A 45-year-old right-handed man, with a history of HIV (and a CD4+ T-cell count of 556, not on anti-retroviral medications), presented to our hospital one day after he had noticed the acute onset of horizontal diplopia, weakness of his left face and right (contralateral) arm and leg – hemiparesis alternans. His history, vital signs, and physical exam were otherwise unremarkable. Results of routine laboratory tests were within normal limits. His initial MRI (fig. , top) revealed FLAIR signal hyperintensity and restriction on diffusion weighted imaging (DWI) in the left pons, indicative of an acute ischemic stroke that is clinically compatible with the Millard-Gubler syndrome. On this same MRI, but slightly more caudal (fig. , bottom), note was made of a subtle, extra-axial, curvilinear, high-signal abnormality on FLAIR, which was also evident on T1, had a high signal intensity on DWI and a matching low signal on apparent diffusion coefficient (ADC) – compatible with diffusion restriction in the subarachnoid space – in the cistern adjacent to the left pons and cerebellum (fig. , red arrows). The etiology of this extra-axial, curvilinear entity was unclear at that time. Concurrent MRA was unremarkable.
Fig. 1 On MRI (top panel), a focal left pontine intra-axial infarct is seen as a high FLAIR signal (left) and DWI restriction (right). Slightly more caudal on this same MRI (bottom panel), there is seen a subtle, extra-axial, curvilinear, FLAIR (upper left) (more ...)
The patient was admitted to the neuroscience intensive care unit, where cardiac telemetry displayed sinus tachycardia, and transthoracic (followed by transesophageal) echocardiography revealed a normal ejection fraction, valves, and chambers, without clot, vegetation, patent foramen ovale or septal defect. Because of his young age (>55) and lack of ‘traditional’ stroke risk factors such as hypertension, diabetes, or heart disease, a hypercoagulable serum panel was ordered. It included anticardiolipin antibodies, lupus anticoagulant, protein C and S levels, anti-thrombin III, fibrinogen, factor VIII, prothrombin 20210, homocystine, lipoprotein (a), and sickle cell screen. All of these tests were negative or within normal limits.
During this stroke workup, the patient gradually developed a severe headache, progressing over a few days with meningismus and stupor. Lumbar puncture revealed an opening pressure of 230 mm H2O, with 250 red blood cells, 75 white blood cells (79% neutrophils), glucose of 80, and protein of 54.
Opportunistic infections such as Cryptococcus, tuberculosis, and syphilis were ruled out, despite low suspicion due to his relatively preserved CD4 count of 556. Acid-fast bacilli test for tuberculosis was negative in his serum and cerebro-spinal fluid (CSF), as was his PPD, and several chest X-rays did not reveal any suspicious lesions, granulomatous or otherwise. The RPR, VDRL, and FTA-ABS tests for syphilis were all non-reactive in his serum and CSF, polymerase chain reaction (PCR) for DNA of Herpes simplex virus 1 and 2, cytomegalovirus and varicella-zoster virus (VZV) were negative in his CSF, and there were no dermatomal vesicles suggestive of VZV anywhere on his body. However, seeping, pustular furuncles, discovered on his knees, were cultured, and grew out methicillin-resistant Staphylococcus aureus (MRSA). Blood cultures also became positive for MRSA and intravenous vancomycin was started.
A second MRI of his brain (fig. , top) showed extension of intra-axial FLAIR signal hyperintensities with diffusion restriction now seen in the bilateral pons and left cerebellum, indicating both new and exacerbating cerebral infarctions. The more caudal subarachnoid space DWI restriction (fig. , bottom) was no longer subtle – increasing in size and expanding more curvilinearly into the left posterior fossa. Communicating hydrocephalus developed, with effacement of the fourth ventricle, dilation of the lateral and third ventricles, and CSF trans-exudation. Another lumbar puncture was performed and it revealed 4 red blood cells, 112 white blood cells (74% neutrophils), glucose of 130, and protein of 2,126. High-dose, broad-spectrum antibiotics (vancomycin, ceftriaxone, and ampicillin) were utilized, along with aggressive intravenous fluids, pressor agents, ventriculostomy, and other supportive care measures. Nevertheless, the patient continued to deteriorate and became comatose. A third and final MRI of his brain was performed (fig. ) which showed marked diffusion restriction and hyperintense FLAIR signals that had spread from the initial extra-axial area into the brainstem parenchyma, encompassing the entire pons, medulla, and left cerebellum. The repeat MRA revealed irregularity and narrowing of the entire vertebro-basilar circulation, including lack of flow-related enhancement in the left vertebral artery and portions of both posterior cerebral arteries (fig. ). The patient soon expired.
Fig. 2 Repeat MRI (top panel) revealed fourth ventricle effacement and infarct extension into the brainstem and cerebellum on FLAIR (left) and DWI (right). On this same MRI (bottom panel), the previously subtle cerebello-pontine angle signal has increased in (more ...)
Fig. 3 A third and final MRI revealed considerable disease progression with marked increase in size of signal abnormalities on FLAIR (upper left) and T1 (upper right) in the brain parenchyma itself. In the subarachnoid space, pons, medulla and cerebellum, the (more ...)
Fig. 4 MRA initially appeared unremarkable (a), but later it appeared vasculitic (b) in the basilar and posterior cerebral arteries, with left vertebral artery dropout. Autopsy revealed patency of the basilar, posterior cerebral and cerebellar arteries (c) but (more ...)
At autopsy, the brain weighed 1,212 g. The basilar artery, posterior cerebral arteries and cerebellar arteries were mostly patent on gross examination (fig. ) but variable arteritis, thick lymphoplasmocytic infiltration, and partial large- and small-vessel occlusion (due to fibrointimal proliferation) were seen on high-power light microscopy (fig. ). The basilar meninges were thickened and contained white purulent material (fig. ) and most of the inferior brainstem and left cerebellum showed recent non-hemorrhagic infarcts. Inflammation and vasculitis also were noted in the cervical spinal cord leptomeninges. Additional gross findings included moderate dilatation of the lateral and third ventricles and aqueduct along with moderate compression of the fourth ventricle. Gram and GMS stains showed copious Gram-Positive cocci (GPC) in chains (fig. ), most likely the same bacteria – MRSA – that grew in the blood and furuncles. Unlike the GPC in the blood and furuncles, however, the GPC in the brain were not amplifiable for MRSA because there were not enough microorganisms with viable DNA, a common post-mortem phenomenon. Broad-spectrum antibiotic use during hospitalization also probably prevented more precise speciation. Nevertheless, paraffin block extraction and PCR testing at autopsy identified housekeeping genes coding for constitutionally expressed beta-globin cell maintenance proteins.
Base of brain gross autopsy reveals basilar meningitis that partially obscures pontine circumferential arteries (arrow). Recent, severe necrosis of the left cerebellar hemisphere (star) and pons is seen.
In the pons, copious Gram-Positive cocci in clusters (arrow), macrophage infiltrates, and capillary proliferation were seen on post-mortem microscopy.