KCMC Case Presentation: A 20 year-old male with Altered Mental Status

1. KCMC Case Presentation:A 20 year-old male with Altered Mental Status Jesse Waggoner Resident, Internal Medicine International Health Elective

2. History of Present Illness • 20 y/o male with no known past medical history • Brought to ED by family for 1 month of malaise and worsening headache • Recently, pt had become lethargic and slow to respond to questions at home • Over the 3 days prior to admission, patient had been vomiting and became unresponsive • No previous history of such episodes

3. Further History • ROS: per family members report, no fevers, chills or night sweats; no diarrhea; no weight loss • Social History: unknown sexual history, no known EtOH abuse or IVDU, worked as a farmer near Moshi • Family History: no significant family medical history known

4. Physical Exam • Vitals: 36.8 115/75 82 15 on 2L NC • Gen: pt lying in bed, responds to pain, GCS 8 (eyes open, withdraws to pain) • Neuro: • CN: pupils 5mm, sluggish, corneal reflexes and gag in-tact • Motor: bulk nml, tone decreased • Reflexes: 2+ DTRs, toes downgoing • HEENT: Fundi show papilledema, op clear • Lungs: CTAB, no w/r/r, limited by pt cooperation • CV: RRR, nl s1 and s2, no m/r/g • Abd: soft, NTND, +bs, no HSM • Ext: no c/c/e, 2+ peripheral pulses • Skin: no rashes or lesions

5. Laboratory Data • Chemistry: • Cr 78 (0.9) • Full Blood Picture: • Hgb 4, WBC 0.6, Plts 25 • Rapid HIV: negative x 2 • Blood culture: no growth • LP not obtained given results of funduscopic exam

6. Imaging • CT brain (on admission): • 3 cm ring enhancing lesion in the R parietal and occipital lobes with surrounding edema and mass effect • No evidence of sinusitis or site for direct extension of infection • Chest X-ray: • No infiltrate, nml cardiac silhouette, no bony lesions

7. Differential Diagnosis • Brain Abscess: no site for direct spread • Tuberculoma • Toxoplasmosis • Primary CNS lymphoma

8. Clinical Course • Pt initially treated with chloramphenicol and ampicillin without clinical deterioration • Following results of CT, antibiotic coverage changed to ceftriaxone and metronidazole • Pt continued to worsen clinically and 4 drug TB therapy (INH, RIF, PZA, EMB) was added along with prednisolone 60 mg/day • Over the following week, pt became more alert per family members’ report • Neurosurgery consulted and felt patient was a poor candidate for surgery

9. Diagnosis • Final diagnosis remains unclear – pt did appear to respond to therapy for TB, though this included high dose steroids • Etiology of pancytopenia is also unknown and leukopenia would have predisposed him to opportunistic pathogens not covered in the treatment regimen • His clinical stability and advanced stage at presentation combined with available diagnostic tests limited our ability to make a definitive diagnosis

10. Discussion • Brain abscess • Microbiology • Diagnosis • CNS Tuberculosis • Meningitis and Tuberculomas • Treatment

11. Brain Abscess • Can result from direct spread (sinusitis, otitis, neurosurgical procedure) or from hematogenous spread (more often multiple abscesses) • Most common location for hematogenous spread: frontal or temporal lobes, frontal-parietal, or parietal • Typically results from a bacterial infection, though in immunocompromised hosts, causes include fungi and other opportunistic pathogens

12. Anaerobes Anaerbic streptococci Bacteroides fragilis Prevotella melaninogenica Propionibacterium Fusobacterium Eubacterium Veillonella Actinomycetes Aerobes Viridans Strep Strep milleri Pneumococcus (rare) Staph aureus Klebsiella pneumoniae Psudomonas Eschericia coli Proteus Microbiology of Brain Abscesses

13. Immunocompromised Toxoplasma Rhodococcus equi Listeria Nocardia Mycobacteria Aspergillus Cryptococcus Coccidioides Candida Zygomycosis Travelers/Immigrants Cysticercosis Entamoeba Schistosoma japonicum Paragonimus Microbiology of Brain Abscesses in Specific Hosts

14. Brain Abscess (continued) • Pts often present with worsening unilateral headache • Changes in mental status develops with worsening cerebral edema and portends a poor prognosis • Exam: fever only present in 50% of cases; focal neurological deficits develop after the headache • Imaging: MRI more sensitive than CT and can differentiate abscess from neoplastic lesions • Diagnosis often comes after guided aspiration or surgery

15. CNS Tuberculosis • Three clinical manifestations: • Meningitis • Tuberculoma • Spinal arachnoiditis • Small tubercules (Rich foci) form during bacteremia following primary or reactivation disease • These can form in the brain or meninges • Development of meningitis or tuberculoma results from progression and possible rupture of these lesions

16. Epidemiology of CNS Tb • Around 1% of Tb cases will develop CNS Tb (6.3% of extrapulm cases) • Signs of Tb outside the CNS are only present in ~50% of cases • In adults, risk factors for developing CNS Tb include: alcoholism, malignancy, immunosuppressive agents, & HIV

17. Tuberculoma • Can present as single or multiple ring-enhancing lesions • Usually present as a mass lesion but can occur in the setting of Tb meningitis (after one ruptures into the subarachnoid space) • More common in developing countries than in the United States • Tb brain abscess is a rare complication – do not see classic granulomas on pathology

18. Diagnosis • CSF classically shows lymphocytic pleocytosis, elevated protein, & hypoglycorrachia in Tb meningitis • Micro: • CSF AFB smears: sensitivity 20-35% for one sample, up to 85% with consecutive samples • Culture: sensitivity 71% • No nucleic acid amplification tests currently approved in US for detection of Tb in CSF • ADA in the CSF cannot reliably distinguish Tb meningitis from bacterial meningitis; also no standard cutoffs • Contrasted MRI more sensitive for findings of CNS Tb than CT • Basal meningeal enhancement • Hydrocephalus • Supratentorial infarctions

19. Treatment • No RCTs have been performed to show the optimal drug regimen, dosage and duration of therapy • Current guidelines recommend initial 4 drug therapy for 2 months followed by 7-10 months of continued 2 drug therapy • INH: good CNS penetration • RIF: penetrates inflamed meninges • PZA: good CNS penetration • EBM: lower CSF concentrations • Glucocorticoids: shown to benefit adults in one RCT, particularly those with less severe disease (study used dexamethasone)

20. References • Kent SJ et al. Tuberculous meningitis: a 30-year review. Clin Infect Dis, 1993; 17: 987-994. • Kumar R et al. Tuberculous brain abscess: clinical presentation, pathophysiology, and treatment (in children). Child’s Nerv Syst, 2002; 18:118-123. • Leonard, J. Central nervous system tuberculosis. UpToDate, acessed 5/20/2009. • Pai et al. Diagnostic accuracy of nucleic acid amplification tests for tuberculous meningitis: a systematic review and meta-analysis. Lancet Infect Dis, 2003; 3: 633-643. • Rock RB et al. Central nervous system tuberculosis: pathogenesis and clinical aspects. Clin Micro Rev, 2008; 21: 243-261. • Seydoux C et al. Bacterial brain abscesses: factors influencing mortality and sequelae. Clin Infect Dis, 1992; 15: 394-401. • Southwick FS. Pathogenesis, clinical manifestations, and diagnosis of brain abscess. UpToDate, accessed 5/20/2009. • Tattevin P et al. Bacterial brain abscesses: a retrospective study of 94 patients admitted to an intensive care unit (1980 to 1999). Am J Med, 2003; 115: 143-146. • Thwaites GE et al. Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults. NEJM, 2004; 351: 1741-1751. • Thwaites GE et al. Improving the bacteriological diagnosis of tuberculous meningitis. J Clin Micro, 2004; 42: 378-9. • Thwaites GE et al. Effect of antituberculosis drug resistance on response to treatment and outcome in adults with tuberculous meningitis. J Infect Dis, 2005; 192: 79-88