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Evolution of brain tuberculomas under standard antituberculous treatment
Journal of Neurological Sciences 156 (1998) 47–52
Evolution of brain tuberculomas under standard antituberculous treatment a, b c d d b A. Awada *, A.K. Daif , M. Pirani , M.Y. Khan , Z. Memish , S. Al Rajeh a
Neurology Section, King Fahad National Guard Hospital, P.O. Box 22490, Riyadh 11426, Saudi Arabia b Division of Neurology, King Saud University, Riyadh, Saudi Arabia c Department of Medical Imaging, King Fahad National Guard Hospital, Riyadh, Saudi Arabia d Infectious Diseases Section, King Fahad National Guard Hospital, Riyadh, Saudi Arabia Received 12 February 1997; received in revised form 30 September 1997; accepted 23 October 1997
Abstract The treatment of brain tuberculomas is primarily medical. Surgery, excision or biopsy, is generally performed when the diagnosis is in doubt or there is no response to medical therapy. The aim of this study was to determine the radiological evolution of intracranial tuberculomas under standard anti-tuberculous drug therapy and to establish guidelines for better management of these patients. Eighteen patients were studied retrospectively. None of them had surgical intervention and all were treated by standard antituberculous drugs and had serial computed tomography (CT) scans until disappearance or stabilization of brain lesions. The regression of lesions’ size and number was slow in the first month (mean 27.3%) then became rapid after this (215% to 220% per month). A paradoxical increase in size was noted in three patients in the first month. All three had associated meningitis. All tuberculomas disappeared on CT scan after 12 months of therapy. Most of the edema images disappeared by 6 months. This study would suggest that a long treatment regimen of 15–18 months may not be necessary in most intracranial tuberculomas occurring in non-immunocompromised patients. It also demonstrates that medical trial in well tolerated suspected cases should last for at least 2 months before considering other etiologies or surgical exploration. 1998 Elsevier Science B.V. Keywords: Tuberculosis; Tuberculomas; Meningitis; Computed tomography
1. Introduction Brain tuberculomas are amongst the rarest intracranial space occupying lesions (SOL) in the developed societies. In the 1960s, they constituted less than 0.2% of all intracranial SOL in England (Maurice-Williams, 1972). In the same period, they accounted for almost 30% of all intracranial SOL in some less developed countries such as India (Dastur et al., 1968), a figure that was reported at the beginning of the 20th Century in Western countries (Garland and Armitage, 1933). Although brain tuberculomas are common in less developed nations, the lack of readily available neuro-imaging facilities has led to an incomplete study of the evolution of these lesions over a prolonged period of observation. *Corresponding author. Fax: 1966 1 2520140.
The exact incidence of intracranial tuberculoma in the Kingdom of Saudi Arabia is not yet established. However, the incidence does appear significant in that 66 cases of intracranial tuberculomas were reported from one large referral hospital in Riyadh, Saudi Arabia between 1978 and 1988 (Jinkins, 1991). Since medical treatment of intracranial tuberculomas has been found to be superior, or at least equal in efficacy to combined surgical and medical treatment (Harder et al., 1983), many suspected brain tuberculomas in our institutions are treated medically. Surgery, either excision or biopsy, is generally performed only when the diagnosis is in doubt or there is no clinical and / or radiological response after a trial of medical treatment, or, if the condition of the patient is critical and does not permit such a trial. The duration of the medical treatment is however largely
0022-510X / 98 / $19.00 1998 Published by Elsevier Science B.V. All rights reserved. PII S0022-510X( 98 )00024-0
A. Awada et al. / Journal of Neurological Sciences 156 (1998) 47 – 52
48
empirical and based mainly on very few publications (Sheller and Des Prez, 1986; Barnes and Barrows, 1993; Berger, 1994) and individual experiences. The aim of our study was to determine the radiological evolution of intracranial tuberculomas under standard antituberculous drug therapy and to establish guidelines for better management of these lesions.
made through the infra and supratentorial compartments respectively. All patients had baseline, pre-treatment CT studies before and after the administration of 100 ml iodinated contrast material. CT studies were repeated intermittently until complete disappearance or stabilisation of lesion(s). The average number of examinations was 4.9 / patient (range 3–10). All images were reviewed and the following lesion parameters were assessed.
2. Patients and methods All cases of suspected intracranial tuberculomas observed over a 6-year period (January 1986–January 1992) in the King Fahad National Guard Hospital and the King Khalid University Hospital in Riyadh, Saudi Arabia were reviewed. Both these institutions are well equipped with modern facilities and offer free medical care. From the total of 32 cases, only 18 were included in this study as they represented those lesions whose natural evolution under medical treatment could be followed to a desired end point by imaging. None of these patients had surgery or was immunocompromised. Initial medical treatment in 15 / 18 cases consisted of three antituberculous drugs and 3 / 18 patients received four drugs for 3 months (Table 1). After this period, all cases received two drugs for another 9–15 months. All patients were initially started on isoniazid (300 mg / day), rifampicin (600 mg / day), and either pyrizinamide (25 mg / kg / day), ethambutol (25 mg / kg / day) or streptomycin (15 mg / kg / day). Some of the drugs had to be stopped because of side effects. Streptomycin was given only when there was associated extracranial tuberculosis. Other drugs such as corticosteroids and antiepileptics were added as necessary. Cranial CT studies were performed on Philips and Siemens units. Five- and 10-mm contiguous scans were
1. Size: the maximum diameter of each lesion was measured and the sum of diameters was plotted at each evaluation, using a method that has been previously used for similar studies on intracranial cysticercosis (Sotelo et al., 1984). The sum of the diameters of the lesion(s) on each follow-up CT study was converted into a percentage on the basis of pre-treatment value (5100%). In 3 / 18 cases of miliary intracranial tuberculosis, the calculations were done by counting the number of lesions and estimating subjectively (and independently by two of the authors) their percentage regression. 2. Edema: this was defined as the hypodense zone around the lesion(s), not fixing the contrast material. 3. Calcification(s): this was defined as areas / foci of significantly increased attenuation, generally more than 100 Hounsfield units, on pre-contrast images around the lesion(s), not modified with contrast administration.
3. Results The 18 cases included in this study comprised of 10 males and eight females. Table 1 shows age at presentation, number of lesions and their intracranial locations. The mean age at presentation was 51 years (range 13–90). In
Table 1 Clinical data, location and number of tuberculomas and treatment received Case
Age / sex
Number
Location(s) of lesions
Treatment a
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
50 / M 50 / M 13 / F 30 / F 65 / F 55 / M 38 / M 70 / F 30 / F 45 / M 55 / F 90 / M 17 / F 70 / F 45 / M 60 / M 60 / M 75 / M
1 1 1 1 1 1 1 1 1 2 2 3 5 6 6 16 24 37
L corona radiata Corpus callosum R cerebellar L frontal Sup. cerebellar peduncle R cerebellar hemisphere (1chest) Cerebellar vermis (1chest) L temporal (1meningitis) R temporal (1meningitis) R parietal Frontal (1meningitis) Corona radiatia R, L (1spine) R temporal R internal capsule both frontal, R parietal Left thalamic, R parietal both frontal Miliary (1meningitis) Miliary Miliary (1meningitis)
IRP IRP IRE IRE IRPS IRS IRES IRP IRP IRE IRE IRP IRE RPE RPE IRPS IPS IRP
a
I, isoniazid; R, rifampicin; P, pyrizinamide; E, ethambutol; S, streptomycin.
A. Awada et al. / Journal of Neurological Sciences 156 (1998) 47 – 52
5 / 18 cases (28%), intracranial tuberculomas were associated with tuberculous meningitis and in 4 / 18 cases (22%) with extracranial tuberculosis. Nine patients (50%) had a single lesion, six others (33%) between two and six lesions and three patients (17%) had miliary brain tuberculomata (Fig. 1). Fig. 2 shows the evolution of the plotted sum of lesion diameters (in percentage) against the month of follow-up.
49
In 3 / 18 cases (17%), there was an initial paradoxical response with increment in size of the lesions following the institution of medical therapy. This was accompanied by clinical worsening in one patient who developed aphasia (case 8). There was no noticeable clinical change in the two other cases but both of them were treated by steroids. All of these three cases had associated tuberculous meningitis. However, by 2 months, the lesions started
Fig. 1. Radiological aspects of brain tuberculomas: (a) single ring-enhanced lesion (case 5); (b) solid lesions (case 14); (c) miliary aspect (case 18); (d) miliary aspect with ring-enhanced lesions (case 17).
50
A. Awada et al. / Journal of Neurological Sciences 156 (1998) 47 – 52
Fig. 2. Evolution of the plotted sum of lesions’ diameters (in percentage) against the month of follow-up, 18 cases.
to decrease in size in all cases and disappeared in 3 / 18 cases by the 5th month. A curve showing the mean (6standard deviation) rapidity of regression of the intracranial tuberculomas is presented in Fig. 3. The regression was slow in the 1st month (mean: 27.3%) then became rapid between the 2nd and 5th months (mean: 215% to 220% / month) and slow again in the next 6 months. No image of tuberculoma was noted after 11 months of therapy. All intracranial tuberculomas showed a varying degree of peri-lesional edema prior to the institution of
treatment. Only 3 / 18 cases (17%) showed some residual edema at 6 months. The lesions lacked any demonstrable edema by CT beyond 9 months (Fig. 4). Dexamethasone was given to 12 patients with significant brain edema and / or associated meningitis and all of them showed good clinical response. Intralesional calcifications appeared between the 4th and 11th months of medical treatment and remained permanent in 6 / 18 cases (33%) (Fig. 4). No calcification appeared in the three cases of miliary tuberculosis or those with associated meningitis.
Fig. 3. Mean6standard deviation of the plotted lesions’ diameters.
A. Awada et al. / Journal of Neurological Sciences 156 (1998) 47 – 52
51
Fig. 4. Evolution of the edema and calcifications.
4. Discussion The great polymorphism of the CT appearance of intracranial tuberculomas (Vengsarkar et al., 1986; Jinkins, 1991) makes it mimic possibly any other type of lesion. A common challenge for the clinician is to determine, in front of a suggestive CT image, which patient is likely to have tuberculoma and thus be treated medically, and which one is likely to have another type of intracranial lesion and be treated surgically. In most cases, the diagnosis is presumptive and based upon the other supportive clinical data and mainly the presence of typical cerebrospinal fluid changes or systemic tuberculosis. However, in endemic areas, solid and ring enhancing lesions are very suggestive (Chambers et al., 1984) and authorize the clinician to undergo a therapeutic trial of antituberculous medications, especially if differential diagnosis is limited to poorly treatable disorders such as metastases or glioblastoma. However, and as shown in our study, an initial worsening of the CT appearance is not uncommon and would have been probably more common if ‘surgical patients’ were included. This phenomenon of initial paradoxical worsening has been reported previously (Chambers et al., 1984) and, moreover, intracranial tuberculomas developing ‘de novo’ during treatment of tuberculous meningitis have also been reported (Lees et al., 1980; Borah et al., 1984; Teoh et al., 1987). It is noteworthy that all our patients with initial worsening had concomitant tuberculous meningitis. This association has helped us to avoid surgical exploration and observe the patients with repetitive brain CTs until a clear response to treatment. A period of 2 months of expectation was necessary in
many of our cases before observing a clear response to treatment. After this period, all the cases started to show decrease in lesion size that became progressively faster in the following 4 months. The abnormal brain images disappeared in all cases by 12 months suggesting that a longer antituberculous therapy is probably unnecessary. In all our cases some degree of edema was noted at the initial brain CT, more than the 71% reported by Jinkins (1991). On the contrary, no calcification was noted initially while it was reported in 3% of the cases of the same author. No edema was noted in any case after 9 months of therapy and calcifications appeared in a third of the cases, a similar frequency to the 31% reported by Jinkins (1991). The edema disappeared after 6 months of therapy in 15 / 18 of our patients and the first calcifications were noted at this same period. This may suggest an inactivation of the disease at 6 months, at least in some cases and is another indication that shorter courses than the classical 15–18 months’ therapy of neurotuberculosis are probably sufficient as in other forms of tuberculosis (Davidson, 1990). In summary, despite the small number of patients reviewed in this study, the following conclusions can be drawn. (1) Medical trial in suspected brain tuberculomas should last at least for 2 months — if the clinical condition is stable — before considering other diagnoses. (2) An initial worsening in the first month can occur in as many as one sixth of the cases. (3) The presence of an associated tuberculous meningitis could be a predisposing factor for the initial worsening. (4) The disappearance of all brain tuberculomas by 11–12 months and the disappearance of edema as well as the appearance of calcifications around the 6th month may suggest that a shorter course of anti-TB
52
A. Awada et al. / Journal of Neurological Sciences 156 (1998) 47 – 52
treatment than the 15–18 months regimen is sufficient, at least for immune-competent patients. (5) A regimen combining isoniazid, rifampicin, pyrizinamide in standard doses has generally been found to be effective for management of most cases of tuberculomas. Pyrizinamide is discontinued after the first 2–3 months and the other two continued till the treatment course is finished. Streptomycin may have to be added to this regimen in patients who are extremely ill or unconscious and corticosteroids were beneficial in the management of patients with tuberculomas, especially those with severe brain edema.
References Barnes, P.F., Barrows, S.A., 1993. Tuberculosis in the 90s. Ann. Intern. Med. 119, 400–410. Berger, J.R., 1994. Tuberculous meningitis. Curr. Opin. Neurol. 7, 191– 200. Borah, N.C., Maheshwari, C. et al., 1984. Appearance of tuberculoma during the course of TB meningitis. J. Neurol. 231, 269–270. Chambers, S.T., Hendrickse, W.A., Record, C. et al., 1984. Paradoxical expansion of intracranial tuberculomas during chemotherapy. Lancet 2, 181–183. Dastur, H.M., Lalitha, V.A., Prabhakar, V., 1968. Pathological analysis of
intracranial space occupying lesions in 1000 cases, including children. J. Neurol. Sci. 6, 575–592. Davidson, P.T., 1990. Treating tuberculosis: what drugs, for how long?. Ann. Intern. Med. 112, 393–395. Garland, H.G., Armitage, G., 1933. Intracranial tuberculomas. J. Pathol. Bacteriol. 37, 461–471. Harder, E., Al Kawi, M.Z., Carney, P., 1983. Intracranial tuberculoma, conservative management. Am. J. Med. 74, 570–576. Jinkins, J.R., 1991. Computed tomography of intracranial tuberculosis. Neuroradiology 33, 126–135. Lees, A.J., MacLeod, A.F., Marshall, J., 1980. Cerebral tuberculomas developing during treatment of tuberculous meningitis. Lancet 1, 1208–1211. Maurice-Williams, R.S., 1972. Tuberculomas of the brain in Britain. Postgrad. Med. J. 48, 678–681. Sheller, J.R., Des Prez, R.M., 1986. CNS tuberculosis. Neurol. Clin. 4, 143–158. Sotelo, J., Escobedo, F., Rodriguez, M. et al., 1984. Therapy of parenchymal brain cysticercosis with praziquantel. N. Engl. J. Med. 310, 1001–1007. Teoh, R., Humphries, M.J., O’Mahony, S.G., 1987. Symptomatic intracranial tuberculoma developing during treatment of tuberculosis. A report of 10 patients and review of the literature. Q. J. Med. 63, 449–460. Vengsarkar, U.S., Pisipaty, R.P., Parekh, B., Panchal, V.G., Shetty, M., 1986. Intracranial tuberculoma and the CT scan. J. Neurosurg. 64, 568–574.
Evolution of brain tuberculomas under standard antituberculous treatment a, b c d d b A. Awada *, A.K. Daif , M. Pirani , M.Y. Khan , Z. Memish , S. Al Rajeh a
Neurology Section, King Fahad National Guard Hospital, P.O. Box 22490, Riyadh 11426, Saudi Arabia b Division of Neurology, King Saud University, Riyadh, Saudi Arabia c Department of Medical Imaging, King Fahad National Guard Hospital, Riyadh, Saudi Arabia d Infectious Diseases Section, King Fahad National Guard Hospital, Riyadh, Saudi Arabia Received 12 February 1997; received in revised form 30 September 1997; accepted 23 October 1997
Abstract The treatment of brain tuberculomas is primarily medical. Surgery, excision or biopsy, is generally performed when the diagnosis is in doubt or there is no response to medical therapy. The aim of this study was to determine the radiological evolution of intracranial tuberculomas under standard anti-tuberculous drug therapy and to establish guidelines for better management of these patients. Eighteen patients were studied retrospectively. None of them had surgical intervention and all were treated by standard antituberculous drugs and had serial computed tomography (CT) scans until disappearance or stabilization of brain lesions. The regression of lesions’ size and number was slow in the first month (mean 27.3%) then became rapid after this (215% to 220% per month). A paradoxical increase in size was noted in three patients in the first month. All three had associated meningitis. All tuberculomas disappeared on CT scan after 12 months of therapy. Most of the edema images disappeared by 6 months. This study would suggest that a long treatment regimen of 15–18 months may not be necessary in most intracranial tuberculomas occurring in non-immunocompromised patients. It also demonstrates that medical trial in well tolerated suspected cases should last for at least 2 months before considering other etiologies or surgical exploration. 1998 Elsevier Science B.V. Keywords: Tuberculosis; Tuberculomas; Meningitis; Computed tomography
1. Introduction Brain tuberculomas are amongst the rarest intracranial space occupying lesions (SOL) in the developed societies. In the 1960s, they constituted less than 0.2% of all intracranial SOL in England (Maurice-Williams, 1972). In the same period, they accounted for almost 30% of all intracranial SOL in some less developed countries such as India (Dastur et al., 1968), a figure that was reported at the beginning of the 20th Century in Western countries (Garland and Armitage, 1933). Although brain tuberculomas are common in less developed nations, the lack of readily available neuro-imaging facilities has led to an incomplete study of the evolution of these lesions over a prolonged period of observation. *Corresponding author. Fax: 1966 1 2520140.
The exact incidence of intracranial tuberculoma in the Kingdom of Saudi Arabia is not yet established. However, the incidence does appear significant in that 66 cases of intracranial tuberculomas were reported from one large referral hospital in Riyadh, Saudi Arabia between 1978 and 1988 (Jinkins, 1991). Since medical treatment of intracranial tuberculomas has been found to be superior, or at least equal in efficacy to combined surgical and medical treatment (Harder et al., 1983), many suspected brain tuberculomas in our institutions are treated medically. Surgery, either excision or biopsy, is generally performed only when the diagnosis is in doubt or there is no clinical and / or radiological response after a trial of medical treatment, or, if the condition of the patient is critical and does not permit such a trial. The duration of the medical treatment is however largely
0022-510X / 98 / $19.00 1998 Published by Elsevier Science B.V. All rights reserved. PII S0022-510X( 98 )00024-0
A. Awada et al. / Journal of Neurological Sciences 156 (1998) 47 – 52
48
empirical and based mainly on very few publications (Sheller and Des Prez, 1986; Barnes and Barrows, 1993; Berger, 1994) and individual experiences. The aim of our study was to determine the radiological evolution of intracranial tuberculomas under standard antituberculous drug therapy and to establish guidelines for better management of these lesions.
made through the infra and supratentorial compartments respectively. All patients had baseline, pre-treatment CT studies before and after the administration of 100 ml iodinated contrast material. CT studies were repeated intermittently until complete disappearance or stabilisation of lesion(s). The average number of examinations was 4.9 / patient (range 3–10). All images were reviewed and the following lesion parameters were assessed.
2. Patients and methods All cases of suspected intracranial tuberculomas observed over a 6-year period (January 1986–January 1992) in the King Fahad National Guard Hospital and the King Khalid University Hospital in Riyadh, Saudi Arabia were reviewed. Both these institutions are well equipped with modern facilities and offer free medical care. From the total of 32 cases, only 18 were included in this study as they represented those lesions whose natural evolution under medical treatment could be followed to a desired end point by imaging. None of these patients had surgery or was immunocompromised. Initial medical treatment in 15 / 18 cases consisted of three antituberculous drugs and 3 / 18 patients received four drugs for 3 months (Table 1). After this period, all cases received two drugs for another 9–15 months. All patients were initially started on isoniazid (300 mg / day), rifampicin (600 mg / day), and either pyrizinamide (25 mg / kg / day), ethambutol (25 mg / kg / day) or streptomycin (15 mg / kg / day). Some of the drugs had to be stopped because of side effects. Streptomycin was given only when there was associated extracranial tuberculosis. Other drugs such as corticosteroids and antiepileptics were added as necessary. Cranial CT studies were performed on Philips and Siemens units. Five- and 10-mm contiguous scans were
1. Size: the maximum diameter of each lesion was measured and the sum of diameters was plotted at each evaluation, using a method that has been previously used for similar studies on intracranial cysticercosis (Sotelo et al., 1984). The sum of the diameters of the lesion(s) on each follow-up CT study was converted into a percentage on the basis of pre-treatment value (5100%). In 3 / 18 cases of miliary intracranial tuberculosis, the calculations were done by counting the number of lesions and estimating subjectively (and independently by two of the authors) their percentage regression. 2. Edema: this was defined as the hypodense zone around the lesion(s), not fixing the contrast material. 3. Calcification(s): this was defined as areas / foci of significantly increased attenuation, generally more than 100 Hounsfield units, on pre-contrast images around the lesion(s), not modified with contrast administration.
3. Results The 18 cases included in this study comprised of 10 males and eight females. Table 1 shows age at presentation, number of lesions and their intracranial locations. The mean age at presentation was 51 years (range 13–90). In
Table 1 Clinical data, location and number of tuberculomas and treatment received Case
Age / sex
Number
Location(s) of lesions
Treatment a
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
50 / M 50 / M 13 / F 30 / F 65 / F 55 / M 38 / M 70 / F 30 / F 45 / M 55 / F 90 / M 17 / F 70 / F 45 / M 60 / M 60 / M 75 / M
1 1 1 1 1 1 1 1 1 2 2 3 5 6 6 16 24 37
L corona radiata Corpus callosum R cerebellar L frontal Sup. cerebellar peduncle R cerebellar hemisphere (1chest) Cerebellar vermis (1chest) L temporal (1meningitis) R temporal (1meningitis) R parietal Frontal (1meningitis) Corona radiatia R, L (1spine) R temporal R internal capsule both frontal, R parietal Left thalamic, R parietal both frontal Miliary (1meningitis) Miliary Miliary (1meningitis)
IRP IRP IRE IRE IRPS IRS IRES IRP IRP IRE IRE IRP IRE RPE RPE IRPS IPS IRP
a
I, isoniazid; R, rifampicin; P, pyrizinamide; E, ethambutol; S, streptomycin.
A. Awada et al. / Journal of Neurological Sciences 156 (1998) 47 – 52
5 / 18 cases (28%), intracranial tuberculomas were associated with tuberculous meningitis and in 4 / 18 cases (22%) with extracranial tuberculosis. Nine patients (50%) had a single lesion, six others (33%) between two and six lesions and three patients (17%) had miliary brain tuberculomata (Fig. 1). Fig. 2 shows the evolution of the plotted sum of lesion diameters (in percentage) against the month of follow-up.
49
In 3 / 18 cases (17%), there was an initial paradoxical response with increment in size of the lesions following the institution of medical therapy. This was accompanied by clinical worsening in one patient who developed aphasia (case 8). There was no noticeable clinical change in the two other cases but both of them were treated by steroids. All of these three cases had associated tuberculous meningitis. However, by 2 months, the lesions started
Fig. 1. Radiological aspects of brain tuberculomas: (a) single ring-enhanced lesion (case 5); (b) solid lesions (case 14); (c) miliary aspect (case 18); (d) miliary aspect with ring-enhanced lesions (case 17).
50
A. Awada et al. / Journal of Neurological Sciences 156 (1998) 47 – 52
Fig. 2. Evolution of the plotted sum of lesions’ diameters (in percentage) against the month of follow-up, 18 cases.
to decrease in size in all cases and disappeared in 3 / 18 cases by the 5th month. A curve showing the mean (6standard deviation) rapidity of regression of the intracranial tuberculomas is presented in Fig. 3. The regression was slow in the 1st month (mean: 27.3%) then became rapid between the 2nd and 5th months (mean: 215% to 220% / month) and slow again in the next 6 months. No image of tuberculoma was noted after 11 months of therapy. All intracranial tuberculomas showed a varying degree of peri-lesional edema prior to the institution of
treatment. Only 3 / 18 cases (17%) showed some residual edema at 6 months. The lesions lacked any demonstrable edema by CT beyond 9 months (Fig. 4). Dexamethasone was given to 12 patients with significant brain edema and / or associated meningitis and all of them showed good clinical response. Intralesional calcifications appeared between the 4th and 11th months of medical treatment and remained permanent in 6 / 18 cases (33%) (Fig. 4). No calcification appeared in the three cases of miliary tuberculosis or those with associated meningitis.
Fig. 3. Mean6standard deviation of the plotted lesions’ diameters.
A. Awada et al. / Journal of Neurological Sciences 156 (1998) 47 – 52
51
Fig. 4. Evolution of the edema and calcifications.
4. Discussion The great polymorphism of the CT appearance of intracranial tuberculomas (Vengsarkar et al., 1986; Jinkins, 1991) makes it mimic possibly any other type of lesion. A common challenge for the clinician is to determine, in front of a suggestive CT image, which patient is likely to have tuberculoma and thus be treated medically, and which one is likely to have another type of intracranial lesion and be treated surgically. In most cases, the diagnosis is presumptive and based upon the other supportive clinical data and mainly the presence of typical cerebrospinal fluid changes or systemic tuberculosis. However, in endemic areas, solid and ring enhancing lesions are very suggestive (Chambers et al., 1984) and authorize the clinician to undergo a therapeutic trial of antituberculous medications, especially if differential diagnosis is limited to poorly treatable disorders such as metastases or glioblastoma. However, and as shown in our study, an initial worsening of the CT appearance is not uncommon and would have been probably more common if ‘surgical patients’ were included. This phenomenon of initial paradoxical worsening has been reported previously (Chambers et al., 1984) and, moreover, intracranial tuberculomas developing ‘de novo’ during treatment of tuberculous meningitis have also been reported (Lees et al., 1980; Borah et al., 1984; Teoh et al., 1987). It is noteworthy that all our patients with initial worsening had concomitant tuberculous meningitis. This association has helped us to avoid surgical exploration and observe the patients with repetitive brain CTs until a clear response to treatment. A period of 2 months of expectation was necessary in
many of our cases before observing a clear response to treatment. After this period, all the cases started to show decrease in lesion size that became progressively faster in the following 4 months. The abnormal brain images disappeared in all cases by 12 months suggesting that a longer antituberculous therapy is probably unnecessary. In all our cases some degree of edema was noted at the initial brain CT, more than the 71% reported by Jinkins (1991). On the contrary, no calcification was noted initially while it was reported in 3% of the cases of the same author. No edema was noted in any case after 9 months of therapy and calcifications appeared in a third of the cases, a similar frequency to the 31% reported by Jinkins (1991). The edema disappeared after 6 months of therapy in 15 / 18 of our patients and the first calcifications were noted at this same period. This may suggest an inactivation of the disease at 6 months, at least in some cases and is another indication that shorter courses than the classical 15–18 months’ therapy of neurotuberculosis are probably sufficient as in other forms of tuberculosis (Davidson, 1990). In summary, despite the small number of patients reviewed in this study, the following conclusions can be drawn. (1) Medical trial in suspected brain tuberculomas should last at least for 2 months — if the clinical condition is stable — before considering other diagnoses. (2) An initial worsening in the first month can occur in as many as one sixth of the cases. (3) The presence of an associated tuberculous meningitis could be a predisposing factor for the initial worsening. (4) The disappearance of all brain tuberculomas by 11–12 months and the disappearance of edema as well as the appearance of calcifications around the 6th month may suggest that a shorter course of anti-TB
52
A. Awada et al. / Journal of Neurological Sciences 156 (1998) 47 – 52
treatment than the 15–18 months regimen is sufficient, at least for immune-competent patients. (5) A regimen combining isoniazid, rifampicin, pyrizinamide in standard doses has generally been found to be effective for management of most cases of tuberculomas. Pyrizinamide is discontinued after the first 2–3 months and the other two continued till the treatment course is finished. Streptomycin may have to be added to this regimen in patients who are extremely ill or unconscious and corticosteroids were beneficial in the management of patients with tuberculomas, especially those with severe brain edema.
References Barnes, P.F., Barrows, S.A., 1993. Tuberculosis in the 90s. Ann. Intern. Med. 119, 400–410. Berger, J.R., 1994. Tuberculous meningitis. Curr. Opin. Neurol. 7, 191– 200. Borah, N.C., Maheshwari, C. et al., 1984. Appearance of tuberculoma during the course of TB meningitis. J. Neurol. 231, 269–270. Chambers, S.T., Hendrickse, W.A., Record, C. et al., 1984. Paradoxical expansion of intracranial tuberculomas during chemotherapy. Lancet 2, 181–183. Dastur, H.M., Lalitha, V.A., Prabhakar, V., 1968. Pathological analysis of
intracranial space occupying lesions in 1000 cases, including children. J. Neurol. Sci. 6, 575–592. Davidson, P.T., 1990. Treating tuberculosis: what drugs, for how long?. Ann. Intern. Med. 112, 393–395. Garland, H.G., Armitage, G., 1933. Intracranial tuberculomas. J. Pathol. Bacteriol. 37, 461–471. Harder, E., Al Kawi, M.Z., Carney, P., 1983. Intracranial tuberculoma, conservative management. Am. J. Med. 74, 570–576. Jinkins, J.R., 1991. Computed tomography of intracranial tuberculosis. Neuroradiology 33, 126–135. Lees, A.J., MacLeod, A.F., Marshall, J., 1980. Cerebral tuberculomas developing during treatment of tuberculous meningitis. Lancet 1, 1208–1211. Maurice-Williams, R.S., 1972. Tuberculomas of the brain in Britain. Postgrad. Med. J. 48, 678–681. Sheller, J.R., Des Prez, R.M., 1986. CNS tuberculosis. Neurol. Clin. 4, 143–158. Sotelo, J., Escobedo, F., Rodriguez, M. et al., 1984. Therapy of parenchymal brain cysticercosis with praziquantel. N. Engl. J. Med. 310, 1001–1007. Teoh, R., Humphries, M.J., O’Mahony, S.G., 1987. Symptomatic intracranial tuberculoma developing during treatment of tuberculosis. A report of 10 patients and review of the literature. Q. J. Med. 63, 449–460. Vengsarkar, U.S., Pisipaty, R.P., Parekh, B., Panchal, V.G., Shetty, M., 1986. Intracranial tuberculoma and the CT scan. J. Neurosurg. 64, 568–574.