CASE PRESENTATION

CC: my head hurts and Im afraid I have meningitis again.

HPI: 31yo c/o headache and neck pain for 3 days, getting progressively worse, similar to previous episode of meningitis in the past. Pain is pounding, all over, 5/10 today, no exacerbating or alleviating factors. Admits to N/V x 1 today, denies fever, chills, rash, SOB, CP

 PMHx
1) HIV with AIDS as of 16 months ago 2) h/o hospitalization for cryptococcal meningitis x 2 3) Visual impairment and hearing loss 2/2 #1

4) h/o oral thrush

5) h/o herpes zoster

Allergies: fish PSHx

1) s/p appendectomy 2) h/o facial fractures

 FHx non-contributory SocHx

Tobacco: 1ppd x 20 years EtOH: denies Drug use: admits to h/o IV cocaine use for ~5 years in

the past, no current use

Medications, noncompliant with all

ARV (type unknown) Dapsone Fluconazole Bactrim

ROS
General: adenopathy, fatigue, chills + fever, +night sweats, +weakness
HEENT: recent trauma, recent change in vision,

discharge, photophobia, lacrimation, dysphagia, vertigo, +neck stiffness, +b/l vision loss, can distinguish light and dark, +hearing loss L ear, unchanged CV: CP, DOE, PND

ROS contd
Pulm: SOB, hemoptysis, pleuritic CP GI/GU: +N/V, diarrhea, constipation,

hematochezia, dysuria, urethral discharge Neuro: +depression, +HA, seizure, syncope, weakness MSK: arthralgia, myalgia

PE
VS: T 98.4

HR 72RR 18 BP 117/67 98% on RA Gen: cachectic with temporal wasting, NAD, cooperative HEENT: +occipital tenderness, +mild nuchal rigidity (but negative Kernigs and Brudzinskis), b/l TM clear, PERRL, oropharynx is clear without erythema or oral thrush, no lymphadenopathy CV: RRR, no murmurs

PE contd
Pulm: CTAB, no wheezes, no rhales, no rhonchi

Abd: NTND, normoactive BS

Neuro: A+O x 3, intact strength and sensation in all

extremeties Ext: no edema, no deformity, no lesions

Labs
UA

CBC

11.3

4.1
33.7 BMP 135 3.0
APTT PT

202

105 28 24 1.19 128

43 13.7

Color Clarity Glucose Bilirubin Ketones Spec. G pH protein Nitrite Leuk Est

Yellow Clear Neg Small Trace >1.030 6.0 30 Neg Neg

CSF

Appearance Glucose Protein RBCs WBC Segs (%) Lymphs(%) Mono (%) Eosinphl (%) Fungal Smear Crypt. Ag VDRL Gram Stain

clear colorless 55 65 96 3 0 100 0 0 Negative Positive Negative no WBCs, organisms

Lymphocyte panel: %Mature T cells (CD3) Absolute CD3 %CD4 (Helper cells) Absolute CD4

94 1501 3 52

[57-85] [840-3060] [30-61] [490-740]

Lymphocyte panel: %Mature T cells (CD3) Absolute CD3 %CD4 (Helper cells) Absolute CD4

94 1501 3 52

[57-85] [840-3060] [30-61] [490-740]

Head CT: no evidence of acute intracranial pathology Cervical CT: No fracture or dislocation

DDX
Cryptococcal Meningitis CNS toxoplasmosis Lymphoma Progressive multifocal encephalopathy Herpes simplex encephalitis CMV Brain abscess

CNS Complications in HIV

Occur in >40% HIV patients

Presenting feature of AIDS in 10-20% of cases

Types of complications
Directly or indirectly from HIV AIDS dementia complex Vacuolar myelopathy Peripheral neuropathies

Immunodeficiency leading to infectious, autoimmune,

or neoplastic processes

CNS Complications in HIV

Occur in >40% HIV patients

Presenting feature of AIDS in 10-20% of cases

Types of complications
Directly or indirectly from HIV AIDS dementia complex Vacuolar myelopathy Peripheral neuropathies

Immunodeficiency leading to infectious, autoimmune,

or neoplastic processes

Opportunistic Infections occur when CD < 200

Immune Reconstitution Inflammatory Syndrome (IRIS)

Collection of inflammatory disorders

associated with paradoxical worsening of preexisting infectious processes or unmasking of subclinical infections following HAART initiation in HIV patients 30-100 days after HAART initiation

Cryptococcal meningitis
Cryptococcus neoformans

encapsulated yeast found in soil and pigeon droppings Spore inhalation pulmonary infection latency reactivation and dissemination +/- visible lesions on head CT

Cryptococcal meningitis
1 million cases worldwide, with 700,000

deaths 2-7 cases per 1000 HIV-infected patients in USA 89% occur as CNS manifestation 4th most common OI (PCP, CMV, mycobacteria) 6-14% mortality Relapse rate 30-50%

Clinical Presentation
Headache (73-81%) Fever (62-88%) Malaise (38-76%) Nausea and vomiting Visual disturbances (30%)

AMS with somnolence (18-28%)

Photophobia (19%)

(8-42%) Stiff neck (22-44%)

Papilledema (10%)
Cranial neuropathies, including nystagmus and

amblyopia (6%)

Neuroimaging
Cryptococcoma in medula Bilateral visual loss due to arachnoiditis at level of optic nerve or invasion of optic nerve

Cryptococcoma in basal ganglia

Diagnosis
Definitive diagnosis by CSF culture Lumbar puncture with opening pressure
Neuroimaging first to r/o mass lesions, risk of

herniation

India Ink stain of CSF Cryptococcal antigen test of CSF

93-100% sensitive; 93-98% specific Serum testing if LP not feasible

CSF analysis
May be normal in 25%, or minimally abnormal in 50% identification by serology and India Ink are crucial
Normal Opening pressure Color Turbidity Mononuclear cells Polymorphonuclear leukocytes Total Protein 50200 mm H2O CSF Colorless Crystal clear <5 per mm3 0 2238 mg/dl Cryptococcus Elevated >200mm H20 (may be normal in 30%) Clear Clear or viscous if numerous cryptococci present Elevated or normal none Slightly abnormal

Glucose

50-80 (60-80% blood glucose)

Normal or low
Approximately 25-30% have normal CSF analysis

Poor prognostic indicators

High CSF cryptococcal antigen titer (>1:1024)

Minimal CSF pleocytosis (<20 cells/microL)

AMS at presentation Positive India Ink preparation

Hyponatremia
Positive cultures from non-meningeal source

Treatment
Medical treatment: 3 phases
Induction Consolidation Maintenance

Manage ICP

Elevated ICP
>200cm H20 Occurs in >50% cases Mechanism?
Cytokine-induced inflammation increased vasulcar

permeability Fungal antigen clogging arachnoid villi impaired resorption

Manage aggressively in symptomatic patients

Daily LPs to reduce opening pressure to <200cm H20 or by

50% of initial value No role of medical management (acetazolamide, mannitol, steroids)

References
Waxman SG. Chapter 24. Cerebrospinal Fluid Examination.

In: Waxman SG, ed. Clinical Neuroanatomy. 26th ed. New York: McGraw-Hill; 2010. http://www.accessmedicine.com/content.aspx?aID=527555 3. Accessed July 22, 2012. NN Singh. CNS Cryptococcus in HIV. Medscape. Updated November 10, 2011. http://emedicine.medscape.com/article/1167389 Cox GM, Perfect JR. AIDS-associated cryptococcal meningoencephalitis. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2012. Cox GM, Perfect JR. Microbiology and epidemiology of cryptococcal infection. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2012.