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Original Investigation
April 2018

Differences in the Reponses to Apheresis Therapy of Patients With 3 Histopathologically Classified Immunopathological Patterns of Multiple Sclerosis

Author Affiliations
  • 1Institute of Neuropathology, University Medical Center Goettingen, Goettingen, Germany
  • 2Department of Medical Statistics, University Medical Center Goettingen, Goettingen, Germany
  • 3Department of Neurology, Mayo Clinic, Rochester, Minnesota
JAMA Neurol. 2018;75(4):428-435. doi:10.1001/jamaneurol.2017.4842
Key Points

Question  Are there any differences in the response to apheresis therapy for steroid refractory relapses among patients with histologically defined immunopathological patterns of multiple sclerosis?

Findings  This cohort study of 69 patients defined 3 patterns of multiple sclerosis and observed functional improvement after apheresis therapy in patients with histological pattern 1 (31%) and pattern 2 (55%), but not in patients with pattern 3. Secondary outcome parameters (magnetic resonance imaging and expanded disability status scale improvement) strongly supported the primary outcome.

Meaning  Response to apheresis therapy may be associated with immunopathological patterns and thus with pathological mechanisms of lesion development.


Importance  Plasma exchange and immunoadsorption are second-line apheresis therapies for patients experiencing multiple sclerosis relapses. Early active multiple sclerosis lesions can be classified into different histopathological patterns of demyelination. Pattern 1 and 2 lesions show T-cell– and macrophage–associated demyelination, and pattern 2 is selectively associated with immunoglobulin and complement deposits, suggesting a humoral immune response. Pattern 3 lesions show signs of oligodendrocyte degeneration. Thus it is possible that pathogenic heterogeneity might predict therapy response.

Objective  To evaluate the apheresis response in relation to histopathologically defined immunopathological patterns of multiple sclerosis.

Design, Setting and Participants  This single-center cohort study recruited 69 patients nationwide between 2005 and 2016. All included patients had a diagnosis of early active inflammatory demyelination consistent with multiple sclerosis; were classified into patterns 1, 2, or 3 based on brain biopsy analysis; and underwent apheresis treatments. Patients who had concomitant severe disease, neuromyelitis optica, or acute disseminated encephalomyelitis were excluded.

Main Outcomes and Measures  The primary therapy outcome was a functionally relevant improvement of the relapse-related neurological deficit. Radiological and Expanded Disability Status Scale changes were secondary outcome parameters.

Results  The mean (SD) age of patients was 36.6 (13.3) years; 46 of the 69 participants (67%) were female. Overall, 16 patients (23%) exhibited pattern 1 lesions, 40 (58%) had pattern 2 lesions, and 13 (19%) had pattern 3 lesions. A functional therapy response was observed in 5 of the 16 patients with pattern 1 disease (31%) and 22 of the 40 patients with pattern 2 disease (55%), but none of the 13 patients with pattern 3 disease exhibited improvement (pattern 2 vs 3 P < .001). Radiological improvements were found in 4 (25%), 22 (56%), and 1 (11%) of patients with patterns 1, 2, and 3, respectively. The respective rates of response measured by changes in Expanded Disability Status Scale scores were 25%, 40%, and 0%. Brainstem involvement was a negative predictive factor for the functional therapy response (logarithmic odds ratio [logOR], −1.43; 95% CI, −3.21 to 0.17; P = .03), while immunoadsorption (as compared with plasma exchange) might be a positive predictive factor (logOR, 3.26; 95% CI, 0.75 to 8.13; P = .01).

Conclusions and Relevance  This cohort study provides evidence that the response to apheresis treatment is associated with immunopathological patterns. Patients with both patterns 1 and 2 improved clinically after apheresis treatment, but pattern 2 patients who showed signs of a humoral immune response benefited most. Apheresis appears unlikely to benefit patients with pattern 3 lesions.