1. CPC:38 year-old AIDS patient with brain and pulmonary lesions
Gregory M. Lucas, MD PhD
Division of Infectious Diseases

2. Pre-Hopkins course
CD4 cell count 3/mm3, HIV RNA>750,000 c/mL, OI – candidal esophagitis
Crack cocaine and alcohol use, no ART, no OI prophylactic medications
Admitted to outside hospital with subacute deterioration in mental status and seizure
CNS and pulmonary lesions noted – induced sputum negative for PCP, AFB
Rx with phenytoin, corticosteroids and fluconazole
Discharged to hospice

3. Hopkins course
P.E. – low-grade fever, hypoxia, encephalopathic, LUE flaccid
Labs – Toxoplasma IgG, serum CRAG negative.
CSF – mildly elevated protein, CRAG negative
Brain imaging – innumerable enhancing masses with edema and mass effect
Chest imaging – Nodular infiltrates (wedge-shaped), pulmonary embolism RLL

4. Could a viral CNS infection present this way?
Herpes viruses – CMV, VZV, HSV can affect the CNS
Typical picture is encephalitis often with ventriculitis
CSF usually abnormal
CNS mass lesions not seen
Couldn’t explain pulmonary findings

5. Initial approach to an AIDS patient with brain lesions
No mass effect, no enhancement with IV contrast
HIV encephalopathy
Progressive multifocal leukoencephalopathy (PML)
Mass effect, enhancement with IV contrast
Abscess
Malignancy

6. Differential diagnosis of contrast-enhancing CNS lesions in an AIDS patient
Abscess
Toxoplasmosis
Cryptococcosis, dimorphic fungi (histoplasmosis, coccidioidomycosis)
Pyogenic abscess (Staph, Strep, polymicrobial)
Tuberculosis
Nocardiosis
Filamentous fungi
Neurocysticercosis
Malignancy
Primary CNS lymphoma
Non-CNS cancer metastatic to brain

7. Toxoplasma gondii
Cats are definitive host, many other animals incidental host
Seroprevalence in Baltimore ~10%
Disease in AIDS is reactivation of latent infection
Pro
Con
Most common cause of brain lesions in AIDS patients
Multiple ring-enhancing lesions typical (basal ganglia, corticomedullary junction cerebrum and cerebellum)
Toxo IgG negative
Lung lesions atypical

8. CNS toxoplasmosis

9. Yeast: H. capsulatum (C. neoformans)
Found worldwide, but geographical variation in intensity of exposure
Lung – fungemia – CNS involvement in 10-20% (usually meningitis)
Histoplasma antigen testing from serum or urine highly accurate in disseminated disease
Pro
Con
May produce nodular lung infiltrates
CRAG negative
Brain abscesses rare with Histo

12. Pyogenic brain abscess
Classification
Extension from sinuses or ear,
“Metastatic” – typically multiple
trauma or post-operative
S. aureus, Streptococci, anaerobic organisms
Pro
Con
Could pulmonary lesions be septic emboli?
High-grade bacteremia should have been readily detected
No association with AIDS

13. Mycobacterium tuberculosis
Infects 1/3 of global population
Transition from latent to active disease occurs in 10% of HIV co-infected patients per year
CNS involvement
Meningitis – prominent basilar meningeal enhancement
Tuberculomas – often multiple, solid-appearing grossly, often accompanied by meningitis
Tuberculous abscess – quite rare, large, solitary, multiloculated
Pro
Con
Appealing explanation for lung-brain involvement
ETOH and drug dependence increases likelihood of exposure
AFB smears (induced sputum) negative at outside hospital
No meningitis

14. Tuberculomas

15. Nocardiosis
“Higher-order” bacteria, gram-positive branching filaments, usually acid-fast
Ubiquitous environmental saprophytes
Defects in cell-mediated immunity important risk factor
Manifestations
Cutaneous infections (nodular lymphangitis, mycetoma)
Pulmonary – disseminated (usually N. asteroides)
Pro
Con
Lung-brain involvement common
Pulmonary nodular infiltrates common
No cavities or pleural effusion

16. Acid fast stain of N. asteroides

17. Nocardia pulmonary infection in transplant patient

18. Nocardia brain abscess

19. Rhodococcus equi Gram-positive, weakly acid-fast rod
May be mistaken for a “diptheroid” contaminant
Causes pneumonia in foals
Present in soil, 1/3 infected have exposure to horses
In immunocompromised humans it presents as a TB mimic – indolent, upper-lobe, cavitary
Difficult to treat
Pro
Con
Dissemination to brain can occur
Rare
No horse exposure
Pulmonary infiltrates with R. equi typically upper lobe cavities

20. Filamentous fungi: Aspergillus, Pseudallescheria, zygomycosis
Neutrophil defects strongest risk factor for invasive aspergillosis–bone marrow transplant, chronic granulomatous disease (CGD)
Other risk factors – steroids, alcoholism
Lung or sinuses typical portal of entry
Dissemination to brain common, never meningitis
Unusual in AIDS patients – very advanced disease, relative neutropenia, steroid use
Notable aspect of pathogenesis is angioinvasion
Pro
Con
Lung involvement with dissemination to brain a hallmark of filamentous fungi
“Wedge” shaped pulmonary infiltrates characteristic
?PE
Rare complication in AIDS
WBC 11,380 at presentation making neutropenia unlikely

21. Aspergillus invading blood vessel

22. Neurocysticercosis Taenia solium (pork tapeworm)
Eat pigs (undercooked) – tapeworm infection – secrete eggs
Eat poop (containing eggs) – cysticercosis (tissue infection with parasites)
Infection common south of the Mexican border
Accounts for 50% of adult onset seizures
Pro
Con
CNS lesions in NC – typically round, fluid filled or calcified
Not AIDS associated
Wouldn’t explain pulmonary process

23. Neurocysticercosis

24. Malignancies

25. Primary CNS lymphoma
2nd Most common cause of ring-enhancing brain lesions in AIDS patients in US
Unlike peripheral lymphomas – PCNSL seen exclusively in advanced disease
Solitary lesion in 50%, multicentric in 50%
Non-Bx methods to distinguish from toxo: Toxo IgG, EBV PCR from CSF, metabolic function scans (SPECT, PET)
Pro
Con
Most common cause of enhancing brain lesion in AIDS patients with negative toxo IgG
Advanced immunosuppression typical
Lung infiltrates would have to be a second process

26. Malignancy metastatic to brain
Most common tumors metastasizing to brain – lung, kidney, colon, breast, melanoma
Kaposi’s sarcoma metastasis to brain extremely rare
Peripheral lymphomas may metastasize to brain
Pro
Con
PE related to hypercoagulability of malignancy
Most common cancers metastasizing to brain not particularly associated with AIDS
Pulmonary lesions don’t look like metastases

27. Differential diagnosis of contrast-enhancing CNS lesions in an AIDS patient
Abscess
Toxoplasmosis
Cryptococcosis
Histoplasmosis
Pyogenic abscess (Staph, Strep, polymicrobial)
Tuberculosis
Nocardiosis
Aspergillosis
Neurocysticercosis
Malignancy
Primary CNS lymphoma
Non-CNS cancer metastatic to brain

28. Clinical diagnosis Pulmonary aspergillosis disseminated to brain
Nocardiosis
Histoplasmosis
Tuberculosis