Effects of Stereo and Screen Size on the Legibility of Three-Dimensional Streamtube Visualization.

We report the impact of display characteristics (stereo and size) on task performance in diffusion magnetic resonance imaging (DMRI) in a user study with 12 participants. The hypotheses were that (1) adding stereo and increasing display size would improve task accuracy and reduce completion time, and (2) the greater the complexity of a spatial task, the greater the benefits of an improved display. Thus we expected to see greater performance gains when detailed visual reasoning was required. Participants used dense streamtube visualizations to perform five representative tasks: (1) determine the higher average fractional anisotropy (FA) values between two regions, (2) find the endpoints of fiber tracts, (3) name a bundle, (4) mark a brain lesion, and (5) judge if tracts belong to the same bundle. Contrary to our hypotheses, we found the task completion time was not improved by the use of the larger display and that performance accuracy was hurt rather than helped by the introduction of stereo in our study with dense DMRI data. Bigger was not always better. Thus cautious should be taken when selecting displays for scientific visualization applications. We explored the results further using the body-scale unit and subjective size and stereo experiences.

Severity of CIND and MCI predict incidence of dementia in an ischemic stroke cohort.

BACKGROUND: The utility of poststroke cognitive status, namely dementia, cognitive impairment no dementia (CIND), mild cognitive impairment (MCI), and no cognitive impairment (NCI), in predicting dementia has been previously examined. However, no studies to date have compared the ability of subtypes of MCI and CIND to predict dementia in a poststroke population. METHODS: A cohort of ischemic stroke patients underwent neuropsychological assessment annually for up to 5 years. Dementia was defined using the DSM-IV criteria. Univariate and multivariable Cox proportional regression was performed to determine the ability of MCI subtypes, CIND severity, and individual domains of impairment to predict dementia. RESULTS: A total of 362 patients without dementia were followed up for a mean of 3.4 years (17% drop out), with 24 developing incident dementia. Older age, previous and recurrent stroke, and CIND and MCI subtypes were significant predictors of dementia. In multivariable analysis controlling for treatment allocation, patients who were older, had previous or recurrent stroke, and had either CIND moderate or multiple domain MCI with amnestic component were at elevated risk for dementia. In multivariable domain analysis, recurrent strokes, age, and previous strokes, verbal memory, and visual memory were significant predictors of dementia. Receiver operating characteristic curve analysis showed that CIND moderate (area under the curve: 0.893) and multiple domain MCI with amnestic component (area under the curve: 0.832) were significant predictors of conversion to dementia. All other classifications of cognitive impairment had areas under the curve less than 0.7. CONCLUSION: Stroke patients with cognitive impairment no dementia (CIND) moderate are at higher risk of developing dementia, while CIND mild patients are not at increased risk of developing dementia.

Diffusion tensor imaging of normal-appearing white matter in mild cognitive impairment and early Alzheimer disease: preliminary evidence of axonal degeneration in the temporal lobe.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) is a sensitive technique for studying cerebral white matter. We used DTI to characterize microstructural white matter changes and their associations with cognitive dysfunction in Alzheimer disease (AD) and mild cognitive impairment (MCI). MATERIALS AND METHODS: We studied elderly subjects with mild AD (n = 6), MCI (n = 11), or normal cognition (n = 8). A standardized clinical and neuropsychological evaluation was conducted on each subject. DTI images were acquired, and fractional anisotropy (FA), axial diffusivity (DA), and radial diffusivity (DR) of normal-appearing white matter (NAWM) in frontal, temporal, parietal, and occipital lobes were determined. These diffusion measurements were compared across the 3 groups, and significant differences were further examined for correlations with tests of cognitive function. RESULTS: Compared with normal controls, AD subjects demonstrated decreased FA and increased DR in the temporal, parietal, and frontal NAWM and decreased DA in temporal NAWM. MCI subjects also showed decreased FA and decreased DA in temporal NAWM, with decreased FA and increased DR in parietal NAWM. Diffusion measurements showed no differences in occipital NAWM. Across all subjects, temporal lobe FA and DR correlated with episodic memory, frontal FA and DR correlated with executive function, and parietal DR significantly correlated with visuospatial ability. CONCLUSIONS: We found evidence for functionally relevant microstructural changes in the NAWM of patients with AD and MCI. These changes were present in brain regions serving higher cortical functions, but not in regions serving primary functions, and are consistent with a hypothesized loss of axonal processes in the temporal lobe.

Galantamine treatment of vascular dementia: a randomized trial.

BACKGROUND: To evaluate efficacy and safety of galantamine for patients with vascular dementia (VaD). METHODS: In this multinational, randomized, double-blind, placebo-controlled, parallel-group clinical trial, 788 patients with probable VaD who also satisfied strict centrally read MRI criteria were randomized to receive galantamine or placebo. Efficacy was evaluated using measures of cognition, daily function, and behavior. The primary efficacy measures were the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog/11) and the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) total score. Secondary outcomes included the Clinician's Interview Based on Impression of Change-Plus Caregiver Input (CIBIC-plus), Neuropsychiatric Inventory, and EXIT-25 for assessment of executive functioning. Safety and tolerability were also monitored. RESULTS: Patients treated with galantamine had a greater improvement in ADAS-cog/11 after 26 weeks compared with placebo (-1.8 vs -0.3; p < 0.001). There was no difference between galantamine and placebo at week 26 on the ADCS-ADL score (0.7 vs 1.3; p = 0.783). Improvement in global functioning measured by the CIBIC-plus associated with galantamine approached significance (p = 0.069). A difference between treatment groups for EXIT-25 favoring galantamine was detected (p = 0.041). Safety data revealed that 13% of galantamine and 6% of placebo patients discontinued treatment because of adverse events. CONCLUSIONS: Significance was not reached for both co-primary endpoints. Galantamine was effective for improving cognition, including executive function, in patients with vascular dementia, with good safety and tolerability. However, improvement in activities of daily living with galantamine was similar to that observed with placebo.

The relationship between homocysteine, cognition and stroke subtypes in acute stroke.

BACKGROUND: Elevations in plasma homocysteine (Hcy) have been associated with an increased risk of stroke and dementia. The mechanisms underlying these associations remain poorly understood. OBJECTIVES: This study examines the relationships between Hcy, cognition, and stroke subtype. We hypothesize that: 1) Hcy levels are inversely related to cognition, 2) Hcy levels are unrelated to stroke subtype, and 3) stroke subtype affects cognition. METHODS: We studied 169 consenting patients admitted for acute stroke during a 4 month period. Blood was drawn for Hcy levels and the Mini-Mental State Examination (MMSE) was administered within 9 days of admission. The Oxfordshire Community Stroke Project Classification was used to characterize stroke subtypes. Correlation between Hcy and MMSE scores was examined as was the relationships between Hcy and stroke subtype, and between stroke subtypes and MMSE scores. RESULTS: A significant inverse correlation between Hcy levels and MMSE scores was demonstrated (r=-0.243, p=0.001). MMSE scores also differed according to the type of stroke, with Total or Partial Anterior Circulation Infarcts (TACI/PACI) scoring lowest (F=8.77, df=2, p<0.001). Hcy levels did not differ between the various stroke subtypes (F=0.21, df=2, p=0.81). Multivariate linear regression analysis showed that age, education, and stroke subtype, but not Hcy, were independent predictors of acute MMSE scores. CONCLUSIONS: In this study sample, there was an inverse relationship between Hcy and cognition in acute stroke patients. However, Hcy was not an independent predictor for cognition in acute stroke after other factors such as stroke subtype and patient age were taken into account. These results suggest that during the acute stage of stroke, stroke subtype is a more important factor in determining cognition than Hcy levels.

Hemidystonia precipitated by acute pontine infarct.

Hemidystonia is frequently due to an underlying structural lesion in the basal ganglia and thalamus. It has been suggested that a preserved corticospinal tract may be required for hemidystonia to manifest. We provide the first report of a patient who presented with rapid-onset hemidystonia precipitated by an acute pontine infarct demonstrated on diffusion-weighted magnetic resonance imaging. Acute dysregulation of pallidal efferents to the pedunculopontine and/or pontine afferents to the thalamus may precipitate hemidystonia.

Late clinical and magnetic resonance imaging follow up of Nipah virus infection.

The Nipah virus is a newly identified paramyxovirus responsible for an outbreak of fatal encephalitis in Malaysia and Singapore. This paper reports the follow up clinical and magnetic resonance imaging findings in 22 affected subjects. Of 13 patients with encephalitis, one died, one was lost to follow up, and seven recovered. Among the four remaining patients, one had residual sixth nerve palsy, another suffered from severe clinical depression, and a third patient had evidence of retinal artery occlusion. One patient with delayed onset Horner syndrome had a single lesion in the cervical spinal cord. The brain magnetic resonance findings were stable or improved in nine patients over 18 months of follow up. Among a second group of nine asymptomatic seropositive abattoir workers, magnetic resonance examination in seven subjects revealed discrete small lesions in the brain; similar to those detected in encephalitis patients. These findings suggest that in addition to encephalitis, the newly discovered Nipah virus affects the spinal cord and the retina. Late clinical and radiological findings can occur in Nipah virus infections as with other paramyxoviruses.

Autonomic dysfunction in Parkinson's disease: a comprehensive symptom survey.

BACKGROUND: Autonomic dysfunction occurs in Parkinson's disease (PD), but few studies have addressed it in a comprehensive manner. METHODS: Autonomic symptoms were evaluated by a questionnaire in sixty-eight subjects (44 patients and 24 controls). RESULTS: PD patients experienced higher frequency and severity of autonomic dysfunction. When all autonomic symptoms were pooled into an aggregate score, differences between patients and controls were highly statistically significant (p<0.0001). 'Increased salivation', 'frequency of dysphagia', decreased 'BM (bowel movement) frequency', i.e. constipation, and 'orthostatic dizziness' were more frequent in PD patients (p<0.05). A prediction model to determine the predictors of autonomic dysfunction was unsuccessful. CONCLUSION: Differences in the prevalence of autonomic symptoms in PD and non-parkinsonian controls are apparent from this study.

Complex movement disorders following bilateral paramedian thalamic and bilateral cerebellar infarcts.

Complex movement disorders (CMD; including tremor, dystonias, choreoatheosis, and myoclonus) following infarcts in the posterior and posterolateral thalamic nuclei have been reported. This case of a 59-year-old man who developed CMD following bilateral paramedian and bilateral cerebellar infarcts illustrates the lack of anatomic specificity and the diverse pathophysiology which may underlie CMD.

Reversible parkinsonism in systemic lupus erythematosus.

Parkinsonism as a manifestation of central nervous system (CNS) lupus is extremely rare. We report the first patient with systemic lupus erythematosus (SLE) who developed a reversible parkinsonian syndrome associated with enhancing subcortical lesions on magnetic resonance imaging (MRI). Following treatment with prednisolone and cyclophosphamide, her bradyphrenia, bradykinesia, hypophonia, rigidity, and abnormal gait progressively improved. Three months after she commenced treatment, repeat MRI scanning demonstrated resolution of the abnormal subcortical white matter enhancement. Our case illustrates unusual clinico-radiologic correlates of reversible parkinsonism in a SLE patient; these findings suggest that disruption of the subcortical frontal pathways may be a possible pathophysiologic mechanism for parkinsonism in cerebral lupus.

Recurrent jaw dislocation after botulinum toxin treatment for sialorrhoea in amyotrophic lateral sclerosis.

Botulinum toxin (BTX) has been used successfully to treat various movement disorders, and is increasingly used for many other medical conditions. Sialorrhoea is a disabling symptom in many neurological patients including those with Parkinson's disease, stroke and amyotrophic lateral sclerosis (ALS). BTX has recently been shown to be effective for treating sialorrhoea. We report an ALS patient who developed recurrent jaw dislocation following BTX treatment for sialorrhoea to highlight the observation that intraparotid BTX may be complicated by jaw dislocations in some at-risk ALS patients. Clinicians using BTX to treat sialorrhoea in ALS need to be aware of this potentially serious complication.

Asia-Pacific Consensus Statement on dementia.

The 12 national Alzheimer's Associations that contributed to this Consensus Statement will continue to network with one another regionally and will continue to share relevant expertise and practical resources. It is expected that regional consensus on dementia will evolve in individual member countries and in the Asia-Pacific region as a whole. It is the hope of the participating members of these two consensus conferences that this document will provide the inspiration, direction, and practical ideas to further advance the goals of national Alzheimer's Associations and to further advance dementia-related medical and service activities within the Asia-Pacific region.

Asia regional meeting of the International Working Group for the Harmonization of Dementia Drug Guidelines: meeting report.

This meeting successfully catalyzed the establishment of a new working alliance between clinical dementia researches in Asia and identified common goals for the group to attain. The progress toward achieving these goals will be examined at the next Asia regional meeting, which is being planned for October 2002 in Beijing, China. This new regional working group will work with the IWG to overcome the existing methodological and regulatory obstacles impeding dementia treatment trials in Asia.

Treatment of agitation in AD: a randomized, placebo-controlled clinical trial.

BACKGROUND: Treatment of agitation is a crucial problem in the care of patients with AD. Although antipsychotic and antidepressant medications and behavior management techniques (BMT) have each been used to treat agitation, clinical trials of these treatments have been characterized by small sample sizes and uncontrolled treatment designs. OBJECTIVE: To compare haloperidol, trazodone, and BMT with placebo in the treatment of agitation in AD outpatients. METHODS: A total of 149 patients with AD and their caregivers participated in a randomized, placebo-controlled, multicenter trial. Blind assessment was conducted at baseline and after 16 weeks of treatment. The three active treatments were haloperidol, trazodone, and BMT. The Alzheimer's Disease Cooperative Study Clinical Global Impression of Change was the primary outcome measure. Secondary outcomes included patient agitation, cognition, and function, and caregiver burden. RESULTS: Thirty-four percent of subjects improved relative to baseline. No significant differences on outcome were obtained between haloperidol (mean dose, 1.8 mg/d), trazodone (mean dose, 200 mg/d), BMT, or placebo. Significantly fewer adverse events of bradykinesia and parkinsonian gait were evident in the BMT arm. No other significant difference in adverse events was seen. Symptoms did not respond differentially to the different treatments. CONCLUSIONS: Comparable modest reductions in agitation occurred in patients receiving haloperidol, trazodone, BMT, and placebo. More effective pharmacologic, nonpharmacologic, and combination treatments are needed.

Outbreak of Nipah-virus infection among abattoir workers in Singapore.

BACKGROUND: In March 1999, an outbreak of encephalitis and pneumonia occurred in workers at an abattoir in Singapore. We describe the clinical presentation and the results of investigations in these patients. METHODS: Clinical and laboratory data were collected by systemic review of the case records. Serum and cerebrospinal fluid (CSF) samples were tested for IgM antibodies to Nipah virus with an IgM capture ELISA. Reverse-transcriptase PCR was done on the CSF and tissue samples from one patient who died. FINDINGS: Eleven patients were confirmed to have acute Nipah-virus infection based on raised IgM in serum. Nipah virus was identified by reverse transcriptase PCR in the CSF and tissue of the patient who died. The patients were all men, with a median age of 44 years. The commonest presenting symptoms were fever, headache, and drowsiness. Eight patients presented with signs of encephalitis (decreased level of consciousness or focal neurological signs). Three patients presented with atypical pneumonia, but one later developed hallucinations and had evidence of encephalitis on CSF examination. Abnormal laboratory findings included a low lymphocyte count (nine patients), low platelet count, low serum sodium, and high aspartate aminostransferase concentration (each observed in five patients). The CSF protein was high in eight patients and white-blood-cell count was high in seven. Chest radiography showed mild interstitial shadowing in eight patients. Magnetic resonance imaging (MRI) showed focal areas of increased signal intensity in the cortical white marker in all eight patients who were scanned. The nine patients with encephalitis received empirical treatment with intravenous aciclovir and eight survived. INTERPRETATION: Infection with Nipah virus caused an encephalitis illness with characteristic focal areas of increased intensity seen on MRI. Lung involvement was also common, and the disease may present as an atypical pneumonia.

An analysis of test bias and differential item functioning due to race on the Mattis Dementia Rating Scale.

The Mattis Dementia Rating Scale (MDRS) is a commonly used cognitive measure designed to assess the course of decline in progressive dementias. However, little information is available about possible systematic racial bias on the items presented in this test. We investigated race as a potential source of test bias and differential item functioning in 40 pairs of African American and Caucasian dementia patients (N = 80), matched on age, education, and gender. Principal component analysis revealed similar patterns and magnitudes across component loadings for each racial group, indicating no clear evidence of test bias on account of race. Results of an item analysis of the MDRS revealed differential item functioning across groups on only 4 of 36 items, which may potentially be dropped to produce a modified MDRS that may be less sensitive to cultural factors. Given the absence of test bias because of race, the observed racial differences on the total MDRS score are most likely associated with group differences in dementia severity. We conclude that the MDRS shows no appreciable evidence of test bias and minimal differential item functioning (item bias) because of race, suggesting that the MDRS may be used in both African American and Caucasian dementia patients to assess dementia severity.

Demographic and clinical features of Alzheimer disease in black Americans: preliminary observations on an outpatient sample in Atlanta, Georgia.

This exploratory study describes the frequency, demographic features, and clinical manifestations of Alzheimer disease (AD) in a sample of demented black outpatients evaluated at the Emory University Alzheimer's Disease Center. The study reviews prospectively collected research data from 88 demented black outpatients who completed a standardized diagnostic evaluation. Forty-seven percent of these patients met NINCDS-ADRDA criteria for probable AD, and 29% met NINCDS-ADRDA criteria for possible AD. The majority of the probable AD patients were women, and many were suffering from comorbid medical illnesses. In the probable AD patients, there was an association between higher levels of education and a higher frequency of affective symptoms, and an association between longer duration of cognitive symptoms and the presence of parkinsonism. Possible AD was also common in this sample of demented black outpatients and was often encountered mixed with vascular dementia.

Dementia in urban black outpatients: initial experience at the Emory satellite clinics.

The purpose of this study is to describe demographic features and clinical diagnoses in a sample of demented urban black outpatients and to report the frequency of different causes of dementia in this patient sample. Retrospective chart review was used to identify demented black outpatients who had completed a full neurodiagnostic evaluation and had received clinical diagnoses using standardized research diagnostic criteria. Probable Alzheimer's disease was the most common cause of dementia in this sample (43% of cases). Probable vascular dementia was uncommon (7%). A multiple etiology dementia was identified in more than one third of the patients.