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|Year : 2018 | Volume
| Issue : 3 | Page : 893-895
Change in the natural profile of Duchenne muscular dystrophy with the judicious use of steroids
Sunil Pradhan, Ananya Das
Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, India
|Date of Web Publication||15-May-2018|
Dr. Sunil Pradhan
Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Pradhan S, Das A. Change in the natural profile of Duchenne muscular dystrophy with the judicious use of steroids. Neurol India 2018;66:893-5
We read with interest the article entitled “Natural history of a cohort of Duchenne muscular dystrophy children seen between 1998 and 2014: An observational study from South India” published in Neurology India (2018; 66:77-82). In this context, we would like to respond to the concerns raised by Sunil KR in a consequent correspondence.
We did an open label controlled trial with prednisolone given in a most accepted dose of 0.75 mg/Kg/day and it is perhaps the only controlled trial done from India extending over a period of nearly 10 years from 1993 to 2003. As the steroids do affect the natural history of DMD, we would like to share some of the important findings of this work through this correspondence. The greatest challenge in using prednisolone is determining the right stage of the disease to start the therapy in because prescribing it at a very early stage has a risk of developing obesity and other long-term adverse effects during the ambulatory stage, thus hampering its prospects when it would be required the most, i.e., when the child is about to become chair bound. On the other hand, prescribing steroids late may not be very effective as then there would not be much muscle mass left to get its benefit. Hence, we chose a standardized stage when the child started falling several times in a day (>10 times) or when he took more than 10 seconds to get-up independently from squatting position. Using this timeline and maintaining an initial 2-monthly follow-up for two years, followed by the simple observation about their age at becoming chair-bound, we made several interesting findings.
Outcome parameters that were used to study power and functionality of these DMD patients were (1) fall frequency, (2) peak expiratory flow rate, (3) limb muscle power, (4) ability to lift weights, (5) time taken in getting up from squatting position, (6) walking 9 metres and (7) climbing 13 stairs. All patients gained weight and had cushingoid facies. In 14 patients, it was quite severe and required withdrawl of prednisolone treatment. Three patients suffered from measles infection after 1.5, 2 and 3 months, four patients developed pulmonary tuberculosis, two developed recurrent throat and chest infection and one had unexplained high leukocyte counts without fever; all of them were withdrawn from therapy. Thus, 24 out of 44 patients needed withdrawal from prednisolone therapy due to obesity or infection related complication. Nearly all drug withdrawals took place in the initial 4 months of onset of trial and no substantial information was available about these dropouts that could have been utilised for intention-to treat-analysis. Complete data for analysis were available for 15 patients in the prednisolone group and 19 patients in the control group.
Thus, nearly half of the patients could not continue prednisolone in the prescribed dose due to adverse effects or acquiring infections. More than half of those who left treatment developed extreme obesity perhaps due to dietary habits including over-feeding in an attempt to improve power; others developed infections. Among those who could continue with steroids without any complications, nearly one-fourth did not show significant improvement in muscle power or functional scales and the treatment was abandoned after six months. In rest of the three-fourths of those patients who could continue the trial, noteworthy benefits were observed in various parameters on each visit.
The maximum improvement was noted between 2 and 4 months after starting steroid therapy while mild improvement in some parameters continued for up to six to eight months [Figure 1]. Combined analysis of all parameters indicated that out of the maximum improvement that was noticed after the 8th month of prednisolone treatment, 49.8% improvement occurred in the initial 2 months, 76.8% by 4 months and 90.3% by 6 months. All parameters remained stabilised for the next 1 year or so, after which there was a slight deterioration. Average deterioration between 18 and 24 months of the trial was 4.77% (52.1% vs. 47.33%) in the prednisolone group and 6.71% (–29.15% vs. –35.86%) in the control group. Thus, the deterioration at 2 years was less than the natural course of events noted in control patients.
|Figure 1: Improvement in Walk Time (WLT = time taken in walking 9 meters), Get-up Time (GTT = time taken in getting-up from squatting position) and Climb Time (CLT = time taken in climbing 13 stairs of 18 cm height each) in prednisolone treated (D) and control (C) patients with DMD. Source: Pradhan S, Ghosh D, et al. Prednisolone in Duchenne muscular dystrophy with imminent loss of ambulation. J Neurol 2006;253:1309-16, with permission|
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The steroids were continued till the patients remained ambulatory and then tapered down and stopped gradually. We analysed only those patients who did not experience major adverse effects and who showed a good initial response and compared them with the similar control group. These prednisolone treated patients and controls became chair bound at the mean age of 169 ± 9 and 132 ± 8 months, respectively. This showed a clear advantage of increased period of ambulation of nearly 3 years in this selected group of patients.
The final inference that could be derived from this study was – “Till the ideal stage of the disease and the type or dosage of starting steroid therapy is defined by specially designed studies, 0.75 mg/Kg/day prednisolone therapy may be started in DMD patients at the stage of frequent falls (>10/day) on walking or increased get-up time (>10 s) as observed while testing Gowers' sign; this improves muscle power and timing of motor performance within 2-4 months of onset of therapy in about 75% of those who tolerate this therapy, with a possible gain of approximately 3 years in terms of independent walking.” Subsequent studies have shown equal efficacy of deflazacort in an equivalent dose of 0.9 mg/Kg/day with a probability of lesser adverse effects and about 3-5 years of gain in terms of the period of ambulation.
This answers to some extent the change in the natural history of DMD with the use of steroid therapy. However, the major questions which remain unanswered are the efficacy of steroid treatment after the child has become chair-bound particularly its effect on cardiac and respiratory functions, the proneness to infections during an advanced stage of the disease if the steroids were continued on a long-term basis, and the problem of nursing these patients during the bedbound stage, with extreme obesity also being associated with some cases.
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Conflicts of interest
There are no conflicts of interest.
| » References|| |
Singh RJ, Manjunath M, Preethish-Kumar V, Polavarapu K, Vengalil S, Thomas PT, et al
. Natural history of a cohort of Duchenne muscular dystrophy children seen between 1998 and 2014: An observational study from South India. Neurol India 2018;66:77-82.
] [Full text]
Sunil K R. Establishing the natural history of disease. Neurol India 2018;66:582.
] [Full text]
Pradhan S, Ghosh D, Srivastava NK, Kumar A, Mittal B, Pandey CM, et al
. Prednisolone in Duchenne muscular dystrophy with imminent loss of ambulation. J Neurol 2006;253:1309-16.
Biggar WD, Harris VA, Eliasoph L, Alman B. Long-term benefits of deflazacort treatment for boys with Duchenne muscular dystrophy in their second decade. Neuromusc Disord 2006;16:249-55.