Multiple sclerosis progression in a natural history study: predictive value of cerebrospinal fluid free kappa light chains.
OBJECTIVE
To determine the relationship between baseline CSF immunologic abnormalities and MS disease progression; To determine progression rates in an untreated, recently-diagnosed MS sample using several validated clinical measures.


BACKGROUND
CSF immune abnormalities are common in MS but have not been linked to disease progression.


METHODS
Thirty-six patients with definite (n = 28), probable (n = 2), or possible (n = 6) MS were studied prospectively. Baseline CSF was analyzed for free kappa and lambda light chains, myelin basic protein, IgG synthesis rate, and IgG index. MS patients were entered into the study within 5 years of symptom onset and examined semiannually for as long as 53.4 months (median length of follow up 38.9 months). MS progression was defined as sustained worsening on the following clinical measurement instruments: the Expanded Disability Status Scale (EDSS), the Ambulation Index (AI), the 9 Hole Peg Test (9HT) and the Box and Blocks test (BBT). Kaplan-Meier estimates of disease progression were calculated and the relationship between baseline CSF values and disease progression was determined using Cox proportional hazards regression models.


RESULTS
By 36 months, 33% (95% CI = 10.3, 55.7) of patients had progressed on EDSS and 49.7% (95% CI = 27.7, 71.7) had progressed on at least one of the outcome measures. Patients with CSF free kappa chain levels in the upper quartile had a significantly higher risk of progression on EDSS (Hazard Ratio 3.78; p = 0.04) and 9HT (Hazard Ratio 10.77, p = 0.04).


CONCLUSIONS
In this study, CSF free kappa light chains predicted subsequent physical deterioration in prospectively evaluated MS patients. If this is confirmed by larger studies, then CSF free kappa light chains could serve as a target for intervention in therapeutic trials.
Rudick
R A
RA
Department of Neurology (Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic Foundation, Ohio 44106, USA.
Medendorp
S V
SV
Namey
M
M
Boyle
S
S
Fischer
J
J
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid / Q000378:metabolism; D007145:Immunoglobulin kappa-Chains / Q000134:cerebrospinal fluid; D007146:Immunoglobulin lambda-Chains / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000473:pathology*; D004676:Myelin Basic Protein / Q000134:cerebrospinal fluid; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012044:Regression Analysis
D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D004676:Myelin Basic Protein