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Dr.Namrata Adulkar, A12530

Abstract:

Duchenne muscular dystrophy (DMD) is a common genetic disorder of childhood that causes progressive muscle degeneration leading to loss of ambulation by early adolescence and mortality by the third or fourth decade of life. The treatment largely involves systemic corticosteroids and supportive care. We present a report of two brothers with DMD who were referred with a new onset of central and peripheral visual field loss in the context of known Idiopathic Intracranial Hypertension (IIH).  They had been diagnosed with this condition 3 years previously following identification of optic disc edema with headaches, raised cerebrospinal fluid (CSF) opening pressures, and normal neuroimaging. They were already on maximal doses of oral acetazolamide and repeated therapeutic lumbar punctures provided insufficient relief of symptoms. Both patients underwent unilateral optic nerve sheath fenestration to relieve the pressure on the optic nerve. One of them stabilised with reduction of papilledema and visual field loss bilaterally, while the other improved on the surgical side but continued to experience visual obscurations and worsening of papilledema on the contralateral side and so required sheath fenestration on the contralateral side.

Keywords: Duchenne muscular dystrophy, idiopathic intracranial hypertension, optic nerve sheath fenestration

Introduction:

Duchenne muscular dystrophy (DMD) is the most common type of muscular dystrophy in childhood. It is caused by mutations of the DMD gene, located on chro­mosome Xp21, which encodes for dystrophin, a 427 kDa protein that is expressed at the muscle sarcolemma.[1] The absence of dystrophin destabilizes the muscle membrane, leading to the clinical features of motor developmental delay, calf hypertrophy, joint contractures, and progressive muscle weakness in affected boys, with markedly elevated serum creatinine kinase that reflects ongoing muscle damage. Progressive muscle degeneration eventually leads to loss of independent ambulation by early adolescence, scoliosis, cardiomyopathy, respiratory insufficiency, and reduced life expectancy, with death occurring before the third or fourth decade of life. [2]

Currently there is no cure for DMD;  treatment strategies focus on optimizing growth and development, promoting well-balanced diet, participating in physical and recreational activity, and early treatment with corticosteroids.[3] Daily oral predni­sone (0.75 mg/kg) or deflazacort (0.9 mg/kg) is generally recommended as a disease-modifying treatment for DMD. [4] Deflazacort is an oxazoline analogue of prednisolone with an estimated dose equivalency of 1.3 mg deflazacort to 1 mg prednisone. Although it is less potent, obesity is less frequently observed than with prednisone and is therefore preferred. Side-effects from chronic administration of corticosteroids remains a challenge in the managaement of these patients. Idiopathic intracranial hypertension (IIH) has been previously documented as a side-effect of corticosteroid treatment. In this report we present two brothers with DMD who presented with acute visual deterioration from IIH.

Case report:

A 22- year-old male patient was seen in the neuro-ophthalmology clinic with visual obscurations and headaches. He was previously diagnosed with DMD and was on oral deflazacort for the past 8 years. He was wheelchair bound and had a BMI of >35 . He was incidentally found to have bilateral optic disc edema, at a postoperative follow-up visit following uneventful bilateral cataract surgery 3 years previously. Raised CSF opening pressures of > 50 mm of Hg along with normal neuroimaging confirmed the diagnosis of IIH. He was treated with oral acetazolamide for six months which was discontinued after he developed hypokalemia. For the past year he underwent multiple therapeutic lumbar punctures to reduce the raised intracranial pressure. However, he continued to experience headaches associated with nausea, vomiting and daily transient episodes of visual obscurations lasting for about 30 seconds.

On examination his best corrected visual acuity was 20/25 in both eyes. He had an afferent pupillary defect on the left. Color vision tested with Ischihara pseudoisochromatic plates was stable with 11/11 in both eyes. Goldmann’s perimetry showed bilateral paracentral disc-based defects on the left eye more than the right. OCT of the optic nerves revealed early nerve fiber layer loss on the left eye with bilateral disc edema.

He underwent left optic nerve sheath fenestration through a medial transconjunctival approach. Postoperatively, he reported good relief of visual symptoms and headaches; and the previous visual field defects resolved bilaterally. He remained free of headaches, obscurations and visual field loss 2 months later although he had some persistent optic disc edema on OCTs. He therefore underwent right optic nerve sheath fenestration.

On his last follow-up visit, he had no new visual or neurological disturbances. Visual acuity was 20/30 OD and 20/20 OS with full color vision, and no afferent pupillary defect. Fundus exam showed a low-grade papilledema while peripapillary OCT showed no thinning of the nerve fibre layer.

His 18 year old younger brother, who also suffered from DMD, had a similar presentation of IIH with papilledema identified bilaterally shortly after uneventful cataract surgery.  He had been followed with stable central and color vision and visual fields until the last visit when he was found to have reduced  central visual acuity of 20/40 OD , 20/30 OS along with a right relative afferent papillary defect, decreased right colour vision  (6/11 Ischihara plates), and bilateral optic nerve pallor and edema. His visual field was constricted on the right; and showed an enlarged blind spot with an inferonasal nerve fibre bundle defect on the left.  His peripapillary OCT found thinning of retinal nerve fibre layer on peripapillary OCT. He underwent right optic nerve sheath fenestration. After the surgery, his visual acuity, color vision and visual fields all stabilized without further deterioration nine months later.

Discussion:

Although IIH is a disorder of overweight women in child bearing age group, there have been two previous reports of idiopathic intracranial hypertension in patients with DMD. Weig and co-workers described the case of a 9- year-old child who developed IIH after receiving deflazacort for 2 years. However the report does not discuss the management of the case.[5]T Willis et al reported a case of an eleven year old patient with DMD who developed IIH after taking daily corticosteroids for four years. He was also medically treated with acetazolamide and furosemide; however, he continued to have persistent symptoms requiring repeat lumbar punctures and insertion of a lumbar-peritoneal shunt.[6]

Chronic administration of corticosteroids is felt to be the underlying cause of the idiopathic intracranial hypertension in these patients. However, morbid obesity caused by prolonged corticosteroid use alongwith the decreased physical activity may also contribute to IIH in patients with DMD. The mechanism underlying the association of obesity and idiopathic intracranial hypertension remains unclear. Sugerman et al. documented elevated intra-abdominal pressure in obese adults with idiopathic intracranial hypertension, as well as increased pleural and cardiac filling pressures. [7] They proposed that these increased pressures would impede venous return from the brain, resulting in increased ICP. Although obesity is less frequently evident in boys with DMD treated with deflazacort rather than prednisone, approximately 10-15% of them still do develop a high BMI [8]. As a result, weight and body mass index need to be followed as carefully in this group as in children treated with prednisone. The dose of deflazacort may need to be reduced if significant obesity develops. Clinical improvement in IIH has been reported to be associated with approximately  6% weight loss [9], but this remains a challenge for individuals suffering from DMD.

Lai et al conducted a meta-analysis of 457 articles on various surgical interventions for IIH that included – ONSF, lumboperitoneal shunt, ventriculoperitoneal shunt, and dural venous sinus stenting. They concluded that similar improvement in visual outcomes occurred across treatment strategies and that there is insufficient evidence to recommend or reject any treatments modalities for IIH.[10] Due to significant systemic comorbidities in our patients and the technical difficulty of shunting with the excessive subcutaneous fat, ONSF was the preferred intervention to relieve the pressure in the optic nerve sheath and prevent further loss of nerve fibers. Although precautions were required during anesthesia because of their obesity, , both tolerated the procedures well with  good surgical results  for bothIn one case, visual function stabilized bilaterally following one-sided fenestration, while in the other, the operated eye stabilized but the opposite side still continued to deteriorate requiring a fenestration on that side as well.

Conclusion :

Patients with DMD may develop IIH and should be screened for this as visual deterioration may develop without the patient’s initial awareness.  Once diagnosed with IIH, these individuals should be closely monitored following initiation of medical therapy, and surgical options offered promptly once visual deterioration develops, as this may become irreversible in spite of adequate decompression.

References:

  1. Mah JK, Korngut L, Dykeman J, Day L, Pringsheim T, Jette N. A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy. Neuromuscul Disord. 2014; 24(6):482–491.
  2. McDonald CM, Henricson EK, Abresch RT, et al. The cooperative inter­national neuromuscular research group Duchenne natural history study – a longitudinal investigation in the era of glucocorticoid therapy: design of protocol and the methods used. Muscle Nerve. 2013;48(1):32–54.
  3. Bushby K, Finkel R, Birnkrant DJ, et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidis­ciplinary care. Lancet Neurol. 2010;9(2):177–189.
  4. Bonifati MD, Ruzza G, Bonometto P, et al. A multicenter, double-blind,randomized trial of deflazacort versus prednisone in Duchenne dystrophy. Muscle Nerve 2000;23:1344e7.
  5. Weig SG, Zinn MM, Howard JF Jr. Idiopathic intracranial hypertension in a child with Duchenne muscular dystrophy. Pediatr Neurol. 2011 Dec;45(6):406-8.
  1. T. Willis, R Kulshrestha , Z Alhaswani. Idiopathic intracranial hypertension requiring a lumbar-peritoneal shunt in a child with Duchenne muscular dystrophy on daily steroids. Abstracts / Neuromuscul Disord 2015; 25: S184–S316.
  1. Sugerman HJ, DeMaria EJ, Felton WL III, Nakatsuka M, Sismanis A. Increased intra-abdominal pressure and cardiac filling pressures in obesity-associated pseudotumor cerebri. Neurology 1997;49:507e11 .
  2. Schara U, Mortier J, Mortier W. Long term steroid therapy in Duchenne muscular dystrophy: Positive results versus side effects. J Clin Neuromusc Dis 2001;2:179e83.
  1. Johnson LN, Krohel GB, Madsen RW, et al. The role of weight loss and acetazolamide in the treatment of idiopathic intracranial hypertension (pseudotumor cerebri). Ophthalmology 1998;105:2313–7.
  2. Lai LT, Danesh-Meyer HV, Kaye AH. Visual outcomes and headache following interventions for idiopathic intracranial hypertension. J Clin Neurosci 2014;21:1670–8.

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