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460 Archives ofDisease in Childhood 1995; 72: 460-465

PERSONAL PRACTICE Arch Dis Child: first published as 10.1136/adc.72.5.460 on 1 May 1995. Downloaded from

Investigation of developmental delay

R W Newton, J E Wraith

The diagnostic process Presenting symptoms Paediatricians will often be asked to see child- ABNORMAL BEHAVIOUR IN THE NEONATAL ren with learning difficulties. They will present PERIOD at a variety of ages in a number of different Apart from obvious dysmorphic features, dis- ways and it is easy to feel unsure how exten- ordered tone, feeding difficulties, irritability, sively to investigate the problem and what and may all signify continuing neuro- advice to give. This article will review the com- logical abnormality. in the limbs mon presentations and suggest a rational and axis raise the possibility of a neuro- approach to investigation. muscular disorder or the Prader-Willi syn- The role of the paediatrician is to help drome. Where hypotonia is confined to the understand the issue of causation, inform the axis, there is usually a central parents of future outlook, deal with any atten- abnormality including the cerebral dysgeneses, dant medical problems, and arrange genetic or hypoxic-ischaemic when it counselling and supportive services. Special may be associated with a full fontanelle due to investigation plays only a small part in this cerebral oedema, irritability, feeding difficul- process. Clinical skills are equally important; a ties, and seizures. child's appearance, pattern of movement, or The commonest cause of persisting hypoto- mode of presentation may all give important nia or feeding difficulty is the presence of one diagnostic clues. of the recognisable forms of learning difficulty Children with learning difficulties present of which Down's syndrome is the commonest. in relatively few well circumscribed ways: Of the metabolic disorders, it should be hypotonia in the newborn period, recognised remembered that the cerebrohepatorenal syn- developmental delay later in infancy or in drome of Zellweger (one of the peroxisomal the early toddler age group, language delay, disorders) can mimic Down's syndrome. It is http://adc.bmj.com/ arrest of development, or difficulties at associated with profound hypotonia as well as school (see below). In each of these groups a craniofacial dysmorphism similar to trisomy the history should detail the pregnancy, 21. The use of one ofthe computer based data- including any drug ingestion or early bases of dysmorphology can be helpful when threatened abortion. The presence of fetal attempting to establish a dysmorphic diag- distress should lead to careful scrutiny of the nosis.4

obstetric notes, though it is now generally Arthrogryposis should make one think of a on September 29, 2021 by guest. Protected copyright. accepted that in order to attribute causation neuromuscular problem or a neuronal migra- to birth asphyxia the presence of hypoxic- tion defect particularly if the hands and arms ischaemic encephalopathy must be estab- are held in a 'decorticate' posture. The pres- lished. A record of cord or early pH ence of and pooling of secretions with measurements as well as neonatal behaviour aspiration makes a congenital myopathy and are important in this respect as not all early particularly nemaline rod myopathy likely. neonatal encephalopathy is due to hypoxic- ischaemic insult. 1-3 Parents in their own mind often attribute their child's difficulties DEVELOPMENTAL DELAY to the events of labour and it can be helpful When children attain developmental skills for them to be taken through details of the significantly more slowly than the average birth. child they may have continuing difficulties A detailed family history is clearly of value with learning in later life. Many standardised especially if supplemented by perusal of the tests are available to back-up an initial Royal Manchester family photograph album. These together with impression at the clinical consultation. The Children's Hospital, home video recordings can give a surprisingly Griffiths, Bailey, and Wechsler scales con- Pendlebury, clear idea of the evolution of a disorder. Many tinue to be the most widely used. Lack of Manchester M27 4HA Department of motor disorders such as the in cere- stimulation due to social disadvantage or pro- Paediatric Neurology bral palsy or the extrapyramidal involvement in longed illness in an infant may result in a tran- R W Newton Rett's syndrome may evolve over a period of sient period of relative delay with subsequent the a on the other assessment in Willink Biochemical time, raising possibility of neurodegener- catch-up; hand, Genetics Unit ative disorder. Careful scrutiny of the history infancy may serve to over estimate the ability J E Wraith often reveals that whereas things have of children with more severe learning difficul- Correspondence to: changed, skills may not actually have been ties, due to an emphasis in the tests on motor Dr Newton. lost. skills. Investigation ofdevelopmental delay 461

'FUNNY WALKS' , neurodegenerative condi- Many disorders with learning difficulties have tion, or congenital infection. The retina should

an associated gait disturbance. The gait should be examined for signs of chorioretinitis or pig- Arch Dis Child: first published as 10.1136/adc.72.5.460 on 1 May 1995. Downloaded from be observed with particular features in mind. mentation to reflect a mitochondrial cytopathy In the absence of a clear heel strike a toe-heel or peroxisomal disorder and structure gait may be due to pyramidal or extrapyra- and viscera should be examined for signs of midal motor dysfunction, a foot drop due to a abnormal storage. lateral popliteal nerve palsy or tight tendo- achilles due to a neuromuscular problem. A wide base seen continuing sbr some months SYNDROMES OF DEVELOPMENTAL ARREST after children first begin to walk may suggest a A number of conditions lead to similar cerebellar problem, the general hypotonia of developmental profiles in that for a while child- the recognisable forms of learning difficulty or ren seem capable of learning; learning then the recently defined carbohydrate deficient slows, arrests, some skills may actually be lost, glycoprotein syndrome.5 Neuromuscular and then learning continues at a slower rate. problems leading to proximal weakness often The child with hydranencephaly (think of lead to a waddling pattern. The weak gluteal pyruvate dehydrogenase deficiency) may well muscles lead the body weight to be transferred return the mother's smile before this skill is outside the weight bearing leg; the resulting lost. Deaf children may babble but then lack- mechanical advantage avoids dropping of the ing input their language development will sub- pelvis away from the weight bearing side. If one sequently fall into deviancy if the problem is side of the body 'mirrors' movement seen on not identified and treated. the other then agenesis of the corpus callosum Children with often make reasonable should be considered. developmental progress in the first year or so, One third of boys with Duchenne muscular their problems only becoming evident when dystrophy have learning difficulties. The aver- there is a greater demand on social contact and age age at which boys with this disorder are language function. Words originally attained taken to doctors with developmental concerns may be lost before the depth of communication is 2-5 years, whereas the average age of diag- difficulty is revealed. A very similar profile is nosis is 5-5 years. A large contribution to this seen in the age related epileptic encepha- delay is a misunderstanding of Gower's sign.6 lopathies. West's syndrome often begins too Most people remember the sign as the need to early in infancy for much difference with other climb up the legs using the hands when rising children to be noticed but in the Lennox- from a supine to standing position. The most Gastaut syndrome, which often presents in the important component, however, is the need to third or fourth year, there is very often a distinct turn prone and in so doing adopting a 'Muslim arrest of developmental progress at the time of prayer position' before rising. This overcomes onset of the disorder. difficulties sustained in attaining a sitting posi- In Rett's syndrome, although in retrospect http://adc.bmj.com/ tion if the rectus abdominus is weak and the movement may have had a 'jerky' quality furthermore allows the hips to be extended throughout infancy, there is often reasonable before rising relative to the position of full hip early developmental attainment before the flexion found in the normal squatting position. process slows and the extrapyramidal features Most children show a Gower's or modified and loss of useful hand function become more Gower's manoeuvre before the age of 3 years. evident.

If it is seen after the age of 3 then it is highly Each of these disorders is determined prena- on September 29, 2021 by guest. Protected copyright. likely that there is a neuromuscular problem in tally. It would appear that the brain is capable need of further investigation, or a cause for of sustaining a certain amount of developmen- central nervous system hypotonia leading to tal progress before its association networks poor stabilisation at the hip. malfunction often with the advent of seizures. The presence of naturally would lead to investigations for basal ganglia dysfunction but the erratic movements of Speech, language, and communication Angelman's syndrome may certainly imitate disorders this, particularly in infancy and it may also be Speech and language disorders are common in an early feature of Friedreich's . childhood, boys being affected twice as often as girls.7 8 The history highlights whether the language problem is isolated or seen in the ABNORMAL HEAD SIZE context of a more global developmental delay. The commonest cause of either a small or large As assessment should be made of language head is to have one or both parents with a opportunity for the child and whether there is similar head size. Familial large heads may any social disadvantage. Children brought up actually accelerate in growth and cross centiles in a bilingual environment tend to develop in the early months of life but usually parallel speech later but then catch up. Left handed- normal centiles after the age of 6 months or ness or ambidexterity is associated with speech so. disorder in half the children involved. Elective In the presence of neurological abnormality mutism, commoner in boys, can usually be the large head may reflect , recognised in the context of unresolved storage disorder, or Canavan's or Alexander's predicament. Children with elective mutism leucodystrophy. often talk freely in certain situations and con- A small head may reflect an underlying tinue to communicate with gesture. 462 Newton, Wraith

Whenever there is indistinct speech and often a word finding difficulty with substitu- impaired language development, it is impor- tions and neologisms. Grammatical rules, in

tant to rule out deafness and to look for particular the complex ones, are often misun- Arch Dis Child: first published as 10.1136/adc.72.5.460 on 1 May 1995. Downloaded from antecedents in the history. Particular attention derstood. should be paid to the pattern of speech/ language disorder. Stuttering or stammering is an interruption (C) Semantic disorder of the normal rhythm of speech and may This refers to a difficulty in understanding the involve involuntary repetition, or prolongation meaning of language. In simple immaturity, or arrest of the sounds. It is very common and children initially overextend the meaning of present in up to 5% of children at school entry. words such as all forms of transport being There is male preponderance with a familial referred to as 'car'. In deviant semantic tendency. There are many similarities between language disorder, word finding difficulties are stammering and simple tics. As children common and the child may be confused by approach certain sounds in a sentence, anxiety synonyms. about the approaching sequence rises, a stereo- typed stutter follows with a release of tension as the sound is passed over. (D) Pragmatic language disorder Dysphonia is rare and may involve the loud- This results in the child being confused by ness, tone, pitch, inflection, or vibrato of the everyday use of language in context. The sound produced. Most neurological causes are immature child may demonstrate this by using mediated through chest wall weakness or spas- impolite forms when asking for things and may ticity leading to an abnormal pattern of flow of have no insight into the use of sarcasm. In expired gases over the vocal cords or to a recur- deviant forms ofthis disorder the child may not rent laryngeal palsy. have the ability to respond to tone of voice; for Dysarthria or difficulty in articulation is example 'the door is open' said sternly may common and persists in one in six children infer that the child should close it. The child beyond the age of 5 years. It can result from merely acknowledges that the door is open and weakness in the bulbar muscles due to a neuro- does not respond to the hint to close it. muscular disease, or poor coordination, or For each type of language disorder, aeti- abnormal tone due to pyramidal, extrapyra- ology should be defined and a treatment plan midal, or cerebellar involvement. drawn up. Most children with developmental commonly accompanies the dysarthria. In language problems show catch-up by the time developmental verbal dyspraxia some children they are 5 or 6 whereas those who showed find the sequencing and fluency of bulbar deviancy in their language development are muscles difficult to control as they do any more likely than not to retain some difficulty. other body musculature. It is rarely an isolated finding and is often seen in association with http://adc.bmj.com/ motor dyspraxia elsewhere, oculomotor dys- Trouble at school praxia, or other forms of learning difficulty. Children who present with behaviour problems at school may be having difficulty with balance, coordination, or learning. This may act as a DEFINITION OF LANGUAGE DISORDER source of frustration when for the first time in SYNDROME their lives children are asked, after school

Neurological and speech therapy assessment entrance, to perform tasks not previously on September 29, 2021 by guest. Protected copyright. will show whether the child's defect represents required of them. The association of poorly set a developmental problem, determined perhaps out and untidy work with specific learning by poor hearing or social disadvantage, which difficulties is a common one. Full assessment will show eventual catch-up or whether by an educational psychologist is indicated and language development is deviant in some way. remedial therapists may be able to offer useful Although many combinations are possible the advice to the child and family. This will include child's difficulties can be broadly placed within what tasks might usefully be pursued to the following groups: encourage good proximal girdle muscle fixation and to facilitate the distal execution of fine motor skills; other tasks will improve body (A) Phonology image and the sequencing of movement. Many children in the early months and years of Tangible success often leads children to feel an language acquisition demonstrate immature improvement in their self esteem which is com- articulation or dyslalia: lisping, rhotism (w for monly low in circumstances where they have r) and sigmatism ('yeth' for 'yes') are common previously been used to failure. examples of this. Where speech and language are deviant, initial consonant deletion is more common such as 'oat' for 'boat'. Physical examination All children with learning difficulties should be examined for the presence of dysmorphism, (B) Lexical syntactic disorders signs of a neurocutaneous syndrome, or stor- In the early acquisition of language children age disorder. Dysmorphism probably arises commonly make grammatical mistakes such as from amplified instability of developmental saying, 'me want ice cream', 'I eated my processes within the fetus when crucial genetic bread'. Where language is deviant there is material is either over or under represented. Investigation ofdevelopmental delay 463

Often similar features are seen in the general acidopathies and urea cycle defects, after population but a particular pattern may strike excluding more common derangements of

the eye and lead to diagnosis. Computerised glucose homoeostasis; urea and electrolytes Arch Dis Child: first published as 10.1136/adc.72.5.460 on 1 May 1995. Downloaded from databases may facilitate this pattern recogni- and calcium and magnesium concentrations tion. Particular features may suggest specific should also be measured. brain abnormalities such as hypertelorism with agenesis of the corpus callosum. A relatively large head or one showing accelerating growth DEVELOPMENTAL DELAY may reflect an underlying hydrocephalus, the Investigation ofchildren with mild to moderate , or a leucodystrophy. learning difficulty alone is rarely rewarding. Signs of a storage disorder include coarse Very occasionally patients with amino or facies, frontal bossing or other skeletal abnor- organic acid abnormalities will be detected, mality, visceromegaly, and cardiac murmurs. but in retrospect there are often clues to their Skin manifestations of the neurocutaneous presence in the past medical history. Some dis- syndromes are diverse and not confined to the orders, such as homocystinuria, may present familiar cafe-au-lait patches in neurofibro- with developmental delay before the onset of matosis or the depigmentation, chagrin more classic features of the disease make the patches, adenoma sebaceum, and subungual diagnosis obvious. fibromata of tuberose sclerosis. Any unusual type III (Sanfilippo's syndrome) is associated skin mark is worthy of note and further refer- with only mild somatic abnormalities and the ence bearing in mind they are often seen to earliest clinical presentation is usually with best advantage under Wood's light. developmental delay alone, particularly speech Examination of the eye may reveal colobo- delay.9 Later the characteristic behavioural mata of the valproate syndrome, the cataracts abnormality with progressive loss of skills of Lowe's syndrome, the dislocated lens of makes the diagnosis easier. Urine screening for homocystinuria or a retinopathy of a mito- amino acids and organic acids as well as glyco- chondrial cytopathy, peroxisomal disorder, or saminoglycans is therefore justified in these congenital infection. Small pale optic discs patients. Detailed lysosomal enzyme studies may reflect septo-optic dysplasia. are not indicated in this group of patients. Critical analysis ofthe gait and identification Children with severe learning difficulties of the motor control system dysfunction may should certainly have a analysis lead to a specific line of investigation. and computed tomography and/or magnetic resonance imaging looking for neuronal migra- tion problems as well as the metabolic investi- Special investigations gations detailed above. Where clinical ABNORMAL BEHAVIOUR IN THE NEONATAL suspicion exists a search of the skin for depig- PERIOD mented patches and other signs of tuberose The presence of limb and axial hypotonia or sclerosis is indicated. http://adc.bmj.com/ arthrogryposis should lead to measurement of serum creatine kinase, electromyography, needle muscle biopsy, and nerve conduction 'FUNNY WALKS' velocity measurement. A clinical suspicion ofweakness should lead to Electron microscopy of muscle should be the estimation of serum creatine kinase, performed particularly when congenital myo- electromyography, needle muscle biopsy, and pathy is suspected. It must be remembered nerve conduction velocity measurement. on September 29, 2021 by guest. Protected copyright. that the Prader-Willi syndrome may lead to Pyramidal gait disturbance should lead to persisting hypotonia and a should computed tomography, looking for abnormali- always be requested in this group with a partic- ties of white matter for underlying structural ular search being made on chromosome 15q. abnormality, blood pH and lactate looking for The presence of dysmorphism should also lead mitochondrial cytopathies, and arylsulphatase to chromosome analysis. A to exclude metachromatic leucodystrophy. If If a neuronal migration problem is suspected clinical suspicion of a mitochondrial disorder magnetic resonance imaging offers exciting persists despite a normal or near normal blood detail of underlying structural abnormalities lactate, the concentration in the cerebrospinal that in turn will lead to growing understanding fluid should be checked and a glucose load of the mechanisms and genetics involved. Our with serial estimation of lactates is indicated. experience is that computed tomography car- Confirmed raised concentrations of lactate ried out in district general hospitals in this should be followed by formal measurement of respect often misses important detail either respiratory chain enzyme activity in muscle through the quality of the scans or the lack of and a screen for mitochondrial DNA muta- neuroradiological opinion. Neuronal migration tions should also be performed on this tissue. problems should be suspected when early Extrapyramidal signs should lead to a search ultrasound either antenatally or postnatally for a family history of Huntington's disease suggests underlying structural abnormality, or (spontaneous mutations are exceptionally when there is a suggestive pattern of arthro- rare), and copper and ceruloplasmin estima- gryposis or seizures. tion for Wilson's disease. Mitochondrial When hypoxic-ischaemic encephalopathy cytopathies should be excluded (above) and has been ruled out the persistence of neuroradiological investigation should search encephalopathy should lead to a full metabolic for caudate atrophy reflecting one of the work up looking for the amino or organic named striatonigral degenerations. Nerve 464 Newton, Wraith

conduction studies and echocardiography may degeneration is suspected children need a full reveal evidence of Friedreich's ataxia. neurometabolic work-up including urine for

Cerebellar signs should lead to a neuro- oligosaccharide and glycosaminoglycan excre- Arch Dis Child: first published as 10.1136/adc.72.5.460 on 1 May 1995. Downloaded from radiological search for a structural abnormality tion, amino and organic acid analyses, and a of the cerebellum and the rare abetalipopro- white cell lysosomal enzyme screen. Ifthese are teinaemia. When seen in the presence of an normal and degeneration persists signs of oculomotor dyspraxia, ataxia telangiectasia, a abnormal storage should be sought on a tissue DNA repair disorder should be considered and biopsy specimen. Skin, rectum, and conjunc- investigated with an estimation ofa fetoprotein tiva have all been used to successfully demon- (raised in that condition), immunoglobulins strate the abnormal process. (an immune paresis is common) and, if clinical suspicion is sustained, irradiation ofwhite cells and analysis of DNA repair should be per- TROUBLE AT SCHOOL formed. Vitamin E deficiency, as a treatable It is rarely worthwhile carrying out any specific cause should be excluded. investigation in the 'clumsy ', as long as there is no suspicion of clinical deterioration. It is more appropriate to ask the ABNORMAL LANGUAGE DEVELOPMENT remedial therapists and clinical psychology Investigation of this group of patients is rarely team for their appraisal of the child's educa- rewarding. DNA analysis for fragile X syn- tional strengths and weaknesses as a basis for drome is justified particularly when the child further remediation. The clinician must be shows autistic features. Where the language aware of other possibilities, however. The disorder is recently acquired then an electro- authors have known children with Duchenne encephalogram may support the diagnosis of muscular dystrophy and ataxia telangiectasia the Landau-Kleffner syndrome. referred at the age of 5 with 'clumsiness' as the main feature.

ABNORMAL HEAD SIZE A large head requires no investigation where Giving the news there are no neurological signs and at least one A word must be said on how to impart inves- parent has the same condition. It must be tigation results to parents. When tests are remembered that children with familial complete and thoughts have been formulated macrocephaly have the appearance of commu- on diagnosis a meeting with both parents nicating hydrocephalus on their computed should be arranged. At least one health tomogram for the first year or so of life which authority has, on the basis of comments later becomes normall'; this observation has received, drawn up guidelines for this led some parents to be given inappropriately process." Parents wish to receive the facts in gloomy information in the past where scans a simple and honest way as soon as they are http://adc.bmj.com/ have been performed (inappropriately!) in this known. The format of this meeting should be disorder. to talk about causation, future outlook, and In early infancy an ultrasound scan will rule how best people in the child's life might out hydrocephalus and in the absence of other help. signs it may be worthwhile adopting a 'wait Where investigation has not revealed a cause and see' policy and monitoring head growth. it is still possible to outline for the parents the Computed tomography may reveal a leucodys- likely mechanism in many cases. These tend to on September 29, 2021 by guest. Protected copyright. trophy which in turn will lead to specific be of prenatal origin where clearly some neurometabolic investigation. The phenotype maturational process has fallen short of full in fragile X syndrome is broad. The investiga- development due to the genetic make-up ofthe tion should be ordered in particularly when child thus creating a brain which is inefficient there is a relatively large head in a child with in all or some of its computing capacity. They below average height who has specific difficul- should know that genetic is not necessarily ties with language and communication. inherited genetic and they should receive Macro-orchidism in this condition only occurs advice on the relative likelihood of each possi- after puberty. bility from the appropriate person. can be the end result of many Parents need to know what the most likely neurometabolic disorders and it is important to result of the learning difficulty on the child's remember maternal phenylketonuria as a life is likely to be as soon as possible. This potential cause. A congenital infection screen helps their psychological adjustment to the and review of the obstetric notes is problem and the resolution of their attendant indicated. grief. Once they are through that phase they are in a better position to face anything that life brings. It is not helpful to them to hear SYNDROMES OF DEVELOPMENTAL ARREST 'Only time will tell'. Certainly by the age of 10 Autism, Rett's syndrome, and the epileptic months or so developmental quotients take on of childhood may all carry some predictive quality and albeit with very their own distinctive patterns on electroen- broad confidence intervals it is possible to cephalography. When the clinical picture and predict whether a child is likely to have mild to electroencephalographic findings are typical of moderate or severe learning difficulties. It is one of these syndromes no further metabolic appropriate to state that there is a chance investigation is warranted. Where neuro- that predictions at that stage may over or Investigation ofdevelopmental delay 465

1 Freeman JM, Nelson KB. Intrapartum asphyxia and underestimate future ability but at least the . 1988; 82: 240-8. parents are being helped to adjust to the most 2 Hagberg B, Hagberg G. The origins of cerebral palsy. In:

likely outcome. David TJ, ed. Recent advances in paediatrics. London: Arch Dis Child: first published as 10.1136/adc.72.5.460 on 1 May 1995. Downloaded from Churchill Livingstone, 1993: 67-83. Parents should be encouraged to have 3 Levene MI. Management and outcome of birth asphyxia. confidence in their own ability as teachers. In: Levene MI, Lilford RJ, eds. Foetal and neonatal neurology and neurosurgery. London: Churchill Research suggests that a few moments each Livingstone, 1995: 427-42. day ofgood quality play has as much impact on 4 Diliberti JH. Use of computers in dysmorphology. Jf Med Genet 1988; 25: 445-53. learning as many hours ofintensive coaching. 12 5 Hagberg BA, Blennow G, Kristiansson B, Stibler H. It is the role of therapists to suggest to parents Carbohydrate-deficient glycoprotein syndromes: peculiar and teachers strategies that might be included group of new disorders. Pediatr Neurol 1993; 9: 255-62. 6 Wallace GB, Newton RW. Gower's sign revisited. Arch Dis in play or the curriculum to encourage the next Child 1989; 64: 1317-9. step in the child's development. 7 Silva PA. Epidemiology, longitudinal course and some associated factors: an update in language developments A second meeting ought to be called soon and disorders. In: Yule W, Rutter M, eds. Clinics in after the first in order to answer the many developmental medicine 101/102. Oxford: McKeith Press, 1987: 1-15. questions that will flood into the parent's 8 Lees J, Urwin S. Children with language disorders. London: minds at this time. Information should be Whurr, 1991. 9 Cleary MA, Wraith JE. Management of mucopolysac- given in a balanced way, being neither too charidosis type III. Arch Dis Child 1993; 69: 403-6. negative nor too positive and for at least part of 10 Alvarez LA, Maytal J, Shinnar S. Idiopathic external child ought to be present hydrocephalus: natural history and relationship to benign the consultation the familial macrocephaly. Pediatrics 1986; 77: 901-7. to show how she or he is valued. Failure to 11 Anonymous. Breaking the news. Blackburn: North West follow these guidelines often results in families Regional Advisory Group on Learning Disability Services, 1992. harbouring resentment towards the messenger 12 Cunningham CC. Early intervention in Down's syndrome. and permanent damage to the doctor/patient In: Hosking G, Murphy G, eds. Prevention of mental handicap: a world view. International Congress and relationship. The value of the investigations Symposium Series 112. London: Royal Society of may then be lost forever. Medicine Services, 1987: 169-82. http://adc.bmj.com/ on September 29, 2021 by guest. Protected copyright.