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Anaesthetic impli- cations of nemaline Mary Cunliffe MB BS FFARCS Frederick A. Burrows MD FRCPC rod

Nemaline rod myopathy is an inherited congenital myo- Nemaline rod myopathy belongs to the group pathy first described in 1963. Affectedpatients character- of congenital sarcoplasmic which in- istically present in infancy with a non-progressive hypo- cludes and mitochondrial my- tonia and symmetrical . The disease opathy. It was first described in 1963,1,2 and except affects all skeletal muscles including the diaphragm with for a single case report 3 there is little in the medical sparing of cardiac and other muscle. Facial dysmor- literature about the anaesthetic management of phism is common as are skeletal deformities, including these patients. kyphosis, scolosis and pectus excavatum. Myopathic patients can present with decreased We present two sisters with nemaline rod myopathy respiratory muscle reserve and as such be unable to and their anaesthetic management for surgery. compensate for the stresses of anaesthesia and Facial dysmorphism was a feature of both cases. Pre- surgery. Anaesthesia in these patients may precipi- operatively, both patients demonstrated poor respiratory tate respiratory failure secondary to the respiratory function on pulmonary function testing. Both cases were depressant effects of drugs, sputum retention lead- successfully managed using controlled ventilation and ing to pneumonia, and ventilatory restriction due to inhalational anaesthetic agents, avoiding muscle re- wound pain. We review our anaesthetic experience laxants. Postoperatively, there were no respiratory com- in two sisters with nemaline rod myopathy, present- plications. ing an anaesthetic technique for these patients Although one case report describes the use of succinyl- which appears to be without complications, and choline and pancuronium in a patient with nemaline rod avoids the use of muscle relaxants. myopathy, we feel that neuromuscular blocking agents Muscular dystrophies and myotonias are associ- should be avoided where possible and only used with ated with abnormal responses to various anaesthetic careful monitoring. agents. Succinylcholine has on rare occasions caused cardiac arrest. Although there has been one case report where muscle relaxants were given to a patient with nemaline rod myopathy, 3 we feel that these drugs should be avoided when possible.

Case 1 Key words Sister one was the first born child of a 27-year-old GENETIC FACTORS: nemaline rod myopathy; woman. Following a difficult breech delivery, she ANAESTHETIC TECHNIQUES: inhalational agents, was found to have severe flexion contractures of muscle relaxants; COMPLICATIONS: pulmonary both hips and little spontaneous movement in all function, difficult intubation. four limbs. The contractions of her hips were treated with passive stretching and traction without From the Department of Anaesthesia, The Hospital for anaesthesia. At age one month a muscle biopsy Sick Children and University of Toronto, Toronto, done using local anaesthesia was normal. The Ontario. presumptive diagnosis was myodystrophia fetalis or Address correspondence to: Dr. F.A. Burrows, The arthrogryposis. One month later a second muscle Department of Anaesthesia, The Hospital for Sick biopsy and electromyogram were done because of Children, 555 University Avenue, Toronto, Ontario, persistent . On this occasion the biopsy M5G 1XS. revealed normal muscle and the electromyogram

CAN ANAESTH SOC J 1985 / 32:5 / pp543-7 544 CANADIAN ANAESTHETISTS' SOCIETY JOURNAL showed atrophic muscle. The presumptive diagno- scoliosis. Her past medical history was unremark- sis was arthrogryposis and the prognosis for both able except for a history of nemaline rod myopathy. physical and mental improvement were thought to Preoperative investigations including blood count, be poor. urea, serum electrolytes, urinalysis, prothrombin By four years of age Sister one could walk. The time, partial thromboplastin time, capillary blood myopathy had not progressed. In view of her gases, chest x-ray and electrocardiogram were all progress, the diagnosis was changed to non- normal. Pulmonary function tests showed a severe progressive spinal muscular atrophy. However, at restrictive defect with a fixed vital capacity of 34 per 12 years of age, a review of her disease process cent of predicted. changed the diagnosis to nemaline rod myopathy. Sister two had dysmorphic facial features includ- Between the ages of six and 16 years, Sister one ing a very narrow mandible and high arched palate. had four anaesthetics for minor orthopaedic and eye Anaesthesia was induced with nitrous oxide, oxy- surgery. On each occason, anaesthesia was induced gen and halothane. At laryngoscopy only the with thiopentone 5mg'kg -I and atropine 0.02 posterior arytenoids were visualized and the trachea mg.kg -t. An endotracheal tube was passed under was intubated with the aid of a styler. Anaesthesia deep halothane anaesthesia without the use of was maintained with nitrous oxide, oxygen and muscle relaxants. Anaesthesia was maintained with isoflurane, and controlled ventilation. Muscle re- nitrous oxide, oxygen and halothane with con- laxants were not used. Because surgery lasted seven trolled ventilation. On each occasion, anaesthesia hours and the blood loss was 2.5 times the patient's and recovery were uneventful. estimated blood volume, Sister two was ventilated At 13 years of age, Sister one presented for overnight in the intensive care unit. She was corrective surgery for a marked thoraco-lumbar extubated the next morning. There were no post- scoliosis. A minor degree of facial dysmorphism operative respiratory complications or coagulation was noted. Preoperative investigations including problems, and the patient was discharged home ten blood count, urea, serum electrolytes, prolhrombin days later. time, partial thromboplastin time, capillary blood gases and chest x-ray were all normal. Pulmonary Discussion function studies demonstrated a restrictive defect, Nemaline rod myopathy often presents in the with a forced vital capacity of 47 per cent of pre- neonatal period with , a weak cry, poor dicted. The electrocardiogram revealed left atrial sucking reflex and dysphagia. These problems may hypertrophy without ventricular chamber enlarge- lead to respiratory distress and cyanosis. Motor ment; however, the heart size on chest x-ray was development is delayed, and crawling and walking normal. Anaesthesia was induced with thiopentone are characteristically late. Most patients with nema- 5 mg'kg -1 and atropine 0.02 mg'kg -~ and an endo- line rod myopathy present in the newborn period tracheal tube inserted under deep halothane anaes- with only a small number presenting later in life. 4 thesia without muscle relaxant. Anaesthesia was The trunk and proximal limb muscles are most maintained with fentanyl and halothane, and con- commonly affected. Distal limb muscles, 5'6 pala- trolled ventilation. No muscle relaxants were used. tal, pharyngeal and facial muscles may also be The blood loss during the scoliosis surgery was 95 involved. Engel described one patient in whom per cent of the estimated blood volume. There were there was loss of muscle bulk in all muscle groups, no coagulation defects despite the large blood loss. and in particular in the paraspinal and proximal limb She was extubated in the recovery room. Postopera- muscles. 5 In that patient, the muscle groups most tive pain was treated initially with morphine, and severely affected were considerably stronger than then after two days with codeine. There were no expected when tested. In autopsy studies, extensive postoperative respiratory complications and she diaphragmatic involvement is reported, 6-9 with was discharged from hospital 12 days later. sparing of cardiac and smooth muscle. Although the nervous system is not commonly Case 2 involved, deep tendon reflexes may be absent. Sister two presented at the age of 14 years for Luque In addition to involvement, rod instrumentation to correct a thoraco-lumbar dysmorphic features are common. The face is Cunliffe and Burrows: NEMALINE ROD MYOPATI-IY 545

characteristically long and slender, with a high have been no extensive pedigrees described for arched palate. Micrognathia and dental malocclu- nemaline rod myopathy to date and sporadic cases sion are also common. Skeletal deformities includ- of the disease have also been recorded. ~2 ing kyphosis, scoliosis, pes cavus and pectus Patients with nemaline rod myopathy can present excavatum are often present. It is the latter ortho- three main problems to the anaesthetist - facial paedic problems which usually require surgery. The dysmorphism, the adequacy of pulmonary func- presence of arachnoidactyly in one patient, has tion, and the question of which anaesthetic agent suggested that the disease resembles Marfan's may be used safely. Preoperative assessment of syndrome without the cardiac lesion.i~ these patients should include an examination of the It has been suggested that nemaline myopathy is a airway for a high arched palate, micrognathia and non-progressive muscle disease. However, there dental malocclusion, which suggest a potentially have been several reports of a severe form of difficult intubation. Pulmonary function studies nemaline rod myopathy which resulted in death in will be useful in assessing the severity of the the first year of life. 7-9 The first fatal case occurred restrictive lung disease due to a combination of the in a patient with severe involvement of the bulbar myopathy and scoliosis. Blood gases indicate the and respiratory muscles, including the diaphragm. 9 adequacy of oxygenation and ventilation. In those Death was due to pulmonary aspiration, and respi- patients with pulmonary problems, chest physio- ratory failure again is a potential problem. A patient therapy should commence preoperatively and con- with a positive muscle biopsy for nemaline rod tinue in the postoperative period. Preoperative chest myopathy may also be symptom free. ~2 Sudden infection should be actively treated and elective progression of the disease in late middle life has also surgery delayed until the infection resolves. A been reported. 6 Because the clinical manifestations complete anaesthetic management including a tech- of the infantile nemaline myopathy and the late nique for securing the airway in view of a difficult onset rod body myopathy are different it has been intubation, difficulty in ventilating the patient dur- suggested that they are distinct entities. In the adult, ing surgery and contingency plans for postoperative rod body myopathies have been associated with ventilation must be considered. other diseases of muscle including dermatomyositis Facial dysmorphism, a common feature of the and polymyositis. ~3 These diseases may represent a disease, was present in both our sisters to a lesser or single disease spectrum with an early or late onset. 6 greater degree. This dysmophism may give rise to Laboratory investigations may help to confirm concern as to the ease of intubation in these patients, the diagnosis of nemaline rod myopathy. Creatin- and an inhalation induction or awake intubation urea has been found in a number of cases, but the may be preferred. Sister two was correctly assessed non-specific nature of the test limits its usefulness. 6 as presenting an intubation problem, because of her usually reveals a non-specific long narrow face, small mandible and high arched myopathy which is not diagnostic for nemaline rod palate. An inhalational induction was performed myopathy. Microscopy of a muscle biopsy speci- and intubation was accomplished with minor diffi- men is the only diagnostic test. Microscopy usually culty. reveals aggregates of rods in the sarcolemma of the The respiratory function of patients with nema- muscle fibre. The rods may be identified with line rod myopathy presenting for scoliosis surgery Gormori's trichrome stain. Negative muscle biop- may be compromised in two ways. Firstly, the sies have been explained by the variability of myopathy itself may affect the respiratory muscles affected fibres in different muscle groups. 6 Never- reducing respiratory reserve. Secondly, severe sco- theless, microscopy of a muscle biopsy specimen liotic curves cause changes in pulmonary function remains the only definitive test of the disease. because of chest wall deformity, pulmonary gas The inheritance pattern is thought to be autoso- exchange is affected by ventilation/perfusion (V/Q) mal dominant with variable penetrance. Nemaline mismatch, producing increases in the alveolar/ rod myopathy may affect both parents and chil- arterial oxygen difference (A-aDO2) and the dead dren. 1'6 In one case, the mother had both central space/tidal volume ratio (VD/VT). Increasing real- core disease and nemaline myopathy, and the distribution increases the patient's ventilatory re- daughter had only central core disease, t~ There quirements and a rising arterial carbon dioxide 546 CANADIAN ANAESTHETISTS' SOCIETY JOURNAL tension reflects an inability to compensate for this. losses during their scoliosis surgery, this had no In long-standing cases, pulmonary hypertension adverse effects on postoperative morbidity. may be present. In addition to chest wall deformity and loss of motor function in these patients, there may be an abnormality of central respiratory control Summary causing sensitivity to depressant drugs such as We have described the anaesthetic management of narcotics, sedatives and general anaesthetics. Pre- six operative procedures in two sisters with nema- operative pulmonary function tests should include line rod myopathy. Special problems associated vital capacity, forced expiratory volume and its with this disease are the presence of dysmophism0 derivatives, and resting arterial gas levels. These poor pulmonary reserve and the choice of anaes- will serve as a baseline against which to compare thetic technique. Inhalational agents appear to be postoperative results. The presence of a bulbar well tolerated in these patients with no side-effects. palsy may further complicate anaesthetic manage- Although one case report has described the use of ment because of the tendency to regurgitation and muscle relaxants in a patient with nemaline rod pulmonary aspiration. myopathy we feel that these agents should be Because myotonias and muscular dystrophies are avoided if possible. Postoperative ventilatory sup- associated with abnormal responses to neuromuscu- port may be required in severely affected patients; lar blocking agents, we felt that they were best however, a meticulous anaesthetic technique can avoided. Heard and Kaplan, however, have re- produce little postoperative morbidity. ported a single case in whom suecinylcholine 1 mg.kg -I and pancuronium 0.08mg.kg -1 were used. 3 The patient had an abnormal response to References succinylcholine with 95 per cent twitch depres- 1 ShyGM, EngelWK, SomersJE, WankoT. Nemaline sion only developing after four minutes. Intubating myopathy - a new . Brain conditions were good and there were no associated 1963; 86: 793-810. rises in the serum potassium level. The response 2 Cohen PE, Murphy EG, Donohue WL. Light and to pancuronium was normal. We have shown that electron microscopic studies of "myogranules" in patients with nemaline rod myopathy can be safely a child with bypotonia and muscle weakness. Can managed without the use of muscle relaxants, Med Assoc J 1963; 89: 983-6. which may be preferable in view of their poor 3 Heard SO, Kaplan RF. Neuromuscular blockade in respiratory reserve and potentially difficult intuba- a patient with nemaline myopathy. Anesthesiology tion. Although many muscle diseases including 1983; 59: 588-90. central core disease and Duchenne muscular dystro- 4 Kuitunen P, Rapola J, Noponen A-L, Donner M. phy are associated with an increased incidence of Nemaline myopathy - case report. Acta Paediatr malignant hyperthermia, 14A5 there has been no Stand 1972; 61: 353-61. reported association between nemaline rod myo- 5 Engel WK, Wanko T, Fenichel GM. Nemaline pathy and malignant hyperthermia. myopathy- a second case. Arch Neurol 1964; 11: If a "wake-up" test is performed during scoliosis 22-39. surgery, the use of inhalational agents may prolong 6 Hopkins IJ, Lindsay JR, Ford FR. Nemaline the time to awakening, but this is not a contraindica- myopathy - a long term clinicopathologic study of tion to their use in these patients. However, if affected mother and daughter. Brain 1966; 89: somatosensory cortical evoked potentials are used 299-310. to assess spinal cord function, inhalational agents 7 Shafiq SA, Dubowitz V, Peterson H de C, Milhorat do affect the results. AT. Nemaline myopathy - report of a fatal case The use of hypotensive anaesthesia to reduce with histochemical and electron microscope studies. blood loss in seoliosis surgery remains a controver- Brain 1967; 90: 817-28. sial subject. In myopathic patients deliberate hypo- 8 Mitshuhiro Tsujhata, Chieko Shimomura, Toshiro tension is probably best avoided in view of the Yoshimura et al. Fatal neonatal nemaline myopathy unpredictability of the patients' response to anaes- - a case report. J Neurol Neurosurg Psych 1983; 46: thetic agents. Although both sisters had large blood 856-9. Cunliffc and Burrows: NEMALINE ROD MYOPATHY 547

9 Kolin IS. Nemaline myopathy - a fatal case. Am J R6sum6 Dis Child 1967; 114: 95-100. La myopathie d la nemaline est une myopathie congdni- 10 Hudgson P, Gardner-Medwin D, Fulthorpe J J, tale d~crite pour la premi~re fois en 1963. Les patients Walton JN. Nemaline myopathy. 1967; affect~s pr~sentent dds l'enfance une hypotonie non 17: 12: 1125-42. progressive et une faiblesse musculaire symdtrique. Cette 11 Afifi AK, Smith JW, Zellweger H. Congenital non- maladie affecte tousles muscles squelettiques incluant le progressive myopathy: central eore disease and diaphragme d l'exception du muscle cardiaque. Le nemaline myopathy in one family. Neurology 1965; dysmorphisme facial est frequent de m~me que des 15: 371-81. difformit~s squelettiques incluant une cyphose, scoliose 12 Gonoatas NK, Shy GM, Godfrey Ell. Nemaline et pectus excavatum. myopathy - the origin of nemaline structures. N On pr~sente le cas de deux soeurs atteintes de myo- Engl J Med 1966; 274: 535-9. pathie d la nemaline qui se uont pr~sent~es pour une 13 Engel WK, Resnick JS. Late onset of rod myopathy correction de scoliose. La conduite anesthr est (a new syndrome). Light and electron microscopic discut~e. La ddformit~ du visage a dtd un probldme darts observations in two cases. Mayo Clin Proc 1966; 41: les deux cas. En pdriode prdopdratoire, les deux patientes 71g-41. avaient une fonction respiratoire perturbde. La conduite 14 Eng GD, Epstein BS, Engel, WK, McKay DW, anesth~sique s'est effectude avec succds en utilisant la McKay R. Malignant hyperthermia and central core ventilation eontrdlde et des agents anesthdsiques d'in. disease in a child with congenital dislocating hips. halation sans relaxant musculaire. En pHiode post- Arch Neurol 1978; 35: 189-97. opdratoire, aucune complication respiratoire fut notre. 15 Brownetl AK, Paasuke RT, Elash A et al. Malignant M~me si un cas a ~t~ rapportd oft la succinylcholine et hyperthermia in Duchenne . le pancuronium ont gtd utilis~s, on croit que les relaxants Anesthesiology 1983; 58: 180-2. musculaires doivent ~tre dvitds si possible et utilisgs uniquement avec une surveillance soutenue.