Restricted Diffusion of Pus in the Subarachnoid Space: MRSA Meningo-Vasculitis and Progressive Brainstem Ischemic Strokes – A Case Report

Extra-axial restriction on diffusion weighted imaging (DWI) is an unusual finding on brain magnetic resonance imaging (MRI). Intra-axial restriction on DWI, however, is common, and can represent brain parenchymal infarction, tumor, abscess, or toxic-metabolic process. The infrequency of extra-axial DWI restriction and the paucity of clinico-pathological correlation in the literature limit its differential diagnosis. Scant case reports suggest that extra-axial DWI restriction could be a lymphoma, neurenteric cyst, or, in one patient, subdural empyema [1,2,3]. We postulate that pus formation must be excluded first, because it can provoke an aggressive meningo-vasculitis with rapidly fatal, intra-axial infarctions. Our patient was a 45-year-old man, presenting to our hospital with left facial droop and right (contralateral) arm and leg weakness. Initial MRI revealed DWI restriction in the left lateral pons, consistent with a classic Millard-Gubler stroke. Also noted was a subtle, extra-axial area of curvilinear diffusion restriction in the left cerebellar-pontine angle's subarachnoid space. Days later, the patient had a headache, and repeat MRI revealed extension of the two DWI lesions – both the intra-axial pontine infarction and the extra-axial area of restricted diffusion in the subarachnoid space. The patient became comatose, a third MRI revealed more extensive DWI restrictions, and he expired despite aggressive care. Autopsy revealed massive brainstem infarcts, a thick lymphoplasmacytic infiltrate, copious Gram-Positive cocci (likely MRSA) and arteries partially occluded with fibrointimal proliferation. This emphasizes the concept that extra-axial DWI restriction can represent pus development in the subarachnoid space – a radiographic marker to identify a patient at risk for demise due to septic, meningo-vasculitic infarctions

Blood‐brain barrier abnormalities in acquired immunodeficiency syndrome: Immunohistochemical localization of serum proteins in postmortem brain

Abnormalities in the blood‐brain barrier (BBB) may be important in mediating some of the tissue damage that accompanies human immunodeficiency virus (HIV) infection of the brain, as well as in facilitating viral entry into the central nervous system. Accordingly, immunohistochemical detection of fibrinogen (FIB) and immunoglobulin G (IgG) was used as a marker of vascular permeability in formalin‐fixed, paraffin‐embedded brains of patients with acquired immunodeficiency syndrome (AIDS) who had HIV encephalitis (HIVE) (n = 17) and those who did not have HIVE (n = 16); nonimmunosuppressed patients served as control subjects (n = 22). The sex ratios and postmortem intervals were similar in all groups (p < 0.05), but the age of the two AIDS groups were younger than the control group (43.2 and 40.9 versus 62.5 yr; p < 0.05). The two AIDS groups had higher immunostaining for FIB and IgG than the control group (p < 0.001 and p < 0.0001, respectively) but did not differ from one another. Furthermore, the two AIDS groups had a significantly higher incidence of combined extravasation of both FIB and IgG, whereas the control group had a significantly higher incidence of negative staining for both proteins (p < 0.002). More than 95% of the microglial nodules of HIV were negative for serum proteins; however, all focal lesions with tissue necrosis, including lymphoma, opportunistic infections, and HIV (rarely), contained extravasated serum proteins. These results indicate that a diffuse BBB leak is present in approximately 50% of all patients with AIDS at the time of autopsy and may be seen in the absence of any other brain pathology, including HIVE. In contrast, focal lesions, including those of HIVE, are associated with BBB changes only when necrosis is present. The pathogenesis of the diffuse leak is unknown but may be related to circulating cytokines. Diffuse BBB breakdown may contribute not only to facilitated viral entry into brain, but also to the diffuse myelin pallor and gliosis common to all patients with AIDS

Angioblastic meningioma with hepatic metastasis

Infrequently, intracranial neoplasms metastasize to extracranial sites. In 1963, Glasauer and Yuan reviewed the 88 reported cases of metastatic intracranial tumours of which approximately two-fifths were meningiomas. This report concerns an angioblastic meningioma with a large hepatic metastasis. Cushing's original classification of angioblastic meningiomas and the differential diagnosis between these tumours and the haemangiopericytoma and cerebellar haemangioblastoma are discussed

Ultrastructure and biochemistry of sympathetic ganglia in idiopathic orthostatic hypotension

The role of transsynaptic dysfunction in the pathogenesis of idiopathic orthostatic hypotension (IOH, or idiopathic autonomic insufficiency) was examined microsocopically and biochemically in autopsy specimens. Light microscopy of the sympathetic ganglia showed abnormalities in all 4 IOH patients, including focal phagocytosis of neurons, increased numbers of satellite cells, and perivascular lymphocytic infiltrates. Electron microscopy revealed proliferation and hypertrophy of satellite cells and abnormalities in the unmyelinated axons. In constrast, the spinal cord intermediolateral columns, containing the presynaptic neurons, were unremarkable in 1 patient, exhibited only mild gliosis in another, and showed neuron loss and fibrillary gliosis in 2 patients. Postsynaptic dopamine‐β‐hydroxylase (DBH) activity was decreased at least fourfold (p < 0.02) in sympathetic ganglia of patients with IOH, while tyrosine hydroxylase (T‐OH) was normal. Ganglion choline acetyltransferase (ChAc) activity, an index of presynaptic function and integrity, was normal in the IOH group. A number of our observations suggest that presynaptic disease is not an absolute requirement for adrenergic abnormalities in IOH. The intermediolateral columns of the spinal cord were histologically normal in 2 of the patients with IOH, and ultrastructural abnormalities in sympathetic ganglia were consistent with primary adrenergic degeneration. In addition, presynaptic ChAc activity was normal in IOH ganglia, whereas postynaptic DBH activity was depressed. Finally, postsynaptic T‐OH activity, which is regulated by transsynaptic mechanisms, was normal in IOH ganglia

Idiopathic myelopathies with white matter vacuolation in non-acquired immunodeficiency syndrome patients

Postmortem examination of 21 patients showed a vacuolar myelopathy resembling that associated with the acquired immunodeficiency syndrome. Underlying diseases included six cases of leukemia or lymphoma, five of carcinoma, three of systemic lupus erythematosus, two of chronic lung disease, and one each of cadaveric renal transplant, cirrhosis, diabetes, hemophagocytic syndrome, and viral encephalitis. Fourteen patients were on long-term steroid therapy and 10 of these also had immunosuppressive chemotherapy. No patient had the acquired immunodeficiency syndrome, although one received blood transfusions in 1978. Signs and symptoms consistent with myelopathy included paraparesis in seven patients, ataxia in one, and bilateral extensor plantar reflexes in one. Microscopic examination showed vacuolation in spinal cord white matter primarily located in posterior and lateral columns. Lipid-laden macrophages and axonal changes were proportional to the severity of the vacuolation, which was severe in five patients, moderate in 10, and mild in six. Eight patients had coexistent viral diseases elsewhere in the central nervous system, but viral-associated antigens or genomic material was not found in regions of vacuolated spinal cord white matter. Although the etiology of these myelopathies is unknown, their association with immune suppression and coexistent viral infection of the central nervous system suggests that an opportunistic viral infection may be important

Relationship between ischemia and ischemic neuronal necrosis to astrocyte expression of glial fibrillary acidic protein

It is not entirely clear whether the proliferative changes in astrocytes following cerebral ischemia are in response to neuronal injury or are secondary to the direct effects of ischemia on the astrocytes. Therefore, the following study examined the relationship between post‐ischemic astrocytosis with the extent of neuronal necrosis and the severity of the ischemia. Astrocyte reactivity was assessed by alterations in glial fibrillary acidic protein (GFAP), using immunohistochemistry and evaluation by optical density analysis. Cerebral ischemia was produced in rats by temporary occlusion of the carotid and vertebral arteris for 2,10 and 30 min. This results in damage to the CA1 neurons after a characteristic delay of several days, the duration of which is inversely proportional to the severity of the ischemia. CA3 neurons are resistant to the ischemia and do not suffer permanent injury. The results showed that GFAP immunoreactivity significantly increased in the CA1 region after all three ischemic intervals but the rise of GFAP in the CA3 area reached significance only after 30 min of ischemia. The peak and duration of the GFAP increases thus correlated with the extent and the maturation of the neuronal necrosis. This suggests that with mild injury (2 and 10 min ischemia), post‐ischemic astrocytosis is closely related to its neuronal environment rather than to the ischemic insult itself. Furthermore, the results showed an initial decrease in and delay of the subsequent GFAP rise. This initial decline in GFAP and the delay in its rise have both been identified in other models of brain injury and may be related in part to transient astrocyte swelling as well as to a finite interval required for sufficient increases in transcriptional activity to affect a noticeable rise in GFAP immunoreactivity

Isolated cerebral mucormycosis: Report of a case and review of the literature

Isolated cerebral mucormycosis is a rare but life-threatening infection that generally occurs in patients with intravenous drug abuse or immune deficiency. We report a case of primary cerebral mucormycosis in a healthy adult. Whole body autopsy in this case revealed cerebral mucormycosis with prominent vascular pathology and hemorrhagic necrosis. No nasal sinus, orbital or other primary locus of fungus infection was discovered. Review of the previously reported 30 cases of isolated cerebral mucormycosis revealed associated systemic predisposition in 11 patients and history of intravenous drug abuse in 17 cases. In the remaining two cases, the diagnosis of fungal infection was made only after surgical exploration. Early tissue diagnosis and the consequent surgical excision of the necrotic tissue and aggressive antifungal therapy might salvage life in this fatal condition