ZeTo or zero tolerance: why is not being adopted my more MSologists? #MSBlog #MSResearch #ClinicSpeak
"We know that when certain neurological systems are involved in MS they indicate a poorer prognosis than others? Why?"
"The motor, cerebellar and bladder systems are the three I am referring to. These systems are the so called efferent, effector or motor systems and characterised by their length and complexity. Motor or effector systems tend not to have as much redundancy in them as sensory or affector systems. Sensory systems have multiple overlapping inputs and if one is damaged and malfunctioning another takes over. For example when joint position is not working the vestibular (inner ear) and vision take over. This is why we get you to close your eyes when you are standing still to test your balance or joint position sensation. Sensory systems are also relatively simple in that they are a one-way relay nerves and don't require coordination to function. In comparison, the motor systems don't have such redundancy built into them and are more complex in that they require coordinated contraction or relaxation of multiple muscles. In addition, the length of the nerve fibres to the lower spinal cord that subserve lower limb power and coordination and bladder function make them particularly vulnerable to damage. Long nerve fibres or axons have a greater chance of being affected by MS compared to short nerve fibres; therefore the long fibre systems act as integrators of damage and if they are affected they simply indicate more lesions. This is simple statistics."
"Why the cerebellar system then? The cerebellum is the minibrain that is situated on the back of your big brain and is responsible for coordinating movement. Again the cerebellum has many fibres pathways that pass up to the brain and down to the spinal cord and are responsible for coordinating movement. Therefore the cerebellar fibres are more likely to be affected by MS lesions and are another integrator of damage. What does this mean? Simply, if you have evidence of fixed impairments in either the motor (weakness, spasticity, altered reflexes), bladder (frequency, urgency, hesitancy) or cerebellar (coordination, balance, eye movements) you are likely to do worse (more attacks or future disability progression) than someone without involvement of these areas."
"How does this information affect me? It may or may not affect you depending on the context you are given this information. The study below refers to motor involvement in CISers and the fact that they are more likely to have a second attack than those CISers without motor involvement. Therefore this information may affect your decision to start a DMT early on, or if you do go onto a DMT you may want to go onto one of the more highly effective DMTs rather than take a chance of being a non-responder on the lower efficacy DMTs. Remember there is a window of opportunity to treat MS to prevent disability; spending several years being a non-responder or sub-optimal responder on the so called 1st-line therapies is time lost. Time is brain; it is best to switch of the shredder off as soon as possible."
"If you have established disease and you are on a DMT and have involvement of these indicator pathways that indicate a poor prognosis you may would want your neurologist to be as vigilant as possible to the possibility of ongoing disease activity so that you can switch or escalate your therapy to a more effective therapy sooner than later. The problem at the moment is that most neurologists simply monitor MSers under their care who on DMTs using clinical criteria; this is simply not good enough in the current era. Most MS disease activity occurs below the clinical surface; do you remember the my iceberg analogy? To get an idea of how active your MS is you need to have regular MRI studies to see if you have acquired new lesions and whether or not any of these lesions are active, i.e. enhance after the administration of gadolinium. In the future the MRI metrics will get more sophisticated and will almost certainly include brain atrophy and gray matter lesions counts as well."
"There has been some criticism from readers that I live in an ivory tower and this sort of monitoring will never happen. This is simply not true. It is happening in a lot of centres across the world, not only at the Royal London Hospital. By asking your neurologist probing questions you will help change practice. Don't accept no for an answer. If you neurologist says no; asked what he/she would like to know about their disease activity status if they had MS? The challenge is to get MSologists to think ZeTo (zero-tolerance) of MS disease activity and to adopt the strategy of treat-2-target of NEDA (no evidence of disease activity). We need to start treating MS actively, and aggressively; only by doing this we will we delay, and in some cases prevent, poor outcomes (disability progression, SPMS, etc.)."
BACKGROUND: Factors determining the person with a clinically isolated syndrome (CISers) likelihood of developing multiple sclerosis (MS) are important for the clinician who needs to identify CISers warranting immunomodulatory treatments.
OBJECTIVE: To determine whether motor abnormalities found during the initial demyelinating event imply an increased risk of a second event within the first year.
METHODS: Fifty-two early onset CISers, volunteered to participate in the prospective study. Motor parameters collected at onset included gait, balance, lower limb peak isometric strength and fatigue index parameters. At the end of one year, CISers were subdivided into two groups, those who had experienced a second demyelinating attack suggestive of MS and those who maintained their clinical status.
RESULTS: Forty-nine CISers were included in the final analysis. Within the first year, 24 CISers experienced a second attack, while 25 maintained their neurological status. CISers who suffered a second demyelinating attack, demonstrated reduced overall lower limb peak strength compared with CISers who maintained their clinical status (411.9 (S.E. = 32.1) vs. 514.8 (S.E. = 34.1). No differences were observed between groups in gait and balance parameters.
CONCLUSION: An initial demyelinating event characterized by reduced lower limb strength can possibly suggest an increased risk of an early second attack.
To read more about NEDA please see the following post:
08 Jan 2013
"I would appreciate your comments on the following beta version of a treatment or monitoring algorithm for relapsing MSers. The idea is to adopt the strategy of treating-2-target; the target being NEDA or no evidence of ...