Contributed by Julia C. Kuehn MD1, Angelika Scheuerle MD2, Jan Bauer MD3, Albert J. Becker MD1, Rainer Wirtz MD4, Jan Lewerenz MD5,*
Departments of 1Neuropathology, Section for Translational Epilepsy Research, University of Bonn Medical Center, Bonn, Germany,
2Neuropathology, Bezirkskrankenhaus GŁnzburg, GŁnzburg, Germany,
3Neuroimmunology, Center for Brain Research, Vienna, Austria,
4Departments of Neurosurgery and
5Neurology, Ulm University, Ulm, Germany
A 64-year-old Caucasian male patient presented with a three-month-history of episodes with visual disturbances and tingling sensations of the left side of his body to a department of neurology. In addition, within the last three weeks preceding the admittance several episodes of irresponsiveness had occurred, in which the patient had paused with eyes open, followed by short-lived aphasia. The patient and his spouse did not report memory deficits beyond these episodes. Neurological examination did not reveal any abnormalities. Cerebral MRI showed FLAIR hyperintensity and slight swelling of the left hippocampus (Figure 1A). 18F-DOPA positron emission tomography showed increased uptake of the medial aspects of the lesion (Figure 1B). T1-weighted images prior and after administration of gadolinium showed contrast enhancement of the same region (Figure 1C/D) EEG showed left frontotemporal slowing. Cerebrospinal fluid (CSF) analysis was normal. Routine laboratory results were inconspicuous with exception of hyponatremia (127 mmol/l). The diagnosis of symptomatic temporal lobe epilepsy as result of the left temporal lesion, most possibly representing a high-grade glioma, was made, surgical resection was suggested and an anticonvulsive therapy with levetiracetam was initiated. After discharge, the patient presented to our Department of Neurosurgery asking for a second opinion. A resection of the lesion was suggested and performed three months after the first symptoms. Post surgery, the patient did not develop new neurological deficits and was sent to rehabilitation. Here, the patient developed frequent complex-partial seizures followed by right-sided hemiparesis, disorientation, long-lasting somnolence and severe memory disturbances. Six months after the initial symptoms, the patient was admitted to our Department of Neurology. Repeated cerebral MRI showed status after resection of the left hippocampus. EEG showed severe generalized slowing, while CSF again was normal.
In H&E stained sections adjacent to the hippocampal formation the cellularity was increased by astrocytes with large cytoplasm and accompanying macrophages and lymphocytes (Figure 2 A/B). Immunostaining with antibodies against glial fibrillary acidic protein (GFAP) revealed numerous GFAP-positive cells with isomorphic, reactive rather than pleomorphic fibrillary morphology (Figure 2C). These cells did not stain positive for MAP2 in favor of a reactive rather than neoplastic process (not shown). No increased mitotic activity, vascular proliferates or necrosis were present. In addition, molecular pathology did not reveal isocitrate dehydrogenase mutations. CD8+ cytotoxic T lymphocytes, some directly adjacent to neurons (arrows / insert) were detected (Figure 2D). Occasional CD138+ plasma cells were mostly localized perivascular as well as sparsely distributed in the parenchyma (Figure 2E). Abundant CD68+ activated microglia cells were found in the limbic structures (Figure 2F). Lymphocytic clusters were clearly restricted to grey matter areas (black asterisk) (Luxol fast blue, Figure 2G). In H&E staining (Figure 2A) as well as NeuN immunohistochemistry (Figure 2H) showed reduced neuronal density, especially in CA4 (asterisks), whereas granule cells (arrows) of the dentate gyrus were spared (Figure 2A/H). Several substantially damaged neurons with hypereosinophilic cytoplasm and pyknotic nuclei (arrow heads) were found (Figure 2A). Some neurons showed substantial deposition of complement C9neo (end complex; arrows) (Figure 2I).