Leena Ketonen

Parietal Occipital Edema in Hypertensive Encephalopathy: A Pathogenic Mechanism

Eight patients with hypertensive encephalopathy from diverse etiologies developed cerebral edema in the vertebrobasilar distribution which resolved after blood pressure was lowered. Parietal occipital edema is a recognized feature of hypertensive encephalopathy. The explanation for this regional pathological variation in hypertensive encephalopathy remains undefined. Some evidence suggests that sympathetic innervation of the anterior cerebral vasculature may be protective, and conversely, the relative lack of sympathetic innervation in the vertebrobasilar vasculature may predispose the parietal occipital region to the development of cerebral edema in hypertensive encephalopathy.

Imaging Changes in Pediatric Intracranial Ependymoma Patients Treated With Proton Beam Radiation Therapy Compared to Intensity Modulated Radiation Therapy

PURPOSE The clinical significance of magnetic resonance imaging (MRI) changes after radiation therapy (RT) in children with ependymoma is not well defined. We compared imaging changes following proton beam radiation therapy (PBRT) to those after photon-based intensity modulated RT (IMRT). METHODS AND MATERIALS Seventy-two patients with nonmetastatic intracranial ependymoma who received postoperative RT (37 PBRT, 35 IMRT) were analyzed retrospectively. MRI images were reviewed by 2 neuroradiologists. RESULTS Sixteen PBRT patients (43%) developed postradiation MRI changes at 3.8 months (median) with resolution by 6.1 months. Six IMRT patients (17%) developed changes at 5.3 months (median) with 8.3 months to resolution. Mean age at radiation was 4.4 and 6.9 years for PBRT and IMRT, respectively (P = .06). Age at diagnosis (>3 years) and time of radiation (≥3 years) was associated with fewer imaging changes on univariate analysis (odds ratio [OR]: 0.35, P = .048; OR: 0.36, P = .05). PBRT (compared to IMRT) was associated with more frequent imaging changes, both on univariate (OR: 3.68, P = .019) and multivariate (OR: 3.89, P = .024) analyses. Seven (3 IMRT, 4 PBRT) of 22 patients with changes had symptoms requiring intervention. Most patients were treated with steroids; some PBRT patients also received bevacizumab and hyperbaric oxygen therapy. None of the IMRT patients had lasting deficits, but 2 patients died from recurrent disease. Three PBRT patients had persistent neurological deficits, and 1 child died secondarily to complications from radiation necrosis. CONCLUSIONS Postradiation MRI changes are more common with PBRT and in patients less than 3 years of age at diagnosis and treatment. It is difficult to predict causes for development of imaging changes that progress to clinical significance. These changes are usually self-limiting, but some require medical intervention, especially those involving the brainstem.

Rosai-Dorfman disease in neuroradiology: Imaging findings in a series of 10 patients

OBJECTIVE Rosai-Dorfman disease is a rare disorder characterized histologically by lymphatic sinus dilatation due to histiocyte proliferation. Our goal was to describe the CT, MRI, and (18)F-FDG (FDG) PET findings in a series of patients with this diagnosis. MATERIALS AND METHODS We retrospectively reviewed the imaging studies of 10 patients with pathologically confirmed Rosai-Dorfman disease who were treated in our institution between January 2004 and December 2007. RESULTS We found the following areas of general involvement: three intracranial, seven head and neck, and three spinal, with some patients having more than one site. Specific sites of involvement included the following: intracranial meninges, n = 2; pituitary, n = 2; lacrimal gland, n = 1; paranasal sinus, n = 3; neck lymph nodes, n = 6; salivary gland, n = 3; tonsil, n = 1; skin, n = 1; spinal meninges, n = 2; vertebral body, n = 1; and thymus, n = 1. The MRI characteristics of the involved areas were generally T1 isointense, T2 isointense, diffusion isointense to gray matter, and intensely enhancing with gadolinium chelate contrast agents. CT images generally showed the lesions were hyperdense to gray matter and intensely enhancing. FDG PET showed variable uptake, with nodal and lacrimal disease generally being FDG avid and other sites not. CONCLUSION Rosai-Dorfman disease has a protean imaging appearance but most frequently presents as neck lymphadenopathy. The disease is frequently multifocal, and a diagnosis in one area should prompt suspicion that other sites may be involved also.

Treatment of Patients With Advanced Neurofibromatosis Type 2 With Novel Molecularly Targeted Therapies: From Bench to Bedside

Minimal treatment options exist for advanced, inoperable neurofibromatosis type 2 (NF2), which is a rare tumor-prone disorder. NF2 results from a mutation in the NF2 tumor-suppressor gene on chromosome 22q12. NF2 is genetically and phenotypically distinguished from neurofibromatosis type 1, which results from a mutation in the NF1 tumor-suppressor gene located on chromosome 17q11.1,2 Clinically, NF2 is inherited in an autosomal dominant fashion and manifests through the appearance of bilateral acoustic neuromas (vestibular schwannomas), which lead to progressive hearing loss.3 Vestibular schwannomas and other lesions seen in patients with NF2 that arise progressively from other sites, such as meningiomas, spinal schwannomas, astrocytomas, ependymomas, rarely neurofibromas, and peripheral neuropathies, lead to profound morbidity in this debilitating disease.1,4 Few options are available to these patients outside of surgery, which is the mainstay of treatment for NF2-associated lesions, and, in some instances, radiation therapy.1,2 Despite our understanding of the underlying genetics and molecular pathophysiology of this disorder, patients become debilitated from tumor-related comorbidities. Recently, the anti–vascular endothelial growth factor (VEGF) antibody bevacizumab and erlotinib exhibited promising activity in pilot trials.5–8 Other than these two agents, no medical options are available for patients with NF2 with surgically unresectable disease. Because patients with NF2 harbor an aberration in a single gene, merlin, the protein product of which impacts multiple signals, including PI3-kinase/Akt, Raf/mitogen-activated protein/extracellular signal-regulated kinase, and mammalian target of rapamycin (mTOR), it is conceivable that one of the many agents that target these pathways that have already shown antitumor activity in malignancies will also cause the regression of NF2-related tumors.9–11 Because of its extreme rarity, conducting large clinical trials in NF2 is generally unfeasible.9 Therefore, we enrolled patients with NF2 onto various rationally targeted trials and sought response signals. We reviewed the records of consecutive patients with NF2 who were referred to the Clinical Center for Targeted Therapy (phase I Clinical Trials Program clinic) who were treated in more than one trial starting in January 2007 to December 2010. All trials were approved by the MD Anderson institutional review board, which also granted a waiver of informed consent and a waiver of authorization for this retrospective study. Patients were evaluated every 6 to 8 weeks for response by using RECIST with computed tomography and magnetic resonance imaging.

Palliative reirradiation for progressive diffuse intrinsic pontine glioma.

ObjectiveDiffuse intrinsic pontine gliomas (DIPGs) are highly aggressive tumors and have a poor prognosis. Nearly all patients experience disease progression after definitive treatment, accompanied by severe neurologic deficits and morbidity. Here, we report a series of patients treated with reirradiation for palliation of symptoms. MethodsSix patients received reirradiation for progressive DIPG at MD Anderson Cancer Center from 2007 to 2009. Progression after initial chemoradiation and salvage chemotherapy had been confirmed clinically and by magnetic resonance imaging. Each case was discussed at a multidisciplinary conference before reirradiation. ResultsInterval between the initial radiation therapy and reirradiation was 8 to 28 months. The initial radiation therapy dose was 54 to 55.8 Gy. Time to initial progression was 4 to 18 months. All of the patients had further progression on salvage chemotherapy. Reirradiation was given with concurrent chemotherapy to a dose of 20 Gy (n=4) or 18 Gy (n=1); 1 patient withdrew care after a single 2-Gy fraction. Four patients had substantial clinical improvement in symptoms, with improvement in speech (n=3), ataxia (n=3), and swallowing (n=2). Three patients showed renewed ability to ambulate after reirradiation. Four patients had decreased tumor size on posttreatment magnetic resonance imaging. The median clinical progression-free survival time was 5 months. Acute radiation-related toxicities were fatigue (n=2), alopecia (n=2), and decreased appetite (n=1). No grade 3 or 4 toxicities were reported. ConclusionsReirradiation with chemotherapy may be feasible to improve symptoms and delay progression with minimal toxicity. Patients who are most likely to benefit may be those with prolonged response to initial therapy and a long interval since initial radiation.

Erdheim-Chester Disease of the Central Nervous System: New Manifestations of a Rare Disease

BACKGROUND AND PURPOSE: ECD is a rare non-Langerhans-cell histiocytosis, which can involve the CNS; therefore, CNS imaging findings have been described in only a small number of patients. To gain additional insight into the CNS manifestations of ECD, we reviewed the findings on imaging of the brain, head and neck, and spine in patients with ECD who presented to our institution. Here, we illustrate manifestations that have not, to our knowledge, been previously described. MATERIALS AND METHODS: CT, MR imaging, and PET/CT studies of the brain, maxillofacial region, and spine were reviewed in 11 patients with ECD. RESULTS: Four new manifestations of ECD were present, including the following: a stellate appearance of intracranial extra-axial lesions, ependymal enhancement along the lateral ventricle with deep linear extension to the lentiform nucleus, irregular enhancement in the pons, and diffuse involvement of the vertebral column on PET/CT. CONCLUSIONS: ECD has a variety of imaging appearances in the CNS, including new manifestations described herein. Neuroradiologists should be aware of these manifestations to avoid mistaking them for other disease processes.

Acute and delayed cerebral infarction after wasp sting anaphylaxis

A 52-year-old man developed a severe anaphylactic reaction after a wasp sting. Slurred speech and left hemiparesis were noted a few hours later. Three-and-one-half weeks later, he became acutely obtunded and quadriparetic. Angiographic studies demonstrated complete and near-complete occlusions of the right and left internal carotid arteries, respectively. A mechanism is suggested for delayed ischemic stroke after wasp sting anaphylaxis that involves cerebrovascular sympathetic innervation.

Wasp sting-associated cerebral infarction : a role for cerebrovascular sympathetic innervation

A 38-year-old man, stung repeatedly by wasps on the left face and neck, had his left internal carotid artery occluded 2 days later. A mechanism for ischemic stroke involving the sympathetic innervation of cerebral vasculature is suggested.

Central neurocytoma responsive to topotecan, ifosfamide, carboplatin

A 5‐year‐old male presented with spinal cord drop metastasis from a recurrent neurocytoma. Topotecan (0.5 mg/m2) and carboplatin (250 mg/m2) were administered on days 1–3 and ifosfamide (1,800 mg/m2) on days 1–5, every 21 days, for three cycles and resulted in complete response without severe complications. A literature review yielded 20 patients with central neurocytoma but no complete responses. The complete response of central neurocytoma to chemotherapy only reported here should be helpful to those caring for patients with this rare tumor. Pediatr Blood Cancer 2008;51:137–140.

Serial MRI and CT findings in infantile Krabbe disease

Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive childhood disorder characterized by severe motor and mental deterioration. The disease has been divided into 3 main types and further subdivided into several subtypes based on age of onset and symptoms. Initial clinical findings and magnetic resonance imaging (MRI) with several follow-up scans are presented to identify the order and extent of white matter involvement and developing brain atrophy in a child with the floppy infant variant of Krabbe disease. When the patients clinical condition proceeded to stage 2, MRI disclosed severe involvement of the deep white matter around the atria and posterior limbs of the internal capsules. At the same time there was progression of normal myelination around the frontal horns. At age 32 months, the patients clinical condition proceeded to stage 3; she did not interact with her environment. MRI revealed a significant decrease of white matter volume, generalized atrophy, and abnormal high signal in all white matter areas except the anterior limbs of the internal capsules. At the same time the volume of the central gray nuclei was decreased and also demonstrated abnormal high signal. Despite its sensitivity, MRI could not differentiate the findings of this variant of Krabbe disease from the classic form; therefore, subclassifications of Krabbe disease should be made on clinical grounds because they cannot be distinguished by biochemical or radiologic (MRI) criteria.