Faculty Bibliography

BACKGROUND:Cholinesterase inhibitors with additional nicotinic activity, such as galantamine, may be useful in PD patients with dementia (PDD) since stimulation of nicotinic receptors may prevent the down-regulation that is likely to accompany cholinesterase inhibition and facilitate dopamine release in the striatum. METHODS:Sixteen PDD patients (six female) with onset of cognitive impairment after at least one year with parkinsonism participated in this open-label trial of galantamine. Cognitive, psychiatric, and motor symptoms were assessed before and after 8 weeks of treatment with galantamine using unstructured clinical assessment as well as rating scales including the Mini-Mental State Examination (MMSE), clock drawing test, verbal fluency and selected items from the Neuropsychiatric Inventory (NPI). RESULTS:Age (mean, SD) was 75.6 (5.2) years, duration of PD 13.4 (5.9), duration of dementia 2.1 (1.7) years, Hoehn and Yahr score was 3.8 (0.8) and baseline MMSE score was 17.7 (6.7). Side-effects caused discontinuation in three patients, but were rare and mild in the remaining 13. Improvement of global mental symptoms was noted in eight patients, whereas worsening was reported in four. Hallucinations improved in seven of the nine patients with hallucinations before treatment. Parkinsonism improved in six patients, but a mild worsening of tremor was noted in three. Clock-drawing improved (p=0.016), and trends towards improvement on MMSE (p=0.09) and verbal fluency (p=0.16) were found. CONCLUSIONS:Although controlled trials are needed, the findings suggest that galantamine is useful in patients with PDD.

RATIONALE AND OBJECTIVES: Recently developed MR imaging techniques using inversion recovery are a sensitive tool to identify and quantify morphologic changes in the substantia nigra due to neurodegeneration. Using a semi-automated computer segmentation technique to isolate the substantia nigra pars compacta (SN(c)), we propose a colored image fusion technique to visually assess the sites of damage in the SN(c) and integrate the information obtained from two implemented inversion-recovery sequences. PATIENTS AND METHODS: Six patients and six age-matched control subjects were scanned using a combination of two MR imaging inversion-recovery (IR) pulse sequences. A subgroup of them was used to develop our technique. Images were blended together into a final (RGBA) image, where A stands for the alpha channel describing transparency. RESULTS: Abnormalities in the SN(c) can be accurately assessed in location, shape, and variations of signal intensities within the segmented SN(c) by varying the transparency (alpha) channel of the color fusion image. Several previous findings such as the lateral-medial gradient of signal change and a ventral-dorsal broadening of the pars compacta are accompanied by an overall mild-to-severe heterogeneity of neurodegeneration patterns. CONCLUSION: Color fusion techniques revealed subtle changes in the neurodegeneration of the substantia nigra in Parkinson disease, which can be helpful for an objective and hence effective visual assessment of disease progression

OBJECTIVE: To determine the metabolic topography of essential blepharospasm (EB). BACKGROUND: EB is a cranial dystonia of unknown etiology and anatomic localization. The authors have used 18F-fluorodeoxyglucose (FDG) and PET with network analysis to identify distinctive patterns of regional metabolic abnormality associated with idiopathic torsion dystonia (ITD), as well as sleep induction during PET imaging to suppress involuntary movements, thereby reducing this potential confound in the analysis. METHODS: Six patients with EB and six normal volunteers were scanned with FDG-PET. Scans were performed twice: once in wakefulness and once following sleep induction. The authors used statistical parametric mapping to compare glucose metabolism between patients with EB and control subjects in each condition. They also quantified the expression of the previously identified ITD-related metabolic networks in each subject in both conditions. RESULTS: With active involuntary movements during wakefulness, the EB group exhibited hypermetabolism of the cerebellum and pons. With movement suppression during sleep, the EB group exhibited superior-medial frontal hypometabolism in a region associated with cortical control of eyelid movement. Network analysis demonstrated a specific metabolic covariance pattern associated with ITD was also expressed in the patients with EB in both the sleep and wake conditions. CONCLUSION: These findings suggest that the clinical manifestations of EB are associated with abnormal metabolic activity in the pons and cerebellum, whereas the functional substrate of the disorder may be associated with abnormalities in cortical eyelid control regions. Furthermore, ITD-related networks are expressed in patients with EB, suggesting a functional commonality between both forms of primary dystonia

BACKGROUND AND PURPOSE: The possibility of using MR imaging as a sensitive marker of the structural changes in Parkinson's disease has been a long-sought goal. We describe a new method for imaging and quantifying the morphologic changes of the substantia nigra in Parkinson's disease and compare radiologic findings with clinical evaluation. METHODS: Using a combination of two MR imaging inversion-recovery pulse sequences, the substantia nigra was imaged in six patients with Parkinson's disease and six age-related control participants. A radiologic index was defined and used to quantify the signal changes that were observed in the patients. The radiologic index was compared with clinical scores obtained from the Unified Parkinson's Disease Rating Scale. RESULTS: The images showed loss of signal in a lateral-to-medial gradient in cases of Parkinson's disease, corresponding to the known neuropathologic pattern of degeneration. The radiologic index was highly correlated with the Unified Parkinson's Disease Rating Scale score, and there was no overlap in radiologic indices between the patient and the control groups (P < .00005). CONCLUSION: This study suggests that MR imaging is sensitive to structural changes in even the earliest cases of Parkinson's disease, thereby indicating the potential for detecting presymptomatic disease. Furthermore, a radiologic measure has been defined that correlates with the conventional clinical measure of disease severity. Therefore, MR imaging could prove to be a sensitive biological marker for objective staging of the disease

RATIONALE AND OBJECTIVES: The authors designed a segmentation technique that requires only minimal operator input at the initial and final supervision stages of segmentation and has computer-driven segmentation as the primary determinant of lesion boundaries. The technique was applied to compute total T2-hyperintense lesion volumes in patients with multiple sclerosis (MS). A semi-automated segmentation technique is presented and shown to have a test-retest reliability of <5%. MATERIALS AND METHODS: The method used a single segmented section with MS lesions. A probabilistic neural net performed segmentation into four tissue classes after supervised training. This reference section was deconstructed into the entire set of possible 4 x 4-pixel subregions, which was used to segment all-brain sections in steps of 4 x 4-pixel, adjacent image blocks. Intra- and interimage variabilities were tested by using 3-mm-thick, T2-weighted, dual-echo, spin-echo MR images from five patients, each of whom was imaged twice on the same day. Five different reference sections and three temporally separated. training sessions involving the same reference section were used to test the segmentation technique. RESULTS: The coefficient of variation ranged from 0.013 to 0.068 (mean +/- standard deviation, 0.037 +/- 0.039) for results from five different reference sections for each brain and from 0.007 to 0.037 (mean, 0.027 +/- 0.021) for brains segmented with the same reference section on three temporally separated occasions. Test-retest (intra-imaging) reliability did not exceed 5% (except for a small lesion load of 1 cm3 in one patient). Interimaging differences were approximately 10%. CONCLUSION: The segmentation technique yielded intra-imaging variabilities (2%-3%, except for very small MS lesion loads) that compare favorably with previously published results. New repositioning techniques that minimize imaging-repeat imaging variability could make this approach attractive for resolving MS lesion detection problems

In general, image analysis of cognitive experiments using functional magnetic resonance imaging techniques has emphasized those regions of the brain where increases in signal intensity, with regard to the reference state, are associated with activation. Nevertheless, a number of recent papers have shown that there are areas of deactivation as well. In this study, we have used a univariate analysis and echo-planar functional magnetic resonance imaging to address the relationship of the reference state to the deactivations. We employed two dichotomous covert tasks, orthographic lexical retrieval and pure visual retrieval, to contrast with the reference state (baseline) of silent counting. Our analysis yielded extensive, task-specific landscapes of regional incremental and decremental responses. We have specifically demonstrated that the decremental responses are not due to activation in the reference state. We have also demonstrated that they are not an artifact of a specific part of the image analysis, and propose that they represent a physiological, task specific signal that should be considered an integral component of neural networks representing brain function

OBJECTIVES: To use MRI in a novel way to image and quantify the changes occurring in the substantia nigra in Parkinson's disease. METHODS: Six patients with idiopathic Parkinson's disease were compared with six age matched control subjects. The subjects were imaged using a combination of pulse sequences hypothesised to be sensitive to cell loss. RESULTS: The images showed patterns of change in patients with Parkinson's disease. Highly significant differences between the patients and control population were found (p<0.001). CONCLUSIONS: This methodology suggests the possibility of detecting presymptomatic disease in those judged to be at risk, and also in confirming the diagnosis in patients with early disease. Furthermore, the technique seems to hold promise as a means for staging the disease, and possibly differentiating other forms of parkinsonism

OBJECTIVES: Functional MRI (fMRI) holds the promise of non-invasive mapping of human brain function in both health and disease. Yet its sensitivity and reliability for mapping higher cognitive function are still being determined. Using verbal fluency as a task, the objective was to ascertain the consistency of fMRI on a conventional scanner for determining the anatomic substrate of language between subjects and between sexes. Comparison was made with previous PET studies. METHODS: Using a 1.5 Tesla magnet and an echoplanar pulse sequence, whole brain fMRI was obtained from 12 normal right handed subjects (6 males and 6 females) as they performed a verbal fluency task. RESULTS: A broadly consistent pattern of response was seen across subjects. Areas showing activation changes included the left prefrontal cortex and right cerebellum, in agreement with previous PET 15O-H2O studies. In addition, significantly decreased responses were seen in the posterior cingulate and over an extensive area of mesial and dorsolateral parietal and superior temporal cortices. The male cohort showed a slight asymmetry of parietal deactivation, with more involvement on the right, whereas the female cohort showed a small region of activation in the right orbitofrontal cortex. There were individual task related regional changes in all 12 subjects with the area showing the most significant change being the left prefrontal cortex in all cases. CONCLUSIONS: Magnetic resonance scanners of conventional field strength can provide functional brain mapping data with a sensitivity at least that of PET. Activation was seen in left prefrontal and right cerebellar regions, as with PET. However, decremental responses were seen over a much larger area of the posterior cortex than had been anticipated by prior studies. The ability to see a response in each subject individually suggests that fMRI may be useful in the preinterventional mapping of pathological states, and offers a non-invasive alternative to the Wada test for assessment of hemispheric dominance. There were no gross differences in the pattern of activation between male and female subjects

Brain activation is accompanied by local decreases in vascular deoxyhemoglobin. Theoretically, gradient-echo and spin-echo sequences show similar sensitivity to capillary deoxyhemoglobin, but spin-echo sequences should be less sensitive to venous deoxyhemoglobin. This is an important distinction in the context of cortical localization. We report herein a direct experimental comparison of a gradient-echo sequence (fast low-angle shot [FLASH]) with a spin-echo sequence (rapid acquisition with relaxation enhancement [RARE]) for functional MRI (fMRI) in seven subjects undergoing visual stimulation. A Student t test analysis was used to locate areas of significant activation, and then computerized image segmentation was performed to determine the type of activated tissue. Contrary to previous reports, both sequences proved equally sensitive to overall activation. RARE activation, however, was more specific for gray matter, as suggested by prior theoretical models