Hippocampal and entorhinal atrophy in mild cognitive impairment: prediction of Alzheimer disease.

OBJECTIVE: To evaluate the utility of MRI hippocampal and entorhinal cortex atrophy in predicting conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD). METHODS: Baseline brain MRI was performed in 139 patients with MCI, broadly defined, and 63 healthy controls followed for an average of 5 years (range 1 to 9 years). RESULTS: Hippocampal and entorhinal cortex volumes were each largest in controls, intermediate in MCI nonconverters, and smallest in MCI converters to AD (37 of 139 patients converted to AD). In separate Cox proportional hazards models, covarying for intracranial volume, smaller hippocampal volume (risk ratio [RR] 3.62, 95% CI 1.93 to 6.80, p < 0.0001), and entorhinal cortex volume (RR 2.43, 95% CI 1.56 to 3.79, p < 0.0001) each predicted time to conversion to AD. Similar results were obtained for hippocampal and entorhinal cortex volume in patients with MCI with Mini-Mental State Examination (MMSE) scores > or = 27 out of 30 (21% converted to AD) and in the subset of patients with amnestic MCI (35% converted to AD). In the total patient sample, when both hippocampal and entorhinal volume were entered into an age-stratified Cox model with sex, MMSE, education, and intracranial volume, smaller hippocampal volume (RR 2.21, 95% CI 1.14 to 4.29, p < 0.02) and entorhinal cortex volume (RR 2.48, 95% CI 1.54 to 3.97, p < 0.0002) predicted time to conversion to AD. Similar results were obtained in a Cox model that also included Selective Reminding Test (SRT) delayed recall and Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol as predictors. Based on logistic regression models in the 3-year follow-up sample, for a fixed specificity of 80%, the sensitivities for MCI conversion to AD were as follows: age 43.3%, MMSE 43.3%, age + MMSE 63.7%, age + MMSE + SRT delayed recall + WAIS-R Digit Symbol 80.6% (79.6% correctly classified), hippocampus + entorhinal cortex 66.7%, age + MMSE + hippocampus + entorhinal cortex 76.7% (85% correctly classified), age + MMSE + SRT delayed recall + WAIS-R Digit Symbol + hippocampus + entorhinal cortex 83.3% (86.8% correctly classified). CONCLUSIONS: Smaller hippocampal and entorhinal cortex volumes each contribute to the prediction of conversion to Alzheimer disease. Age and cognitive variables also contribute to prediction, and the added value of hippocampal and entorhinal cortex volumes is small. Nonetheless, combining these MRI volumes with age and cognitive measures leads to high levels of predictive accuracy that may have potential clinical application.

Reversible leukoencephalopathy associated with cerebral amyloid angiopathy.

The authors describe three patients with reversible leukoencephalopathy associated with cerebral amyloid angiopathy (CAA). Rapid progression of neurologic symptoms was followed by dramatic clinical and radiographic improvement. Pathologically, CAA was associated with varying degrees of inflammation ranging from none to transmural granulomatous infiltration. In the appropriate clinical context, the MRI finding of lobar white matter edema with evidence of prior hemosiderin deposition may indicate the presence of a reversible CAA leukoencephalopathy.

Urgent endovascular revascularization for symptomatic intracranial atherosclerotic stenosis.

BACKGROUND: Endovascular revascularization for intracranial atherosclerotic stenoses is being increasingly performed at major medical centers and has been reported to be technically feasible and safe. The authors report their experience with patients who underwent such a procedure for impending stroke and neurologic instability. METHOD: All 18 patients (21 intracranial lesions) treated between 1997 and 2002 at the authors' institution with endovascular revascularization were retrospectively reviewed. Each patient had failed maximal medical therapy and was thought to be at high risk for an imminent stroke. RESULTS: Endovascular revascularization was performed on eight distal internal carotid artery lesions, six middle cerebral artery lesions, four intracranial vertebral artery lesions, and three basilar artery lesions. Recanalization was complete in 5 arteries (Thrombolysis in Myocardial Infarction [TIMI] Grade III), partial in 14 arteries (TIMI Grade II), and complete occlusion (TIMI 0) developed in 1 artery. In a patient with a tight basilar stenosis, no angioplasty could be performed because of the inability to cross the stenosis with the guidewire. Major periprocedural complications occurred in 9 (50%) patients: intracranial hemorrhage in 3 (17%), disabling ischemic stroke in 2 (11%), and major extracranial hemorrhage in 4 (22%). Three patients died: one from intracerebral hemorrhage and two from cardiorespiratory failure. CONCLUSIONS: Endovascular revascularization of intracranial vessels is technically feasible and may be performed successfully. However, periprocedural complication and fatality rates in neurologically unstable patients are high. The results suggest that patient selection, procedure timing, and periprocedural medical management are critical factors to reduce periprocedural morbidity and mortality.

Pituitary lymphoma presenting as fever of unknown origin.

An 86-yr-old woman presented with fever of unknown origin. When laboratory evaluation revealed partial hypopituitarism, a magnetic resonance imaging scan of the head was performed and revealed a sellar mass consistent with a pituitary adenoma. Only after other possible etiologies for fever were excluded did she undergo transsphenoidal resection of the sellar mass, which proved to be a B-cell lymphoma. Primary central nervous system lymphoma of the pituitary region is a rare cause of a sellar mass, and this is the first reported case of pituitary lymphoma whose presenting manifestation was fever of unknown origin. Several disease processes can manifest themselves as fever and a sellar mass, including lymphomas. In our case, only surgical biopsy could make a diagnosis and distinguish this process from the more common pituitary adenoma.

Sarcoidosis within a pituitary adenoma.

A 54 year old man presented with frontal headaches for one year. A CT scan of the head revealed a pituitary mass. He denied a change in vision or galactorrhea, but did have decreased frequency of erections and a recent episode of renal stones. On physical exam, the cranial nerves were normal. Visual field exam revealed mild bilateral temporal defects. The genitalia were normal and the testes were soft. Laboratory evaluation revealed: Na, 134 mM/l; K, 6.7 mM/l; Cl, 104 mM/l; HCO3, 22 mM/l; BUN, 47 mg/dl; Cr, 8.3 mg/dl; Ca, 12.5 mg/dl; Phos, 5.5 mg/dl; prolactin, 32.0 ng/ml; T4, 4.46 microg/dl; TSH, 2.07 microU/ml; LH, 18.1 mIU/ml; FSH 3.2 mIU/ml; alpha subunit 1.6 ng/ml; testosterone 255 ng/dl; cortisol, 20.3 microg/dl; cortisol after 250 microg cortrosyn, 38.5 microg/dl (time 60 minutes); growth hormone, 1.4 ng/ml; IGF-1, 47 ng/ml; PTH, <1 pg/ml; 25-hydroxyvitamin D, 14 ng/ml; 1,25-dihydroxyvitamin D, 69 pg/ml. These results were felt to be consistent with a non-PTH-mediated hypercalcemia, such as humoral hypercalcemia of malignancy, or a vitamin D-mediated hypercalcemia, such as lymphoma, sarcoidosis or tuberculosis. Head MRI demonstrated a 3.5 x 3.5 x 2.5 cm heterogeneous mass enlarging the sella, deforming the clivus and compressing the cavernous sinus, basilar artery and left side of the optic chiasm. There was a small focus of high signal in the superior part of the mass on the T1-weighted image from either a proteinaceous cyst with early calcium deposition or sub-acute blood. These radiographic findings were felt to be consistent with a pituitary adenoma. The patient was treated with intravenous hydration and thyroxine 50 microg daily and underwent a transsphenoidal resection of the pituitary lesion. Pathologic examination revealed a pituitary adenoma with multiple granulomas and crystalline material; this was consistent with sarcoid within the adenoma. Post-operatively, the serum LH fell to 5.5 mIU/ml. A subsequent transbronchial biopsy revealed multiple non-caseating granulomas. A serum ACE level was elevated at 132.6 U/l. He received oral prednisone 60 mg daily with resolution of the hypercalcemia. Neurosarcoidosis occurs in 5 to 15% of patients with sarcoidosis and can involve the hypothalamus and pituitary gland. This is the first reported case of sarcoidosis occurring within a pituitary adenoma.

A modified transorbital baboon model of reperfused stroke.

BACKGROUND AND PURPOSE: Although pathophysiological studies of focal cerebral ischemia in nonhuman primates can provide important information not obtainable in rodent models, primate experimentation is limited by considerations of cost, availability, effort, and ethics. A reproducible and quantitative model that minimizes the number of animals necessary to detect differences between treatment groups is therefore crucial. METHODS: Eight male baboons (weight, 22+/-2 kg) underwent left transorbital craniectomy followed by 1 hour of temporary ipsilateral internal carotid artery occlusion at the level of the anterior choroidal artery together with bilateral temporary occlusion of both anterior cerebral arteries (A1) proximal to the anterior communicating artery. A tightly controlled nitrous oxide-narcotic anesthetic allowed for intraoperative motor evoked potential confirmation of middle cerebral artery (MCA) territory ischemia. Animals survived to 72 hours or 10 days if successfully self-caring. Outcomes were assessed with a 100-point neurological grading system, and infarct volume was quantified by planimetric analysis of both MRI and triphenyltetrazolium chloride-stained sections. RESULTS: Infarction volumes (on T2-weighted images) were 32+/-7% (mean+/-SEM) of the ipsilateral hemisphere, and neurological scores averaged 29+/-9. All animals demonstrated evidence of hemispheric infarction, with damage evident in both cortical and subcortical regions in the MCA vascular territory. Histologically determined infarction volumes differed by <3% and correlated with absolute neurological scores (r=0.9, P:=0.003). CONCLUSIONS: Transorbital temporary occlusion of the entire anterior cerebral circulation with strict control of physiological parameters can reliably produce reperfused MCA territory infarction. The magnitude of the resultant infarct with little interanimal variability diminishes the potential number of animals required to distinguish between 2 treatment regimens. The anatomic distribution of the infarct and associated functional deficits offer comparability to human hemispheric strokes.

Radiation doses during CT fluoroscopy.

CT fluoroscopy (CTF) is a relatively new imaging modality that is particularly useful for performing complex biopsy procedures. Despite the obvious benefits, the potential exists to deliver considerable radiation doses to both the patients and medical staff. The purpose of our study was to quantify the radiation levels based upon typical clinical procedures. To assess the potential radiation risks, the patient radiation doses via the CT dose index (CTDI) method were measured during CTF for a GE Pro-Speed CT scanner using standardized head and body phantoms and a CT ionization chamber. The measurements were performed for a variety of kVp, mA, and slice thickness settings. To determine patient radiation doses, the CT kVp, mA, and total CTF scan times were recorded for various biopsy procedures. To determine the radiation doses to the hands of the radiologists, a radiation survey meter was used to measure the scattered radiation from standard phantoms. The effectiveness of various types of leaded gloves and shields were also determined. The measured CTDI values ranged from 20.4 cGy min(-1) to 63.1 cGy min(-1) of CTF. For a group of 78 patients, the clinically utilized imaging times varied from 13.0 to 407 s with an mean time of 96.6 s +/- 78.9 s (1 standard deviation). The scattered x-ray radiation at the position of the radiologists hands performing the biopsy procedures was measured to be 0.6 to 1.5 mGy min(-1). The thin leaded gloves provided a relatively minimal reduction in the scattered radiation to the hands between 11% and 44% dependent upon the kVp and the type of glove. However, floor mounted radiation shields reduced the scattered radiation levels to the body by 94% to 99%. In comparison to standard x-ray fluoroscopy, CTF employs much higher radiation dose rates due to the higher kVp, mA, and rotating geometry. It is important to minimize the radiation dose to patients and staff by limiting the imaging times, employing lower mA settings, and using appropriate radiation protection measures.

Management of residual dysplastic vessels after cerebral arteriovenous malformation resection: implications for postoperative angiography.

OBJECTIVE: The verification of surgical resection of cerebral arteriovenous malformations (AVMs) relies on angiography. Abnormal vasculature often is identified after removal of the AVM. Differentiation of dysplastic feeding vessels that resemble the neovascularity of moyamoya disease, as distinct from residual AVM, is crucial for preserving critical brain areas. We review a large experience with immediate postoperative angiography after AVM resection and discuss the implications for management of abnormal dysplastic vessels discovered after AVM resection. METHODS: Beginning in 1992, 86 consecutive patients with AVMs underwent operations by standard protocol for immediate postoperative angiography under the same general anesthetic. Angiographic interpretation dictated admission to the intensive care unit or return to the operating room for further resection. RESULTS: In 78 patients, the angiogram revealed complete resection. Two patients were returned to the operating room, one for residual malformation with an early draining vein, and one for resection of residual dysplastic vessels. There was one postoperative hemorrhage in a patient whose postoperative angiogram was falsely negative for AVM. Six patients with residual dysplastic vessels mimicking residual AVM, but without an early draining vein, were managed conservatively. Delayed follow-up angiography demonstrated spontaneous involution of these abnormal vessels in all of these patients. CONCLUSION: Residual dysplastic feeding vessels resembling the neovascularity of moyamoya disease but not associated with an early draining vein do not necessarily represent residual malformation after AVM resection. The abnormal vessels will proceed to complete spontaneous resolution. Given the difficulty of interpreting intraoperative angiography, immediate postoperative angiography may be a viable alternative after AVM resection.

Spinal myoclonus induced by an intrathecal catheter.

We report a case of spinal myoclonus induced by the tip of an intrathecal catheter in a 35-year-old patient with severe, adult-onset, generalized dystonia of unknown cause, treated for 2 years using intrathecal baclofen. One month after a falling episode, the patient developed focal myoclonus of the right proximal leg whenever she stood up from a seated position. The electrophysiologic recordings were compatible with spinal segmental myoclonus, originating at a focus corresponding to the L2-S2 segments. At this site, the tip of the intrathecal catheter was demonstrated by myelography to be in close proximity to the nerve roots and conus medullaris. The myoclonus resolved promptly once the catheter tip was withdrawn. We review the literature on spinal myoclonus and discuss the possible mechanisms of spinal myoclonus pertaining to the present case. This report represents an unusual complication of intrathecal catheter systems that, if recognized, can lead to prompt therapeutic intervention.

Massive intracranial arachnoid cyst in a developmentally normal infant: case report and literature review.

Intracranial arachnoid cysts are developmental anomalies that are generally asymptomatic. We describe a 6-month-old boy with macrocephaly but normal neurological development who was found to have a rare, massive basal arachnoid cyst occupying most of the cranium and extending superiorly, causing significant shift due to mass effect. A cystoperitoneal shunt was placed, producing both a decrease in the arachnoid cyst dimensions and a concomitant reexpansion of parenchyma. After consideration of various management options, such a shunt system appears to offer a low risk of complications and a high likelihood of success.

Radiographic features of central nervous system vasculitis.

Central nervous system (CNS) vasculitis refers to primary and secondary disorders of the CNS vasculature. Most authorities agree that CNS vasculitis is a potentially serious disorder; therefore, prompt diagnosis and initiation of therapy are high priorities in treatment. Remarkable progress has been made in the diagnosis, evaluation, and treatment of this disorder. This article examines many aspects of the radiographic evaluation of CNS vasculitis.

Atlantoaxial degenerative articular cysts.

Cysts associated with spinal joints are not a common cause of neurological symptoms. The authors report a series of five patients with cysts of the atlantodental articulation and review five additional cases from the literature. The patients ranged from 60 to 85 years of age and included three men and seven women. No patient had evidence of rheumatoid arthritis or previous trauma. The cysts caused ventral cervicomedullary compression, did not enhance on magnetic resonance imaging, and were not associated with widening of the anterior atlantodental interval or osseous degeneration of the dens. All patients improved postsurgery. Fusion was required if a transoral procedure was performed. Patients undergoing posterior decompressions were clinically and radiographically stable after operation.

Subacute sclerosing panencephalitis and acquired immunodeficiency syndrome: role of electroencephalography and magnetic resonance imaging.

Subacute sclerosing panencephalitis (SSPE) had largely disappeared from the United States because of nearly universal measles vaccination, but it has reemerged in children infected with human immunodeficiency virus (HIV). Two children with SSPE are described. The first was HIV positive and presented with seizures and encephalopathy at the age of 21 months. The second developed myoclonus and dementia at age 4 years; she was not infected with HIV, but her mother had acquired immunodeficiency syndrome. Magnetic resonance imaging findings were nonspecific and could have been compatible with HIV encephalopathy. Electroencephalography was characteristic of SSPE, showing high-voltage, periodic slow-wave complexes and background slowing. The diagnosis of SSPE was confirmed by brain biopsy or high measles antibody titers in the cerebrospinal fluid.

Electroencephalography in lacunar infarction.

To determine the occurrence and clinical implications of electroencephalographic (EEG) abnormalities in patients with acute lacunar infarction, we conducted a single-blinded EEG study in 55 patients. Twenty-nine (53%) had mild EEG abnormalities, which were focal and ipsilateral to the side of infarction in 7 patients (13%). Abnormalities were more common in patients with evidence of a prior stroke (10 of 12 patients, 83%). However, 43% (16 of 37 patients) of those without historical or radiologic evidence of a prior stroke also had mild EEG abnormalities. This represents a higher incidence of routine EEG abnormalities in lacunar infarction than is generally assumed. Indeed, these findings are more consistent with recent quantitative EEG studies that consistently have shown high rates of abnormalities in lacunar infarction. We did not find major EEG abnormalities, such as continuous or nearly continuous focal delta activity, in any patient with first lacunar infarction. We conclude that within the first 48 h after a first ischemic infarction, when computed tomography often fails to show abnormalities, an EEG that shows lateralized major abnormalities is useful in excluding the diagnosis of either lacunar infarction or infarction limited to the brain stem. Mild abnormalities occur more often than previously thought in lacunar infarction and do not exclude this diagnosis.

A comparison of cerebral SPECT abnormalities in HIV-positive homosexual men with and without cognitive impairment.

OBJECTIVE: To determine whether technetium Tc 99m exametazime (HMPAO) single-photon emission computed tomography (SPECT) can distinguish between human immunodeficiency virus (HIV)-positive homosexual men with normal neuropsychologic test results and HIV-positive homosexual men with abnormal neuropsychologic test results. DESIGN: Neurologic, neuropsychologic, magnetic resonance imaging, and Tc 99m HMPAO SPECT examinations were performed on 10 HIV-positive homosexual men without cognitive impairment and five HIV-positive homosexual men with cognitive impairment. PATIENTS: Human immunodeficiency virus-positive homosexual men from New York City were recruited for the study. MAIN OUTCOME MEASURES: Findings on SPECT scans were evaluated qualitatively for focal defects, heterogeneity of the cortical margin, white matter hypoperfusion, and decreased global cortical uptake. All SPECT focal defects were coregistered with magnetic resonance images; SPECT heterogeneity and global cortical uptake were also measured quantitatively. RESULTS: Coregistration with magnetic resonance imaging revealed that 63% of the focal SPECT defects corresponded to brain gyri and 37% corresponded to sulci. There was no significant difference in the frequency of qualitative or quantitative SPECT abnormalities between HIV-positive homosexual men ith and without cognitive impairment. However, after examining individual neuropsychologic test factors, impaired motor speed performance was associated with decreased quantitative global cerebral uptake. CONCLUSIONS: Qualitative SPECT abnormalities are not increased in frequency in HIV-positive homosexual men with global cognitive impairment compared with those in HIV-positive homosexual men without cognitive impairment. Impaired motor speed performance may be associated with decreased quantitative global cerebral uptake.

Effects of coregistration of MR to CT images on MR stereotactic accuracy.

Coregistration of different modality imaging serves to increase the ease and accuracy of stereotactic procedures. In many cases, magnetic resonance (MR) stereotaxis is supplanting computerized tomography (CT). The advantages of increased anatomical detail and multiplanar imaging afforded by MR, however, are offset by its potential inaccuracy as well as the more cumbersome and less available nature of its hardware. A system has been developed by one of the authors by which MR imaging can be performed separately without a stereotactic fiducial headring. Then, immediately prior to surgery, a stereotactic CT scan is obtained and software is used to coregister CT and MR images anatomically by matching cranial landmarks in the two scans. The authors examined this system in six patients as well as with the use of a lucite phantom. After initially coregistering CT and MR images, six separate anatomical (for the patients) and eight artificial (for the phantom) targets were compared. With coregistration, in comparison to CT fiducial scans, errors in each axis are less than or equal to 1 mm using the Cosman-Roberts-Wells system. In fact, the coregistered images are more accurate than MR fiducial images, in the anteroposterior (p = 0.001), lateral (p < 0.05), and vertical (p < 0.03) planes. Three-dimensional error was significantly less in the coregistered scans than the MR fiducial images (p < 0.005). The coregistration procedure therefore not only increases the case of MR stereotaxis but also increases its accuracy.

Fetomaternal hemorrhage as an etiology of neonatal stroke.

We report a term infant who presented with focal seizures and was diagnosed with a large left hemispheral infarct. Evaluation revealed extensive fetomaternal hemorrhage and subsequent neuroimaging disclosed a classic border zone infarct consistent with a hypoperfusion injury. We postulate that fetomaternal hemorrhage should be considered in the differential causation of neonatal stroke. The unilaterality of the lesion in this patient is difficult to explain.