Bernard Verbeeten

Predicting Survival in Patients with Early Alzheimer’s Disease

We investigated whether an index based on clinical features, electroencephalogram and computed tomography is useful to predict survival in early Alzheimer’s disease. One hundred and sixty-three consecutively referred patients to an outpatient memory clinic and first diagnosed with Alzheimer’s disease (105 ‘probable’ and 58 ‘possible’, NINCDS-ADRDA criteria) were studied and outcome measure was death. Cox proportional hazards regression analysis and Kaplan-Meier survival curves were used to investigate relations between baseline parameters and survival. Eighty-four patients (51.5%) died during the follow-up period that extended to 5.8 years, with a median duration of survival after entry of 4.3 years. Baseline factors that were statistically significant and independently related to increased risk of mortality were high age, male sex, poor cognitive function as measured with the CAMCOG, low alpha and beta power on electroencephalogram, and temporoparietal atrophy on computed tomography scan. These results were independent of the diagnosis probable or possible Alzheimer’s disease. Based on the coefficients from the regression equation, we computed a survival index for each patient and we constructed three groups according to tertiles of this index. After 5.2 years of follow-up, survival curves showed a low mortality group with 81.7% patients alive (median survival at least 5.7 years), an intermediate mortality group with 35.9% patients alive (median survival 3.8 years), and a high mortality group with no patients alive (median survival 2.3 years). Log rank tests were statistically significant for comparisons between all three groups. We conclude that an overall index combining demographic, cognitive, electroencephalogram and computed tomography features is a strong predictor of survival in early Alzheimer’s disease.

Demonstration of a reduction in muscarinic receptor binding in early Alzheimer's disease using iodine-123 dexetimide single-photon emission tomography

Decreased muscarinic receptor binding has been suggested in single-photon emission tomography (SPET) studies of Alzheimers disease. However, it remains unclear whether these changes are present in mildly demented patients, and the role of cortical atrophy in receptor binding assessment has not been investigated. We studied muscarinic receptor binding normalized to neostriatum with SPET using [123I]4-iododexetimide in five mildly affected patients with probable Alzheimers disease and in five age-matched control subjects. Region of interest (ROI) analysis was performed in a consensus procedure blind to clinical diagnosis using matched magnetic resonance (MRI) images. Cortical atrophy was assessed by calculating percentages of cerebrospinal fluid in each ROI. An observer study with three observers was conducted to validate this method. Alzheimer patients showed statistically significantly less [123I]4-iododexetimide binding in left temporal and right temporo-parietal cortex compared with controls, independent of age, sex and cortical atrophy. Mean intea-observer variability was 3.6% and inter-observer results showed consistent differences in [123I]4-iododexetimide binding between observers. However, differences between patients and controls were comparable among observers and statistically significant in the same regions as in the consensus procedure. Using an MRI-SPET matching technique, we conclude that [123I]4-iododexetimide binding is reduced in patients with mild probable. Alzheimers disease in areas of temporal and temporoparietal cortex.

Single-photon emission computed tomography and early death in acute ischemic stroke.

Single-photon emission computed tomography with thallium-201-labeled diethyldithiocarbamate was performed in 26 consecutive patients less than or equal to 24 hours after a supratentorial brain infarction. Computed tomography excluded other relevant pathology. Two observers assessed the initial regional cerebral blood flow deficit using a semiquantitative visual method. The size of the initial flow deficit correlated negatively with the Barthel Index score (performance of the activities of daily living) after 6 months but not with the motricity index score (a measure of severity of the hemiparesis) after 6 months. The initial flow deficit was strongly correlated with early death from tentorial herniation; all five patients with the largest initial flow deficits died less than or equal to 6 days after the stroke, but among the 21 patients with smaller initial flow deficits only one died early (p = 0.00018, Fishers exact two-tailed test). Although depressed level of consciousness, conjugate gaze deviation, and severe hemiparesis were more prevalent in the group of six patients who died early, the differences in prevalence between this group and the 20 patients who survived were not significant. Single-photon emission computed tomography is a relatively simple method to semiquantitatively measure a blood flow disturbance immediately after its occurrence. The magnitude of this blood flow disturbance is strongly related to early death from tentorial herniation. Because of these properties, single-photon emission computed tomography to measure regional cerebral blood flow can be of great use in acute stroke research.

Perineural tumor extension along the trigeminal nerve: magnetic resonance imaging findings

OBJECTIVE To evaluate the magnetic resonance imaging (MRI) findings of 15 patients with perineural tumor extension along the trigeminal nerve in correlation with clinical data. METHODS The clinical records and MRI studies of 15 patients with perineural tumor extension along the trigeminal nerve were retrospectively reviewed. Imaging studies included plain and contrast-enhanced thin section T1-weighted spin echo (T1-WSE) MRI with and without fat-suppression. The studies were compared to determine which sequence provided greatest tumor conspicuity and best depiction of tumor extent. The conspicuity of these tumors was assessed on the available sequences by two observers by consensus. RESULTS The contrast-enhanced T1-weighted spin echo fat-suppressed images (T1-WSECEFS) demonstrated greatest tumor conspicuity and best depiction of tumor extent in the extracranial head and neck and skull base region. The conventional T1-weighted spin echo pre- and postcontrast images were, however, diagnostic of perineural tumor extension in 11 patients due to the presence of considerable tumor bulk and extension well above the skull base. In the other four patients the perineural tumor was poorly visualized on the conventional T1-WSE images and well visualized on the fat-suppressed images. The mandibular division of the trigeminal nerve (V3) was most commonly involved (n = 10), followed by the maxillary (V2; n = 5) and ophthalmic (V1; n = 2) division. Two patients had both mandibular as well as maxillary nerve involvement. The finding of perineural tumor extension had significant impact on patient management: based on the MR imaging study, the primary tumor was considered inoperable (n = 13), the extent of surgery was expanded (n = 2) and radiation therapy (RT) ports were extended (n = 12). CONCLUSION Complete trigeminal nerve imaging is recommended when evaluating (suspected) head and neck malignancies with a high risk for perineural extension. In these cases thin section axial and coronal precontrast T1-WSE MR images and postcontrast T1-WSE MR images with fat-suppression should be obtained. In the rare event that artifacts degrade the quality of the fat-suppressed images, contrast-enhanced T1-WSE sequences without fat-suppression can additionally be used.

Determinants of Quantitative Spectral Electroencephalography in Early Alzheimer’s Disease: Cognitive Function, Regional Cerebral Blood Flow, and Computed Tomography

Electroencephalography (EEG) bands may have different clinical or physiological correlates at initial diagnosis of Alzheimer’s disease (AD). We studied 163 consecutive patients with probable (n = 105) and possible (n = 58) AD with measurements of cognitive function (CAMCOG), regional cerebral blood flow (rCBF) with single photon emission computed tomography using technetium-99m-labeled hexamethylpropylene amine oxime, and computed tomography (CT). Lower CAMCOG scores were significantly and most strongly associated with lower parieto-occipital and fronto-central alpha power. In a separate analysis of cognitive domains, disturbances in language, praxis, attention, and abstraction were also significantly and most consistently related to decrease in alpha power. Presence of cortical atrophy as measured on CT showed some statistically significant relations with EEG bands, but these associations were not consistent. Lower temporal and parietal rCBF were significantly related to lower parieto-occipital alpha activity. Presence of leukoaraiosis was significantly associated with lower beta values, but also with higher absolute theta and delta activity. The results suggest that alpha on EEG is most closely linked to cognitive function and rCBF, while beta and theta activity more likely reflect lower cortical or subcortical changes. Our study thus provides evidence that the EEG bands reflect differential pathophysiologic changes in AD.

T2-Weighted Hyperintense MRI Lesions in the Pons in Patients With Atherosclerosis

BACKGROUND AND PURPOSE Pontine hyperintense lesions (PHL) on T2-weighted MRI have been recognized recently. Histopathological findings resemble periventricular leukoaraiosis, and a vascular etiology has been suggested. We studied the frequency and the associated factors of PHL in patients with symptomatic atherosclerosis. METHODS Two independent observers assessed brain MRIs in a prospective cohort of patients with symptomatic atherosclerosis. Only patients in whom both observers scored PHL on T2- and proton density-weighted images, but not on T1-weighted images, were considered to have the lesion. RESULTS We studied 229 patients 31% presenting with ischemic stroke, 31% with myocardial infarction, and 38% with peripheral artery disease. Both observers scored PHL in 23% of all patients. Patients with PHL were significantly older and had more lacunar infarcts and periventricular leukoaraiosis than patients without PHL. There were more women, more hypercholesterolemic and diabetic patients, and more cortical infarcts on MRI (P = NS). After logistic regression the presence of leukoaraiosis (odds ratio, 2.4; 95% confidence interval, 1.6 to 3.4) and lacunar infarcts (odds ratio, 2.2, 95% confidence interval, 1.5 to 3.1) remained independently associated with PHL. PHL was more common in patients with ischemic strokes (39%) than in patients with myocardial infarctions (11%) or peripheral artery disease (19%) (P < .001). CONCLUSIONS We found that PHL on T2- and proton density-weighted MR images are often found in patients with symptomatic atherosclerosis. The association with periventricular leukoaraiosis and lacunar infarcts suggests that PHL is a variant of leukoaraiosis, with possibly the same pathophysiology. The clinical symptoms and consequences of PHL, however, are not yet clear.

Electromyographic and Computed Tomographic Findings in Five Patients with Monomelic Spinal Muscular Atrophy

Five patients with monomelic spinal muscular atrophy are described. Clinical features included insidious onset of wasting and weakness of one limb, lack of involvement of the cranial nerves, brain stem, pyramidal tracts and sensory system, and a stable condition over a period of 4-20 years. Clinical findings, electromyography and/or muscle biopsy were consistent with anterior horn cell lesion. Central cavities were excluded by magnetic resonance imaging studies of the spinal cord. Computed tomography of skeletal musculature and electromyography indicated more diffuse lower motor neuron involvement by revealing abnormalities in clinically unaffected muscles in 4 of the 5 patients. Myokymic discharges were found in the affected limb of 1 patient.

Measurement of temporal regional cerebral perfusion with single-photon emission tomography predicts rate of decline in language function and survival in early Alzheimer's disease

Abstract. We determined the relationship between regional cerebral blood flow (rCBF) measured with single-photon emission tomography (SPET) and decline in cognitive function and survival in Alzheimer’s disease. In a prospective follow-up study, 69 consecutively referred patients with early probable Alzheimer’s disease (NINCDS/ADRDA criteria) underwent SPET performed at the time of initial diagnosis using technetium-99m-labelled hexamethylpropylene amine oxime. Neuropsychological function was assessed at baseline and after 6 months and survival data were available on all patients, extending to 5.5 years of follow-up. Lower left temporal (P<0.01) and lower left parietal (P<0.01) rCBF were statistically significantly related to decline in language function after 6 months. The association between left temporal rCBF and survival was also statistically significant (P<0.05) using Cox proportional hazards regression analysis. Performing analysis with quartiles of the distribution, we found a threshold effect for low left temporal rCBF (rCBF<73.7%, P<0.01) and high risk of mortality. In this lowest quartile, median survival time was 2.7 years (follow-up to 5.2 years), compared with 4.4 years in the other quartiles (follow-up to 5.5 years). Kaplan-Meier survival curves showed statistically significant (P<0.05, log rank test) survival curves for the lowest versus other quartiles of left temporal rCBF. All results were unaffected by adjustment for age, sex, dementia severity, duration of symptoms, education and ratings of local cortical atrophy. We conclude that left temporal rCBF predicts decline in language function and survival in patients with early probable Alzheimer’s disease, with a threshold effect of low rCBF and high risk of mortality.

Three-dimensional models of the tracheostoma using stereolithography

The availability of an accurate three-dimensional (3-D) model of the tracheostoma and trachea of the laryngectomy patient would be of great help in prototyping of endotracheal prostheses. Stereolithography has been described for skull and jaw models but never for soft-tissue reconstructions of the trachea. CT was performed on tracheostomas of 8 patients. The CT data were used to make 3-D models by means of stereolithography. Inverted CT data were used to create air contour models of the same tracheostomas. Eight soft-tissue and 8 air contour models were reconstructed from CT data, showing accuracy and great detail. In this paper we present a previously unreported application of the stereolithography technique. Measurements and prosthesis prototyping, which are impossible to perform on tracheostomas in patients, can now be executed safely. We are using the 3-D tracheostoma models in our research project to develop an endotracheal fixation method for tracheostomal valves.

Progressive multifocal leukoencephalopathy in a case of acquired immune deficiency syndrome

The case of a 40-year-old homosexual male with A.I.D.S. (Acquired Immune Deficiency Syndrome) and P.M.L. (Progressive Multifocal Leukoencephalopathy) is described. The importance of a brain biopsy for diagnostic procedures, especially in the case of a patient with A.I.D.S. is stressed. The diagnosis P.M.L. has been made by means of light- and electronic microscopical examination, and the presence of JCV-DNA in the brain tissue has been confirmed by dot hybridization. Various antiviral treatments did not show any effect on the course of the P.M.L.