Contributed by Fabio Rogerio, MD, PhD1, Luciano de Souza Queiroz, MD, PhD, Fabiano Reis, MD, PhD, Aya Fukuda, MD, Nivaldo Adolfo Silva Junior MD, Andrei Fernandes Joaquim MD, PhD
DIAGNOSIS
Neurotuberculosis with parenchymatous acute arteritis and cortical infarction.
DISCUSSION
This case caused considerable diagnostic difficulty. Among the possibilities we considered based on neuroimaging features were a neoplasm, possibly lymphoma, and granulomatous disease, by fungi such as cryptococcosis, paracoccidioidomycosis or by other agents, including syphilis and toxoplasmosis. Non infectious, granulomatous inflammation was also raised, particularly sarcoidosis and angiitis (Wegener's disease). The absence of basal leptomeningitis did not favor chronic infection.
Stereotaxic biopsy itself was challenging as the lesions were deep seated and only very small fragments were obtained. The fortunate finding of granulomas in one minute sample demonstrated the infections nature of the disease. The other fragments, unexpectedly, yielded non specific necrotizing inflammation in which fibrinoid vasculitis with thrombosis was prominent, but no granulomas. The final diagnosis was established by the positivity for acid-fast bacilli on Ziehl-Neelsen stain.
Tuberculosis came as a surprise as there was no indication of lung disease, chronic meningitis elsewhere and by the fact that bacilli were found only in necrotic tissue, not in granulomas. We presume that the vascular pathology was an immune-mediated allergic reaction, rather than the classical pathophysiological process associated with tubercle bacilli with production of epithelioid and Langhans giant cells. In this context it has been hypothesized that upon brain invasion, tubercle bacilli may reside at least initially in endothelial cells of the microvasculature, thus eliciting an inflammatory reaction towards vascular structures (1).
The clinical and pathological picture we describe here appears to be extremely rare. We were able to obtain only a single case in the literature (2) in a 37 year old man receiving prednisone and indomethacin for treatment of Still's disease. M. tuberculosis was demonstrated in CSF cultures and a necrotizing vasculitis was found in cerebral arterioles at post mortem examination, including bacilli invading vascular walls.
An unusual feature of the present case was the topography of the lesions, which were nearly symmetrical, centered in the midline, involving the corpus callosum and cingulate cortex. The common sites of tuberculosis involvement include the basal leptomeninges and large cerebral blood vessels. Vasculitis of the internal carotid and basilar arteries, as well as the middle cerebral arteries lead to infarctions of whole vascular territories. In our patient the lesions as seen on MRI did not fit into a vascular territory, though they were localized to the anterior cerebral arteries. Further, the lesions affected basically small cortical arteries and veins rather than larger branches. It is reported that in tuberculous infection, cortical and subcortical white matter can also be affected, most commonly with HIV co-infection (4). However, our patient is HIV negative.
The necrotizing nature of the vascular lesions differed from the far more common proliferative endarteritis caused by chronic infectious cerebral diseases. It is described in tuberculous meningitis, affecting both small arteries and veins (3). In the present case however the lesions were situated in the cerebral cortex itself, as documented by the presence of necrotic neurons nearby. It appears that this kind of vascular injury was of importance in the MRI appearances, as it disrupted the blood brain barrier causing widespread edema of the neighboring white matter and discrete contrast enhancement of the lesions.
The present case appears to be unique as regards the site and histological nature of the tuberculous lesions and illustrates the many facets that this ever present infection may assume.
REFERENCES
Contributed by Fabio Rogerio, MD, PhD1, Luciano de Souza Queiroz, MD, PhD, Fabiano Reis, MD, PhD, Aya Fukuda, MD, Nivaldo Adolfo Silva Junior MD, Andrei Fernandes Joaquim MD, PhD
International Society of Neuropathology