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Central nervous system tuberculoma: a case report1
The Journal of Emergency Medicine, Vol. 16, No. 5, pp. 719 –722, 1998 Copyright © 1998 Elsevier Science Inc. Printed in the USA. All rights reserved 0736-4679/98 $19.00 1 .00
PII S0736-4679(98)00084-5
Clinical Communications
CENTRAL NERVOUS SYSTEM TUBERCULOMA: A CASE REPORT Paulo Berger,
MD,
James Larson,
MD,
and David Guss,
MD
Department of Emergency Medicine, University of California, San Diego Medical Center, San Diego, California Reprint Address: Paul Berger, MD, Department of Emergency Medicine, UCSD Medical Center (8676), 200 West Arbor Drive, San Diego, CA 92103-8676
e Abstract—Pediatric cerebral tuberculoma is a disease rarely encountered in the United States. We report a case of central nervous system tuberculoma in a 6-month-old infant who presented to the emergency department with isolated right upper extremity paralysis. The discussion includes a brief review of central nervous system tuberculomas. © 1998 Elsevier Science Inc.
CASE REPORT A 6-month-old Hispanic male of immigrant parents was brought to the Emergency Department (ED) of the University of California at San Diego Medical Center. He was brought for evaluation of an isolated right arm paralysis. He awoke spontaneously and appeared normal to the family in every way except for the lack of movement in the right upper extremity. There was no reported trauma recent or past, nor any history of neurologic disease. The child had otherwise been well without fevers, vomiting, cough, irritability, or seizures. Past medical history was provided by the aunt. The child was born at term with an uncomplicated vaginal delivery. At age 11 weeks, the infant was hospitalized for 3 days with cough, tachypnea, and bilateral pulmonary interstitial infiltrates. He was treated with i.v. cefuroxime followed by oral erythromycin for presumed pneumonia; no bronchial washings were obtained. A subsequent visit at age 15 weeks showed continued tachypnea, retractions, bilateral otitis media, and increased reticular nodular densities of the left lower lobe. The patient was hospitalized for 1 day and started on amoxicillin/clavulinate for otitis media. A nasal swab was positive for parainfluenza III. Both parents were tuberculin purified protein derivative (PPD) positive with a negative chest x-ray, but two paternal uncles were known to have active TB; therefore, PPD and controls were placed and the child was scheduled for follow up in the clinic 2 days later. The child did not return to clinic but instead remained
e Keywords—tuberculosis; tuberculoma; miliary tuberculosis; pediatric central nervous system
INTRODUCTION Mycobacterium Tuberculosis (TB), the organism historically responsible for “white plague and galloping consumption,” is still a major cause of morbidity and mortality across the world. In the United States, in which a widespread effort has been focused to fight tuberculosis, the public health campaign has recently suffered significant setbacks. The emergence of HIV, often in conjunction with intravenous (i.v.) drug use, has hampered efforts to control this microorganism and predisposed to the emergence of resistant strains (1). In addition to immunocompromised patients, recent immigrants and those at the extremes of age are most susceptible to infection. A pediatric case of miliary tuberculosis with an uncommon presentation of cerebral tuberculoma is presented. A review of this rare complication of tuberculosis is included.
Clinical Communications (Pediatric) is coordinated by Roger Barkin,
RECEIVED: 29 April 1997; FINAL ACCEPTED:16 December 1997.
SUBMISSION RECEIVED:
1 December 1997; 719
MD,
of HealthONE, Denver, Colorado
720
in Tijuana, Mexico with his mother who had been deported. Approximately 3 days after discharge, the child was taken to a pediatric clinic in Mexico where a PPD was again placed and subsequently read as negative. At age 22 weeks, a third PPD was placed, which was positive to 11 mm induration. Three days prior to his present hospitalization, he was started on isoniazid, rifampin, and pyrazinamide by physicians in Mexico. Examination on presentation revealed an alert, interactive 6-month-old male with an obvious paucity of right arm movement. Vital signs were a temperature of 37.2°C (98.9°F), heart rate 133 beats/min, respiratory rate 36 breaths/min, blood pressure 86/58 mmHg, and weight of 6.98 Kg (5–10 percentile). He was normocephalic with an open flat anterior fontanel, pupils were equal and reactive to light, and eyes revealed a slight leftward gaze preference. Ears, nose, and throat were normal. Chest examination was significant for coarse breath sounds diffusely with mildly decreased sounds at the left base. He had a normal cardiovascular, abdominal, and genitourinary examinations. The right upper extremity was atraumatic, without focal tenderness, swelling, or rashes. There were symmetric distal pulses with immediate capillary refill in all extremities. Motor tone in the right upper and lower extremities was diminished. There was no response to noxious stimuli of the right arm and only a weak flexor response to stimulation of the right leg. The left upper and lower extremities moved spontaneously with brisk response to painful stimulation. The deep tendon reflexes were markedly diminished on the right compared to the left. With this presentation our differential diagnosis included intercranial or spinal cord neoplasm or abscess, focal peripheral neuropathy from direct trauma, traction injury, inflammatory, or demyelination processes. We also considered a Todd’s paralysis or an extremity fracture with secondary hesitation of movement. A computed tomography (CT) scan of the head, with and without contrast, was obtained (Figure 1). There was evidence of infarction in the distribution of the left middle cerebral artery as well as of the basal ganglia, along with five contrast enhancing lesions in vascular distributions with surrounding edema. There was no evidence of impending herniation. Lumbar puncture at admission showed a total white blood cell count of 129 per mm3, 24% neutrophils, 20% lymphocytes, and 56% macrophages. CSF protein was 76 mg/dL, and glucose was 50 mg/dL. Ziehl–Neelsen stain and Gram’s stain were negative for bacteria. The chest x-ray study demonstrated an increase in the density of previously noted reticular nodular infiltrates. The peripheral white blood cell count was 17,900 per mm3 with 12% neutrophils and 80% lymphocytes. Serum chemistries were within normal limits. The infant was admitted to the pediatric intensive care
Berger et al.
Figure 1. Infant male presenting with isolated limb paralysis. Head CT scan demonstrating multiple contrast-enhancing tuberculomas (small arrows) with surrounding edema and areas of tissue infarction (large arrows).
unit. On the night of admission, seizure activity was noted for the first time. He had multiple focal tonic-clonic seizures limited to the right face and upper extremity. This progressed to a single more prolonged generalized seizure that required i.v. lorazepam and phenobarbital. On Day 2, the seizures continued despite therapeutic phenobarbital levels so phenytoin was started. Seizures were controlled on these agents. A diagnosis of cerebral tuberculosis was made based on clinical and radiographic findings. He was discharged on hospital Day 18 with slowly improving right facial droop and upper extremity weakness. There was no further seizure activity. As a consequence of his mother’s deportation to Mexico, follow up had to be arranged with pubic health officials in Tijuana, Mexico. Discharge medications included isoniazid, rifampin, intramuscular (i.m.) streptomycin, prednisone, phenobarbital, dilantin, and folate supplementation.
DISCUSSION Mycobacterium tuberculosis is an aerobic nonmotile bacteria characterized by slow growth (2). The most common manifestations of infection are pulmonary; however, a wide range of organs can be affected result-
CNS Tuberculoma
ing in pericarditis, pleural effusions, peritonitis, and meningitis. An estimated 1.7 billion persons, one-third of the world’s population, are infected. This reservoir of infected persons results in 8 million cases of active tuberculosis and 2.9 million deaths annually (1). In the United States, the groups with higher risk are indigent minorities, those infected with HIV, prison inmates, and foreigners from countries in which tuberculosis is endemic. Patients at the extremes of age are particularly susceptible to active infection. In the United States the number of cases in children younger than 5 years of age increased 49% from 1987 to 1991 (1,3,4,). In addition to clinical manifestations, the diagnosis of tuberculosis is confirmed with microbiologic analysis of sputum samples and skin testing with the purified protein derivative. Skin testing evaluates a cell mediated, delayed type hypersensitivity response to tuberculin antigen. Nonreactivity to PPD is a recognized phenomenon in up to 25% of patients with active culture-positive TB. Among the variables described as contributing to this lack of response are type and dose of antigen, malnutrition, age, and disease conditions known to depress cellular immunity (5). Central nervous system tuberculosis, most often manifested as meningitis, accounts for fewer than 0.5% of cases of tuberculosis in the United States (6). Tuberculomas are defined as space occupying lesions caused by the tubercule bacillus producing neurologic symptoms. Tuberculomas may be present with or without meningitis, may lead to meningitis, or may develop during the treatment of tuberculous meningitis (7,8). Intracranial tuberculomas are formed by hematogenous spread from a primary site of infection. Initial microscopic tubercules fuse to form macroscopic tuberculomas of up to several centimeters in diameter (9). These foci in the brain parenchyma are known as Rich’s foci and can progress to form several different entities. They may cause poorly localized areas of cerebritis with or without meningitis, go on to abscess formation with surrounding encapsulation, or become the more classic solid encapsulated tuberculomas. They may also reach the surface of the brain, rupture and cause meningitis (9,10). The patient presented in this case had evidence of tuberculomas and tuberculous meningitis. The diagnosis of an intracranial tuberculoma is rare in the industrialized world. Tuberculomas are more common in developing countries, representing 10 – 40% of all space occupying intracranial lesions (6). As with our case, many reports of intracranial tuberculomas in the United States are in recent immigrants from areas where tuberculosis is endemic. Central nervous system tuberculosis may not have a definable extracranial foci of infection, and this frequently results in misdiagnosis. The most common pre-
721
senting signs and symptoms of a tuberculoma are cranial nerve palsies, hemiparesis, and focal seizures (8,9,11). In a case series of nine children diagnosed with intracranial tuberculoma, the most common presenting symptoms were fever (9/9), lethargy (6/9), seizures (3/9), and gaze disturbance (2/9). The duration of symptoms prior to admission was 1–21 days (mean 9.8; Reference 12). The case we present is unique with an initial isolated limb hemiparesis despite extensive intracranial findings. The other classic clinical findings did not manifest in this patient until after admission. Diagnosis of tuberculomas has been advanced with the use of head CT scan. The findings on CT scan vary with the stage of the disease. Tuberculomas are often multiple and start as isodense or slightly hyperdense areas that enhance with contrast. Surrounding areas of low attenuation represent edema and necrosis. More mature tuberculomas may show calcification or central necrosis and peripheral organization producing ring shadows (9,11,13). The radiographic changes described also may be seen in brain abscess, certain brain tumors, and in resolving intracerebral hematomas. In children with tuberculomas, 63% are found within the cerebellum whereas adults more often manifest supratentorial lesions (14). Infratentorial tuberculomas present as a single lesion, while supratentorial lesions are more frequently multiple (15). Cerebral infarction associated with tuberculoma and tuberculous meningitis in the distribution of the middle cerebral artery has been reported in children and appears to be a predictor of poor clinical outcome. Passage of vessels through areas of granuloma formation induces perivascular inflammation, vascular obstruction, and infarction (12). Ventriculomegaly resulting from cerebellar tuberculomas obstructing cerebral spinal fluid flow is encountered in children and often requires shunt surgery. Management of intracranial tuberculoma has been most widely studied in India. Conservative management with multiple anti-tuberculous medications is considered most effective (16,17). For drug treatment of tuberculosis meningitis, the American Academy of Pediatrics recommends a 12-month regimen using the initial daily treatment with isoniazid, rifampin, pyrazinamide, and streptomycin for 2 months, followed by isoniazid and rifampin administered daily or twice weekly under direct observation for 10 months (18). Steroids may be used to reduce the edema and subsequent mass effect associated with tuberculomas (16). There are reports of paradoxical expansion of tuberculomas during antituberculous treatment and close monitoring of patients beginning antituberculoma therapy is warranted (19). A similar increase in systemic manifestation of various spirochetal infections has been described after initiation of antibiotic therapy (20). In miliary tuberculosis, there is a state of
722
Berger et al.
overall immune suppression. Once antimicrobial therapy is initiated, there is a heightened inflammatory response, presumably from release of intracellular antigenic substances. Lesions that had been silent become symptomatic. Steroids help diminish the inflammatory immune response. Surgery is reserved for life-threatening mass effect, hydrocephalous, failed medical therapy, or uncertain diagnosis (21). Children with tuberculoma as the sole abnormality on CT scan have a good prognosis (16). The presence of infarction or significant ventriculomegaly defines a more complicated clinical course in which full neurologic recovery is doubtful.
CONCLUSION After several decades of consistent declines, the incidence of tuberculosis is once again increasing in the United States. A case of tuberculoma and cerebral infarction, an uncommon extrapulmonary complication of tuberculosis, is presented. This diagnosis should be considered when patients at risk for tuberculosis or those having recently initiated anti-tuberculous therapy develop focal neurologic deficits or seizures. Early recognition and treatment can result in full recovery.
REFERENCES 1. Barnes P, Barrows S. Tuberculosis in the 1990s. Ann Intern Med. 1993;119:400 –10. 2. Volk W, Benjamin D, Kadner R, Parsons J. Essentials of medical microbiology. Philadelphia: Lippincott; 1986:471– 6. 3. Kochi A. The global tuberculosis situation and the new control strategy of the World Health Organization. Tubercle. 1991;72:1– 6. 4. Rieder H, Cauthen G, Kelly G, et al. Tuberculosis in the United States. JAMA. 1989;262:3:385–9. 5. Nash DR, Douglass JE. Anergy in active pulmonary tuberculosis. Chest. 1980;77:32–7. 6. Sheller J, Des Prez R. CNS Tuberculosis. Neurol Clin. 1986;4:1: 143–58. 7. Malone J, Paparello S, Rickman L, et al. Intracranial Tuberculoma developing during therapy for tuberculous meningitis. West J Med. 1990;152:188 –90. 8. Teoh R, Humphries M, O’Mahony G. Symptomatic intracranial tuberculoma developing during treatment of tuberculosis: a report of 10 patients and review of the literature. Quart J Med. 1987;63: 241:449 – 60. 9. Loizou L, Anderson M. Intracranial tuberculomas: Correlation of computerized tomography with clinicopathological findings. Quart J Med 1982;104 –14. 10. Bhargava S, Gupta AK, Tandon PN. Tuberculous meningitis: a computerized tomography study. Br J Radiol. 1982;55:189 –96. 11. Whelan M, Stern J. Intracranial tuberculoma. Radiology. 1981; 138:75– 81.
12. Wallace R, Burton E, Barret F, et al. Intracranial tuberculosis in children: CT appearance and clinical outcome. Pediatr Radio. 1991; 21:241– 6. 13. Vengsarkar U, Pisipaty R, Parekh B, et al. Intracranial tuberculoma and the CT scan. J Neurosurg. 1986;64:568 –74. 14. Dastur D, Lalitha V, Prabhakar V. Pathological analysis of intracranial space-occupying lesions in 1000 cases including children. J Neurol Sci. 1968;6:575–92. 15. Wistrak B, Ellis G. Intracranial tuberculosis:.manifestations on computerized tomography. South Med J. 1985;78:386. 16. Bhagwati S, Parulekar G. Management of intracranial tuberculoma in children. Child’s Nerv Syst. 1986;2:32– 4. 17. Ramamurthi B, Ramamurthi R, Vasudevan M. Changing concepts in the treatment of tuberculomas of the brain. Child’s Nerv Syst. 1986;2:242–3. 18. Committee on Infectious Diseases. Chemotherapy for tuberculosis in infants and children. Pediatrics. 1992;89:1:161–5. 19. Lees A, Marshall J, MacLeod A. Cerebral tuberculomas developing during treatment of tuberculous meningitis. Lancet. 1980; 1208 –11. 20. Griffin, G. E. New insights into the pathophysiology of the JarischHerxheimer reaction. J Antimicrobial Chemother. 1992;29:613– 6. 21. Chambers S, Record C, Smith H: Paradoxical expansion of intracranial tuberculomas during chemotherapy. Lancet. 1984;181– 4.
PII S0736-4679(98)00084-5
Clinical Communications
CENTRAL NERVOUS SYSTEM TUBERCULOMA: A CASE REPORT Paulo Berger,
MD,
James Larson,
MD,
and David Guss,
MD
Department of Emergency Medicine, University of California, San Diego Medical Center, San Diego, California Reprint Address: Paul Berger, MD, Department of Emergency Medicine, UCSD Medical Center (8676), 200 West Arbor Drive, San Diego, CA 92103-8676
e Abstract—Pediatric cerebral tuberculoma is a disease rarely encountered in the United States. We report a case of central nervous system tuberculoma in a 6-month-old infant who presented to the emergency department with isolated right upper extremity paralysis. The discussion includes a brief review of central nervous system tuberculomas. © 1998 Elsevier Science Inc.
CASE REPORT A 6-month-old Hispanic male of immigrant parents was brought to the Emergency Department (ED) of the University of California at San Diego Medical Center. He was brought for evaluation of an isolated right arm paralysis. He awoke spontaneously and appeared normal to the family in every way except for the lack of movement in the right upper extremity. There was no reported trauma recent or past, nor any history of neurologic disease. The child had otherwise been well without fevers, vomiting, cough, irritability, or seizures. Past medical history was provided by the aunt. The child was born at term with an uncomplicated vaginal delivery. At age 11 weeks, the infant was hospitalized for 3 days with cough, tachypnea, and bilateral pulmonary interstitial infiltrates. He was treated with i.v. cefuroxime followed by oral erythromycin for presumed pneumonia; no bronchial washings were obtained. A subsequent visit at age 15 weeks showed continued tachypnea, retractions, bilateral otitis media, and increased reticular nodular densities of the left lower lobe. The patient was hospitalized for 1 day and started on amoxicillin/clavulinate for otitis media. A nasal swab was positive for parainfluenza III. Both parents were tuberculin purified protein derivative (PPD) positive with a negative chest x-ray, but two paternal uncles were known to have active TB; therefore, PPD and controls were placed and the child was scheduled for follow up in the clinic 2 days later. The child did not return to clinic but instead remained
e Keywords—tuberculosis; tuberculoma; miliary tuberculosis; pediatric central nervous system
INTRODUCTION Mycobacterium Tuberculosis (TB), the organism historically responsible for “white plague and galloping consumption,” is still a major cause of morbidity and mortality across the world. In the United States, in which a widespread effort has been focused to fight tuberculosis, the public health campaign has recently suffered significant setbacks. The emergence of HIV, often in conjunction with intravenous (i.v.) drug use, has hampered efforts to control this microorganism and predisposed to the emergence of resistant strains (1). In addition to immunocompromised patients, recent immigrants and those at the extremes of age are most susceptible to infection. A pediatric case of miliary tuberculosis with an uncommon presentation of cerebral tuberculoma is presented. A review of this rare complication of tuberculosis is included.
Clinical Communications (Pediatric) is coordinated by Roger Barkin,
RECEIVED: 29 April 1997; FINAL ACCEPTED:16 December 1997.
SUBMISSION RECEIVED:
1 December 1997; 719
MD,
of HealthONE, Denver, Colorado
720
in Tijuana, Mexico with his mother who had been deported. Approximately 3 days after discharge, the child was taken to a pediatric clinic in Mexico where a PPD was again placed and subsequently read as negative. At age 22 weeks, a third PPD was placed, which was positive to 11 mm induration. Three days prior to his present hospitalization, he was started on isoniazid, rifampin, and pyrazinamide by physicians in Mexico. Examination on presentation revealed an alert, interactive 6-month-old male with an obvious paucity of right arm movement. Vital signs were a temperature of 37.2°C (98.9°F), heart rate 133 beats/min, respiratory rate 36 breaths/min, blood pressure 86/58 mmHg, and weight of 6.98 Kg (5–10 percentile). He was normocephalic with an open flat anterior fontanel, pupils were equal and reactive to light, and eyes revealed a slight leftward gaze preference. Ears, nose, and throat were normal. Chest examination was significant for coarse breath sounds diffusely with mildly decreased sounds at the left base. He had a normal cardiovascular, abdominal, and genitourinary examinations. The right upper extremity was atraumatic, without focal tenderness, swelling, or rashes. There were symmetric distal pulses with immediate capillary refill in all extremities. Motor tone in the right upper and lower extremities was diminished. There was no response to noxious stimuli of the right arm and only a weak flexor response to stimulation of the right leg. The left upper and lower extremities moved spontaneously with brisk response to painful stimulation. The deep tendon reflexes were markedly diminished on the right compared to the left. With this presentation our differential diagnosis included intercranial or spinal cord neoplasm or abscess, focal peripheral neuropathy from direct trauma, traction injury, inflammatory, or demyelination processes. We also considered a Todd’s paralysis or an extremity fracture with secondary hesitation of movement. A computed tomography (CT) scan of the head, with and without contrast, was obtained (Figure 1). There was evidence of infarction in the distribution of the left middle cerebral artery as well as of the basal ganglia, along with five contrast enhancing lesions in vascular distributions with surrounding edema. There was no evidence of impending herniation. Lumbar puncture at admission showed a total white blood cell count of 129 per mm3, 24% neutrophils, 20% lymphocytes, and 56% macrophages. CSF protein was 76 mg/dL, and glucose was 50 mg/dL. Ziehl–Neelsen stain and Gram’s stain were negative for bacteria. The chest x-ray study demonstrated an increase in the density of previously noted reticular nodular infiltrates. The peripheral white blood cell count was 17,900 per mm3 with 12% neutrophils and 80% lymphocytes. Serum chemistries were within normal limits. The infant was admitted to the pediatric intensive care
Berger et al.
Figure 1. Infant male presenting with isolated limb paralysis. Head CT scan demonstrating multiple contrast-enhancing tuberculomas (small arrows) with surrounding edema and areas of tissue infarction (large arrows).
unit. On the night of admission, seizure activity was noted for the first time. He had multiple focal tonic-clonic seizures limited to the right face and upper extremity. This progressed to a single more prolonged generalized seizure that required i.v. lorazepam and phenobarbital. On Day 2, the seizures continued despite therapeutic phenobarbital levels so phenytoin was started. Seizures were controlled on these agents. A diagnosis of cerebral tuberculosis was made based on clinical and radiographic findings. He was discharged on hospital Day 18 with slowly improving right facial droop and upper extremity weakness. There was no further seizure activity. As a consequence of his mother’s deportation to Mexico, follow up had to be arranged with pubic health officials in Tijuana, Mexico. Discharge medications included isoniazid, rifampin, intramuscular (i.m.) streptomycin, prednisone, phenobarbital, dilantin, and folate supplementation.
DISCUSSION Mycobacterium tuberculosis is an aerobic nonmotile bacteria characterized by slow growth (2). The most common manifestations of infection are pulmonary; however, a wide range of organs can be affected result-
CNS Tuberculoma
ing in pericarditis, pleural effusions, peritonitis, and meningitis. An estimated 1.7 billion persons, one-third of the world’s population, are infected. This reservoir of infected persons results in 8 million cases of active tuberculosis and 2.9 million deaths annually (1). In the United States, the groups with higher risk are indigent minorities, those infected with HIV, prison inmates, and foreigners from countries in which tuberculosis is endemic. Patients at the extremes of age are particularly susceptible to active infection. In the United States the number of cases in children younger than 5 years of age increased 49% from 1987 to 1991 (1,3,4,). In addition to clinical manifestations, the diagnosis of tuberculosis is confirmed with microbiologic analysis of sputum samples and skin testing with the purified protein derivative. Skin testing evaluates a cell mediated, delayed type hypersensitivity response to tuberculin antigen. Nonreactivity to PPD is a recognized phenomenon in up to 25% of patients with active culture-positive TB. Among the variables described as contributing to this lack of response are type and dose of antigen, malnutrition, age, and disease conditions known to depress cellular immunity (5). Central nervous system tuberculosis, most often manifested as meningitis, accounts for fewer than 0.5% of cases of tuberculosis in the United States (6). Tuberculomas are defined as space occupying lesions caused by the tubercule bacillus producing neurologic symptoms. Tuberculomas may be present with or without meningitis, may lead to meningitis, or may develop during the treatment of tuberculous meningitis (7,8). Intracranial tuberculomas are formed by hematogenous spread from a primary site of infection. Initial microscopic tubercules fuse to form macroscopic tuberculomas of up to several centimeters in diameter (9). These foci in the brain parenchyma are known as Rich’s foci and can progress to form several different entities. They may cause poorly localized areas of cerebritis with or without meningitis, go on to abscess formation with surrounding encapsulation, or become the more classic solid encapsulated tuberculomas. They may also reach the surface of the brain, rupture and cause meningitis (9,10). The patient presented in this case had evidence of tuberculomas and tuberculous meningitis. The diagnosis of an intracranial tuberculoma is rare in the industrialized world. Tuberculomas are more common in developing countries, representing 10 – 40% of all space occupying intracranial lesions (6). As with our case, many reports of intracranial tuberculomas in the United States are in recent immigrants from areas where tuberculosis is endemic. Central nervous system tuberculosis may not have a definable extracranial foci of infection, and this frequently results in misdiagnosis. The most common pre-
721
senting signs and symptoms of a tuberculoma are cranial nerve palsies, hemiparesis, and focal seizures (8,9,11). In a case series of nine children diagnosed with intracranial tuberculoma, the most common presenting symptoms were fever (9/9), lethargy (6/9), seizures (3/9), and gaze disturbance (2/9). The duration of symptoms prior to admission was 1–21 days (mean 9.8; Reference 12). The case we present is unique with an initial isolated limb hemiparesis despite extensive intracranial findings. The other classic clinical findings did not manifest in this patient until after admission. Diagnosis of tuberculomas has been advanced with the use of head CT scan. The findings on CT scan vary with the stage of the disease. Tuberculomas are often multiple and start as isodense or slightly hyperdense areas that enhance with contrast. Surrounding areas of low attenuation represent edema and necrosis. More mature tuberculomas may show calcification or central necrosis and peripheral organization producing ring shadows (9,11,13). The radiographic changes described also may be seen in brain abscess, certain brain tumors, and in resolving intracerebral hematomas. In children with tuberculomas, 63% are found within the cerebellum whereas adults more often manifest supratentorial lesions (14). Infratentorial tuberculomas present as a single lesion, while supratentorial lesions are more frequently multiple (15). Cerebral infarction associated with tuberculoma and tuberculous meningitis in the distribution of the middle cerebral artery has been reported in children and appears to be a predictor of poor clinical outcome. Passage of vessels through areas of granuloma formation induces perivascular inflammation, vascular obstruction, and infarction (12). Ventriculomegaly resulting from cerebellar tuberculomas obstructing cerebral spinal fluid flow is encountered in children and often requires shunt surgery. Management of intracranial tuberculoma has been most widely studied in India. Conservative management with multiple anti-tuberculous medications is considered most effective (16,17). For drug treatment of tuberculosis meningitis, the American Academy of Pediatrics recommends a 12-month regimen using the initial daily treatment with isoniazid, rifampin, pyrazinamide, and streptomycin for 2 months, followed by isoniazid and rifampin administered daily or twice weekly under direct observation for 10 months (18). Steroids may be used to reduce the edema and subsequent mass effect associated with tuberculomas (16). There are reports of paradoxical expansion of tuberculomas during antituberculous treatment and close monitoring of patients beginning antituberculoma therapy is warranted (19). A similar increase in systemic manifestation of various spirochetal infections has been described after initiation of antibiotic therapy (20). In miliary tuberculosis, there is a state of
722
Berger et al.
overall immune suppression. Once antimicrobial therapy is initiated, there is a heightened inflammatory response, presumably from release of intracellular antigenic substances. Lesions that had been silent become symptomatic. Steroids help diminish the inflammatory immune response. Surgery is reserved for life-threatening mass effect, hydrocephalous, failed medical therapy, or uncertain diagnosis (21). Children with tuberculoma as the sole abnormality on CT scan have a good prognosis (16). The presence of infarction or significant ventriculomegaly defines a more complicated clinical course in which full neurologic recovery is doubtful.
CONCLUSION After several decades of consistent declines, the incidence of tuberculosis is once again increasing in the United States. A case of tuberculoma and cerebral infarction, an uncommon extrapulmonary complication of tuberculosis, is presented. This diagnosis should be considered when patients at risk for tuberculosis or those having recently initiated anti-tuberculous therapy develop focal neurologic deficits or seizures. Early recognition and treatment can result in full recovery.
REFERENCES 1. Barnes P, Barrows S. Tuberculosis in the 1990s. Ann Intern Med. 1993;119:400 –10. 2. Volk W, Benjamin D, Kadner R, Parsons J. Essentials of medical microbiology. Philadelphia: Lippincott; 1986:471– 6. 3. Kochi A. The global tuberculosis situation and the new control strategy of the World Health Organization. Tubercle. 1991;72:1– 6. 4. Rieder H, Cauthen G, Kelly G, et al. Tuberculosis in the United States. JAMA. 1989;262:3:385–9. 5. Nash DR, Douglass JE. Anergy in active pulmonary tuberculosis. Chest. 1980;77:32–7. 6. Sheller J, Des Prez R. CNS Tuberculosis. Neurol Clin. 1986;4:1: 143–58. 7. Malone J, Paparello S, Rickman L, et al. Intracranial Tuberculoma developing during therapy for tuberculous meningitis. West J Med. 1990;152:188 –90. 8. Teoh R, Humphries M, O’Mahony G. Symptomatic intracranial tuberculoma developing during treatment of tuberculosis: a report of 10 patients and review of the literature. Quart J Med. 1987;63: 241:449 – 60. 9. Loizou L, Anderson M. Intracranial tuberculomas: Correlation of computerized tomography with clinicopathological findings. Quart J Med 1982;104 –14. 10. Bhargava S, Gupta AK, Tandon PN. Tuberculous meningitis: a computerized tomography study. Br J Radiol. 1982;55:189 –96. 11. Whelan M, Stern J. Intracranial tuberculoma. Radiology. 1981; 138:75– 81.
12. Wallace R, Burton E, Barret F, et al. Intracranial tuberculosis in children: CT appearance and clinical outcome. Pediatr Radio. 1991; 21:241– 6. 13. Vengsarkar U, Pisipaty R, Parekh B, et al. Intracranial tuberculoma and the CT scan. J Neurosurg. 1986;64:568 –74. 14. Dastur D, Lalitha V, Prabhakar V. Pathological analysis of intracranial space-occupying lesions in 1000 cases including children. J Neurol Sci. 1968;6:575–92. 15. Wistrak B, Ellis G. Intracranial tuberculosis:.manifestations on computerized tomography. South Med J. 1985;78:386. 16. Bhagwati S, Parulekar G. Management of intracranial tuberculoma in children. Child’s Nerv Syst. 1986;2:32– 4. 17. Ramamurthi B, Ramamurthi R, Vasudevan M. Changing concepts in the treatment of tuberculomas of the brain. Child’s Nerv Syst. 1986;2:242–3. 18. Committee on Infectious Diseases. Chemotherapy for tuberculosis in infants and children. Pediatrics. 1992;89:1:161–5. 19. Lees A, Marshall J, MacLeod A. Cerebral tuberculomas developing during treatment of tuberculous meningitis. Lancet. 1980; 1208 –11. 20. Griffin, G. E. New insights into the pathophysiology of the JarischHerxheimer reaction. J Antimicrobial Chemother. 1992;29:613– 6. 21. Chambers S, Record C, Smith H: Paradoxical expansion of intracranial tuberculomas during chemotherapy. Lancet. 1984;181– 4.