untitled Introduction Intracranial tuberculosis is an important cause of morbidity and mortality in developing countries where tuberculosis is endemic.1 In the central nervous system tuberculosis manifests as cerebritis, cerebral abscess, tuberculoma, and tubercu- lous meningitis (TBM).1-5 TBM is thought to arise from cerebrospinal fluid (CSF) seeding of a ruptured pial or subependymal granuloma.2-5 Tuberculomata result from haemato- genous dissemination and histologi- cally are granulomas with central areas of caseous necrosis.2-5 Tuberculomata may develop whilst patients are on treatment for TB.6 The co-occurrence of intracranial tuberculoma and TBM is well recog- nized.2-5 Medical therapy is effective for both forms, with a high cure rate in TBM, and a regression in size of the lesion with improvement of neuro- logical deficit in tuberculoma.1-6 Deterioration in patients with TBM is caused by the development of obstructive hydrocephalus or cerebral infarction on the basis of endarteri- tis.1-7 Deterioration in patients with tuberculoma may result from para- doxical expansion of the lesion, poor treatment compliance, and postulated haemorrhage into the tuberculoma.5,6 Intracranial haemorrhage as a com- plication of TBM has been described, albeit rarely.8-16 There are a few case reports of patients with TBM compli- cated by intraventricular, intracerebral and subarachnoid haemorrhage on an aneurysmal or non-aneurysmal basis.8-16 We describe here a patient with TBM and an associated left cerebellar tuberculoma who suddenly deterio- rated and died on treatment. A large haemorrhage involving the right cere- bellum, with subarachnoid extension was demonstrated on computed tomography (CT) scan of the brain and at postmortem. These findings are discussed with respect to the pos- sible mechanism/s of haemorrhage in intracranial tuberculosis. Case report A 22-year-old black female patient presented with headache, drowsiness and disorientation. Clinically she had marked neck stiffness, multiple cra- nial nerve palsies (right third and sev- enth, bilateral sixth), and bilateral pyramidal tract signs. Fundoscopy was normal. The patient was HIV- negative. CSF analysis revealed a protein of 5 g/100 ml, 81 lymphocytes per ml, 3 neutrophils per ml, glucose of 1.9 mmol/l and a positive TB enzyme-linked immunosorbent assay (ELISA). CT scan of the brain showed a left cerebellar ring-enhancing mass lesion abutting the adjacent brain- stem, hydrocephalus with obstruction at the fourth ventricle, and increased basal meningeal enhancement (Fig. 1a). A diagnosis of TBM with left cere- bellar tuberculoma and obstructive hydrocephalus was made. Oral anti- tuberculous therapy (4-drug regi- men) was commenced. Gradual clini- cal improvement was noted with complete resolution of the sixth nerve palsies and partial resolution of the right third and seventh nerve palsies. Serial fortnightly CT scans revealed diminishing diameter of the tubercu- loma, and resolution of the hydro- cephalus. Approximately 9 weeks after com- mencing anti-tuberculous therapy, the patient developed a sudden severe generalised headache and became comatose. A CT scan of the brain revealed a large haemorrhage in the right cerebellar hemisphere with extension into the brainstem and the subarachnoid space (Fig. 1b). The patient died shortly thereafter. CASE REPORT 16 SA JOURNAL OF RADIOLOGY • July 2005 Haemorrhage in intracranial tuber- culosis M Modi FCRad (SA), MMed Department of Radiation Sciences University of the Witwatersrand Johannesburg A Mochan FCP (SA) G Modi PhD (Lond), FCP (SA), FRCP (Lond) Department of Neurosciences University of the Witwatersrand Johannesburg M J Hale FCPath (SA) Department of Anatomical Pathology University of the Witwatersrand Johannesburg 16-18pgs 9/28/05 9:21 AM Page 16 Autopsy findings Examination of the cranial con- tents revealed extensive subarachnoid haemorrhage overlying the brainstem on the right extending caudally to involve the right cerebellum and obscuring the Circle of Willis. A lep- tomeningitis was present. A 10 mm tuberculoma was found in the left cerebellar hemisphere. Examination of the left vertebral artery showed sev- eral small white nodules (granulo- mas) on the adventitia running along its length. Microscopically, the meninges showed a florid granulomatous inflammatory reaction with caseous necrosis, epitheloid histiocytes, and cuffing by lymphocytes and plasma cells. The left vertebral artery and many of the meningeal arteries and arterioles showed pronounced intimal proliferation and endarteritis obliter- ans associated with fibrin platelet thrombus and total vascular occlu- sion. A striking feature seen in some vessels was fragmentation and loss of the internal elastic lamina (Fig. 2). This occurred in areas of the vessel wall where granulomatous inflamma- tion (Fig. 2, arrow) was present in the adventitia. A specific site of origin for the subarachnoid haemorrhage was not identified. The lesion in the left cerebellar hemisphere showed histopathological features of a tuber- culoma and was surrounded by a moderate degree of perilesional oede- ma. Discussion Intracranial haemorrhages sec- ondary to or in association with TBM have been ascribed to aneurysmal rupture following the formation of mycotic aneurysms, or to non- aneurysmal rupture as a consequence of weakening of the vessel wall by the granulomatous inflammation.8-16 In terms of the latter it has been pro- posed (but to date not pathologically proven as far as we are aware) that the granuloma produces disintegration of a vessel wall with resultant haemor- rhage.13 Tuberculoma in association with an A-V fistula causing haemor- rhage has also been described.17 In our patient at autopsy we found numerous deficiencies in the internal elastic lamina of the meningeal blood vessels in addition to the expected intimal proliferation and endarteritis obliterans with fibrin platelet throm- bus and vascular occlusion. The defi- ciencies or fragmentations of the internal elastic lamina were found in areas of the vessel wall where granulo- matous inflammation was present, providing the pathological evidence for the proposed mechanism of non- aneurysmal haemorrhage in patients with TBM. The granuloma in the adventitia invades and gradually weakens the vessel wall leading to dis- integration as represented by the frag- mentation of the internal elastic lami- na seen in our case, with or without mycotic aneurysm formation and consequent rupture. The pathological process describ- ed in the meningeal vessels is akin to that which occurs in the pulmonary circulation with pulmonary tubercu- losis except that in the pulmonary ves- sels the chronic granulomatous infil- trate not only causes inflammatory disintegration of the wall but leads to aneurysm formation as described by Rasmussen.18 Rupture of the aneurysm results in pulmonary haemorrhage and haemoptysis. In the CASE REPORT 17 SA JOURNAL OF RADIOLOGY • July 2005 Fig. 1a. CT scan of the brain (post intravenous contrast) in a patient with tuberculous meningi- tis demonstrating a left cerebellar enhancing lesion abutting the adjacent brainstem (tuber- culoma); increased basal meningeal enhance- ment and obstructive hydrocephalus with associated subependymal oedema. Fig. 1b. CT scan of the brain (non-contrast) demonstrating a large right-sided cerebellar haemorrhage with extension into the adjacent brainstem and subarachnoid space. Fig. 2. Photomicrograph showing a medium- sized artery exhibiting fragmentation and loss of the internal elastic lamina accompanied by granulomatous inflammation in the adventitial tissue (arrow). (H&E – original magnification x 100). 16-18pgs 9/28/05 9:21 AM Page 17 brain we propose that this process results in haemorrhage in the intrac- erebral, intraventricular, and sub- arachnoid spaces. Our case highlights intracranial haemorrhage as a potential additional cause of death in TBM. Treatment would require search for an aneurysm if patients survive. This has been reported previously.15 The use of steroids in our patient to prevent or reduce the inflammatory response and the accompanying vasculitis is contentious. Had the patient been treated with steroids from the outset, is it possible that the disintegration of the internal elastic lamina by the inflammatory process would not have occurred and the consequent rupture with haemorrhage could have been prevented. A Cochrane database review concluded that adjunctive steroids might be of benefit in patients with TBM, but the evidence is incon- clusive.19 References 1. Karstaedt AS, Valtchanova S, Barriere R, Crewe- Brown HH. Tuberculous meningitis in South African urban adults. QJM 1998; 91: 743-747. 2. Gray F, Nordmann P. Bacterial infections. In: Graham DI, Lantos PL, eds. Greenfield’s Neuropathology. 6th ed. Vol 2. 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