Cynthia T. Welsh

Cerebral Blood Volume Measurements by Perfusion-Weighted MR Imaging in Gliomas : Ready for Prime Time in Predicting Short-Term Outcome and Recurrent Disease?

BACKGROUND AND PURPOSE: Current classification and grading of primary brain tumors has significant limitations. Our aim was to determine whether the relative cerebral volume (rCBV) measurements in gliomas may serve as an adjunct to histopathologic grading, with a hypothesis that rCBV values are more accurate in predicting 1-year survival and recurrence. MATERIALS AND METHODS: Thirty-four patients with gliomas (WHO grade I-IV, 27 astrocytomas, 7 tumors with oligodendroglial components) underwent contrast-enhanced MR rCBV measurements before treatment. The region of interest and the single pixel with the maximum CBV value within the tumors were normalized relative to the contralateral normal tissue (rCBVmean and rCBVmax, respectively). Karnofsky performance score and progression-free survival (PFS) were recorded. Receiver operating characteristic curves and Kaplan-Meier survival analysis were conducted for CBV and histologic grade (WHO grade). RESULTS: Significant correlations were detected only when patients with oligodendrogliomas and oligoastrocytomas were excluded. The rCBVmean and rCBVmax in the astrocytomas were 3.5 ± 2.9 and 3.7 ± 2.7. PFS correlated with rCBV parameters (r = −0.54 to −0.56, P ≤ .009). WHO grade correlated with rCBV values (r = 0.65, P ≤ .0002). rCBVmax >4.2 was found to be a significant cutoff value for recurrence prediction with 77.8% sensitivity and 94.4% specificity (P = .0001). rCBVmax ≤3.8 was a significant predictor for 1-year survival (93.7% sensitivity, 72.7% specificity, P = .0002). The relative risk for shorter PFS was 11.1 times higher for rCBVmax >4.2 (P = .0006) and 6.7 times higher for WHO grade >II (P = .05). The combined CBV−WHO grade classification enhanced the predictive value for recurrence/progression (P < .0001). CONCLUSIONS: rCBV values in astrocytomas but not tumors with oligodendroglial components are predictive for recurrence and 1-year survival and may be more accurate than histopathologic grading.

Molecular evidence of apoptotic death in malignant brain tumors including glioblastoma multiforme: Upregulation of calpain and caspase-3

Cell death in the core of human brain tumors is triggered by hypoxia and lack of nutrients, but the mode of cell death whether necrosis or apoptosis is not clearly defined. To identify the role of apoptosis in brain tumor cell death, we investigated macromolecular (RNA and protein) synthesis and activity in the central to peripheral region of benign [desmoplastic infantile ganglioglioma (DIG) and transitional meningioma (TMG)] and malignant [ependymoma (END), anaplastic astrocytoma (APA), and glioblastoma multiforme (GBM)] brain tumors derived from five patients who had not received previously radiotherapy or chemotherapy. Normal brain tissue (NBT) served as control. RT‐PCR analysis of tumor tissues covering central to peripheral regions detected mRNA overexpression of pro‐apoptotic gene bax in malignant tumors, indicating a commitment to apoptosis. The mRNA expression of calpain (a Ca2+‐dependent cysteine protease) and calpastatin (endogenous calpain inhibitor) was altered resulting in an elevated calpain/calpastatin ratio. Calpain content and activity were increased, suggesting a role for calpain in cell death. In the mitochondria‐dependent death pathway, caspase‐9 and caspase‐3 were also overexpressed in tumors. The increased caspase‐3 activity cleaved poly(ADP‐ribose) polymerase (PARP). Agarose gel electrophoresis detected a mixture of random and internucleosomal DNA fragmentation in malignant brain tumors. Overexpression of pro‐apoptotic bax, upregulation of calpain and caspase‐3, and occurrence of internucleosomal DNA fragmentation are now presented indicating that one mechanism of cell death in malignant brain tumors is apoptosis, and that enhancement of this process therapeutically may promote decreased tumor growth.

Intracranial Atherosclerosis: Correlation Between In-vivo 3T High Resolution MRI and Pathology

BACKGROUND High-resolution MRI (HRMRI) is a promising tool for studying intracranial atherosclerotic disease (ICAD) in-vivo, but its use to understand the pathophysiology of ICAD has been limited by a lack of correlation between MRI signal characteristics and pathology in intracranial arteries. DESCRIPTION OF CASE A patient with symptomatic left cavernous carotid stenosis underwent 3T HRMRI and died 4 days later. In-vivo HRMRI and postmortem histopathology images were compared. MRI signal characteristics consistent with atherosclerotic plaque composed of lipid and loose matrix, fibrous tissue, and calcium were correlated with pathology findings. Intraplaque hemorrhage was not present on HRMRI or pathology. CONCLUSIONS This report demonstrates correlation between atherosclerotic plaque components visualized on 3T HRMRI images obtained in-vivo and pathological specimens of a symptomatic ICAD plaque, providing an important step in developing HRMRI as an in-vivo research tool to understand ICAD pathology.

Correlation between Cerebral Blood Volume Measurements by Perfusion-Weighted Magnetic Resonance Imaging and Two-Year Progression-Free Survival in Gliomas

Our goal was to determine whether relative cerebral blood volume (rCBV) can serve as an adjunct to histopathologic grading in the assessment of gliomas, with the hypothesis that rCBV can predict two-year survival. We evaluated 29 newly diagnosed gliomas (13 WHO grade II, seven grade III, nine grade TV; 17 astrocytomas, 12 oligodendroglial tumors). Dynamic susceptibility-weighted contrast-enhanced perfusion MR images and CBV maps were obtained. rCBVmax measurements (maximum tumor CBV/contralateral normal tissue CBV) and progression-free survival (PFS) were recorded. Receiver operating characteristic curves and Kaplan-Meier survival curves were calculated for rCBVmax and histologic grade. rCBVmax measurements differed between gliomas without (2.38 +/− 1.22) and with progression (5.57 +/− 2.84) over two years. The optimal rCBVmax cut-off value to predict progression was 2.95. rCBVmax < 2.95 was a significant predictor of two-year PFS, almost as accurate as WHO grade IT In the pure astrocytoma subgroup, the optimal rCBVmax cut-off value to predict progression was 2.85. In this group rCBVmax < 2.85 was a significant predictor of two-year PFS, an even better predictor of two-year PFS than WHO grade IT rCBVmax can be used to predict two-year PFS in patients with gliomas, independent of pathologic findings, especially in tumors without oligodendroglial components.

MRI findings of crossed cerebellar diaschisis in a case of Rasmussen’s encephalitis

We report the case of an 11-year-old girl with a medical history significant for Rasmussen’s encephalitis (RE), manifesting with intractable complex partial seizures, who developed severe brain hemiatrophy and MRI evidence of contralateral cerebellar atrophy due to crossed cerebellar diaschisis (CCD). The patient was born full term and had a normal childhood until seizures started at the age of six. Neurological examination disclosed only a slight right hemiparesis. Clinically, seizures lasted between 1 and 3 min and were accompanied by focal twitches of the right arm and foot. EEG revealed intermittent electroclinical seizures with left temporal onset spreading throughout the left hemisphere, followed by rhythmic sharp and slow waves over the right hemisphere. Brain MRI showed high T2-signal intensity in patchy areas of the cortex of the left hemisphere (Fig. 1a–c). Brain biopsy disclosed findings compatible with Rasmussen’s encephalitis (Fig. 2). Several therapeutic treatments, including seizure medicines (valproic acid, phenytoin carbamazepine, lorazepam), immunotherapy with IVIg, and vagus nerve stimulation, were unsuccessful in managing the progression of the disease or controlling seizures. There was no change in seizure frequency despite all therapies. Follow-up brain MRI at the age of 11 (Fig. 1d–f) demonstrated interval increase of atrophy of the left sylvian region, the left temporal lobe and the left occipital lobe. Striking interval atrophy of the right cerebellum, consistent with CCD, was also evident. The patient subsequently underwent left functional hemispherectomy achieving mild reduction of seizures. Rasmussen’s encephalitis is a rare hemispheric inflammatory disease of the brain generally manifesting with intractable seizures, cognitive decline and progressive neurological deficits. Normally this disorder affects children while an adult onset of the disease is less frequent and associated with a less aggressive course [1, 2]. Crossed cerebellar diaschisis is a condition in which cerebellar hypometabolism is noted in association with injuries to the contralateral cerebral hemisphere. It is ascribed to functional cerebellar disconnection from the cerebral cortex of the contralateral hemisphere. Interruption of the cerebro-pontine-cerebellar pathway is thought to be the most likely mechanism of this remote transneuronal metabolic depression [3]. CCD is frequent in patients with hemispheric strokes, and it is usually shown with nuclear medicine techniques while it is more rarely demonstrated on MRI [4, 5]. SPECT findings of CCD have been described in patients with RE whereas its correlate on MRI has been seldom reported [6–10]. A. Cianfoni M. L. Bradshaw Neuroradiology Section, Radiology Department, Medical University of South Carolina (MUSC), Charleston, SC, USA

Atypical Cystic Meningioma of the Trigeminal Nerve in a Pediatric Patient

SUMMARY: We report an unusual case of atypical cystic meningioma of the trigeminal nerve proved by histology in a 15-year-old white girl. A review of the literature showed that this is only the second reported case of a meningioma of the trigeminal nerve without dural attachment and the first occurrence in a pediatric patient.

Calcifying Pseudoneoplasm of the Cervicomedullary Junction: Case Report and a Literature Review.

BACKGROUND Calcifying pseudoneoplasm of the neuroaxis (CAPNON) is a rare, slow-growing tumor of a fibro-osseous origin that may present anywhere in the neuroaxis. Although typically benign, symptoms of CAPNONs typically present secondary to compression and surrounding mass effect. Histologically, the tumor has the characteristics of a foreign body reaction with giant cells, ossification, and the formation of psammoma bodies. On imaging, they can easily be confused with malginant lesions such as chondrosarcoma or chondroblastoma or even more benign pathologies like meningioma. CASE DESCRIPTION We present a case of a patient with an incidentally found calcifying pseudoneoplasm involving the cervicomedullary junction with further involvement of the vertebral artery and the hypoglossal nerve. We also review the literature on these tumors to date. CONCLUSION Calcifying pseudoneoplasm of the neuroaxis is a slow-growing, benign, noninfiltrative lesion whose pathogensis and natural history remains unclear. It can appear anywhere in the neuroaxis and does not have a prevelant location. Because of the indolent course and relative rarity of this tumor, there are no current guidelines on the immediate and long-term management of CAPNONs. This entity, although quite rare, should be considered in the differential for calcified lesions at the cervicomedullary junction. The consensus for treatment of CAPNONs when symptomatic is surgical resection.

Intracranial Angiomatoid Fibrous Histiocytoma: Case Report and Literature Review.

BACKGROUND Angiomatoid fibrous histiocytoma (AFH) is a rare and low-grade soft tissue lesion that typically arises from subcutaneous and deep dermal tissue of extremities. The first case was reported in 1979 by Enzinger and has since become known as a distinct entity. AFH has been increasingly reported in different organ systems, with rare reports of primary intracranial AFH. To date there have been 3 reports of intracranial AFH and 1 report of metastasis to the brain, most of which were in young adults. CASE DESCRIPTION In this paper, we present a case of an older patient with a large, petrous apex AFH that was clinically mistaken for a trigeminal nerve schwannoma. We discuss radiographic and histologic features initially found and the findings that ultimately led to the diagnosis of AFH. We also discuss the findings noted in all other reports of intracranial AFH. CONCLUSION We present a rare case of intracranial AFH in a patient relatively old for onset of diagnosis. To date, only 3 prior cases of AFH have been reported. The radiographic findings were nonspecific and initially pointed toward a diagnosis of schwannoma, whereas histopathology seemed to initially suggest meningioma. Further pathologic consultation finally confirmed AFH as the diagnosis. We suspect there are more cases of intracranial AFH that are misdiagnosed due to variability of findings on pathology. The behavior of this tumor remains in question as 1 of the 3 reported cases demonstrated significant recurrence. As such, gross total resection of this lesion is preferable.

Pseudoneoplasms in the nervous system

Pseudotumors are frequent in the nervous system and form a category of lesions that are fraught with peril for the pathologist unaware of the similarities and differences with neoplasms. The most common pseudoneoplasms in the nervous system are demyelinative, inflammatory and vascular. Even normal histology can be mistaken for neoplasm.

The Supratentorial Mass in an Adult

36-year-old male Pain in right eye CT of orbits demonstrated left frontal abnormality Normal neurologic exam