A conscientious hypertensive who had seizures after a trek.
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Drinking↗
Biomedical subjects
A D Korczyn
Publications and source records attributed to A D Korczyn.
High b value q-space-analyzed diffusion MRI in vascular dementia: a preliminary study.
High b value diffusion weighted magnetic resonance imaging (high-b DWI) was used to characterize white matter changes in the brain of patients with vascular dementia (VaD). Hyperintense white matter areas detected by T2-weighted magnetic resonance imaging (MRI) represent lesions, also termed leukoaraiosis that are very common in VaD as well as in other types of dementia. Therefore, the role of white matter changes in the cognitive and memory decline that occurs in VaD patients is still under debate. High-b DWI, analyzed using the q-space approach, is a more sensitive MRI method for detection of white matter changes. High-b DWI revealed massive white matter loss in VaD patients that surpassed the boundaries of T2 hyperintensities. This technique, therefore, might serve as a better indication for the extensive nerve fiber loss in the white matter that is caused by vascular disease.
Aged↗
High b-value q-space analyzed diffusion-weighted MRI: application to multiple sclerosis.
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) which affects nearly one million people worldwide, leading to a progressive decline of motor and sensory functions, and permanent disability. High b-value diffusion-weighted MR images (b of up to 14000 s/mm(2)) were acquired from the brains of controls and MS patients. These diffusion MR images, in which signal decay is not monoexponential, were analyzed using the q-space approach that emphasizes the diffusion characteristics of the slow-diffusing component. From this analysis, displacement and probability maps were constructed. The computed q-space analyzed MR images that were compared with conventional T(1), T(2) (fluid attenuated inversion recovery (FLAIR)), and diffusion tensor imaging (DTI) images were found to be sensitive to the pathophysiological state of white matter. The indices used to construct this q-space analyzed MR maps, provided a pronounced differentiation between normal tissue and tissues classified as MS plaques by the FLAIR images. More importantly, a pronounced differentiation was also observed between tissues classified by the FLAIR MR images as normal-appearing white matter (NAWM) in the MS brains, which are known to be abnormal, and the respective control tissues. The potential diagnostic capacity of high b-value diffusion q-space analyzed MR images is discussed, and experimental data that explains the consequences of using the q-space approach once the short pulse gradient approximation is violated are presented.
Animals↗
A six-month multicentre, double-blind, bromocriptine-controlled study of the safety and efficacy of ropinirole in the treatment of patients with Parkinson's disease not optimally controlled by L-dopa.
OBJECTIVES: To compare the safety and efficacy of ropinirole and bromocriptine as adjunct therapy in patients with Parkinson's disease (PD) not optimally controlled by L-dopa. METHODS: A randomised, double-blind trial in which 555 patients were assigned to three treatment groups according to the level of daily dosage of L-dopa, presence of motor fluctuations, and use of dopamine agonist before study entry. Patient response was defined as at least a 20% reduction in daily L-dopa dose plus: for patients with no prior treatment and no motor fluctuations, a 20% reduction in UPDRS motor score; for patients with motor fluctuations, a 20% reduction in time spent "off"; and for patients already taking an agonist, an improvement on the CGI scale. RESULTS: Safety assessments showed no significant differences in the two treatment groups for patients without prior dopamine-agonist therapy. In the group of patients with prior dopamine-agonist therapy, more patients reported adverse events in the ropinirole group (90% versus 79%, p < 0.001). The proportions of responders tended to be higher in ropinirole groups compared with bromocriptine groups and, in the subgroup with motor fluctuations, this difference was statistically significant (9.1% versus 0.0%, respectively; p < 0.05). CONCLUSIONS: Both drugs were well tolerated. In patients receiving a relatively high dose of L-dopa and requiring the addition of a dopamine agonist to control motor fluctuations or dyskinesias, ropinirole was significantly more effective than bromocriptine.
Adult↗
Quality of sexual life in Parkinson's disease.
Ninety-one consecutive patients with Parkinson's disease (PD) were asked to grade their general satisfaction from life (GSL) and completed the PDQ-39 and the quality of sexual life questionnaire (QoSL-Q). The reliability of the QoSL-Q was 0.74. Satisfaction from sexual life as reflected by the QoSL-Q significantly decreased with aging (P<0.01) and advanced disease (P<0.05). No correlation was found between the PDQ-39 and the QoSL index. The correlation between the PDQ-39 and GSL (r=-0.334) improved by adding the QoSL-Q, as a 9th dimension to the PDQ-39 (r=-0.405). The QoSL-Q is a reliable tool assessed a unique and important dimension not evaluated by the PDQ-39.
Aged↗
Dosing with ropinirole in a clinical setting.
OBJECTIVES: To determine the optimal dose of ropinirole (ReQuip) for treatment of early Parkinson's disease (PD). MATERIALS AND METHODS: Six-month data were gathered from three trials of monotherapy in patients with PD. RESULTS: Seventy-five percent of patients who experienced a therapeutic response did so at <or= 7.5 mg/day. Patients whose dose was increased by more than four titration levels from weeks 4-24 (mean total increase 14.8 mg/day) tended to show greater improvements than those whose dose increase was smaller (mean increase 3.4 mg/day) (17.4% vs 10.8%, respectively). Mean doses continued to increase throughout the 3- and 5-year trials (3-year trial at endpoint, 10.4 mg/day; 5-year trial at 3 years and at endpoint, 14.1 and 14.9 mg/day, respectively). CONCLUSION: Although a therapeutic response may be expected at <or= 7.5 mg/day, these data suggest a benefit for continued dose titration in most patients with early PD. For some patients, the maximum recommended dose (24 mg/day) may be necessary.
Adult↗
Stroke in hospitalized patients: are there special risk factors?
BACKGROUND AND PURPOSE: The occurrence of stroke in patients hospitalized for various illnesses remains a particular challenge for neurologists. Determining the potential causes for these particular cerebrovascular events may help to define the population at risk and to take measures in order to prevent stroke during hospitalization. The aim of our study was to evaluate the potential risk factors associated with stroke, which occurred in patients hospitalized for other illnesses. METHODS: This retrospective case-control study based on data of patients who underwent an ischemic stroke while being hospitalized not because of stroke and a control group of patients admitted during the same period who were matched for age and sex to the study patients. Common vascular risk factors, e.g. fever, leukocytosis, blood pressure, hemoglobin, cardiac arrhythmia and dehydration, were compared between the study and control groups. RESULTS: Of 2,247 consecutive patients with ischemic stroke, the stroke had occurred during hospitalization not related to any surgical procedure in 80 (3.5%). Six parameters were found as being significant independent risk factors for in-hospital stroke: fever and leukocytosis during hospitalization, elevated diastolic and unstable blood pressure, dehydration and past history of myocardial infarction. CONCLUSION: Careful monitoring of temperature, blood count, blood pressure, and clinical and laboratory signs of dehydration is needed to prevent in-hospital stroke.
Aged↗
Behavioral and cognitive deficits occur only after prolonged exposure of mice to antiphospholipid antibodies.
The antiphospholipid (Hughes) syndrome (APS) includes systemic and central nervous system (CNS) pathology associated with antibodies to a complex of phospholipids and beta2-glycoprotein I (beta2-GPI). Beta2-GPI immunized mice develop systemic manifestations of APS and we presently examined CNS manifestations in this APS model. Female BALB/c mice were immunized once with beta2-GPI in complete Freund's adjuvant (CFA) or with CFA alone (controls). A staircase test and a T-maze alternation test were performed to test behavior and cognition in independent groups of mice 6, 12 and 18 weeks following the immunization. The APS mice developed elevated levels of antibodies against negatively charged phospholipids and beta2-GPI. Neurological impairment was detected only 18 weeks after the induction of the APS and consisted of both cognitive (53 +/- 4 vs 71 +/- 3% correct choices in the T-maze alternation for APS vs control mice, P < 0.001) and behavioral changes (higher number of rears (18 +/- 2 vs 11 +/- 1, P < 0.006) and higher number of stairs climbed (12 +/- 2 vs 7 +/- 1, P < 0.02). This is the first report of cognitive deficits in this APS model and demonstrates the time course for the development of previously described behavioral changes. The mechanism involved in these CNS manifestations remains to be elucidated.
Animals↗
The effects of APOE genotype on age at onset and progression of neurodegenerative diseases.
APOE genotype influences the age at onset of some neurodegenerative diseases such as AD and the rate of progression in others such as MS. The authors hypothesize that APOE genotype ubiquitously determines the efficacy of neuronal maintenance and repair in these diseases and that the seemingly divergent clinical effects are due to the stage of disease at which the diagnosis is made. Early diagnosis facilitates the measurement of effects on disease progression rate, whereas late diagnosis results in a marked effect of APOE genotype on disease onset.
Age of Onset↗
The value of muscle exercise in patients with amyotrophic lateral sclerosis.
The role of physical activity for patients with amyotrophic lateral sclerosis (ALS) is controversial. Twenty-five ALS patients were randomized to receive a moderate daily exercise program (n=14) or not to perform any physical activity beyond their usual daily requirements (n=11). At baseline and after 3, 6, 9 and 12 months, patients were assessed by manual muscle strength testing, the Ashworth spasticity scale, ALS functional rating scale (FRS), fatigue severity scale, a visual analogue scale for musculoskeletal pain and the quality-of-life scale (SF-36). At 3 months, patients who performed regular exercise showed less deterioration on FRS and Ashworth scales, but not on other parameters. At 6 months, there was no significant difference between groups, although a trend towards less deterioration in the treated group on most scales was observed. At 9 and 12 months, there were too few patients in each group for statistical evaluation. Our results show that a regular moderate physical exercise program has a short-lived positive effect on disability in ALS patients and should be recommended.
Adult↗
Hallucinations in Parkinson's disease.
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Aged↗
Unverricht-Lundborg disease in a five-generation Arab family: instability of dodecamer repeats.
BACKGROUND: Unverricht-Lundborg disease (ULD) is the prototypical form of progressive myoclonus epilepsy, and subjects are usually very photosensitive. ULD is caused by mutations in the cystatin B (CSTB) gene; the most common mutation is expansion of a dodecamer repeat near the promoter. The authors studied a five-generation Arab family with ULD lacking photosensitivity. METHODS: An Arab family from the Galilee region of Israel with progressive myoclonus epilepsy was clinically evaluated. Blood samples were obtained from three living affected and 16 unaffected individuals. Expansion of dodecamer repeat in the CSTB gene was examined. RESULTS: The three living affected individuals showed spontaneous and action myoclonus, ataxia, and mild dementia. EEG in two individuals showed generalized polyspike-wave without photosensitivity. The family structure with large sibships and multiple consanguineous loops allowed the authors to examine the gene over four generations of adults. The three living affected individuals were homozygous for repeat expansions and 11 of the 16 unaffected family members were heterozygous. Instability was demonstrated by the presence of expansions of different sizes occurring on the same haplotype background in this inbred family. Fragment size variations could be unequivocally detected in two sibships. The expansions were in the 49 to 54 dodecamer repeat range. Changes in one generation were small, 1 to 4 repeat units, consisting of either enlargements or contractions. CONCLUSIONS: Instability of the expanded dodecamer repeats in the cystatin B gene is frequent. Almost invariably, a small change is observed in parent-child transmission. The lack of photosensitivity in this family is unexplained.
Adult↗
Association of APOE epsilon4 allele with survival in amyotrophic lateral sclerosis.
APOE epsilon4 allele is associated with poorer outcome in degenerative neurological diseases. Its role in amyotrophic lateral sclerosis (ALS) is still unclear. The aim of the present study was to further analyze the association of APOE epsilon4 allele with progression and survival of ALS. One hundred consecutive ALS patients (53 males) and 133 controls were genotyped for the APOE epsilon4 allele. The association of this allele with survival to death or tracheostomy was analyzed by Kaplan-Meier survival analysis. The frequency of the APOE epsilon4 allele in ALS patients was slightly higher (15.1%) than in the control group (10.9%). Patients with or without an APOE epsilon4 allele had a similar age of onset and frequency of bulbar onset. There was a significant shortening of the 50% probability of survival (by 32 months) in patients carrying the APOE epsilon4 allele (p=0.03). In conclusion, carrying an APOE epsilon4 allele is a poor prognostic factor in ALS. This is compatible with a role of apolipoprotein on neuronal survival and repair.
Adult↗
Quantitative measurements of mouse brain thrombin-like and thrombin inhibition activities.
Thrombin-like enzymatic activity was measured in mouse brain homogenates and slices by cleavage of a peptide substrate, N-p-Tosyl-Gly-Pro-Arg-7-amido-4-methylcoumarin. The activity was localized mainly to white matter. However, it was not affected by specific thrombin inhibitors, and was found to represent the sum of at least two enzyme activities, a prolyl endopeptidase and an aminopeptidase. By specifically inhibiting this endogenous activity in combination with exogenously added thrombin, mouse brain tissue was shown to express a capacity of thrombin inhibitory activity equivalent to 0.2 mU thrombin/mg brain tissue. The present study offers a simple and reliable method for measuring total thrombin inhibitory activity in brain.
Aminopeptidases↗
The nigrostriatal dopaminergic system in familial early onset parkinsonism with parkin mutations.
Nigrostriatal dopaminergic function and cerebral energy metabolism were measured with PET in two brothers with early-onset parkinsonism caused by mutation of the parkin gene. Energy metabolism did not differ, but the nigrostriatal dopaminergic pattern was clearly different than that of sporadic PD. Thus parkinsonism in these two patients was shown to be pathophysiologically different than PD.
Age of Onset↗
Autonomic dysfunction in experimental autoimmune neuritis: heart rate.
Autonomic nervous system (ANS) dysfunction occurs in more than half of Guillain--Barré syndrome (GBS) patients and is an important cause of death in the disease. In this study we examined heart rate (HR) changes in an animal model of GBS, experimental autoimmune neuritis (EAN), induced by immunization with myelin extracted from bovine spinal roots. The animals developed progressive motor weakness accompanied by significant weight loss and hypothermia. HR was measured in 33 EAN rats at rest (rHR) and followings stressful stimulation (sHR). Average pre-immunization rHR was 341+/-28 beats per minute (b.p.m.) and sHR was 486+/-21 bpm. Although the mean rHR in rats with EAN was not significantly different compared to that at baseline, there was a significant increase of variation of rHR with six rats demonstrating bradycardia (<280 b.p.m.) and 10 tachycardia (>400 b.p.m.) (P<0.01, F-test). sHR in EAN rats was significantly lower (P<0.01), suggesting sympathetic system impairment. These findings may serve as a basis for testing treatments of ANS dysfunction in EAN.
Animals↗
Antibodies to brain antigens following stroke.
Cerebral necrosis following stroke exposes brain antigens to the immune system, potentially initiating an antibody response. The authors measured levels of antibodies to specific neuronal antigens, neurofilaments (NF), and a ubiquitous antigen, cardiolipin (CL), in 45 patients following an acute first-ever stroke, within 48 hours, and 1, 3, and 6 months later. The mean levels of anti-NF antibodies were elevated compared with baseline at 1, 3, and 6, months (p = 0.012, 0.002, and 0.003 by paired t-test). Anti-CL levels did not change significantly.
Acute Disease↗
APOE genotype is a major predictor of long-term progression of disability in MS.
BACKGROUND AND OBJECTIVE: The authors recently reported that the APOE epsilon4 allele is associated with significantly greater progression of disability in a 2-year follow-up of patients with MS. In this study, these findings are substantiated and extended in a much larger group of patients followed for up to 40 years. METHODS: Two hundred five patients with clinically definite MS who were genotyped for the APOE epsilon4 carrier state were included. Groups of patients with (n = 41) and without (n = 164) APOE epsilon4 alleles were compared for latency to expanded disability status scale (EDSS) scores of 4.0 and 6.0 by Kaplan-Meier analysis with the log rank test. The results were adjusted for age at onset and sex by Cox regression analysis. RESULTS: The APOE epsilon4 allele frequency in patients with MS (0.10) was similar to that in the general Israeli population. There was a significant effect of APOE genotype on the latency to reach EDSS 4.0 and 6.0 (p = 0.0002 and p = 0.0006 by two-tailed log rank test). Median latencies were shorter by 12 and 11 years in the APOE epsilon4 group for these outcomes. These results were significant after adjustment for age at onset and sex. CONCLUSIONS: The APOE epsilon4 allele is associated with significantly faster progression of disability in MS. This is the first genetic factor to be identified with a major impact on the progression of disability in this disease.
Adult↗