Cognitive dysfunction evaluation in multiple sclerosis patients treated with interferon beta-1b: an open-label prospective 1 year study.
BACKGROUND
The cognitive impairment (frontal, parietal) in many patients with multiple sclerosis does not correlate with the degree of neurological disability and disease duration. Frontal/prefrontal cognitive impairment requires neuropsychological diagnostic tools.


OBJECTIVE
To evaluate the clinical effect of IFNbeta-1b (Betaferon) treatment on cognitive function and event-related potential as compared to the clinical course (EDSS) in MS patients during 1 year of follow-up.


METHODS
This prospective open-label design study included 16 consecutive patients with relapsing forms of MS attending the MS outpatient clinic. Mean EDSS score was calculated prior to starting treatment. Parietal lobe event-related potential P300 was elicited using an auditory physical stimulus to an alert subject. Mean P300 amplitude and latency were calculated for the group before treatment. The Wisconsin Card Sorting Test, which measures frontal lobe functions, was performed before the treatment. After 1 year of treatment a second P300 and Wisconsin test were performed and the mean change between visit 1 and baseline was calculated for each parameter. Correlation between the change in P300 and the Wisconsin test score at baseline was measured using the paired t-test.


RESULTS
There was a significant reduction in P300 amplitude and latency after 1 year of treatment with IFNbeta-1b: from 20.3 +/- 8.3 microv to 13.1 +/- 10.6 microv (P = 0.026) for amplitude, and from 312.9 +/- 15.6 msec to 302.0 +/- 17.0 msec (P = 0.002) for latency. The Perseverative Response (raw score) and the Perseverative Response U.S. Census age-matched standard score showed a significant improvement--from 20.7 +/- 30.7 to 13.1 +/- 10.6 (P = 0.001) and 96.7 +/- 15.7 to 100.1 +/- 11.1 (P = 0.0025) respectively--after 1 year of treatment. A mild but not significant improvement was observed on the EDSS after 1 year of treatment: 2.9 +/- 0.5 to 2.8 +/- 1.1.


CONCLUSIONS
A cognitive decline in MS patients may have a negative impact on the quality of life, affecting all active daily living domains. IFNbeta-1b, a disease-modifying therapy, has demonstrated a positive therapeutic effect on cognitive dysfunction, unrelated to its effect on the EDSS score and course of the disease.
Flechter
Shlomo
S
Multiple Sclerosis Clinical Research and Therapy Service, Department of Neurology, Assaf Harofeh Medical Center, Zerifin, Israel. shlomofl@asaf.health.gov.il
Vardi
Jacob
J
Finkelstein
Yoram
Y
Pollak
Lea
L
D000161:Acoustic Stimulation; D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000175:diagnosis* / Q000209:etiology; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects; D006801:Humans; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000188:drug therapy*; D009483:Neuropsychological Tests; D010044:Outpatient Clinics, Hospital; D010296:Parietal Lobe / Q000187:drug effects; D011446:Prospective Studies; D011788:Quality of Life; D013997:Time Factors; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D000068576:Interferon beta-1b; D016899:Interferon-beta