Case Report Intramedullary Tuberculoma in a Patient with Human Immunodeficiency Virus Infection and Disseminated Multidrug-Resistant Tuberculosis: Case Report Maria A. Barges, MD;” Maria I. Carmo, MD;t Maria R. Sambo, MD;+ Fernando C. Borges, MD;* Carlos M. Aratijo, MD;* Maria J. Campos, MD;* Alda M. Jacinto, MD;$ Kamal Mansinho, MD;* and Orlando C. L&so, MD+ Intramedullary tuberculomas are extremely rare, being present in approximately 2 of every 100,000 cases of tuberculosis and 2 of every 1000 cases of tuberculosis of the central nervous system.‘-* Infection with human immunodeficiency virus (HIV) increases the risk of tuber- culosis, which may occur at any stage of immunodefi- ciency. Extrapulmonary disease is more common in patients with HIV infection.5-s The authors believe that the following is the first report of an intramedullary tuber- culoma, associated with HIV infection, in a patient with disseminated multidrug-resistant tuberculosis. The patient’s neurologic condition improved after an anti- tuberculosis retreatment regimen that included isoniazid, pyrazinamide, amikacin, and ciprofloxacin. CASE REPORT The patient was a 26year-old white Portuguese man with a history of intravenous drug use; he was found to be seropositive for HIV-l in 1991. In July 1993, the patient was diagnosed with disseminated tuberculosis and was initially treated with rifampin, isoniazid, pyrazinamide, and ethambutol. Marked symptomatic improvement was noticed during the first 4 weeks of treatment, but there- after several relapses occurred, owing to poor compli- ance with therapy In January 1994, ciprofloxacin was substituted for ethambutol, because of the emergence of ethambutol resistance. In May 1994, the patient experi- enced a left cervicobrachialgia and progressive weakness, Departments of *Internal Medicine, ‘Neurology, *Infectious Diseases and Tropical Medicine, and ‘Neuroradiology, Hospital Egas Monk, Lisbon, Portugal. Address correspondence to Dr. Maria A. Borges, Rua Ptiblia Horthsia de Castro, n”4,Y esq”, Alfornelos, 2700 Amadora, Portugal. numbness, and paresthesia of upper extremities with occasional urinary incontinence. In July 1994, the patient developed seizures, and com- puted tomography (CT) showed intracranial hypodense contrast-ring-enhancing mass lesions (Figure 1). Cerebral biopsy was not done. Antituberculosis therapy was con- tinued, and a 2-month course of pyrimethamine and sul- fadiazine was administered, with clinical improvement. In November 1994, CT was normal. In February 1995, the patient was hospitalized because of severe neck pain, progressive weakness, numb- ness, and paresthesia of both arms, more marked on the left. On physical examination, wasting was the only sig- nificant finding. Neurologic examination showed a fully alert, oriented, and cooperative patient. He complained of severe pain in the neck and marked tenderness was found on the cervical spine. There was prominent wasting of the intrinsic hand muscles and strength in the upper limbs was graded distally and proximally, as O/5 and 3/5, respectively, on the left; 3/5 and 4/5, respectively, on the right. Deep tendon reflexes were absent in the upper limbs, the left knee jerk was brisker, and extensor plan- tar reflex was present on the left. A marked decrease in sensation to pinprick and vibration was found from C2 to Tl, bilaterally Joint position sense was impaired in the fingers. Ancillary tests showed a white blood cell count of 2.7 X 109/L with 66% granulocytes and 20% lymphocytes. The serum alkaline phosphatase level was 171 U/L; the gamma glutamyltransferase level was 292 U/L; and the aspartate aminotransferase level was 87 U/L. The total bilirubin level was 2.4 mg/dL, and the conjugated biliru- bin level was 0.6 mg/dL. Blood cultures were positive for Mycobacterium tuberculosis. The patient’s total CD4 lymphocyte count was 0.07 X lob/L. A skin test with five tuberculin units of purified pro- tein derivative (PPD) was negative. A cerebrospinal fluid (CSF) profile revealed an elevated protein level of 115 mg/dL, with a glucose level of 46 mg/dL and a white blood cell count of 1 X lob/L, with 100% monocytes. 164
Transcript
Case Report
Intramedullary Tuberculoma in a Patient with Human Immunodeficiency Virus Infection and Disseminated Multidrug-Resistant Tuberculosis: Case Report Maria A. Barges, MD;” Maria I. Carmo, MD;t Maria R. Sambo, MD;+ Fernando C. Borges, MD;* Carlos M. Aratijo, MD;* Maria J. Campos, MD;* Alda M. Jacinto, MD;$ Kamal Mansinho, MD;* and Orlando C. L&so, MD+
Intramedullary tuberculomas are extremely rare, being present in approximately 2 of every 100,000 cases of tuberculosis and 2 of every 1000 cases of tuberculosis of the central nervous system.‘-* Infection with human immunodeficiency virus (HIV) increases the risk of tuber- culosis, which may occur at any stage of immunodefi- ciency. Extrapulmonary disease is more common in patients with HIV infection.5-s The authors believe that the following is the first report of an intramedullary tuber- culoma, associated with HIV infection, in a patient with disseminated multidrug-resistant tuberculosis. The patient’s neurologic condition improved after an anti- tuberculosis retreatment regimen that included isoniazid, pyrazinamide, amikacin, and ciprofloxacin.
CASE REPORT
The patient was a 26year-old white Portuguese man with a history of intravenous drug use; he was found to be seropositive for HIV-l in 1991. In July 1993, the patient was diagnosed with disseminated tuberculosis and was initially treated with rifampin, isoniazid, pyrazinamide, and ethambutol. Marked symptomatic improvement was noticed during the first 4 weeks of treatment, but there- after several relapses occurred, owing to poor compli- ance with therapy In January 1994, ciprofloxacin was substituted for ethambutol, because of the emergence of ethambutol resistance. In May 1994, the patient experi- enced a left cervicobrachialgia and progressive weakness,
Departments of *Internal Medicine, ‘Neurology, *Infectious Diseases and Tropical Medicine, and ‘Neuroradiology, Hospital Egas Monk, Lisbon, Portugal.
Address correspondence to Dr. Maria A. Borges, Rua Ptiblia Horthsia de Castro, n”4,Y esq”, Alfornelos, 2700 Amadora, Portugal.
numbness, and paresthesia of upper extremities with occasional urinary incontinence.
In July 1994, the patient developed seizures, and com- puted tomography (CT) showed intracranial hypodense contrast-ring-enhancing mass lesions (Figure 1). Cerebral biopsy was not done. Antituberculosis therapy was con- tinued, and a 2-month course of pyrimethamine and sul- fadiazine was administered, with clinical improvement. In November 1994, CT was normal.
In February 1995, the patient was hospitalized because of severe neck pain, progressive weakness, numb- ness, and paresthesia of both arms, more marked on the left. On physical examination, wasting was the only sig- nificant finding. Neurologic examination showed a fully alert, oriented, and cooperative patient. He complained of severe pain in the neck and marked tenderness was found on the cervical spine. There was prominent wasting of the intrinsic hand muscles and strength in the upper limbs was graded distally and proximally, as O/5 and 3/5, respectively, on the left; 3/5 and 4/5, respectively, on the right. Deep tendon reflexes were absent in the upper limbs, the left knee jerk was brisker, and extensor plan- tar reflex was present on the left. A marked decrease in sensation to pinprick and vibration was found from C2 to Tl, bilaterally Joint position sense was impaired in the fingers.
Ancillary tests showed a white blood cell count of 2.7 X 109/L with 66% granulocytes and 20% lymphocytes. The serum alkaline phosphatase level was 171 U/L; the gamma glutamyltransferase level was 292 U/L; and the aspartate aminotransferase level was 87 U/L. The total bilirubin level was 2.4 mg/dL, and the conjugated biliru- bin level was 0.6 mg/dL. Blood cultures were positive for Mycobacterium tuberculosis. The patient’s total CD4 lymphocyte count was 0.07 X lob/L.
A skin test with five tuberculin units of purified pro- tein derivative (PPD) was negative. A cerebrospinal fluid (CSF) profile revealed an elevated protein level of 115 mg/dL, with a glucose level of 46 mg/dL and a white blood cell count of 1 X lob/L, with 100% monocytes.
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Intermedullary Tuberculoma / Barges et al 165
Figure 3. T2-weighted MRI showing a hypointense lesion with edema.
Figure 1. Axial cranial CT showing two nodular enhancing lesions with marked perifocal edema. The left temporal lobe shows a hypodense area, due to edema associated with a third lesion.
Microscopic examination of stained specimens of the fluid showed no acid-fast bacilli, fungi, or other micro- organisms, and cultures were negative. Toxoplasma anti- body and cryptococcal antigen tests on CSF and sernm were negative.
Chest radiography revealed bilateral apical scarring, similar to previous findings. A CT scan of the cervical spine revealed a widened cord from Cl to ~6. Magnetic resonance imaging (MRI) demonstrated a focal swelling of the cord in the cervical segment, due to the presence of an intramedullary nodular lesion at the level of C4, hyperintense in Tl-weighted MRI and with marked enhancement after intravenous gadolinium (Figure 2). In T2-weighted MRI, the lesion was hypointense, with asso- ciated hyperintensity above and below, indicating edema (Figure 3).
The patient continued on antituberculous therapy, and amikacin was added. He also continued to receive
Figure 2. Leff, A sagittal Tl-weighted MRI of the cervical spine, revealing a cord edema associated with a nodular hyperintense lesion at the C4 level. Right, Gadolinium-enhanced MRI of the cervical spine, revealing an enhancing homogeneous intramedullary lesion.
Figure 4. MRI of the cervical spine, demonstrating the clear reduction of the dimensions and mass effect of the intramedullaty tuberculoma.
166 International Journal of Infectious Diseases / Volume 2, Number 3, January-March 1998
antiretroviral therapy and prophylaxis against Pneumo- cystis and toxoplasmosis. His condition improved gradu- ally, and on the seventh day of therapy the strength in the upper limbs was graded 3/5 (distally), 5/5 (proximally) on the left and 5/5 on the right; sensation was normal. The patient was discharged 4 weeks after admission, but he returned in May 1995 because paresthesia and weakness had worsened, despite good compliance with therapy (self-reporting). Sputum acid-fast stains were again posi- tive and cultures grew rifampin-resistant M. tuberculosis. Thoracic CT revealed cavitations on the apical left lung. A liver biopsy was performed. Histologic examination was normal, with a negative search for acid-fast bacilli (stain and culture). A 4-week course of steroids (pred- nisolone, 40 mg/d) was added to the current treatment, with improvement of the neurologic abnormalities. A repeat MRI, performed 3 months after the first, showed a clear reduction of the mass effect and dimensions of the lesion (Figure 4). The patient’s neurologic examination gradually improved, and he was discharged in June 1995. He had no complaints, and neurologic examination was normal, except for the presence of a brisker knee jerk and an extensor plantar response on the left. He completed 18 months of retreatment regimen with isoniazid, pyraz- inamide, amikacin, and ciprofloxacin. On follow-up, 1 year later (June 1996) neurologic findings remained stable and all cultures and smears were negative. Additional MRI studies were not done.
DISCUSSION
The incidence of tuberculosis has increased in recent years, at least in part as a result of the ongoing worldwide epidemic of acquired immunodeficiency syndrome (AIDS). In addition, the occurrence of outbreaks caused by multidrug-resistant M. tuberculosis has become increasingly a matter of concern.6-9 The risk of progres- sion of tuberculosis may be greater in HIV-infected intra- venous drug users than in other HIV-infected populations. 8,9 Central nervous system tuberculosis is a rare entity affecting 0.5 to 2% of patients with systemic tuberculosis.3 The majority of the lesions are intracranial, with the ratio of intracranial to intramedullary lesions ranging from 2O:l to 4&l, depending on the series.‘,”
Intramedullary spinal tuberculoma is a rare condi- tion. Only three cases have been documented in the lit- erature, since Lin’s review of the subject in 1960, with 105 cases.‘s3s4 In agreement with previous reports, intra- medullary spinal tuberculoma seems to be a disease of relatively young patients and probably originates from hematogenous seeding from an extraneural focus (usually pulmonary or renal), or as a part of miliary tuberculosis9 The uncommon involvement of the spinal cord compared to the brain, suggests that the location of these lesions is
determined by the relative distribution of neural tissue within the nervous system, in conjunction with local fac- tors, such as blood flow, although other factors may be involved.1~3~10
The patient discussed here is the first case reported in the literature of an intramedullary tuberculoma asso- ciated to multidrug-resistant disseminated tuberculosis, including intracerebral, and HIV infection. His presenta- tion was similar to that of cases reported in the pre-AIDS era,5 with motor and sensory deficits and, like many other patients, he had extraspinal tuberculosis, with culture- documented pulmonary disease and presumed cerebral tuberculomas. It is possible that the brain abscesses seen during an earlier admission were due to toxoplasmosis, despite negative serology, as he improved clinically and radiographically after a course of sulfadiazine and pyrimethamine. The authors emphasize the difficulty in differentiating these lesions from those of other etiolo- gies. l1 However, it is known that a strong correlation exists between them and disseminated tuberculosis.1-5,12~13 In this case, there was a disseminated tuberculosis with a protracted and relapsing symptomatology and persis- tently positive cultures, due to noncompliance and drug (ethambutol and rifampin) resistance.13-I5 In spite of the lack of a biopsy, the clinical and neuroradiologic improve- ment observed with adequate antituberculous therapy strongly suggests a tuberculous etiology.11~13~14 The relative roles of steroids and antituberculous therapy in the improvement seen on the second MRI remain uncertain.
Intramedullary tuberculoma, although a rare entity, must be considered in the differential diagnosis of sub- acute spinal cord compression, particularly in patients with evidence of extraneural tuberculous disease.1-5~7~9,11~13-1s The advent of MRI may facilitate the diagnosis of an intramedullary mass consistent with tuberculoma.12,13 Medical therapy remains the mainstay of treatment, but when confronted with a progressing neurologic deficit, the neurosurgeon may need to remove the lesion.1.7-‘1,15~‘6 In patients managed with appropriate therapy, the prog- nosis for neurologic improvement is good.lm3 Although results of treatment of multidrug-resistant tuberculosis in HIV-infected patients are usually poor, with high rates of treatment failure and mortality,13 vigorous and appropri- ate antituberculous treatment is always worth trying.
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