Jonathan D. Trobe

Background: Intraventricular blockage of cerebrospinal drainage by brain tumors has been proposed as a more powerful mechanism of producing high intracranial pressure (ICP) than tumor size. We tested that hypothesis by investigating the MRI signs closely associated with high ICP in brain tumors. Methods: We conducted a single-institution retrospective chart review of patients with brain tumors between 1990 and 2023. We selected 100 cases from a larger eligible cohort without regard to clinical or imaging features. Based on ophthalmologic examination, 57 patients had papilledema and 43 patients did not. The study neuroradiologist, masked as to the presence of papilledema, noted relevant MRI brain and eye signs. Associations between these MRI signs and papilledema were analyzed statistically. Results: The median age of patients with papilledema was significantly younger than that of patients without papilledema. Among the MRI brain signs, the degree of ventriculomegaly was most highly associated with papilledema, and a temporal horn size of greater than 10 mm predicted a 100% chance of papilledema in patients aged 20 years or younger. Tumor size was not associated with papilledema. Posterior scleral flattening and optic disc protrusion were also highly associated with papilledema but were often difficult to identify because of their subtlety. Conclusions: The degree of ventriculomegaly, especially of the temporal horn, was the MRI brain sign most associated with papilledema, whereas tumor size was not associated with papilledema. These findings support the idea that intraventricular obstruction of cerebrospinal fluid flow is more likely than tumor size to elevate ICP. Together with posterior scleral flattening and optic disc protrusion, ventriculomegaly can be used to predict with high probability the presence of elevated ICP and as a substitute for finding papilledema on ophthalmologic examination, a service that may not be available in low resource settings.

A 12-year-old boy developed acute headache and vomiting. MRI brain showed a partially cystic suprasellar mass. He underwent cyst fenestration, but the cyst regrew, so he underwent transcranial subtotal resection of the mass. The pathologic diagnosis was adamantinomatous craniopharyngioma. Residual tumor was treated with proton beam radiation therapy, and panhypopituitarism was treated with hormone replacement therapy, including growth hormone. Serial brain MRI scans over several years showed no evidence of tumor recurrence. But at four years after radiation, surveillance MRI showed a new focus of nonenhancing FLAIR hyperintensity in the left basal ganglia attributed to gliosis caused by radiotherapy. Seven months later, he developed progressive right hemiparesis, expressive aphasia, and blurred vision, prompting reevaluation. MRI brain showed new enhancing and T2/FLAIR hyperintense lesions in the midbrain, basal ganglia, thalamus, anterior temporal lobe, and optic tract. The abnormal regions showed low diffusivity and relatively high regional blood flow. Stereotactic biopsy disclosed a WHO Grade 4 astrocytoma, likely radiation-induced. A germline ataxia telangiectasia mutation was found in the tumor tissue. The risk of radiation-induced pediatric brain malignancies is low but may have been increased by the mutation.

Background: Third nerve palsies (TNPs) may not resolve after intervention for intracranial aneurysms that have compressed the nerve. The disability related to this lingering condition has not been assessed with the support of patient self-report. Methods: A single-institutional retrospective study of patients with TNP who had undergone interventions for intracranial aneurysms. We used residual primary-position diplopia, a narrow zone of single binocular vision, and vision-obscuring ptosis to divide TNP recovery into complete, incomplete nondisabling, and incomplete disabling outcomes based on medical record documentation and patient self-report derived from telephonic interviews. Results: In a cohort of 33 patients, 13 (39%) had complete TNP recovery. There were 11 patients (33%) with lingering visual disability from diplopia or ptosis present before ophthalmic interventions. Of the 6 patients who underwent ophthalmic interventions, visual disability was relieved in only 2 patients, leaving 9 patients (27%) with lingering impairment in instrumental activities of daily living. Telephonic interviews of 23 patients (70% of the cohort) confirmed that the outcome criteria we applied were accurate in assessing visual disability in 17 patients (74%). Univariate analysis using the Fisher exact test showed that aneurysmal clipping as a treatment modality was the only clinical feature associated with a favorable TNP outcome. Conclusions: In applying a novel method of assessing disability, this study showed that more than one-quarter of patients undergoing procedures for brain aneurysms had lingering disability from third nerve palsy–associated diplopia or ptosis, despite later ophthalmic interventions. Patient self-report gleaned from telephonic interviews was valuable in largely validating the assessment method derived from medical records and in revealing differences between physician and patient estimation of disability.

Background: Posterior cerebral artery (PCA) strokes account for up to 10% of all ischemic strokes, often presenting with homonymous hemianopia. The proportion of these strokes attributed to various etiologies varies widely in previously published studies, owing largely to differing patient populations, definitions of stroke pathogenesis, and vascular territories involved. The Causative Classification System (CCS), an automated version of the Stop Stroke Study (SSS) Trial of Org 10,172 in Acute Stroke Treatment (TOAST) system, allows for a more rigorous assignment of stroke etiology. Methods: We excerpted clinical and imaging data on 85 patients who had PCA stroke with homonymous hemianopia examined at the University of Michigan. We compared the stroke risk factor profile of our PCA cohort with that of 135 patients with stroke in the distribution of the internal carotid artery (ICA) and middle cerebral artery (MCA) in an unpublished University of Michigan registry. We applied the CCS web-based calculator to our PCA cohort to determine stroke etiology. Results: In our PCA cohort, 80.0% had at least 2 conventional stroke risk factors and 30.6% had 4 risk factors, most commonly systemic hypertension. The risk factor profile of our PCA cohort resembled that of our ICA/MCA cohort except that the mean age of our PCA cohort was more than a decade younger and had a significantly lower frequency of atrial fibrillation (AF) than our ICA/MCA cohort. In nearly half of the patients with AF in our PCA cohort, AF was diagnosed after the stroke. Among stroke etiologies in our PCA cohort, 40.0% were of undetermined cause, 30.6% were from cardioaortic embolism, 17.6% were from other determined causes, and only 11.8% were from supra-aortic large artery atherosclerosis. Strokes after endovascular or surgical interventions were prominent among other determined causes. Conclusions: Most patients in our PCA cohort had multiple conventional stroke risk factors, a finding not previously documented. Mean age at stroke onset and AF frequency were lower than in our ICA/MCA cohort, in agreement with previous studies. As some other studies have found, nearly 1/3 of strokes were attributed to cardioaortic embolism. Within that group, AF was often a poststroke diagnosis, a finding not previously highlighted. Compared with earlier studies, a relatively high portion of strokes were of undetermined etiology and of other determined etiologies, including stroke after endovascular or surgical interventions. Supra-aortic large artery atherosclerosis was a relatively uncommon explanation for stroke.

Background: Posterior cerebral artery (PCA) stroke is a common cause of homonymous hemianopia and other neurologic deficits associated with more proximal ischemia in the vertebrobasilar circuit. Localization of the process can be challenging unless the symptom complex is well recognized, yet early diagnosis is critical to forestall dangerous driving and repeated stroke. We undertook this study to provide additional detail about the presenting symptoms and signs and their correlation with imaging abnormalities and stroke etiology. Methods: Retrospective study of medical records of patients presenting to a single tertiary care academic center between 2009 and 2020 with homonymous hemianopia from PCA stroke. We excerpted data on symptoms, visual and neurologic signs, incident medical procedures and diagnoses, and imaging features. We determined stroke etiology using the Causative Classification Stroke system. Results: In a cohort of 85 patients, 90% of strokes occurred without preceding symptoms. But in retrospect, 10% of strokes did have warning symptoms. In 20% of patients, strokes followed within 72 hours of a medical or surgical procedure or newly identified medical condition. In the subgroups of patients whose records contained a description of visual symptoms, 87% reported the visual sensation as negative, and 66% realized that it was located in a hemifield in both eyes. Concurrent nonvisual symptoms were present in 43% of patients, consisting commonly of numbness, tingling, and new headache. Infarction located outside the visual cortex affected primarily the temporal lobe, thalamus, and cerebellum, reflecting the widespread nature of ischemia. Nonvisual clinical manifestations and arterial cutoffs on imaging were associated with thalamic infarction, but the clinical features and location of the infarction did not correlate with the etiology of the stroke. Conclusions: In this cohort, clinical localization of the stroke was aided by the fact that many patients could lateralize their visual symptoms and had nonvisual symptoms suggestive of ischemia affecting the proximal vertebrobasilar circuit. Numbness and tingling were strongly linked to concurrent thalamic infarction. Clinical features and infarct location were not associated with the etiology of the stroke.

Background: Imaging diagnosis of clival cancer may be difficult, in part because of normal variation in marrow signal with aging. Identifying whether clival cancer has damaged the sixth cranial nerve is a further challenge because minimal clival abnormalities could impinge on the nerve, which travels very close to the clivus. Methods: Two neuroradiologists, who were unaware of previous imaging and clinical diagnoses, reviewed MRI studies of 25 patients with cancer but no clival involvement and no sixth nerve palsy, 24 patients with clival cancer but without sixth nerve palsy, and 31 patients with clival cancer and sixth nerve palsy. The radiologists were tasked with determining whether there was clival cancer, whether there was a sixth nerve palsy and its laterality, and with indicating the pulse sequences used to make those determinations. Results: Both neuroradiologists correctly identified all 25 cases with a normal clivus. In about half of those cases, they depended on finding a homogeneously bright marrow signal; in the remaining cases, they excluded cancer by determining that the clivus was not expanded and that there were no focal signal abnormalities. Both neuroradiologists correctly identified clival cancer in 54 (98%) of the 55 cases with and without sixth nerve palsy. In doing so, they relied mostly on clival expansion but also on focal signal abnormalities. Both neuroradiologists were at least 80% correct in identifying a sixth nerve palsy, but they often incorrectly identified a palsy in patients who did not have one. When there was a one-sided signal abnormality or the clivus was expanded in one direction, both neuroradiologists were accurate in identifying the side of the sixth nerve palsy. Conclusion: Current MRI pulse sequences allow accurate differentiation of a normal from a cancerous clivus. When the marrow signal is not homogeneously bright in adults, cancer can be diagnosed on the basis of clival expansion or focal signal abnormalities. MRI is less accurate in predicting the presence of a sixth nerve palsy. However, the side of a unilateral palsy can be predicted when the clivus is clearly expanded in one direction or there is a focal signal abnormality on one side.