 1991;114:1005)

Most + for life despite Rx 10%-25% → neg.

↑ protein, ↑ lymphs (>5) support dx


+CSF-VDRL (any titer) = neurosyphilis


TPPA, Treponema pallidum particle agglutination; FTA-abs, fluorescent treponemal antibodies; Se, sensitive; Sp, specific; AI, autoimmune; TP, treponemal.


JAMA 2003;290:1510.


When to do an LP: (Clin Infect Dis 2009;48:816): (1) Neuro/ocular sx, (2) Late latent syphilis or ? duration in HIV pt, (3) Active tertiary syphilis, (4) Rx failure (see below), (4) Serum RPR ≥1:32 or CD4 count ≤350 cells/mm3 in HIV+ w/or w/o neuro sx.

Imaging: Variable: nl, ischemic strokes w/lacunar features, nonspecific WM lesions incl periventricular, mesiotemporal T2-weighted hyperintensities, meningeal enhancement, arteritis/vasculitis on angiography. Cases in recent years w/mesiotemporal T2-weighted hyperintensities resembling HSV or limbic encephalitis.

Syphilis Treatment (PCN, penicillin; MU, million units; doxy, doxycycline)



  • 1°/2°/early latent dz: Benzathine PCN G IM 2.4 MU × 1. PCN allergic → doxy 100 mg bid × 14 days or tetracycline 500 mg qid × 14 days or ceftriaxone 1 g IV/IM qd × 10 days. Azithromycin may be effective in 1° & 2° syphilis but high % resistance in several major cities.


  • Late latent or nonneurologic tertiary syphilis: Benzathine PCN G IM 2.4 MU wkly for 3 wk. If PCN allergic: doxy 100 mg bid × 28 days or tetracycline 500 mg qid × 28 days.


  • Neurosyphilis, incl ocular or auditory dz: Aqueous crystalline PCN G 3-4 MU q4h × 14 days or 18-24 MU qd in continuous infusion × 10-14 days or procaine PCN3 2.4 MU IM qd + probenecid 500 mg PO qid × 14 days; desensitize pts w/PCN allergy.

Note: Beware Jarisch-Herxheimer reaction (fever/chills, HA, myalgias) from endotoxin release 4-12 h after first injection of PCN.


Follow up: (1) Repeat serologic tests & clinical f/u at 1, 3, 6, & 12 mo (and 24 mo for late latent/tertiary dz or HIV pts). (2) Treatment failure = persistent si/sx & failure of nontreponemal tests to ↓ fourfold (two dilutions) w/in 6-12 mo of Rx in early syphilis & 24 mo in late syphilis, or fourfold ↑ at any stage; 5% in non-HIV vs. 20% in HIV pts. (3) Repeat LP: 3-6 mo after Rx & then q6mo until CSF normalizes.


NEUROLEPTOSPIROSIS


Epidemiology



  • Leptospirosis transmitted by urine of infected animal


  • Rats, mice moles, most common vector

General: Neurologic manifestations in 10%-15% of cases. Consider in pts w/acute hepatorenal dysfxn & altered MS in or from endemic areas. Consider in ddx of acute aseptic meningitis/meningoencephalitis a/w conjunctival suffusion & often w/jaundice, although these findings may be absent.

Presentation: Typically fever, chills, HA, vomiting, AMS; szs & focal deficits less common. May cause meningitis ± encephalitis

Dx: Imaging: nl or may show diffuse cerebral edema. CSF: ↑ lymphs common (<500 cells/mm3). Can detect serum & CSF antibodies. organism can be found in blood & CSF for first 7-10 days. After 7-10 days can be found in urine. Confirm w/ELISA and PCR. Gold standard for dx: MAT (microscopic agglutination test).

Rx: Options: PCN G, ampicillin, & doxycycline for less severe cases.

Prognosis: Significantly altered MS & ↑ ↑ CSF protein are poor prognostic findings.


HIV INFECTION OF THE NERVOUS SYSTEM

Epidemiology: >1/2 HIV pts have neuro si/sx; complications include opportunistic infxns, direct effect of HIV virus on nervous system, & adverse effects of antiretroviral Rx.


HIV-associated neuropathy

Presentation: 20%-60% HIV pts—Distal, symmetric, polyneuropathy, affects small ± large sensory fibers. Si/Sx: Combination of pos neuropathic sx (paresthesia, pain) and neg neuropathic sx (numbness, imbalance); usually no motor sx. Neuropathic pain 50%-90% of patients. Neuropathy does not correlate w/viral load or CD4 count. Also ↑ risk for entrapment neuropathy (e.g., carpal tunnel). DM, INH exposure, malnutrition ↑ risk. Older dideoxynucleotide antiretroviral agents: didanosine (ddI), stavudine (d4T), and zalcitabine (ddC) sensory polyneuropathy clinically indistinguishable from HIV-induced neuropathy. Less common presentations: AIDP, CIDP, mononeuritis multiplex w/and w/out concurrent CMV infxn

Exam: ↓ sensation (can be all modalities, esp pain & temp; JPS often ok); ↓ ankle reflexes; strength typically preserved. Diagnosis: Exclude other causes/mimics of axonal sensory polyneuropathy (DM, B12 def, renal/liver dz, thyroid dz, syphilis) & concomitant exposure to neurotoxic meds commonly used in HIV pts (e.g., antineoplastic drugs, INH, thalidomide). EMG: Axonal, length-dependent predominantly sensory polyneuropathy (but can be nl if mostly small unmyelinated fibers affected); uncommonly e/o demyelination/remyelination. AIDP/CIDP: (often w/CSF ↑ protein & mild pleocytosis), polyradiculopathy (often 2/2 CMV in late HIV dz, CSF ↑ polys, ↑ protein, ↓ glucose; send CSF for viral PCR; Rx w/IV ganciclovir, Foscarnet.

Treatment: Supportive. Symptomatic Rx: TCAs, gabapentin, pregabalin, lamotrigine, duloxetine. Identify & treat confounding factors such as DM.

Acute neuromyopathy mitochondrial toxicity: Resemble GBS, associated w/several NRTIs, particularly w/d4T, also zidovudine (AZT), ddI, and lamivudine (3TC), either alone or in combination. Lactic acidosis suggests acute mitochondrial toxicity possibly 2/2 metabolic effects of the nucleoside analogs. Acute cauda equina syndrome: Rapidly developing painful paraparesis w/bladder and bowel involvement; characteristic of CMV polyradiculitis in advanced immunodeficiency.

HIV-associated myopathy: (1) Zidovudine myopathy: Fatigue, prox muscle weakness & atrophy, myalgias. More common after cumulative dose >200 g. Ragged red fibers seen on electron microscopy. Ddx: preserved DTR and sensation unlike CIDP or other neuropathy. CK usu ↑. Rx: d/c zidovudine; CK and muscle pain dec first, later return of muscle strength. (2) Pyomyositis: Rare. Indurated, tender muscle mass. Dx: nl-high CPK. Ultrasound, CT scan, & MRI helpful. Aspirate & culture. Rx: IV abx & surgical drainage as needed. (3) Nemaline rod myopathy: Subacute development of weakness & atrophy. ↑ CPK. Nemaline rods on bx w/variable muscle necrosis & inflammation. Rx: steroids, ?IVIg. (4) HIV wasting illness: Prox weakness & atrophy w/diarrhea, fever, cachexia. CPK usu wnl. (5) Diffuse infiltrative lymphocytosis
syndrome: B/l salivary gland enlargement or xerostomia. CD8 polyclonal lymphocytic infiltrate on bx of minor salivary gland. May initially p/w myositis, neuropathy, or mononeuritis multiplex. Rx: steroids. (6) Opportunistic infxn or tumor infiltration of muscle.

HIV-associated myelopathy (“vacuolar myelopathy”): Pathologic diagnosis. Characteristic pathology at autopsy in ˜55% of patients dying from AIDS. Clinical myelopathy is less common. ↓ incidence due to ART; ˜5%-10% untreated pts affected; CD4 usu <350/mm3.

Presentation: Gradual onset weeks-months leg weakness, spasticity, gait ataxia 2/2 ↓ proprioception; urinary incontinence less common. Typically painless & mimics subacute combined degeneration of B12 deficiency. Commonly parallels development of HIV-associated dementia (HAD).

Exam: Symm. spastic paraparesis; hyperreflexia, often sparing upper extremities; upgoing toes. Less commonly: Impaired proprioception in legs less common. Typically no sensory level.

Dx: of exclusion clinically. B12 level, serum syphilis & viral testing, CSF analysis w/syphilis testing & viral PCRs, MRI spinal cord w/gado. CSF: Few cells. MRI: Of spine often nl or nonspecific hyperintensity; later → cord atrophy. Pathology: Axonal injury, macrophage infiltration, & vacuolation of lateral/dorsal columns; T > C, L spine.

Rx: Starting ART after vacuolar myelopathy usu does not improve sx. Symptomatic Rx of spasticity & neurogenic bladder. Physical therapy.
































Other Causes of Myelopathy in HIV


HIV myelitis a/w seroconversion: Self-limited, transient paraparesis. HIV abs may be neg. Send HIV viral load


HTLV I & II: Progressive painful spastic paraparesis, develops over years; common coinfxn w/HIV in pts from HTLV endemic areas; more rapid decline in HIV+ than in HIV- pts. CSF = significant pleocytosis. Serum & CSF HTLV abs.


Epidural abscess: Fever, back pain, radicular sx. Rapidly → spastic paraparesis. MRI to visualize abscess. IV abx, ±surgical decompression.


VZV myelitis: Usu few weeks after skin eruption. Ipsil. weakness. Spinothalamic/dorsal column impairment. CSF pleocytosis. Dx w/CSF PCR or cx. MRI: Enhancement at infxn site.


CMV myelitis: Rare (more often causes radiculopathy). CD4 usu <50/mm3.


Rapidly progressive development of spinal cord lesion. CSF w/marked pleocytosis, ↑ protein, & often ↓ glucose. Dx w/CSF PCR; also r/o retinitis & viremia. MRI: Enhancement of affected area. Rx: IV ganciclovir or Foscarnet.


HSV myelitis: Rare, presentation similar to CMV myelitis. Unlike CMV myelitis, much less marked CSF pleocytosis. Dx w/CSF PCR &/or cx. Rx: IV high-dose acyclovir.


Syphilis: Acute/subacute spastic paraparesis; impaired proprioception; bowel/bladder disturbance & sensory level. CSF: Pleocytosis, ↑ protein; +serum RPR, CSF VDRL or FTA abs.


Spinal tuberculosis: CD4 count usu <250/mm3. Often in conjunction w/TB meningitis.


Other: Vitamin B12 deficiency, idiopathic transverse myelitis, multiple sclerosis, lymphoma.


HAND, HIV-associated neurocognitive disorders.


References: Neurol Clin 2008;26:799; Lancet Neurol 2005;9:543.



Three conditions w/in the spectrum of HAND: Asymptomatic neurocognitive impairment (ANI); mild neurocognitive disorder (MND); HIV-associated dementia (HAD).

Epidemiology: Overall incidence ↓ w/widespread ART of HAD. Milder cognitive dysfxn, still common (20%-69%) in HIV+ pts. Presentation: Progressive cognitive, behavioral, & motor dysfxn, similar to a subcortical dementia. ↓ memory, attention; psychomotor slowing. Depressive sx, agitation, apathy, change in personality; less commonly psychosis & mania. Motor impairment (tremor, gait disturbance, spasticity); may resemble Parkinson dz. Frontal release signs, hyperreflexia. Sx may develop acutely over weeks-months. Milder forms of cognitive motor dysfxn, may precede HAD. Sx may wax and wane.

Risk factors: Low CD4 count, older age at seroconversion, anemia, ↑ age, duration of dz, low BMI, IVDU. CSF & plasma viral load (VL) do not clearly predict progression to HAD (but possible assn b/n CSF VL & severity of HAD). E4 isoform of apolipoprotein E is a/w severity of dementia (Neurology 2004;63:626).


Ddx: CNS lymphoma, CMV encephalitis, progressive multifocal leukoencephalopathy (PML), toxoplasmosis, TB, cryptococcal meningitis, neurosyphilis, depression, vascular dementia, neurodegenerative dementia.

Workup: Imaging: May be nl, esp early on; cerebral/basal ganglia atrophy, ventricular enlargement & diffuse white matter T2 hyperintensities, often isointense on T1. MR spectroscopy: ↑ Choline (astrocytosis) & decrease in N-acetylaspartate (neuronal injury). CSF: Often w/pleocytosis & ↑ protein & IgG. Neuropsych testing: Psychomotor & memory deficits.

Rx: ART improves neuropsych testing in HAD (J Neurovirol 2000;6:84; Neurology 2006;67:311). In some pts w/subacute HIV encephalitis, dementia improves markedly w/ART → should be considered reversible cause of dementia. Controversy re: Whether certain regimens superior; stavudine, zidovudine, abacavir, lamivudine, efavirenz, nevirapine, indinavir appear to have best CNS penetration. No clear role currently for neuroprotective agents (e.g., selegiline or minocycline) (Neurology 2007;69:1314). Ineffective Rx: Memantine (AIDS 2007;21(14):1877), transdermal selegiline (Neurology 2007;69:1314) minocycline (Neurology 2013;80:196)

Prognosis: Both HAD & HAND predict ↓’d survival regardless of whether on ART.


INTRACRANIAL OPPORTUNISTIC INFECTIONS











Toxoplasma gondii Cryptococcus neoformans Cytomegalovirus (CMV) Fungal Encephalitis

Progressive Multifocal Leukoencephalopathy (PML) Herpes Varicella-Zoster Virus (VZV)


Initial eval: (1) Detailed H&P, incl travel, exposures, meds. (2) Eval risk factors for opportunistic infxns. (3) Don’t forget usual infxns seen in non-HIV pts incl CD4 count, VL, current ART, prophylaxis, CBC w/diff, LFTs, hepatitis serologies, RPR, PPD, chest x-ray, crypto Ag, toxo serology.

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Aug 17, 2016 | Posted by in NEUROLOGY | Comments Off on Neurologic Infectious Diseases

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