David M. Yousem

Watershed Strokes After Cardiac Surgery. Diagnosis, Etiology, and Outcome

Background and Purpose— Watershed strokes are more prevalent after cardiac surgery than in other stroke populations, but their mechanism in this setting is not understood. We investigated the role of intraoperative blood pressure in the development of watershed strokes and used MRI to evaluate diagnosis and outcomes associated with this stroke subtype. Methods— From 1998 to 2003 we studied 98 patients with clinical stroke after cardiac surgery who underwent MRI with diffusion-weighted imaging. We used logistic regression to explore the relationship between mean arterial pressure and watershed infarcts, between watershed infarcts and outcome, and &khgr;2 analyses to compare detection by MRI versus CT of watershed infarcts. Results— Bilateral watershed infarcts were present on 48% of MRIs and 22% of CTs (P<0.0001). Perioperative stroke patients with bilateral watershed infarcts, compared with those with other infarct patterns, were 17.3 times more likely to die, 12.5 and 6.2 times more likely to be discharged to a skilled nursing facility and to acute rehabilitation, respectively, than to be discharged home (P=0.0004). Patients with a decrease in mean arterial pressure of at least 10 mm Hg (intraoperative compared with preoperative) were 4.1 times more likely to have bilateral watershed infarcts than other infarct patterns. Conclusions— Bilateral watershed infarcts after cardiac surgery are most reliably detected by diffusion-weighted imaging MRI and are associated with poor short-term outcome, compared with other infarct types. The mechanism may include an intraoperative drop in blood pressure from a patients baseline. These findings have implications for future clinical practice and research.

White matter changes are correlated significantly with radiation dose. Observations from a randomized dose-escalation trial for malignant glioma (Radiation Therapy Oncology Group 83-02).

Background. A Phase I/II randomized dose‐seeking trial was performed to document the severity, time course, and significance of white matter changes seen on serial imaging scans (magnetic resonance imaging, computed tomography) associated with bis‐chlorethyl nitrosourea (BCNU) and hyperfractionated cranial irradiation.

Leptomeningeal metastases: Mr evaluation

Forty patients with positive CSF cytology for subarachnoid dissemination of neoplasms were examined by magnetic resonance (MR) imaging for the detection of intracranial or intraspinal CSF metastases. The MR evidence of cerebral leptomeningeal metastases was noted in 12 of 54 unenhanced (22.2%) and 7 of 20 (35%) gadolinium-enhanced studies. However, in only 2 of the 20 (10%) gadolinium-enhanced scans did the enhanced brain images alone demonstrate the presence of CSF seeding. Four of 29 (13.8%) unenhanced studies of the spine and 6 of 16 (37.5%) gadolinium-enhanced spine studies were positive for neoplastic deposits on the spinal nerves or cord. Magnetic resonance without and with gadolinium enhancement was most likely to be positive in studies of patients with a non-CNS primary malignancy (16/51 = 31.4%) and least accurate with lymphoma or leukemia (1/18 = 5.6%). Although gadolinium administration increases the ability of MR to detect leptomeningeal metastases (particularly in the spine), the overall sensitivity of unenhanced and enhanced MR examinations is low (19.3 and 36.1%, respectively) in patients with proven cytological evidence of neoplastic seeding.

Advantages and disadvantages of three‐dimensional computed tomography intraoperative localization for functional endoscopic sinus surgery

Intraoperative three‐dimensional computed tomography (3‐D CT) localization has been available for use during functional endoscopic sinus surgery (FESS) for several years, although relatively few otolaryngologists operate in conjunction with this technology. Proponents of intraoperative localization believe that operating with stereotaxis enhances surgical precision and reduces complications. A 1‐year review was conducted at the University of Pennsylvania from January 1994 through January 1995. During this period 5% of sinus operations were performed in conjunction with intraoperative localization. The advantages and disadvantages of using intraoperative localization were evaluated for each case. Also examined were type and indication for surgery, anesthesia used, added time, and cost. Overall, intraoperative localization was found to be helpful when anatomy was distorted or obscured. However, selecting patients who may have benefited from localization was often not possible using preoperative data. Ideally, localization should be available for all FESS. Criteria are outlined which will need to be met prior to localization becoming a significant aspect of FESS.

Association, commissural, and projection pathways and their functional deficit reported in literature.

Abstract: This study demonstrates normal white matter structures of the supratentorial system revealed by diffusion tensor imaging. Their anatomic connections and functional significance are discussed in the context of the lesion-induced deficits reported in the literature, which may not fully represent the lesion-induced effects on the white matter function and may not be entirely specific to the tract discussed. Nevertheless, understanding the most common effects of lesions on the functional connectivity provides a framework that we can use in advanced neuroimaging studies, like diffusion tensor imaging, functional magnetic resonance imaging, and positron emission tomography, and in our daily clinical practice.

Olfactory dysfunction in multiple sclerosis: relation to longitudinal changes in plaque numbers in central olfactory structures.

Article abstract Scores on the University of Pennsylvania Smell Identification Test (UPSIT), as well as the numbers of MRI-determined plaques within the inferior frontal and temporal lobes, were obtained on three or four separate occasions in each of five MS patients over an 18- to 20-month period. A close association was observed, longitudinally, between the remission and exacerbation of plaque numbers and UPSIT scores, with more plaques reflecting lower UPSIT scores. These observations further support the hypothesis that olfactory loss in MS is associated with fluctuations in plaque numbers in central olfactory brain regions.

Reduction of Disease Activity and Disability With High-Dose Cyclophosphamide in Patients With Aggressive Multiple Sclerosis

OBJECTIVE To explore the safety and effectiveness of high-dose cyclophosphamide (HiCy) without bone marrow transplantation in patients with aggressive multiple sclerosis (MS). DESIGN A 2-year open-label trial of patients with aggressive relapsing-remitting multiple sclerosis (RRMS) given an immunoablative regimen of HiCy (50 mg/kg/d for 4 consecutive days) with no subsequent immunomodulatory therapy unless disease activity reappeared that required rescue therapy. SETTING The Johns Hopkins University Multiple Sclerosis Center, Baltimore, Maryland. Patients A total of 21 patients with RRMS were screened for eligibility and 9 patients were enrolled in the trial. Patients were required to have 2 or more gadolinium-enhancing lesions on each of 2 pretreatment magnetic resonance imaging scans, at least 1 clinical exacerbation in the 12 months prior to HiCy treatment, or a sustained increase of 1.0 point or higher on the Expanded Disability Status Scale (EDSS) in the preceding year. Intervention Patients received 50 mg/kg/d of cyclophosphamide intravenously for 4 consecutive days, followed by 5 mug/kg/d of granulocyte colony-stimulating factor 6 days after completion of HiCy treatment, until the absolute neutrophil count exceeded 1.0 x 10(9) cells/L for 2 consecutive days. MAIN OUTCOME MEASURES The primary outcome of the study was the safety and tolerability of HiCy in patients with RRMS. Secondary outcome measures included a change in gadolinium-enhancing lesions on magnetic resonance images and a change in disability measures (EDSS and Multiple Sclerosis Functional Composite). RESULTS Nine patients were treated and followed up for a mean period of 23 months. Eight patients had failed conventional therapy and 1 was treatment naive. The median age at time of entry was 29 years (range, 20-47 years). All patients developed transient total or near-total pancytopenia as expected, followed by hematopoietic recovery in 10 to 17 days, stimulated by granulocyte colony-stimulating factor. There were no deaths or unexpected serious adverse events. There was a statistically significant reduction in disability (EDSS) at follow-up (mean [SD] decrease, 2.11 [1.97]; 39.4%; P = .02). The mean (SD) number of gadolinium-enhancing lesions on the 2 pretreatment scans were 6.5 (2.1) and 1.2 (2.3) at follow-up (81.4% reduction; P = .01). Two patients required rescue treatment with other immunomodulatory therapies during the study owing to MS exacerbations. CONCLUSION Treatment with HiCy was safe and well tolerated in our patients with MS. Patients experienced a pronounced reduction in disease activity and disability after HiCy treatment. This immunoablative regimen of cyclophosphamide for patients with aggressive MS is worthy of further study and may be an alternative to bone marrow transplantation. Published online June 9, 2008 (doi:10.1001/archneurol.65.8.noc80042).

Hyperintense Dentate Nuclei on T1-Weighted MRI: Relation to Repeat Gadolinium Administration

This is a retrospective review of the medical records of 706 consecutive patients who were treated with irradiation for primary brain tumors at The Johns Hopkins Medical Institutions between June 1995–January 2010. The authors found that the appearance of hyperintense dentate nuclei (HDN) is likely permanent, given the long follow-up time of the study, and a significant association between HDN and repeated contrast-enhanced MR studies. A significant increase in the likelihood of HDN occurred after 4 or more enhanced scans, and total dose of 77 ml of gadolinium contrast agent. They found no association between radiation exposure and HDN. BACKGROUND AND PURPOSE: A hyperintense appearance of the dentate nucleus on T1-weighted MR images has been related to various clinical conditions, but the etiology remains indeterminate. We aimed to investigate the possible associations between a hyperintense appearance of the dentate nucleus on T1-weighted MR images in patients exposed to radiation and factors including, but not limited to, the cumulative number of contrast-enhanced MR images, amount of gadolinium administration, dosage of ionizing radiation, and patient demographics. MATERIALS AND METHODS: The medical records of 706 consecutive patients who were treated with brain irradiation at The Johns Hopkins Medical Institutions between 1995 and 2010 were blindly reviewed by 2 readers. RESULTS: One hundred eighty-four subjects were included for dentate nuclei analysis. Among the 184 subjects who cumulatively underwent 2677 MR imaging studies following intravenous gadolinium administration, 103 patients had hyperintense dentate nuclei on precontrast T1-weighted MR images. The average number of gadolinium-enhanced MR imaging studies performed in the group with normal dentate nuclei was significantly lower than that of the group with hyperintense dentate nuclei. The average follow-up time was 62.5 months. No significant difference was observed between hyperintense and normal dentate nuclei groups in terms of exposed radiation dose, serum creatinine and calcium/phosphate levels, patient demographics, history of chemotherapy, and strength of the scanner. No dentate nuclei abnormalities were found on the corresponding CT scans of patients with hyperintense dentate nuclei (n = 44). No dentate nuclei abnormalities were found in 53 healthy volunteers. CONCLUSIONS: Repeat performance of gadolinium-enhanced studies likely contributes to a long-standing hyperintense appearance of dentate nuclei on precontrast T1-weighted-MR images.

Olfactory Dysfunction in Multiple Sclerosis

To the Editor: Multiple sclerosis, the most common neurologic disease in young adults, is accompanied by focal demyelinating plaques within the central nervous system, which can be quantified in vi...

Neuroradiologic manifestations of Loeys-Dietz syndrome type 1.

BACKGROUND AND PURPOSE: Loeys-Dietz syndrome (LDS) is a recently described entity that has the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Its neuroradiologic manifestations have not been well delineated. We sought to describe the neuroradiologic features of LDS and to assess the manifestations that would warrant follow-up imaging. MATERIALS AND METHODS: Two neuroradiologists retrospectively reviewed CT angiography (CTA), MR imaging, and plain film studies related to the head and neck in 25 patients ranging from 1 to 55 years of age, all of whom had positive genetic testing and clinical characteristics of LDS. Arterial tortuosity was evaluated by subjective assessment of 2D and 3D volumetric CTA and MR angiography data. Craniosynostosis and spinal manifestations were assessed by using plain films and CT images. MR images mostly of the head were reviewed for associated findings such as hydrocephalus, Chiari malformation, etc. Clinical manifestations were collated from the electronic patient record. RESULTS: All patients had extreme arterial tortuosity, which is characteristic of this syndrome. Thirteen patients had scoliosis, 12 had craniosynostosis, 8 had intracranial aneurysms, 6 had spinal instability, 3 had dissections of the carotid and vertebrobasilar arteries, 3 had hydrocephalus, 4 had dural ectasia, 2 had a Chiari malformation, and 1 had intracranial hemorrhage as a complication of vascular dissection. CONCLUSIONS: Significant neuroradiologic manifestations are associated with LDS, predominantly arterial tortuosity. Most of the patients in this series were young and, therefore, may require serial CTA monitoring for development of intra- and extracranial dissections and aneurysms, on the basis of the fact that most of the patients with pseudoaneurysms and dissection were older at the time of imaging. Other findings of LDS such as craniosynostosis, Chiari malformation, and spinal instability may also need to be addressed.