residents’ room  
The use of intra-detrusor onabotulinumtoxinA in patients with  
myasthenia gravis  
1
1
1,2  
Ian Wright, MD; Andrea Civitarese, BSc; Richard Baverstock, MD  
1
2
Alberta Cancer Centre, Calgary, AB, Canada; Univesity of Calgary, Calgary, AB, Canada  
Cite as: Can Urol Assoc J 2016;10(5-6):E184-5. http://dx.doi.org/10.5489/cuaj.3678  
Published online May 12, 2016.  
altering treatment from patients with OAB and MG when  
there is no clear evidence of morbidity. We report two cases  
in which Botox was successfully used without complication  
in patients with comorbid OAB and MG.  
Abstract  
®
The use of intra-detrusor onabotulinumtoxinA (Botox ) in patients  
Case reports  
with myasthenia gravis has not been reported, and little evidence  
exists to substantiate a complete contraindication of Botox use in  
this population. Here, we present two cases of comorbid overac-  
tive bladder (OAB) and myasthenia gravis successfully treated with  
intra-detrusor Botox.  
Our first case is a 70-year-old woman with urinary urgency,  
frequency, and mixed incontinence who was referred to our  
multidisciplinary bladder clinic after failing two anticholin-  
ergic medications due to side effects of dry mouth and dry  
eyes. At the time of initial referral in 2008, she did not have  
a diagnosis of MG. She was treated with intra-detrusor injec-  
tion of Botox 200 units in October 2008, with significant  
improvement in her OAB symptoms (as documented in a  
validated OAB patient-reported outcome tool) and quality of  
life. She went on to have three subsequent treatments with  
200 units in Oct. 2009, Oct. 2010, and July 2011. It should  
be noted that Botox was used in this patient prior to Health  
Canada approval for idiopathic OAB. It was used off-label  
in some refractory OAB patients at a dose of 200 units, as  
this reflected our clinical practice in neurogenic patients.  
She was diagnosed with MG by a neurologist in the fall  
of 2011. Her main symptoms included daytime fatigue,  
profound sweating, episodic swallowing difficulties, and  
bilateral ptosis. Her treatment consisted of prednisone 15  
mg, mestinon, and IVIG 150 mg monthly divided in two  
doses. She wished to continue with her Botox treatments,  
as her symptoms, reported by a standardized OAB tool,  
had increased to severe while off of Botox. After consulting  
her neurologist, permission was given to go ahead with a  
reduced dose of 100 units of intra-detrusor Botox. She went  
on to have 100 units injected in Oct. 2013 with excellent  
effect. There was no worsening of her neurologic symptoms  
or progression of her MG on followup. She went on to have  
a further 100 units July 2014, again with no neurologic  
deterioration.  
Introduction  
®
Intra-detrusor onabotulinumtoxinA (Botox ) is commonly  
used in the treatment of patients with both neurogenic detru-  
sor overactivity and idiopathic overactive bladder (OAB)  
who have failed anticholinergic therapy. This biologic toxin  
works by binding to receptors on presynaptic motor neurons  
and preventing release of acetylcholine into the neuromus-  
cular junction. When injected into the detrusor muscle,  
partial chemical denervation of the muscle occurs, manifest-  
ing as local muscle paralysis.  
Given the mechanism of action of Botox, the product  
monograph warns that “extreme caution” should be exer-  
cised when administering this drug to patients with neu-  
romuscular junction disorders. The most common of such  
conditions is myasthenia gravis (MG), an autoimmune dis-  
order in which an antibody-mediated, T-cell-dependent  
process targets acetylcholine receptors on the postsynaptic  
membrane of the neuromuscular junction. This presents as  
weakening of the voluntary (skeletal) muscles of the body.  
The condition can deteriorate and can eventually lead to  
1
2
3
respiratory failure.  
The use of intra-detrusor Botox in patients with MG has  
not been reported and there is a paucity of evidence to  
support an absolute contraindication to its use in this popu-  
lation. Further, it is a clinical challenge to withhold life-  
Our second case is an 80-year-old woman referred in  
January of 2013 with poorly controlled OAB and a Grade  
E184  
CUAJ • May-June 2016 • Volume 10, Issues 5-6  
2016 Canadian Urological Association  
©
oꢀabꢁꢂulꢃꢀuꢄꢂꢁxꢃꢀA uꢅꢆ ꢃꢀ mG  
7
3
cystocele. Her primary urinary bother was that of nocturia  
for the treatment of dystonia. The case study concludes that  
every two hours with severe nighttime urgency and a very  
poor quality of life. She had previously been diagnosed with  
MG and followed by a neurologist. She was taking mesti-  
non, an acetylcholinesterase inhibitor, for control of her  
MG symptoms, which precluded the use of anticholinergic  
medications. Her MG symptoms were mild, manifesting only  
as bilateral ptosis.  
individuals with underlying neuromuscular conditions can  
develop more generalized weakness after Botox treatment  
and that caution should be used when administering Botox  
to these individuals, even in small doses.  
We have presented two cases of comorbid OAB and MG  
that have successfully been treated with intra-detrusor Botox.  
Both patients were treated after careful consultation with  
their neurologist. We have also limited the dosage to 100  
units in order to minimize the heightened theoretical risk  
of systemic side effects in the setting of MG. This report  
highlights the lack of evidence to support the practice of  
withholding Botox from all patients with MG.  
®
She was started on mirabegron (Myrbetric ) 50 mg daily  
and a pessary was fitted for her cystocele. Mutichannel  
urodynamics confirmed terminal detrusor overactivity at  
reduced bladder volumes. Her symptoms were not well-  
controlled on Myrbetriq and she subsequently requested  
Botox therapy. After consulting her neurologist, permission  
was given to proceed with Botox treatment at a dose of 100  
units. In April 2015, she received her first treatment. She  
reported no worsening of her neurological status at her one-  
month followup. Her nocturia improved to once every four  
hours and led to a significant improvement in her quality of  
life. We plan to continue with Botox injections for ongoing  
symptom control.  
Competing interests: Dr. Baverstock has served as an Advisory Board member for Allergan, Astellas,  
and Pfizer; a member of the Speakers’ Bureau for Allergan, AMS, Astellas, and Pfizer; received  
payment/grants/honoraria from Allergan, AMS, Astellas, and Pfizer; and has participated in clinical  
trials for Allergan, Astellas, and Pfizer. The remaining authors declare no competing financial or  
personal interests.  
This paper has been peer-reviewed.  
Discussion  
The medical literature is sparse when reporting the use of  
Botox in patients with MG. Most of the available experi-  
ence is reported in the use of Botox for cosmetic indica-  
tions and in those with dystonia. One case study describes  
References  
1
.
Allergan, Inc. Clostridium botulinum type A neurotoxin complex (900kD) Sterile vacuum-dried concentrate  
powder for solution for injection 50, 100 and 200 Allergan units per vial Neuromuscular Paralytic Agent.  
Botox Product Monogram 2014; Retrieved from http://www.allergan.ca/assets/pdf/ca_botox_pm.pdf.  
Accessed November 30, 2015.  
4
a 49-year-old woman with both MG and cervical dystonia.  
The individual was treated for her dystonia using Botox,  
with no observed flare in her MG symptoms. Her MG did  
not progress following the Botox treatment. Another study  
reports treatment of dystonia with Botox in an individual  
2
.
Bird SJ. Clinical Manifestations of Myasthenia Gravis. UpToDate 2015; Version 12: Topic 5170.  
3. Office of Communications and Public Liaison. Myasthenia Gravis Fact Sheet. National Institute of  
Neurological Disorders and Stroke 2015; c2015 [updated 2015 July 27]; NIH Publication No. 10-768.  
Retrieved from http://www.ninds.nih.gov/disorders/myasthenia_gravis/detail_myasthenia_gravis.  
htm. Accessed December 11, 2015.  
4
5
6
5
with comorbid MG. The treatment was successful and,  
.
.
.
Goncalves MR, Barbosa E, Zambon AA, et al. Treatment of cervical dystonia with botulinum toxin in  
a patient with myasthenia gravis. Arq Neuropsiquiatr 1999;57:683-5. http://dx.doi.org/10.1590/  
S0004-282X1999000400024  
Fasano A, Bentivoglio A, IalongoT, et al. Treatment with botulinum toxin in a patient with myasthe -  
nia gravis and cervical dystonia. Neurology 2005;64:2155-6. http://dx.doi.org/10.1212/01.  
WNL.0000165997.77985.32  
using EMG guidance and small dosage, the individual was  
safely treated without any side effects or generalized weak-  
ness. This was partially achieved through use of a more  
concentrated solution than usual to prevent spreading of  
the Botox to other muscle areas.  
Dressler D. Subclinical myasthenia gravis causing increased sensitivity to botulinum toxin therapy. J Neural  
Transm 2010;117:1293-4. http://dx.doi.org/10.1007/s00702-010-0481-9  
Other research suggests that pre-existing conditions, such  
as MG, may increase the potency of Botox-type drugs, caus-  
7. Iwase T, Iwase C. Systemic effect of local and small-dose botulinum toxin injection to unmask subclinical  
myasthenia gravis. Graefes Arch Clin Exp Ophthalmol 2006;244:415-6. http://dx.doi.org/10.1007/  
s00417-005-0130-4  
6
ing adverse effects, such as muscle weakness. However,  
it is also suggested that this can be corrected for by dose  
adjustment. A similar suggestion is made in a case study that  
reports MG symptoms worsening post-Botox administration  
Correspondence: Dr. Andrea Civitarese, Alberta Cancer Centre, Calgary, AB, Canada; andrea@vesia.ca  
CUAJ • May-June 2016 • Volume 10, Issues 5-6  
E185