Are you a good, or bad, recoverer from relapses? #ClinicSpeak #MSBlog #MSResearch
"The study below shows that if you have a poor recovery from relapses you are much more likely to enter the clinically-apparent progressive phase of the disease sooner; in fact in this study it was ~22 years sooner (8.3 years vs. 30.2 years). These results are important for several reasons:
- Firstly, it is clear that recovery from relapse is determined by the amount of functional reserve. If you have spare capacity in the affected, and compensatory, neuronal pathways you are more likely to make a good, or complete, recovery from relapses. Functional reserve is dictated by how long you have had MS and the lesion load in the affected pathway. The more damage you have, the less reserve you have, the more likely you will have poor recovery. This is why we say 'treat early and effectively'; 'time is brain' (and spinal cord).
- Age is another factor; the younger you are the more likely you are to recover function. This is simple biology; ageing affects the regenerative capacity of all tissues. This helps explain why age is the best predictor of the onset of the clinically-apparent secondary progressive phase of MS. Please note I use this term clinically-apparent as there is evidence that the pathological substrate that underpins progressive MS is there from the beginning. This is why we are actively promoting the concept that early effective treatment is in fact a treatment strategy that is targeting progressive MS. It is better to prevent the onset of progressive MS than to try and treat it.
- DMTs reduce the severity of attacks and hence result in better recovery from relapses. It is now clear that DMTs, in particular highly-effective DMTs, not only reduce the attack frequency, but also reduce attack severity (need for steroids and/or hospital admission). This is why DMTs delay the onset of clinically-apparent SPMS; despite some commentators saying the opposite there is now data to support this position.
- Another factor that is lesions location. Brainstem, cerebellar, or spinal cord relapses were associated with a poor recovery from the initial relapse. I have discussed this topic before. I suspect that sensory relapses are more likely to be due to smaller, less damaging, lesions. Why? Sensory, or so called afferent, systems (vision, hearing, cutaneous sensation) are more likely to cause symptoms from small lesions as these symptoms are optimised to sense the environment. In comparison, motor or efferent systems (coordination, power) are more likely to cause symptoms when affected by larger more damaging lesions. This is why we take lesions in motor, or efferent, systems more seriously.
- Genetic factors may also play a role. In the animal model of MS, or EAE, some strains of mice recover more quickly than others and the best recoverers become progressive more slowly. Those strains who do badly and recovery less well are more likely to become progressive sooner. As yet we haven't convincingly defined genetic factors in people with MS that predict recovery, but I am sure there are several to be found.
How is the relevant to you, a person with MS? I think it is highly relevant. If you have non-recovery from early relapses this is a poor prognostic sign and hence you may want to choose one of the big guns (highly effective therapies) from the beginning. If you have active MS you almost certainly want to be on a DMT to prevent new lesions from forming and to become attack free. In essence you want to have NEDA (no evident disease activity) and preferably no ongoing end-organ damage (normalised brain atrophy rates). I am sure some of you may agree with me on this, whilst others will disagree. I think preventing end-organ damage is a no-brainer."
"Please note, one way of acquiring disability is non-recovery from relapses, and not only the gradual progression we see in the clinically apparent progressive phase of the disease (SPMS & PPMS). Non-recovery from relapses is more common than we realise. I simply don't understand why someone with MS would take the chance of having relapses, when they can reduce their chances with effective DMTs (licensed or unlicensed). I stress unlicensed DMTs, because in resource poor settings people with MS still have affordable options."
Epub: Novotna et al. Poor early relapse recovery affects onset of progressive disease course in multiple sclerosis. Neurology. 2015 J. pii: 10.1212/WNL.0000000000001856.
OBJECTIVE: To evaluate the relationship between early relapse recovery and onset of progressive multiple sclerosis (MS).
METHODS: We studied a population-based cohort (105 patients with relapsing-remitting MS, 86 with bout-onset progressive MS) and a clinic-based cohort (415 patients with bout-onset progressive MS), excluding patients with primary progressive MS. Bout-onset progressive MS includes patients with single-attack progressive and secondary progressive MS. "Good recovery" (as opposed to "poor recovery") was assigned if the peak deficit of the relapse improved completely or almost completely (patient-reported and examination-confirmed outcome measured ≥6 months post relapse). Impact of initial relapse recovery and first 5-year average relapse recovery on cumulative incidence of progressive MS was studied accounting for patients yet to develop progressive MS in the population-based cohort . Impact of initial relapse recovery on time to progressive MS onset was also studied in the clinic-based cohort with already-established progressive MS (t test).
RESULTS: In the population-based cohort, 153 patients (80.1%) had on average good recovery from first 5-year relapses, whereas 30 patients (15.7%) had on average poor recovery. Half of the good recoverers developed progressive MS by 30.2 years after MS onset, whereas half of the poor recoverers developed progressive MS by 8.3 years after MS onset (p = 0.001). In the clinic-based cohort, good recovery from the first relapse alone was also associated with a delay in progressive disease onset (p < 0.001). A brainstem, cerebellar, or spinal cord syndrome (p = 0.001) or a fulminant relapse (p < 0.0001) was associated with a poor recovery from the initial relapse.
CONCLUSIONS: Patients with MS with poor recovery from early relapses will develop progressive disease course earlier than those with good recovery.
OBJECTIVE: To evaluate the relationship between early relapse recovery and onset of progressive multiple sclerosis (MS).
METHODS: We studied a population-based cohort (105 patients with relapsing-remitting MS, 86 with bout-onset progressive MS) and a clinic-based cohort (415 patients with bout-onset progressive MS), excluding patients with primary progressive MS. Bout-onset progressive MS includes patients with single-attack progressive and secondary progressive MS. "Good recovery" (as opposed to "poor recovery") was assigned if the peak deficit of the relapse improved completely or almost completely (patient-reported and examination-confirmed outcome measured ≥6 months post relapse). Impact of initial relapse recovery and first 5-year average relapse recovery on cumulative incidence of progressive MS was studied accounting for patients yet to develop progressive MS in the population-based cohort . Impact of initial relapse recovery on time to progressive MS onset was also studied in the clinic-based cohort with already-established progressive MS (t test).
RESULTS: In the population-based cohort, 153 patients (80.1%) had on average good recovery from first 5-year relapses, whereas 30 patients (15.7%) had on average poor recovery. Half of the good recoverers developed progressive MS by 30.2 years after MS onset, whereas half of the poor recoverers developed progressive MS by 8.3 years after MS onset (p = 0.001). In the clinic-based cohort, good recovery from the first relapse alone was also associated with a delay in progressive disease onset (p < 0.001). A brainstem, cerebellar, or spinal cord syndrome (p = 0.001) or a fulminant relapse (p < 0.0001) was associated with a poor recovery from the initial relapse.
CONCLUSIONS: Patients with MS with poor recovery from early relapses will develop progressive disease course earlier than those with good recovery.
CoI: multiple