Preliminary Observations On APOE Epsilon4 Allele And Progression Of Disability In Multiple Sclerosis
Chapman J, Sylantiev C, Nisipeanu P, Korczyn AD
Arch Neurol 1999 Dec;56(12):1484-7
Tel Aviv Medical Center, Dept of Neurology and NeuroImmunology Clinic, Israel
PMID# 10593303; UI# 20058876
Apolipoprotein E expression is increased in regenerating Neural tissue and the APOE epsilon4 allele is associated with impaired Neuronal repair.
Since repair is essential for the restoration of Central Nervous System function following Multiple Sclerosis (MS) relapses, APOE genotype may influence clinical progression of the disease.
To examine the association of the APOE genotype with disease susceptibility and progression in MS.
Patients And Methods
APOE genotyping was determined by polymerase chain reaction and restriction enzyme digestion in 47 patients with MS who had been followed up every 3 months for 2 years as part of an open-label clinical trial with Copaxone (Glatiramer Acetate).
The Expanded Disability Status Scale (EDSS) was used to assess clinical progression.
Nine patients were Heterozygous and 1 patient was Homozygous for the APOE epsilon4 allele, for a frequency of 12% (11/94), which is similar to that of the general Israeli population.
The APOE epsilon4 carriers had a mean +/- SE EDSS score of 3.10+/-0.45 at entry, which was not significantly different from the remaining 37 patients (2.62+/-0.25).
During the observation period, the EDSS score of the APOE epsilon4 carriers deteriorated to 4.00+/-0.63 while the other patients remained stable with an EDSS score of 2.74+/-0.31.
The interaction of genotype with disability over time was significant (P = .02 by repeated-measures analysis of variance). There were no differences in the number of relapses occurring in the 2 groups.
These preliminary observations suggest that APOE genotype may influence disease progression in MS. The APOE epsilon4 allele was not associated with an increased risk of MS or relapses.
Association Of The APOE Epsilon4 Allele With Disease Activity In Multiple Sclerosis
Evangelou N, Jackson M, Beeson D, Palace J
J Neurol NeuroSurg Psychiatry 1999 Aug;67(2):203-5
Univ of Oxford, Dept of Clinical Neurology, UK
PMID# 10406990; UI# 99337757
Allelic variants of the APOE Gene are known to influence the course of many neurological diseases and there is increasing evidence that ApoliPoprotein E (APOE) is a pivotal component in reinnervation and Dendritic remodelling after Neuronal injury.
Previous studies did not show significant differences in the APOE allele frequencies in Multiple Sclerosis compared with controls but did not examine for correlation with disease severity. This study explores the relation of APOE genotypes with the disease severity.
Ninety five patients with Multiple Sclerosis were studied. Age of onset, type, and activity of the disease were recorded prospectively and genotyping was performed according to standard protocols.
APOE allele frequencies of the group as a whole, the Relapsing group, or the Primary/Progressive group were not significantly different from those reported from matched historical controls.
The epsilon4 allele was found to be more common in patients with a more aggressive type of Multiple Sclerosis (odds ratio=2.95, p=0.03).
Although APOE does not seem to be implicated in the early PathoGenesis of the disease, patients possessing the epsilon4 allele might have a reduced capacity for Neuronal remodelling after relapses.
Disease Steps In Multiple Sclerosis: A Longitudinal Study Comparing Disease Steps And EDSS To Evaluate Disease Progression
Hohol MJ, Orav EJ, Weiner HL
Mult Scler 1999 Oct;5(5):349-354
Brigham and Women's Hospital, Multiple Sclerosis Unit of the Center for Neurologic Diseases, Dept of Medicine, Division of Neurology, Harvard Medical School, Boston, Massachusetts, USA
Clinical assessment of outcome in Multiple Sclerosis (MS) patients is problematic since the disease can affect different aspects of the Central Nervous System and follow a variable course. Recently, we developed Disease Steps, a simple approach for evaluating disease progression.
Previously, we found that Disease Steps was easy to use, had uniformly distributed scores and low inter-rater variability. Our current objective was to test the long-term use of Disease Steps together with the most widely utilized clinical outcome measure in MS, the Expanded Disability Status Scale (EDSS) in assessing clinical progression.
Over 4 years, 804 patients were classified using both EDSS and Disease Steps. Each patient was assessed at least twice. Follow-up results included annual status and time-to-event analysis examining median staying times within a level of Disease Steps or EDSS. We found that the two scales behaved similarly and correlated strongly with each other.
For both Disease Steps and EDSS, patients with milder levels of disability and Relapsing/Remitting disease demonstrated a higher likelihood of changing scores over time and shorter median staying times compared to more disabled, Chronic/Progressive patients.
These findings have important implications for patient selection in clinical trials and for the design of future measurements of clinical outcome in MS. Furthermore, Disease Steps may serve as a simple, practical tool for the nonspecialty Neurologist to follow patients over time and serve as a guide in therapeutic decision making.
Our findings further document the general progressive nature of MS when a large cohort is followed in an MS specialty clinic over time.
Serial Analysis Of Magnetization-Transfer Histograms And Expanded Disability Status Scale Scores In Patients With Relapsing/Remitting Multiple Sclerosis
Patel UJ, Grossman RI, Phillips MD, Udupa JK, McGowan JC, Miki Y, Wei L, Polansky M, van Buchem MA, Kolson D
AJNR Am J Neuroradiol 1999 Nov-Dec;20(10):1946-50
Florida Community Imaging Centers, Dept of Radiology, Dunedin, USA
PMID# 10588123; UI# 20053344
Background & Purpose
Magnetization Transfer ratio Histogram peak height (MTR-HPH) has been shown to correlate with Macroscopic and Microscopic Brain Disease in patients with Multiple Sclerosis (MS).
We studied the changes in MTR-HPH and in Kurtzke's Expanded Disability Status Scale (EDSS) scores over time in a group of patients with Relapsing/Remitting MS.
Twenty adult patients with Relapsing/Remitting MS (four men and 16 women) were followed up for a period of 334 to 1313 days. In all, 86 MR imaging studies of the Brain were obtained, and MTR-HPH was calculated for each MR examination by using a semiautomated technique.
Changes in MTR-HPH were compared between patients over the study's duration. A Neurologist specialized in the care of MS patients assessed the EDSS score for each patient as a measure of clinical disability.
Serial MR data showed a subtle but significant decline in MTR-HPH with time. No significant changes in EDSS scores were noted over the same period.
Patients with Relapsing/Remitting MS have a significant progressive decline in normalized MTR-HPH, which is independent of EDSS score.
MTR-HPH measurements can be used to monitor subclinical disease in patients with Relapsing/Remitting MS over a short time frame of 1 to 4 years. This parameter might be applied in future therapeutic trials to assess its usefulness.
APOE And Risk Of Cognitive Impairment In Multiple Sclerosis
Oliveri RL, Cittadella R, Sibilia G, Manna I, Valentino P, Gambardella A, Aguglia U, Zappia M, Romeo N, Andreoli V, Bono F, Caracciolo M, Quattrone A
Acta Neurol Scand 1999 Nov;100(5):290-5
Univ of Catanzaro, Institute of Neurology, Dept of Medical Sciences, Italy
PMID# 10536914; UI# 20005306
The APOE Gene polymorphism and the -491 A/T polymorphism in its regulatory region have been associated with an increased risk for developing Alzheimer's Disease.
We examined these polymorphisms in Multiple Sclerosis (MS) patients, to determine if a Genetic predisposition may explain the risk for developing Cognitive Decline in MS.
Material And Methods
Eighty-nine Relapsing/Remitting and Secondary/Progressive MS patients underwent to a full NeuroPsychological battery as well as to determination of APOE and -491 A/T polymorphisms. Genetic analysis was also performed in 107 population controls.
The APOE polymorphism was not associated with the risk of Cognitive Impairment in MS patients. The AA genotype of the -491 A/T polymorphism in the APOE regulatory region was more frequent in cognitively impaired than in Cognitively preserved MS subjects.
The AA homozygous state of the -491 A/T polymorphism of the APOE regulatory region is associated with Cognitive Impairment in patients with MS.