A previously healthy 23-year-old man presented with fever, occasional headache and vomiting since 4 days, one episode of generalized tonic clonic seizures 2 days prior to admission to the hospital followed by altered sensorium and left sided weakness. At admission to the neurological services, he was afebrile, not opening eyes to painful stimuli. Neurological examination revealed Glasgow Coma Scale (GCS) of 7/15, E1V2M4 with left hemiparesis. Both pupils were asymmetric and not reactive to light. The extraocular movements were restricted and ocular fundus revealed blurring of disc margins. Deep tendon reflexes were brisk and plantar response was extensor on the left and flexor on the right side. Routine hematological and biochemical parameters were normal. The serological tests for HIV, HBsAg, homocysteine, rheumatoid factor and antinuclear antibody were negative. Antemortem cerebrospinal fluid (CSF) analysis could not be done as lumbar puncture was clinically contraindicated. Electrocardiogram showed T wave depression in V1-V4 leads. Chest X-ray revealed inhomogeneous opacities in the left mid and lower zones with bilateral hilar prominence.
Cranial computed tomography (CT) scan highlighted hemorrhagic lesion in the right thalamus and right medial temporal lobe with multiple cerebral and cerebellar ring enhancing lesions. MRI brain [Figure 1a-e] revealed heterogeneous mixed signal intensity changes in the right thalamus, caudate, medial temporal region suggestive of hemorrhagic infarct with extensive perilesional edema extending into right internal and external capsules and corona radiata. The lesions bloomed on flash 2D sequences suggesting accumulation of paramagnetic substance, due to evolving hemorrhage. Lesions which were iso to hyper intense on T1WI and predominantly hypo intense on T2WI (T2 shortening) were noted in the right cerebral peduncle of midbrain suggestive of tuberculoma. Diffusion weighted imaging (DWI) revealed hyper intensity in the right thalamus, medial temporal and midbrain (facilitated diffusion) and hypo intensity in pons (restricted diffusion). Hemorrhage was extending into the lateral ventricle in both the occipital horns. The third and lateral ventricles were dilated with minimal periventricular hyper intensity suggestive of uncompensated hydrocephalus. Multiple rounded lesions iso intense on T1 and hypo intense on T2WI suggesting tuberculous granulomas were noted in the left side of pons, bilateral parasaggital basifrontal zones and left postero medial parietal lobe. There was diffuse sulcal hyper intensity on fluid-attenuated inversion recovery imaging (FLAIR) images suggestive of meningitis. MR venogram revealed non-visualization of the bilateral internal cerebral veins, vein of Rosenthal, vein of Galen and proximal segment of straight sinus and left transverse sinus (images are not available for documentation).
A diagnosis of pulmonary tuberculosis with multiple intracranial tuberculomata and thrombosis of cerebral deep venous system was made. Possibility of cerebral toxoplasmosis was also considered in view of multiple ring enhancing lesions. He received both antituberculous and antitoxoplasma chemotherapy with folinic acid for 5 days. He succumbed on the 6th day of admission to the hospital. Smear from the basal exudates of the brain revealed acid fast organisms by Ziehl-Neelsen stain. Serum and CSF samples collected at autopsy were negative for IgG/IgM antibody to Mycobacterium tuberculosis, Toxoplasma gondii and Cysticercosis.
Autopsy confined to the examination of the brain only was conducted 18 h postmortem with informed consent of close relatives. The brain weighed 1200 g and was edematous. Dural venous sinuses and superficial anastomotic veins were patent. The leptomeninges were hazy and had occasional tubercles in the parietal area along the course of the veins. The base of the brain had thick hemorrhagic exudate filling the chiasmatic, interpeduncular and pontine cisterns extending to foramen of Lushka, entrapping the cranial nerves and cerebral vessels. The internal carotid and vertebro basilar system were patent with no evidence of atherosclerosis. The crus cerebri on the right was necrotic and hemorrhagic dissecting down from the thalamus to midbrain and the medial temporal lobe on the right was softened. Bilateral cerebellar tonsilar herniation was noted, in spite of mega cisterna magna. On slicing the brain small tuberculomata were found in the left parietal cortex, pons and cerebellum corresponding to lesions on imaging. The right thalamic nucleus, internal capsule, putamen, hippocampus and right half of splenium of the corpus callosum showed hemorrhagic softening, rupturing into the third and lateral ventricle and extending down. The pons and medulla oblongata were enclosed in hemorrhagic inflammatory exudates. At the lower pontine tegmentum and along the foramina of Lushka on both sides, close to choroid plexus tiny tuberculomas were seen in the cerebellum. On the surface the pontine and cerebellar veins were found thrombosed and enclosed in the exudate [Figure 1f-i].
The histological examination of the representative neuroanatomical areas revealed multiple tuberculomas with caseous necrosis, perilesional edema and reactive astrocytosis. Small venous channels draining into the pontomesencephalic veins and the cerebellar veins were found thrombosed and enclosed in tuberculous inflammatory exudates. Similar to arteries, some of the small veins revealed granulomatous phlebitis. The topographic distribution of hemorrhage lesions correspond to the venous drainage area of basal vein of Rosenthal, anterior and posterior mesencephalic veins. The transverse pontine veins, the retrotonsilar veins of the cerebellum and segment of internal cerebral veins and thalamo-striate veins bilaterally but asymmetrically revealed tuberculous thrombophlebitis along with arteritis of the small perforator vessels, thus highlighting the hemorrhagic lesions and masking the small arterial ischemic lesions. Though the tuberculomas indicate chronic pathology, the acute phlebitis suggests an acute exacerbation of an immune complex mediated granulomatous pathology (Theortical possibility of immune reconstitution secondary to ATT needs to be considered).