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Ann Ibd. Pg. Med 2016. Vol.14, No.2 110-113

INTRODUCTIONNemaline Rod Disease, otherwise known as NemalineMyopathy (NM) is a congenital myopathy characterizedby hypotonia, muscle weakness and often skeletaldeformities with the presence of nemaline rods in themuscle biopsy1-3. Facial and respiratory muscles canbe involved in NM and several patients with thecondition have been known to experience respiratoryfailure2-4. Cardiac involvement, particularly dilatedcardiomyopathy, may occur 3,4 and cardiac andrespiratory involvement have been documented asindices of worse prognosis1,2.

Myasthenia Gravis (MG) is a group of autoimmuneneuromuscular diseases characterized by abnormalneurotransmission at the motor endplate resulting fromdestruction of acetylcholine receptors by antiacetylcholine receptor antibodies3,4. It is characterizedby varying degree of muscle weakness, most patients(85%) presenting with ocular symptoms ranging fromptosis, diplopia or blurred vision while others couldpresent with leg, arm, face, neck and trunk weakness,bulbar symptoms and generalized fatigue 4.Autoimmune MG in children is most commonlydivided into neonatal transient and juvenile types, onsetof which is usually after 10 years of age4. Withouttreatment, MG can become progressive and lifethreatening, especially when the bulbar and respiratorymuscles are affected1, 2. The heart is not involved inmyasthenia gravis and electrocardiographic findingsremain normal while roentgenogram of the chest often

reveals an enlarged thymus1. Most patients usuallyrespond well to anticholinesterases with or without avariety of immunosuppressive medications2.

We present the case of an 11 year old Nigerian girlwith suspected nemaline rod disease.

CASE REPORTAAM was an eleven year old female adolescent whowas referred from a tertiary paediatric centre to thePaediatric Neurology Clinic, University CollegeHospital, Ibadan on account of drooping of theeyelids of 2 years duration, easy fatigability andbreathlessness of 6 months duration and 1 week historyof swollen feet.

She was apparently well until 2 years prior topresentation when she developed drooping of botheyelids which usually worsened as the day progressed.There was associated limbs weakness, difficulty withswallowing of solid diet and occasionally of liquidswith concormitant reduced calorie intake and weightloss over about 18 months. She was initiallycommenced on oral Pyridostigmine and Prednisolonewithout any significant improvement and later triedon oral Neostigmine which improved ocularsymptoms but was later discontinued when patientdeveloped severe diarrhoea. She was admitted twicein the 4 months preceding her presentation at ourfacility on account of severe respiratory distress, during

NEUROMUSCULAR DISEASE MIMICKING MYASTHENIA GRAVIS IN ANIGERIAN FEMALE ADOLESCENT: COULD THIS BE NEMALINE ROD

DISEASE?O.A. Oyinlade, I.A. Lagunju, and B.E. Adebayo

1. Department of Paediatrics, College of Medicine, University of Ibadan/University College Hospital, Ibadan

Correspondence:Dr. O.A OyinladeNeurology unit,Department of Paediatrics,College of Medicine,University of Ibadan/University College Hospital,Ibadan.E mail: ladealex2005@yahoo.com

ABSTRACTBackground: Nemaline rod disease is a congenital myopathy,presentation of which may mimic myasthenia gravis.Methods: We report a suspected case of nemaline rod disease in afemale adolescent who presented with features similar tomyasthenia gravis but failed to respond effectively to itsconventional management. She had features of respiratory failureand cardiomyopathyResult: Patient had a turbulent clinical course and finallysuccumbed to illness on the fifth day of admission.Conclusion: This report is meant to sensitize child neurologistsand general paediatricians on the need to have a broad spectrumof considerations in the management of suspected myastheniagravis, especially when response to anticholinesterase is poor.

Keywords: Nemaline disease, Myasthenia gravis, Anticholinesterase

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one of which she was placed on mechanical ventilation.A week prior to presentation, her conditiondeteriorated with severe effort intolerance, difficultywith breathing, orthopnoea, Paroxysmal NocturnalDyspnoea (PND) and swelling of both feet all ofwhich were not associated with cough or change inurinary output and frequency. There was no historyof bluish discoloration of the lips or extremities.

Pregnancy, delivery and neonatal periods wereuneventful and developmental milestones were withinnormal limits. She was born into a monogamousfamily setting and there was no similar history in anyother member of the family.

Findings on examination revealed a chronically ill girl,mildly pale with bilateral periorbital and peripheraloedema up to the mid-thigh, anicteric, not cyanosedand without significant peripheral lymphadenopathy.She was dyspnoeic with flaring of the alae nasi andshallow respiratory excursions. Respiratory rate was36 cycles per minute with fine crepitations at the rightlung base. Pulses were small volume and regular witha rate of 124 beats per minute. Blood pressure was100/60mmHg, Jugular venous pressure was raised.The apex beat was displaced to the fifth left intercostalspace lateral to the mid-clavicullar line. Auscultationrevealed a gallop rhythm with a loud pulmoniccomponent of the second heart sounds. The abdomenwas distended with ascites demonstrable by shiftingdullness and a non-tender hepatomegaly measuring2cm below the right costal margin. She was conscious,alert and well-oriented with intelligent conversation.There was no ptosis or opthalmoplegia on arrival.Cranial nerves were intact with normal muscle toneand grade 5 muscle power in all limbs. Gait was normal.An assessment of background Myasthenia Gravis inremission with Cor Pulmonale to rule outCardiomyopathy and Chronic renal failure was made.She was commenced on intravenous frusemide 40mg(1mg/kg/dose) 8 hourly for 24 hours and oralspironolactone, hydrochlorothiazide and lisinopril.Electrolyte, Urea and Creatinine were within normallimits. Chest x-ray showed cardiomegaly(Cardiothoracic ratio = 66%) and fluffy cotton woolopacities in both middle and lower lung zones. Noenlargement of thymic shadow was noticed.Electrocardiographic features were in keeping withright ventricular hypertrophy while Echocardiographyby the paediatric cardiologist showed biventriculardysfunction worse on the right, all in keeping withcardiomyopathy. Patient was reported to beseronegative for acetycholine receptor antibody at thereferral centre.

She was recommenced on low dose pyridostigmine(30mg qds) on the second day of admission, havingbeen off the medication and oral prednisolone forabout 3 weeks prior to presentation. This was howeverdiscontinued on the third day when she developedtremors and muscle fasiculations after about 24 hoursof commencement. About 42 hours into admission,she developed worsening respiratory distressnecessitating Intensive Care Unit admission withmechanical ventilation. She was subsequently reviewedafter which MG was then considered unlikely on thebasis of (1) Lack of response to anticholinergic agents;(2) repeated episodes of cholinergic crisis even withlow dose anticholinesterase; (3) lack of response tocorticosteroids; (4)features of congestive cardiac failurewith acute pulmonary oedema and (5) recurrentepisodes of severe respiratory distress requiringmechanical ventilation. A possibility of Congenitalmyopathy ? type to keep in view Nemaline Rod Diseasewith respiratory muscle weakness was subsequentlyentertained.

She was weaned off anticholinesterase andElectromyography, Muscle biopsy and serumcreatinine kinase were requested but could not all bedone before demise. Clinical conditions remainturbulent until she succumbed to the illness on the fifthday of admission.

DISCUSSIONIt is well documented in the literature that ocularsymptoms (ptosis, diplopia or blurred vision) are theearliest, commonest and the most constant signs inpatients with MG1,2. It is therefore not surprising thatMG was the foremost diagnosis considered in themanagement of this patient. The presence of limbweakness and associated difficulty in swallowing furtherstrengthened this consideration. Although MG couldsometimes present with respiratory difficulty especiallywhen not promptly diagnosed and treated, most ofthe patients respond well to anticholinesterase andimmunosuppressive therapy1,2. The poor response ofthis patient to anticholinesterase and immuno-suppressive therapy with prednisolone, which isconsidered by many as the most effective oralimmunosuppressive agent in MG 2, the presence ofrecurrent respiratory difficulty requiring mechanicalventilation and cardiac involvement in this patient addweight to the possibility of NM, a condition whichhas been reported to be associated with facial and limbweaknesses, cardiac involvement and respiratoryfailure3-5 all of which were present in this patient.

Our inability to obtain muscle biopsy for definitivediagnosis in this patient before her demise makes

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diagnostic challenges in a developing economy like oursvery obvious. Six different forms of NM have beendescribed with variable prognoses6 while severalauthors have reported variable clinical manifestationsof the conditions from infants with the infantile typethrough adolescent to the adults forms3,7, 8 but sufficientdata depicting the condition in Nigerian and Africanchildren are lacking. However, the onset of symptomsin this patient in late childhood suggest she had thejuvenile variant of NM. In addition, the fact that patientwas a female with symptoms beginning with droopingof the eyelids before involvement of other musclegroups make the diagnosis of muscular dystrophyunlikely.

Tensilon test could not be done in this patient becauseof its inavailability. Although neostigmine was availableand could have been utilized as an alternative, patienthad earlier showed adverse effect when she was triedon neostigmine in the past ( She had profuse diarrhoeawhen she was tried on neostigmine as earlier stated).Hence, attempting neostigmine test in the setting ofsuch adverse reaction could have been fatal and mighthave accelerated patient’s demise. Even when low dosepyridostigmine was commenced as an alternative,patient still manifested adverse effect on the secondday which eventually led to the withdrawal ofanticholinesterase from her therapy. We acknowledgethat ice pack test should have been performed in thispatient since it is very cheap and reports has shownthat cold improves neuromuscular transmission9. Thiscould have further assisted in clarifying the diagnosis.However, situations in which ice pack test was positivein patients with ptosis and underlying diagnosis stillremain unclear have been reported, thus leading to acautionary note on relying on it solely for diagnosis ofmyasthenia gravis9. Plasmapheresis and intravenousimmunoglobulin were not readily available forutilization during the course of management.

Although evidences abound that NM is a genetic diseasecommonly involving the mutation of the nebulin gene10,there have been documented reports of itsdemonstration in Human Immunodeficiency Virus(HIV) myopathies4,11, thus suggesting a possibleautoimmune component in its aetiopathogenesis.There is no cure for NM as at present12. Some patientswith the disorder are able to lead an active life,especially when there is no cardiac and respiratoryinvolvement3.

Patients with cardiac involvement have been reportedto benefit from Angiotensin Converting Enzymeinhibitors, â blockers or angiotensin receptor blocker4

while some authors have documented the beneficialeffects of L-tyrosine, a non-essential amino acid which

is a precursor or catecholamines which possibly explainits beneficial effects6. Ivabradine, a cardiotonic agent,has been used in some patients with NM whodeveloped heart failure unresponsive to â blockers11.

CONCLUSIONAlthough this report is limited by lack of definitivediagnosis with muscle biopsy, the diagnostic puzzlebetween MG and NM at the presentation of thispatient is very obvious and the eventual considerationof NM during a later review in the course ofmanagement on the ground of previous history offacial weakness, dysphagia, respiratory and cardiacinvolvement and poor response to anticholinesteraseand immunosuppressive therapy with oralprednisolone agrees with documented clinical courseof NM3-5, while the presence of respiratory failureand cardiovascular compilations likely worsened theprognosis in this patient. We wish to therefore sensitizeclinicians in resource poor setting and developingeconomies to these rare conditions which couldsometimes present as diagnostic and managementchallenges.

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