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Anaesthesia and Rett Doug Maguire use MD CRCe, Cathy Bachman MD FRCPC syndrome: a case report

Rett syndrome is" a neurological disorder of females charac- spastic hop. Communication was limited to pointing and terized by dementia, autism, movement disorders and an crying. Formal assessment at age seven estimated devel- abnormality of respiratory control. opment at the one-year level. Since that time there have A 14-year-old girl with Rett Syndrome underwent spinal been small gains in social, development but also deteriora- fusion surgery under general anaesthesia. No exacerbation of tion of motor skills. Extensive investigations failed to the respiratory control defect with surgery and anaesthesia was provide a diagnosis until the diagnosis of Rett syndrome observed. Hypothermia. ongoing blood loss and a normal anion was recently recognized. gap acidosis were encountered, but were not attributable to Previous general anaesthesia for diagnostic CT scan at features of this disorder. six years of age had been uneventful. Seizures, present since age six, were well controlled with valproate. She Rett syndrome is a progressive neurological disease found had a weak non-productive cough. There was no history exclusively in females, characterized by dementia, autis- of recurrent pneumonia. Her parents had noted episodes tic behaviour, stereotyped hand movements and an of irregular breathing; these were most often during sleep abnormality of respiratory control.1 We recently anaes- and not associated with cyanosis. thetized a patient who demonstrated most of the features On examination, she was 24 kg, normotensive, afebrile of this disorder. Anaesthetic experience in patients with and not distressed. Her head was small with the circum- this disease has not previously been reported. ference less than the third percentile. The airway was normal apart from excessive secretions. A thoracic Case report scoliosis was present. Auscultation of the heart and chest A 14-year-old white female with Rett Syndrome was was unremarkable. The extremities were cool, without scheduled for elective Harrington Rod spinal fusion for clubbing or cyanosis. Muscle mass was diminished, tone correction of a scoliosis curve of 58 ~ by the Cobb increased and reflexes were brisk. method, which had rapidly progressed despite bracing. Preoperative haemoglobin concentration was 129 g-L-j On admission to the hospital initial examination by the and biochemistry was normal. The heart and lungs were attending anaesthetist revealed a pleasant looking, frail, normal on chest x-ray. The ECG was unremarkable. Lack red headed child displaying a great deal of hand wringing. of patient cooperation prevented pulmonary function She was unable to speak and sat supported in a wheel- testing. chair, totally dependent in all aspects of daily care. The child was quiet on arrival in the operating room Early history included term vaginal forceps delivery without premedication. Monitors were established and with normal Apgar scores. Birth weight was 3.5 kg. She anaesthesia induced by mask with balothane and nitrous was reported to be smiling at 6 weeks, head holding at oxide. The trachea was intubated with a 6.0 mm oral four months, sitting at ten months and feeding herself at tracheal tube following administration of paneuronium one year. Between 12-18 months of age previously 2.5 mg. The patient was placed prone on a Relton Hall acquired speech and interest in surrounding~ were lost. frame. Ventilation was controlled using a circle system She never crawled but learned to walk by age four with a and Ohio ventilator. Anaesthesia was maintained with N20 2 L- min- i, 02 1.6 L" min- ~, isoflmane 0.5-1.0 per cent and 7 mg morphine. Monitoring included nasal Key words pharangeal temperature, intra-arterial catheter, foley COMPLICATIONS: dementia; respiratory, apnoea; catheter, pulse oximeter, end-tidal carbon dioxide, INHERITED DESEASE: Rett syndrome, anaesthesia; inspired-expired isoflurane and oxygen concentrations. SYNDROME: Rett. Intraoperatively her temperature fell to 33.5 ~ C within two hours despite warming of the room to 26 ~ C, warming From the Department of Anaesthesia, University of Manitoba the IV solution and heating and humidifying the inspired Children's Hospital. 840 Sherbrook St., Winnipeg, Manitoba gases. Estimated blood loss of 1300 ml was replaced with R3A ISI. packed cells and normal saline. Haemodynamic variables Address correspondence to: Dr, C. Baehman. and arterial blood gases were stable.

CAN J ANAESTH 1989 / 36:4/pp478-81 magalre and Bachman: ANAESTHESIA AND RETT SYNDROME 479

At the completion of surgery the trachea was reintubat- with genetic data but hard to confirm as affected girls are ed with a nasal tracheal tube and the patient was unlikely to bear children. transferred to the ICU without awakening. Mechanical Neurological, respiratory, cardiovascular and meta- ventilation was continued. Normothermia was achieved bolic features of this disorder present potential anaesthetic following three hours of surface warming. In the first ten problems. Considerations arising from neuromuscular hours following surgery, 300 ml packed blood cells, 250 involvement include lack of cooperation, control of ml fresh frozen plasma and 1.5 L crystalloid, primarily seizures and limb movements, positioning and selection normal saline, were administered to manage ongoing of muscle relaxants. Medical manipulations or introduc- blood loss and maintain haemodynamic stability. An tion to the operating room may precipitate behavioural arterial blood gas measurement two hours post- problems which can be associated with respiratory irreg- operatively during controlled ventilation (FIO2 0.4) ularities.SHeavy preoperative sedation may prevent such showed PaO2 = 108 mmHg, PCO2 = 37 mmHg, pH = a response but could have undesirable side effects. Music 7.29. I'IC03 = 17.6 and base excess - 8.3. The metabolic is said to have a calming effect in patients with Rett acidosis was associated with a normal anion gap and syndrome and achieve a temporary cessation of stereotyp- corrected as volume status normalized. The lungs were ic movements.6 Familiar music accompanying these ventilated overnight and the patient maintained satisfacto- children may be useful before induction of anaesthesia. ry arterial blood gases after extubation. Post-extubation, The muscle wasting and altered muscle tone demand close pulse oximetry monitoring for six hours in the ICU did not attention to p~per positioning. Cooperman7 has described detect any episodes of desaturation. She was discharged increases in serum potassium concentration following home on the tenth postoperative day. succinylcholine in patients with various neuromuscular disorders. For this reason we used a non-depolarizing Discussion muscle relaxant and selected pancuronium for its cardio- In 1966 Rett described a syndrome of progressive vascular stimulating effects. deterioration of higher brain function occurring only in These children may be at risk of reeurrem aspiration girls. 2 This illness had remarkably consistent clinical and impaired respiratory function from muscle weakness features including a period of normal development for the and thoracic deformity. In addition, abnormal patterns of first 4-18 months followed by rapid developmental respiration are characteristic. Polygraphic studies reveal regression leading to dementia associated with severe that breathing is stable and regular during sleep. Wakeful- autistic behaviour, Acquired elements of language were ness is associated with periods of disorganized, ineffec- lost, purposeful movement of the hands was lost and tive respiratory efforts, frequently mixed with apnoea, s,s stereotypic handwashing movements were exhibited, l Episodes of irregular breathing resulted in significant Axial hypotonia and limb spasticity frequently develop. arterial oxygen desaturation and loss of consciousness Various movement disorders were exhibited, including during severe episodes.9 An impairment of the behaviour- choreoathetosis, dystonia, myoclonic jerk and stereotypic al control system of breathing which is considered to be a automatism.l'3 forebraln function has been suggested, s The rapid devel- In the chronic phase there is diffuse and progressive opment of desaturation may be due to the high expiratory muscle wasting. Growth stagnation occurs involving position of the diaphragm during apnoea. Other investiga- weight, stature and, in particular, microeephaly. Survival tors have demonstrated evidence of upper airway obstruc- beyond age 30 has been reported, but is not common. tion suggesting a combined central and obstructive role in With age advancing into the teens most are functionally the observed disorganized respiratory pattern. restricted to a wheelchair. 1 Cirignotta et al. S have suggested that the frequent Although described over 20 years ago, widespread desaturafions may cause permanent hypoxic damage and awareness of this syndrome is very recent. Prevalence contribute to the progressive cerebral deterioration. The studies now indicate that it is not a rare phenomenon. It is influence of anaesthetic agents on respiratory patterns estimated that among the population of severely retarded during the perioperative period is not known. A typical females the prevalence may be as high as 25 per cent. 4 history of apnoea was not elicited in our patient. This To date, no studies have clarified the pathogenesis or information must be interpreted with caution as polygraph cause of this disorder, and no diagnostic laboratory test monitoring has demonstrated breathing impairment in all has been identified. The diagnosis is made by exclusion of Rett patients that have been studied, s,s Episodes of de- other causes of developmental delay and by compatible saturation have been recorded at a time when parents or clinical features. The sex distribution is inconsistent with nurses reported the child quiet and breathing regularly, s an acquired disease. The hypothesis of an x-linked Marked variability between examinations has also been dominant mutation which is lethal for males is consistent observed. A negative history for apnoea may be unrelia- 480 CANADIAN JOURNAL OF ANAESTHESIA ble. All patients with suspected Rett syndrome should be lout, ataxia, loss of use of the hands and an impairment of considered to have a disorder of respiratory control and to respiratory control leading to frequent oxygen desatura- experience periods of desaturation. tions. The neurological features of this disorder and the Preoperative assessment of respiratory function should cardiorespiratory manifestations of co-existing problems address the potential for aspiration, respiratory muscle such as scoliosis, together with a concern for exacerbation weakness and apnoea. Exercise testing and formal pulmo- of the respiratory defect necessitates careful preoperative nary function testing are unlikely to be available. Con- assessment. Our patient with Rett syndrome tolerated trolled ventilation and perioperative arterial blood gas anaesthesia well; in particular apnoea and oxygen desat- monitoring is indicated. The patient presented had mini- uration were not observed. Complications common to this mal respiratory symptoms, no evidence of recurrent type of surgery such as blood loss, hypothermia and aspiration and a normal chest x-ray. Postoperative control metabolic acidosis were encountered. Careful anaesthetic of ventilation was planned until rewarming occurred. It techniques regarding positioning, temperature loss, fluid was continued overnight because of ongoing blood loss management and observation of respiratory function are and minor haemodynamic instability. Supplementary required to avoid potential complications. Awareness of oxygen and saturation monitoring perioperatively appear this syndrome is important since similar patients might be to be warranted. The requirement for post-surgical admis- encountered with increasing frequency for incidental or sion to the ICU should take into account the severity of corrective surgery. The anaesthetist is in a position to symptoms, nature of surgery and anaesthesia. contribute to the further experience necessary to deter- Cardiovascular considerations of patients with neuro- mine if these patients are at increased risk during the muscular scoliosis have been well described by Kafer. a0 perioperative period. Vasomotor disturbances leading to cool limbs with tropic changes are seen in 50 per cent of older affected children. References Profuse sweating may also be observed. Unintentional 1 Al.Moteen M, Philippart M, Shields WD. gett syndrome:a hypothermia occurred in our patient. A thin body habitus, commonly overlooked progressive encephalopathy in girls. suspension in the Relton-Hall frame and a large exposed Am J Dis Child 1986; 140: 761-5. evaporative operative surface all contributed to cooling. 2 RettA. Ueber ein eigenartiges himatropisches Syndrome Aggressive attempts to control heat loss are required. bei Hyperammonamie im Kindersalter. Wien Med Metabolic abnormalities have been studied extensive- Wochenschr 1966; 116: 723-38. ly. Elevated ammonia concentrations were reported in 3 ttagberg B, Aicardi J, Dins K, Ramos O. A progressive Rett's original paperz but are not seen as a consistent syndrome ofantism, dementia, ataxia and loss of parposeful feature of the condition. Increased concentrations of lactic hand use in girls: Rett's syndrome: Report of 35 Cases. acid have also been reported. 3 Zoghbi etal. lj studied the Ann Neurol 1984; 14: 471-9. CSF of affected patients specifically to consider the 4 Hagberg B. Rett's syndrome: prevalence and impact on possibility of an abnormality in neurotransmitter func- progressive severe mental retardation in girls. Acta Paediatr tion. Dopamine serves as a synaptic transmitter in the Scand 1985; 74: 405-8. basal ganglia which are involved with the control of 5 Cirignotta F, Lugaresi E, Montagna P. Breathing movement. Seritonin and norepinephrine have a role in impairment in Rett syndrome. Am J Med Genet 1986; 24 sleep-wake cycles and control of autonomic systems. The Suppl 1: 167-73. function of these neurotransmitters can be indirectly 6 Wesecky, A. Music therapy for children with Ren assessed by quantitative analysis of their metabolites in syndrome. Am J Med Genet 1986; 24 Supp J: 253-7. the CSF. Zoghbi II has reported a reduction in dopamine 7 Miller RD. Anesthesia, 2nd ed. New York: Churchill and norepinephrine metabolites in six patients studied. Livingstone, 1986: 920. Defficiency of the enzyme tyrosine hydroxylase could 8 Glaze DG, FrostJD Jr., Zoghbi HY, Percy AK. Ren's account for the reduced levels of neurotransmitter meta- syndrome: characterization of respiratory panems and sleep. bolites. Ann Neurol 1987; 21: 377-82. A normal anion gap metabolic acidosis developed 9 Lugaresi E, Cirignotta F, Montagna P. Breathing in the postoperatively. Although patients with this syndrome Rett syndrome. Brain Dcv 1985; 7: 329-33. have been reported to develop lactic acidosis, the acidosis 10 Kafer ER. Respiratory and cardiovascular functions in in our patient could be attributed to rapid IV fluid seoliosis and the principles of anesthetic management. administration. Anesthesiology 1980; 52; 339-51. I 1 Zoghbi HY, Percy AK, Glaze DG, Butler IJ, Riccardi Summary VM. Reduction of biogenic amine levels in the Rett Rett syndrome is a recently recognized neurological syndrome. N Engl J Med 1985; 313: 921-4. disorder of females, typified by dementia, autistic behav- Maguire and Bachman: ANAESTHESIA AND RETT SYNDROME 481

R~sum~ Le syndrome de Rett, qui n' atteint que les femmes, se distingue par de la d~mence, de l' autixme, de l' incoordination musculaire et un contr61e anormal de la respiration. R~cemment, nous avons fait une anesth~sie g~n~rale pour arthrod~se vert~brale chez une patiente de 14 ans, victime de ce syndrome. L'hypothermie, les pertes sanguines et l'acidose m~tabolique encourues ont dtd dans les limites habituelles de ce genre d' op~ration. Le contrOle anormal de sa respiration ne s'est pas aggrav# lots de l' intervention.