TABLE 3.
Summary of clinical features, CSE findings, PCR assay results, and outcomes for 9 patients with suspected TBMa
| Parameter | Confirmed cases
|
Highly probable cases
|
|||||||
|---|---|---|---|---|---|---|---|---|---|
| Case 1 | Case 2 | Case 3 | Case 4 | Case 5 | Case 6 | Case 7 | Case 8 | Case 9 | |
| Age (yr)/sex | 73/M | 76/M | 35/F | 65/F | 52/M | 24/F | 44/F | 59/F | 44/M |
| Past medical history (background disease) | Diabetes mellitus, renal cancer, hypertension | CML, atrial fibrillation, hypertension | SLE | Diabetes mellitus | Alcoholism, alcoholic cirrhosis, diabetes mellitus | SLE, lupus nephritis, APS | RPGN, CRF (hemodialysis) | MS, hyperlipidemia | ATL |
| Administration of corticosteroid (mg/day) | PSL:20 | PSL:20 | PSL:20 | PSL:30 | |||||
| Clinical stage upon admissionb | III | III | II | I | II | I | III | II | III |
| CSF findings upon admission (before treatment) | |||||||||
| Cells/μl [M:P] | 288 [75:141] | 165 [462:34] | 208 [170:455] | 107 [161:0] | 18 [27:26] | 30 [69:21] | 60 [41:138] | 40 [121:0] | 117 [345:7] |
| Protein (mg/dl) | 299 | 569 | 300 | 70 | 135 | 25 | 70 | 359 | 87 |
| Glucose (mg/dl) | 13 | 46 | 13 | 48 | 54 | 30 | 52 | 78 | 48 |
| Cl (mEq/l) | 96 | 97 | 94 | 122 | 96 | 118 | 116 | 125 | 130 |
| ADA (IU/l) | 23.4 | 12.3 | 16.3 | 7.8 | 8.6 | 4.4 | N.D. | 3.7 | 3.9 |
| AFB smear | − | − | − | − | − | − | − | − | − |
| Tb culture | + | + | − | − | − | − | − | − | − |
| Single PCR assay | + | + | − | − | − | − | − | − | − |
| Nested PCR assay | + | + | + | + | + | + | + | + | + |
| Copy number by QNRT-PCR assay (copies/250 μl CSF) | 2.6 × 104 | 1.6 × 104 | 9.0 × 102 | 1.4 × 103 | 6.7 × 102 | 4.8 × 103 | 3.8 × 103 | 1.4 × 103 | 5.6 × 103 |
| Cranial MRI findings | |||||||||
| Meningeal enhancement | + | + | + | − | + | − | − | − | + |
| Hydrocephalus | + | − | + | − | + | − | − | + | − |
| Cerebrovascular disorder | + | + | + | − | + | − | + | − | − |
| IFM | + | − | + | − | + | + | − | − | − |
| M. tuberculosis outside CNS | |||||||||
| Pulmonary (sputum or ball) | + | + | − | − | + | − | − | − | + |
| Gastric aspirate | + | − | − | − | + | − | − | − | + |
| Urine | − | − | − | − | − | − | − | − | − |
| Peripheral blood | − | − | − | − | − | − | − | − | − |
| Treatment | |||||||||
| INH (mg/day) | 500 | 600 | 800 | 450 | 500 | 500 | 200 | 600 | 500 |
| Intrathecal administration (mg) | 100 (3 times/week) | ||||||||
| RFP (mg/day) | 600 | 600 | 600 | 450 | 450 | 450 | 225 | 450 | 450 |
| PZA (g/day) | 1.5 | 1.5 | 1.5 | 1.5 | 1 | 2 | 1.5 | 2 | 2 |
| EB (mg/day) | 750 | 750 | |||||||
| SM (g/day) | 1 | 1 | 1 | 1 | 1 | 1 | 1 | ||
| Anticonvulsant | Phenytoin | Phenytoin | Valproate sodium | Phenytoin Phenobarbital | |||||
| V-P shunt | + | − | + | − | − | − | − | − | |
| Complication | SIADH/hyponatremia, acute renal failure, DIC/ARDS | Drug-induced hepatopathy drug-induced paracusis | SIADH/hyponatremia, left facial palsy | − | Symptomatic epilepsy | − | Symptomatic epilepsy, Acute pancreatitis | − | Leukemic meningitis (Intrathecal administration of carcinostatics) |
| Outcomec | Death | Recovery | Recovery | Recovery | Recovery | Recovery | Recovery | Recovery | Death |
| Clinical criteria and supporting evidenced | All A and three B (1,2,3) | All A and all B | All A and three B (1,2,4) | All A, and three B (1,2,4) | All A and all B | All A and three B (1,2,4) | All A and three B (1,2,4) | All A and three B (1,2,4) | All A and three B (1,2,3) |
CML, chronic myelocytic leukemia; SLE, systemic lupus erythematosus; APS, antiphospholipid syndrome; RPGN, rapidly progressive glomerulonephritis; CRF, chronic renal failure; MS, multiple sclerosis; ATL, adult T-cell leukemia; M, mononuclear cell; P, polymorphonuclear cell; ADA, adenosine deaminase; Tb, tuberculosis; INH, isoniazid; RFP, rifampin; PZA, pyrazinamide; EB, ethambutol; SM, streptomycin sulfate; DX, dexamethasone; PSL, prednisolone; V-P shunt, ventricle-peritoneal shunt; IFM, intracranial focal mass; SIADH, syndrome of inappropriate secretion of antidiuretic hormone; DIC, disseminated intravascular coagulation; ARDS, adult respiratory distress syndrome. −, negative; +, positive.
According to the clinical stages defined by the British Medical Research Council (11): stage I, no definite neurological symptoms; II, signs of meningeal irritation with slight clouding of consciousness and neurologic defects; III, severe clouding of consciousness and neurologic defects.
Outcome classified as recovery with minor or no neurological impairment, severe neurologic impairment, or death.
A, the clinical criteria suggestive of TBM are fever, headache, and neck stiffness of more than 1 week duration. B, supporting evidence for TBM includes (i) compatible abnormal CSF findings that included increased white cell counts with lymphocytes predominating, hypoglycorrhachia, protein concentration of >100 mg/dl, adenosine deaminase (ADA) greater than 10 IU/liter and negative results for routine bacterial and fungal cultures; (ii) MRI findings suggesting tuberculous involvement of the CNS (basal exudates, hydrocephalus, and intracranial focal mass, etc.); (iii) presence of tuberculosis in the body outside of the CNS or a history of tuberculosis; and (iv) clinical response to antituberculosis therapy. The suspected TBM cases were classified as “confirmed” cases (having bacterial isolation of M. tuberculosis, such as CSF culture, or being AFB smear positive) or “highly probable” cases (meeting all the above clinical criteria and with all three types of supporting evidence positive).