Diagnostic Challenges of Central Nervous System Tuberculosis

Abstract

Central nervous system tuberculosis (TB) was identifi ed in 20 cases of unexplained encephalitis referred to the California Encephalitis Project. Atypical features (encephalitic symptoms, rapid onset, age) and diagnostic challenges (insensitive cerebrospinal fl uid [CSF] TB PCR result, elevated CSF glucose levels in patients with diabetes, negative result for tuberculin skin test) complicated diagnosis.T uberculosis (TB) of the central nervous system (CNS) is classically described as meningitis. However, altered mental status, including encephalitis, is within the spectrum of clinical manifestations. Because early treatment can dramatically improve outcomes, consideration of TB as a potential pathogen in CNS infections, including encephalitis, is vital. The California Encephalitis Project (CEP), initiated in 1998 to study the causative agents, epidemiology, and clinical features of encephalitis, has identifi ed 20 cases of culture-confi rmed tuberculous encephalitis. In most instances, TB was not initially considered to be a likely cause. The StudyReferrals are received by the CEP statewide from clinicians seeking diagnostic testing for immunocompetent patients, including TB PCR testing when appropriate, who meet the CEP case defi nition of encephalitis (1). Mycobacterial testing was often also conducted by the referring hospital. Inclusion criteria for this report were a positive cerebrospinal fl uid (CSF) culture for Mycobacterium tuberculosis complex or a positive CSF TB PCR result. Clinical data were compiled from case history forms and other medical records when available. To evaluate differences among causes of encephalitis, TB patients were compared with CEP patients with cases of enterovirus and herpes simplex virus 1 (HSV-1) encephalitis. Demographic, clinical, and laboratory data were compared by using the Fisher exact test, χ 2 test, or Kruskal-Wallis test as appropriate (statistical signifi cance was set at α = 0.05).From June 1998 through October 2005, a total of 1,587 patients were enrolled in the CEP; 20 patients fulfi lled criteria as TB cases. Demographic and clinical information for the study population are detailed in the online Appendix Table (available from www.cdc.gov/EID/content/14/9/ 1473-appT.htm). Median age was 41 years (range 8 months to 77 years). The median time from symptom onset to fi rst lumbar puncture was 5 days (range 0-62 days). Seventeen patients (85%) had a second lumber puncture.In general, CSF values became more abnormal over time, with increasing leukocyte counts and protein levels and decreasing glucose levels (Appendix Table). Most patients had a CSF mononuclear cell predominance, although 4 patients (21%) had a neutrophil predominance. All patients had cranial neuroimaging, magnetic resonance imaging (18 of 20), and computed tomography (20 of 20) (Appendix Table; Table). Results of computed tomography scans were often normal (50%).Of patients in whom the results of a recent tuberculin skin test (TST) were known, 59% (10 of 17) had a negative result (Appendix Table). M...

Intracranial Tuberculoma in Non-immunosuppressive State

“…17) PCR may have low sensitivity for the detection of CSF tuberculosis. 4) The sensitivity and specificity of nucleic acid amplification tests for tuberculous meningitis have been reported to be 0.56 and 0.98, respectively. 14) The sensitivity has been reported to be as low as 48%.…”

Comparación de adenosina deaminasa y detección de anticuerpos anti-antígeno A60 para el diagnóstico de meningitis tuberculosa

“…El rendimiento diagnóstico de IgM anti-A60 (sensibilidad de 94,1% y especificidad de 80,4%) resultó incluso superior a lo reportado en numerosos estudios para la RPC de M. tuberculosis en LCR 3,6,23 . Este hallazgo pudiese explicarse por la gran antigenicidad de M. tuberculosis que resulta en la producción de anticuerpos detectables mediante ELISA pese a que la carga misma de antígenos micobacterianos sea muy baja en la muestra de LCR 8,24 .…”

“…Tiene una alta morbi-mortalidad que sólo puede ser evitada mediante el rápido inicio de tratamiento correcto 2 . No obstante, con frecuencia la administración de terapias antituberculosas es tardía debido a que la forma de presentación clínica y las alteraciones del LCR son inespecíficas, sumado a que no existen tests diagnósticos rápidos suficientemente sensibles y específicos 3 . La baciloscopia tiene baja sensibilidad en LCR y el cultivo de micobacterias es muy lento (30 a 60 días) y, si bien la determinación de adenosina deaminasa (ADA) es una herramienta de uso común en el proceso diagnóstico de la MTBC, también presenta resultados variables de sensibilidad y especificidad (rango 58-83% y 71-95%, respectivamente, en diferentes estudios) 4,5 .…”

Seizure increases electroencephalographic abnormalities in children with tuberculous meningitis

“…Given the difficulties in obtaining a rapid diagnosis, therapy must often be initiated empirically. (20) In the present study, radiograph interpretation should have been performed, and EEG might be useful to monitor TBM patients, if interpreted by professionals in the field of clinicalradiological findings. This study shows the importance of EEGs to detect seizure activity and risk of epilepsy in children with TBM.…”