Metachronous, multicentric giant cell tumor of the sphenoid bone with histologic, CT, MR imaging, and positron-emission tomography/CT correlation.

Giant cell tumor (GCT) of the sphenoid bone is a relatively rare entity and metachronous multicentric GCT of the sphenoid is even rarer; we are aware of only 3 previous cases in the literature. We describe here a tumor of the sphenoid bone that was identified 15 years after multiple resections of a GCT of the left inferior pubic ramus. Correlation is made between the histopathologic findings, MR imaging of the brain, CT of the head, and fusion positron-emission tomography (PET)/CT scan performed with fluorine-18 fluoro-2-deoxy-D-glucose (18F-FDG). This report is the first to describe the appearance of a GCT of the sphenoid bone on a fusion PET/CT examination. High metabolic activity in the base of the skull adjacent to the middle cranial fossa was demonstrated in a fashion similar to that of the known pelvic lesion. This case also demonstrates that the increased metabolic activity seen in a GCT of the sphenoid bone may be partially obscured by the adjacent physiologic high metabolic activity of the brain.

Inflammatory myofibroblastic tumor of the orbit with associated enhancement of the meninges and multiple cranial nerves.

Inflammatory myofibroblastic tumor (IMT), Tolosa-Hunt syndrome (THS), and idiopathic hypertrophic pachymeningitis (IHP) seem to be part of a spectrum of disorders that have diverse locations but similar histologic and imaging findings. We report a case of a 50-year-old man presenting with multiple progressive cranial nerves palsies with leptomeningeal cranial nerve enhancement on MRI (II, V1-V3, and X), orbital and infraorbital masses, prominence within the left cavernous sinus, and diffuse dural enhancement. Biopsies of the orbital lesion and infraorbital nerve revealed IMT. The patient's lesions, symptoms, and dural enhancement quickly improved with steroid administration and nearly resolved over multiple subsequent scans over the next few months. This case illustrates a rare case of pseudotumor mimicking a more aggressive appearance that would usually portend a case of malignancy. There is a potential association of IMT, THS, and IHP, which may have existed in a concomitant fashion in this patient. The case also describes the unique finding of enhancement of the cisternal segments of multiple cranial nerves (simulating leptomeningeal malignant involvement), which may be related to inflammatory perineural edema or ischemic neuropathy.

Tau suppression in a neurodegenerative mouse model improves memory function.

Neurofibrillary tangles (NFTs) are the most common intraneuronal inclusion in the brains of patients with neurodegenerative diseases and have been implicated in mediating neuronal death and cognitive deficits. Here, we found that mice expressing a repressible human tau variant developed progressive age-related NFTs, neuronal loss, and behavioral impairments. After the suppression of transgenic tau, memory function recovered, and neuron numbers stabilized, but to our surprise, NFTs continued to accumulate. Thus, NFTs are not sufficient to cause cognitive decline or neuronal death in this model of tauopathy.

Severe subcortical degeneration in macaques infected with neurovirulent simian immunodeficiency virus.

Infection with human immunodeficiency virus-1 (HIV-1), the causative agent of acquired immunodeficiency syndrome (AIDS) in humans, causes a spectrum of neuropathology that includes alterations in behavior, changes in evoked potentials, and neuronal degeneration. In the simian immunodeficiency virus (SIV) model of HIV infection, affected monkeys show clinical symptoms and neurological complications that mimic those observed in human neuro-AIDS. To investigate the relationship between morphological correlates and neurophysiological deficits, unbiased stereology was used to assess total neuron number, volume, and neuronal density for all neurons in the globus pallidus (GP) and for dopamine (DA)-containing neurons in the substantia nigra (SN) in eight macaques inoculated with macrophage-tropic, neurovirulent SIV (SIVmac R71/17E), and five control animals. There was a significant difference between rapid progressors and controls for both neuron number (P < .01) and neuronal density (P < .05) in the GP, and for neuron number (P < .05) in the SN. Neuron loss ranged from 6% to 70% in the GP and from 10% to 50% in the SN. Neuropathological analyses confirmed neuroAIDS-like changes in brain, including microglial nodules, extensive perivascular cuffing and/or the presence of multinucleated giant cells, and alterations in neuronal morphology in the majority of the rapid progressors. By comparison, slow progressors showed little, if any, neuropathology. These neuropathological changes in SIV-infected monkeys indicate that neuron death and morphological alterations in the basal ganglia may contribute to the motor impairments reported in the SIV model and, by analogy, in the subset of patients afflicted with motor impairment in human neuro-AIDS.

Fatal chemotherapy-induced encephalopathy following high-dose therapy for metastatic breast cancer: a case report and review of the literature.

Chemotherapy-induced encephalopathies occur in a variety of clinical settings and the most detailed accounts have been described following combination methotrexate and radiation therapy. The case described herein developed severe encephalopathy following a high-dose chemotherapy protocol used in the treatment of metastatic carcinoma of the breast. Visual symptoms developed 3 weeks after completing high-dose chemotherapy and peripheral blood hematopoietic stem cell transplantation. Over the next several weeks, additional neurologic deficits developed and continued to progress despite various treatment interventions. Diffuse deep gray matter damage was identified on MR imaging and a brain biopsy revealed pathological findings similar in many respects to those described for methotrexate/radiation, cisplatin, BCNU and/or 5 FU/levamisole-related leukoencephalopathy. The patient succumbed to complications resulting from the CNS disorder, 8 weeks after the onset of symptoms. This case is unusual for two reasons. First, the patient developed severe encephalopathy following a high-dose chemotherapy protocol commonly used in the treatment of metastatic breast carcinoma and second, the encephalopathy involved primarily deep gray matter structures rather than white matter.

Brainstem and cortical Lewy bodies in patients presenting clinically with Alzheimer's disease.

In order to study the clinical overlap between neuropathologically defined Lewy body disease (LBD) and Alzheimer's disease, we examined the brains of 37 demented and 13 non-demented subjects. Nigral Lewy bodies (LBs) were present in 16/37 dementia patients, 13 of which had LBD. Eight of these 13 were clinically indistinguishable from AD patients, and in these cases isocortical neurofibrillary tangle (NFT) formation was rare. Thus, although the two conditions were clinically similar in this series, LBD could be distinguished from AD pathologically not only by the presence of nigral LBs but also by the relative paucity of isocortical NFTs.

Clinical presentations in monozygotic twins with dementia with Lewy bodies.

BACKGROUND: Dementia with Lewy bodies (DLB) is widely recognized as the second most common neurodegenerative cause of dementia in patients over the age of 65. The clinical distinction between DLB and Alzheimers's disease (AD) can be difficult due to the significant clinical overlap between the two disorders. Although the specificity of current consensus criteria is high, the sensitivity of case detection is lower and more variable. In some cases, the diagnosis is only made at postmortem examination. CASE REPORT: Monozygotic twins with the neuropathological diagnosis of Lewy body disease are presented in this report. Despite a very similar presentation and a comparable course of illness, the twins received different clinical diagnoses during life, one DLB and the other AD. This highlights the difficulty of making a clinical diagnosis of DLB, which very much depends on recognizing the features of fluctuation in level of awareness, hallucinations, delusions and the occurrence of falls, and the interpretation of the importance of these signs and symptoms. Pathological examination was virtually identical for the two cases showing the classic neuropathological features of Lewy Body disease.

Spectrum of clinical and histopathologic responses to intracranial electrodes: from multifocal aseptic meningitis to multifocal hypersensitivity-type meningovasculitis.

PURPOSE: We sought to characterize and compare the histopathologic and clinical changes elicited by subdural and depth electrodes in subjects undergoing epilepsy surgery evaluation. METHODS: A retrospective review of clinical records, imaging and histopathologic studies of epilepsy surgery cases requiring subdural strips and depth electrodes for localization of epileptogenic tissue was performed between 1993 and 1999. Forty-nine subjects had a combination of subdural and depth, whereas 10 had depth electrodes only. Histopathologic changes were classified as mild, moderate, or severe based on the density, extent, and composition of the inflammatory infiltrate. RESULTS: Subdural electrodes induced a clinical picture of transient aseptic meningitis; histopathologically, the infiltrates were moderate in degree in the majority (73%) and severe in the remainder (27%), with T cells and eosinophils infiltrating the cortex and arteriolar walls (hypersensitivity-type response). Depth electrodes alone caused minimal or no symptoms of meningeal irritation; the cellular response elicited by these electrodes was mild in five and moderate in the remaining five cases; severe inflammation was not observed in this group. Although the proportion of small clinically silent hematomas was larger in cases with depth (five of 59) compared with subdural electrodes (one of 49), microhemorrhages were considerably more numerous with subdural than with depth electrodes. CONCLUSIONS: These results suggest that the spectrum of brain responses to foreign bodies is wide, ranging from self-limited physiologic to hypersensitivity-type reactions of varying severity. Subdural strips elicited more intense inflammation than did depth electrodes. The histopathologic extent of the reaction to either type of electrodes could not be precisely defined because of the retrospective nature of this study. History of allergy to latex or previous craniotomies are probable risk factors for the hypersensitivity-type reaction. Surgical outcome, excellent in the majority, was independent of the severity or type of inflammation, and there have not been neurologic or systemic sequelae.

Early diagnosis of dementia.

Until recently, the most significant issue facing a family physician regarding the diagnosis and treatment of dementia was ruling out delirium and potentially treatable etiologies. However, as more treatment options become available, it will become increasingly important to diagnose dementia early. Dementia may be suspected if memory deficits are exhibited during the medical history and physical examination. Information from the patient's family members, friends and caregivers may also point to signs of dementia. Distinguishing among age-related cognitive decline, mild cognitive impairment and Alzheimer's disease may be difficult and requires evaluation of cognitive and functional status. Careful medical evaluation to exclude treatable causes of cognitive impairment is important. Patients with early dementia may benefit from formal neuropsychologic testing to aid in medical and social decision-making. Follow-up by the patient's family physician is appropriate in most patients. However, a subspecialist may be helpful in the diagnosis and management of patients with dementia with an unusual presentation or following an atypical course.

Intron-exon swapping of transglutaminase mRNA and neuronal Tau aggregation in Alzheimer's disease.

In order to understand the mechanism for insoluble neurotoxic protein polymerization in Alzheimer's disease (AD) brain neurons, we examined protein and gene expression for transglutaminase (TGase 2; tissue transglutaminase (tTG)) in hippocampus and isocortex. We found co-localization of tTG protein and activity with tau-positive neurofibrillary tangles, whereas mRNA and sequence analysis indicated an absolute increase in tTG synthesized. Although apoptosis in AD hippocampus is now an established mode of neuronal cell death, no definite underlying mechanism(s) is known. Since TGase-mediated protein aggregation is implicated in polyglutamine ((CAG)(n)/Q(n) expansion) disorder apoptosis, and expanded Q(n) repeats are excellent TGase substrates, a role for TGase in AD is possible. However, despite such suggestions almost 20 years ago, the molecular mechanism remained elusive. We now present one possible molecular mechanism for tTG-mediated, neurotoxic protein polymerization leading to neuronal apoptosis in AD that involves not its substrates (like Q(n) repeats) but rather the unique presence of alternative transcripts of tTG mRNA. In addition to a full-length (L) isoform in aged non-demented brains, we found a short isoform (S) lacking a binding domain in all AD brains. Our current results identify intron-exon "switching" between L and S isoforms, implicating G-protein-coupled signaling pathways associated with tTG that may help to determine the dual roles of this enzyme in neuronal life and death processes.