Clinic speak: how good are steroids for treating relapses?

Think twice before accepting steroid treatment for your relapse. #MSBlog #MSResearch #ClinicSpeak

"The study below mirrors my clinical experience that steroid treatment for relapses is unpredictable and at worst dangerous. Clinicians have a 'must  treat worldview' and have developed a culture that favors treatment over no treatment. When someone comes in with a relapse we tend to reach for the prescription pad and prescribe steroids. The data favoring steroid treatment of relapses is weak and if anything marginal. Firstly, the outcome at 6 months after a relapse is independent of whether, or not, you receive steroids. All that steroids do is speed up your rate of recovery from a relapse by about two weeks; in other words you get back to you old baseline, or new baseline, 2 weeks earlier if you have steroid treatment. Secondly, the evidence that steroids makes a difference when given 5 weeks after the onset of a relapse is non-existent; in other words if you are going to be treated with steroid you need to receive them as soon as possible after the onset of an attack. Thirdly, the dose counts; most studies of low dose oral have not shown a benefit. Therefore you need high intravenous or oral steroids. I would recommend the following protocols only: 
  1. 1g or 1,000mg methylprednisolone intravenously for 3 days
  2. 500mg methylprednisolone intravenously for 5 days
  3. 500mg methylprednisolone orally for 5 days
The oral methylprednisolone tablets are 100mg in size and not always available. When they are not available I simply instruct the pharmacist to dispense the liquid intravenous formulation that can be taken orally by being mixed with fruit juice. Please note that many pharmacists don't like doing the latter. 

Please note high-dosed pulsed steroids  have side effects. The following is a list of the more common ones:

  1. Increased appetite, weight gain
  2. Water retention with leg swelling or a swollen, "puffy" face
  3. Nervousness, restlessness
  4. Insomnia
  5. Sudden mood swings (happiness and sadness)
  6. Hypomania (persistent euphoria or extreme happiness) and rarely acute psychosis
  7. Avascular necrosis of the hip and other bones
  8. Thrombosus or clots
  9. Allergic reactions; this is not an allergic reaction to steroids, but to the incipients in the solution. If you are allergic to the IV formulation you can still take high-dose oral steroids.
With prolonged administration: 
  1. Muscle weakness
  2. Blurred vision
  3. Increased growth of body hair
  4. Easy bruising
  5. Lower resistance to infection
  6. Acne
  7. Osteoporosis (bone thinning)
  8. Diabetes or worsening of diabetes
  9. High blood pressure
  10. Stomach irritation
  11. Cataracts or glaucoma
As I have stated many  times before on this blog, avascular necrosis and psychosis are the side effects that worry me the most. As with all treatments there is a risk:benefit ratio and in my opinion  the risks of steroids outweigh the benefits for mild and sometimes moderate attacks. Obviously if your relapse is preventing you from functioning normally then speeding up the recovery is worthwhile. 

Some neurologists still use an oral taper; i.e. after the pulse of high-dose steroids is finished you go onto oral steroids that are then weaned over a 4-8 week period. There is no evidence that a taper makes any difference to the rate of recovery. I don't use it as it causes a large number of side effects. My only exception to this rule is rebound after the Lazarus effect. The Lazarus effect this is when MSers with a severe relapse, which renders them bed-bound, respond dramatically to a pulse of steroids; they literally get up and start walking 24-48 hours after starting steroids. If they then deteriorate after the pulse of steroids is finished and respond to a second course of steroids I will prescribe a taper to try and prevent a further deterioration. The latter presumably occurs from swelling of the a lesion in the spinal cord and a taper prevents this from reoccurring. Please note that since the wide-spread use of DMTs the number of  severe spinal relapses has plummeted and hence I have not seen a Lazarus effect in years. Since we have started using DMTs for treating RRMS not only has the number of relapses plummeted, but also the severity. Another reason for neurologists to use DMTs liberally. 

Another trend that has taken off in recent times is the use of monthly pulsed steroids as a DMT; typically 1g or 1,000 mg methylprednisolone intravenously monthly. In my opinion the evidence supporting this treatment is poor and hence I don't use it personally. The exception being is that if someone is referred to me on this treatment I tend to let them decide whether or not they want to continue, or not, with their monthly infusions after I have explained my position. In general, most MSers stop after hearing about the side effects. I have had one MSer referred to me with such bad osteoporosis from pulsed monthly steroids that she developed a spontaneous vertebral compression fracture. Hence the need to have a baseline bone density scan and to be put on osteoporosis prophylaxis if you are going to stay on steroids long-term."

The following is a short survey I would like you to complete on steroid use in MS:

Epub: Nickerson M, Marrie RA.The multiple sclerosis relapse experience: patient-reported outcomes from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry. BMC Neurol. 2013 Sep;13(1):119.

BACKGROUND: Among MSers with relapsing-remitting multiple sclerosis, relapses are associated with increased disability and decreased quality of life. Relapses are commonly treated with corticosteroids or left untreated. They aimed to better understand MSer perceptions of the adequacy of corticosteroids in resolving relapse symptoms.

METHODS: They examined self-reported data from 4482 participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry regarding evaluation, treatment, and recovery from relapses.

RESULTS: Forty percent (1775/4482) of respondents were simply observed for disease worsening, whereas 25% (1133/4482) were treated with intravenous methylprednisolone (IVMP) and 20% (923/4482) with oral corticosteroids; additional treatments included adrenocorticotropic hormone, plasmapheresis, intravenous immunoglobulin, and others. Among MSers who responded to questions about their most recent relapse, 32% (363/1123) of IVMP-treated and 34% (301/895) of oral corticosteroid-treated MSers indicated their symptoms were worse one month after treatment than pre-relapse, as did 39% (612/1574) of observation-only MSers; 30% (335/1122) of IVMP-treated MSers indicated their treatment made relapse symptoms worse (13% [145/1122]) or had no effect (17% [190/1122]), as did 38% (340/894) of oral corticosteroid-treated MSers (worse, 13% [116/894]; no effect, 25% [224/894]) and 76% (1162/1514) of observation-only MSers (worse, 17% [264/1514]; no change, 59% [898/1514]).

CONCLUSIONS: Overall, MSers with relapsing multiple sclerosis who receive treatment report better outcomes than those who are simply observed. However, a sizeable percentage of MSers feel that their symptoms following corticosteroid treatment are worse than pre-relapse symptoms and that treatment had no effect or worsened symptoms. MSer perceptions of relapse treatment deserve more attention, and more effective treatment options are needed.

Other posts on steroids:

13 Aug 2013
"In general I try and avoid high-dose steroids to treat acute relapses simply because of the potential complications. This case report is a reminder of one of the rare complications of this treatment; i.e. a clot in one of the venous ...
21 Mar 2013
"My first poster today at the AAN. The data speaks for itself. Treatment with BG12 reduces the need for steroids and hospitalizations. This data supports health economic arguments for BG12." ...
27 Jan 2013
METHOD: In a prospective study, we evaluated the MSers who received high-dose intravenous methylprednisolone for acute attacks. By repeated physical and laboratory examinations and history taking, MSers were ...
30 May 2013
#MSBlog #MSResearch. "My poster from the ISPOR 18th Annual International Meeting in New Orleans. The main finding is that BG12 or DMF reduces the proportion of relapses needing to be treated with intravenous steroids.

09 Nov 2011
Background and purpose: Temporary discontinuation of natalizumab/Tysabri is sometimes considered because of the observed risk of progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis (MS) ...
10 Jun 2012
Methods: Body composition and BMD were measured by dual-energy X-ray absorptiometry in 104 ambulatory men with MS (mean age 45.2 yr) chronically treated with low-dose GC and in 54 healthy age-matched men.
25 Jul 2012
Epub: Rakusa et al. Testing for urinary tract colonisation before high-dose corticosteroid treatment in acute multiple sclerosis relapses: prospective algorithm validation. Eur J Neurol. 2012. doi: ...
06 Feb 2012
Aim. This study was designed to examine the possible role of high-dose intravenous methylprednisolone (IVMP) in the development of venous thrombosis (VT). The cerebral one anecdotally had been reported in patients with ...

04 Jan 2012
This is a report five MSers with femoral head necrosis who had RRMS and received different doses of methyl prednisolone. The cases consisted of 3 females and 2 males. The duration of disease varied between 1 and 3 ...

17 Dec 2012
Second-line treatments of steroid-unresponsive MS relapses and a possible algorithm for MS relapse management are also reviewed in this article. Whilst this is taking the coals to Newcastle if you are a RRMSer, some of the ...

21 Aug 2013
The other advantage of having less severe relapses for MSers is fewer course of high-dose steroids and hence less side effects and lower chances of those severe and unpredictable adverse events, for example avascular ...

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