Lee H, Narayanan S, Brown RA, Chen JT, Atkins HL, Freedman MS, Arnold DL. Brain atrophy after bone marrow transplantation for treatment of multiple sclerosis.Mult Scler. 2016. pii: 1352458516650992. [Epub ahead of print]
BACKGROUND:A cohort of patients with poor-prognosis multiple sclerosis (MS) underwent chemotherapy-based immune ablation followed by immune reconstitution with an autologous hematopoietic stem cell transplant (IA/aHSCT). This eliminated new focal inflammatory activity, but resulted in early acceleration of brain atrophy.
OBJECTIVE:We modeled the time course of whole-brain volume in 19 patients to identify the baseline predictors of atrophy and to estimate the average rate of atrophy after IA/aHSCT.
METHODS:Percentage whole-brain volume changes were calculated between the baseline and follow-up magnetic resonance imaging (MRI; mean duration: 5 years). A mixed-effects model was applied using two predictors: total busulfan dose and baseline volume of T1-weighted white-matter lesions.
RESULTS:Treatment was followed by accelerated whole-brain volume loss averaging 3.3%. Both the busulfan dose and the baseline lesion volume were significant predictors. The atrophy slowed progressively over approximately 2.5 years. There was no evidence that resolution of edema contributed to volume loss. The mean rate of long-term atrophy was -0.23% per year, consistent with the rate expected from normal aging.
CONCLUSION:Following IA/aHSCT, MS patients showed accelerated whole-brain atrophy that was likely associated with treatment-related toxicity and degeneration of "committed" tissues. Atrophy eventually slowed to that expected from normal aging, suggesting that stopping inflammatory activity in MS can reduce secondary degeneration and atrophy.
We have been talking about HSCT and it is quite effective at inducing NEDA, but the drugs used to get rid of the immune system can be damaging. So in this study they see brain shrinkage.
Whilst you may expect some shrinkage because the drugs will get rid of inflammation and swelling and eventually the rate of brain loss is at the level of age-related loss in healthly individuals. But they think that the drugs cause some nerve damage. They are probably right because ProfG showed that these drugs cause nerve damage.
Petzold A, Mondria T, Kuhle J, Rocca MA, Cornelissen J, te Boekhorst P, Lowenberg B, Giovannoni G, Filippi M, Kappos L, Hintzen R.Evidence for acute neurotoxicity after chemotherapy.
Ann Neurol. 2010;68:806-15. doi: 10.1002/ana.22169