Recurrent Vomiting in Childhood, Especially of Neurolog ica I Origin

A CHILD whose presenting symptom is repeated vomiting is bound to be a cause of great concern. Vomiting can be due to a number of neurological and other causes, most of which will be identified by associated symptoms and signs. These include raised intracranial pressure, causes of which include cerebral oedema, haemorrhage, hydrocephalus and tumours, such as an ependymoma of the floor of the fourth ventricle, which may cause vomiting even in the absence of raised intracranial pressure. Lower cranial nerve lesions and cerebellar signs are common. Vomiting during radiotherapy obviously can cause serious problems, as it can with chemotherapy. The latter may be mediated in part through the 5-HT3 receptor, so mdansetron, a selective 5-HT3 receptor antagonist may help to prevent it ' . This substance may also help in the treatment of other types of vomiting, such as that which occurs postoperatively2.

Other causes of vomiting include: meta- bolic disturbance, for example organic acidaemias, aminoacidopathies, hyper-

ammonaemic syndromes, Reye syndrome and ME1.A.S syndrome; infections, especially meningitis, encephalitis,- brain abscess and urinary infections; diencephalic syndrome; lead, poisoning; intestinal disorders such as pyloric stenosis. hiatus hernia (especially when it is associated with complex contortions of the head, neck and trunk in Sandifer syndrome), constipation and intussusception; and disturbances of labyrinthine function, for instance vestibular neuronitis, particularly the variety known as benign paroxysmal vertigo. This condition usually starts during the first few years of life, and presents with unsteadiness, falling and obvious distress, but vomiting is also common3.

This annotation is mainly concerned with conditions in which vomiting is associated with few, or no, other symptoms or signs.

A number of disturbances of CNS function can present with vomiting. Migraine is an obvious example, the

'typical headache frequently preceding the sickness; eating disorders; and vomiting as a hysterical symptom4. Diagnosis of these conditions is usually apparent from the history.

Cyclic vomiting When repeated vomiting occurs, un- associated with other symptoms in childhood, a frequent cause may be cyclic vomiting. This condition has been defined as bouts of vomiting that recur after 463

intervals of varying lengths, and continue for days to weeks’. HOYT and STICKLER^ stress that the diagnosis can be suspected only when scveral attacks have occurred and other known causes of vomiting have been excluded. The recurring, prolonged attacks of severe vomiting have no apparent cause, and may be associated with headache, abdominal pain and fever. The onset is usually sudden; the child becomes drowsy and lethargic, and vomits for long periods. Dehydration, electrolyte disturbances (especially hypo- chloraemic alkalosis) and ketosis with ketonuria occur as a result.

Hoyt and Stickler studied 44 patients, 82 per cent of whom started to have attacks of vomiting before the age of six; and in all but one patient they stopped before the age of 14. The mean duration of the symptoms was six years; 64 per cent of the attacks lasted for four days or less and usually occurred at intervals of a few months. Associated headache was noted in 16 patients, fever in 19, abdominal pain in 19, constipation in three and loose stools in three. 16 of the children with headache had a family history of migraine and five had relatives with cyclic vomiting. No significant abnormalities were found on examination, and x-rays of the upper gastro-intestinal tract and skull were normal. Nine patients had had an appendectomy and three an exploratory laparotomy before attending the clinic.

EEG FINDINGS An EEG had been carried out on 14 patients in Hoyt and Stickler’s series. 10 records were normal; of the four abnormal records, one showed paroxysmal dys- rhythmia, two a generalized dysrhythmia and one a generalized dysrhythmia with rhythmic posterior slow-wave discharges. MAC KEITH and PAMPIGLIONE’ reviewed the EEGS of 52 children with cyclic vomiting. Their mean age was nine years. Four children were examined during an attack; in one the record was normal, in one it was borderline, one was mildly abnormal, and one showed irregular 3 to 7c/s activity and a few sharp waves, especially over the right frontal area. Of the remainder, 12 had normal EEGs, and 25 were borderline or mildly abnormal. 11

464 had definitely abnormal records with

sharp waves outside the parietal- temporal regions, marked asymmetries and paroxysmal changes of various types. Two children had generalized bursts of fairly irregular spike and wave complexes, unassociated with clinical signs.

PSYCHIATRIC FIKDINGS Of Hoyt and Stickler’s 44 children, 14 were assessed by a child psychiatrist, and a variety of emotional disorders and behavioural problems were present. REINHART ef al.’ approached the prob- lem of cyclic vomiting from the psychiatric point of view. They reviewed 16 children with this diagnosis. Five had been referred for a psychiatric opinion or treatment, four had had laparotomies with no significant abnormalities found, and seven had had no surgery or psychiatric intervention. There seems to be no doubt that the attacks of vomiting can be precipitated by emotional stress’, so it may well be that cyclic vomiting is a psychosomatic syndrome-a somatic reaction to psychological stress. Several factors are involved: a child who is liable to such a disorder, an anxious parent and the effect this may have on the relation- ship with the child, and a triggering stress.

TREATMENT As with any condition of uncertain origin, the treatments of cyclic vomiting are many and varied. During attacks, dehydration and metabolic disorders obviously have to be rectified. Otherwise the main concern should be to advise the avoidance of stress and, if there is an obvious psychiatric disorder in the child or family, to give appropriate therapy. Recurrent abdominal pain among children usually seems to respond to treatment with reassurance and explanation once organic causes have been excluded”.

RELATIONSHIPS WITH OTHER DISORDERS Cyclic vomitin is a common disorder. RUTTER er dR, in their Isle of Wight survey, found that 1 . 5 per cent of nine- to 1 I-year-olds vomited repeatedly. HAMMOND9 has considered possible links with epilepsy and migraine. Vomiting certainly occurs in the context of epilepsy, but the question is whether abdominal

pain is a manifestation. of abdominal epilepsy, an entity separate from the clonic movements that might be part of a focal seizure, and from the aura related to a psychomotor attack of temporal lobe origin. DOUGLAS and WHITE’S’’ criteria for a diagnosis of abdominal epilepsy are abdominal pain-which should be par- oxysmal and of short duration- associated with transient disturbances of awareness or consciousness manifested by unresponsiveness, lethargy, confusion or prolonged post-ictal sleep. There should be changes in the EEG of a specific epileptic type, such as paroxysmal spike-wave activity or bi-temporal spiking, and the patient should show a specific response to anticonvulsant drugs. Although there may be more EEG abnormalities in the records of children with cyclic vomiting than in those of controls’, these do not prove a diagnosis of epilepsy. In very selected instances when the clinical picture is suggestive of epilepsy, it may be justifiable to give anticonvulsant drugs a trial”, so long as it is realized that abdominal epilepsy is a rare disorder and that cyclic vomiting is most unlikely to have anything to do with epilepsy.

An association with migraine is more of a possibility: there seems to be no doubt that a number of children with attacks of vomiting develop migraine in adolescence, and the increased incidence of migraine among parents of children with cyclic vomiting may be significant’. Some of the findings in these children, such as ketosis, are obviously secondary to the vomiting, but there are other suggestions of an underlying biochemical disorder that may account for the attacks of both vomiting and classical migraine’. I t is now generally assumed that migraine is of neurogenic originI4, and it may be significant that a high incidence of perinatal hazards have been found among children with recurrent vomiting”.

In a follow-up of 12 patients with cyclic vomiting in childhood aged between 17 and 27 years, vomiting persisted in seven patients, and abdominal pain had been a feature in nine and had continued into adult life in six. Six of the patients had had headaches in childhood, and eight had definite attacks of migraine in adult life. Eight had symptoms of a psycho-

logical disturbance, four were depressyd, three had symptoms of abnormal anxiety and one a personality defect. The history of seven of the patients suggested the importance of emotional stress as a precipitating factor for the gastro- intestinal symptoms and migraine. In the control group, the corresponding numbers were much smaller. These findings show that symptoms of severely affected patients tended to persist, but that there was no evidence of any underlying organic abnormality. The most likely explanation seemed to be that these patients were consitutionally pre- disposed to develop migraine, and that during childhood this predisposition manifested as attacks of vomiting. Stress was undoubtedly related to both kinds of attacks, and if severe episodes of vomiting necessitated admission to hospital, serious psychological problems in the children and their families were likely’.

As far as cyclic vomiting is concerned, a detailed history, especially of the pattern of symptoms, is essential for making the correct diagnosis. Symptoms usually stop by puberty, but attacks of vomiting rightly should be a matter of concern to parents and doctors.

Gastro-oesophageal re flux Rumination in infancy, which is sometimes associated with vomiting (or rather food spilling from the mouth), is. certainly a worry to parents. I t starts at about six months of age and can last for a year or more. Food is brought up into the mouth, sometimes by thrusting the fingers to the back of the throat; and rhythmical chewing movements can be seen. Since the action seems to be a form of self-grati- fication16, the child may have to be observed surreptitiously otherwise the manoeuvre is unlikely to occur. The child may fail to thrive and become mal- nourished, so the condition is potentially life-threatening. BRUNOD and BAUDON” studied six boys aged five to 14 months with growth retardation and vomiting. The mothers had noted the vomiting, but not the rumination. No abnormalities were noted on investigation, and the diagnosis was based on observation.

The condition is thought to result from a disturbed mother-child relationship,

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with insufficient maternal care in the form of physical contact and gratification. Treatment consists of giving thickened feeds and semi-solids to make regurgi- tation more difficult, and sedatives also may be helpful. I f the rumination is started by putting fingers into the mouth, the arms can be splinted and the infant should be distracted after feeding. The social and emotional environment must be corrected, with the establishment of a satisfactory parent-child relationship16.

Repeated vomiting is sometimes found among children with severe cerebral palsy, necessitating feeding by a naso- gastric tube, and even enterostomy, to maintain nutrition and prevent loss of weight”. I f the tube has to be maintained in srtu for prolonged periods, it is possible that reflex responses between the uppcr- intestinal tract and the brainstem may be disordered. This may complicate the situation by adding the symptom of vomiting to the problems of feeding and swallowing.

Attacks of vomiting are not uncommon among children with severe learning difficulties, especially if they need long- term hospital care. In a study by SOKDHEIMER and 20 such children were identified. 15 had gastro- oesophageal reflux diagnosed by x-ray examination, the acid reflux test, or both. Oesophagitis was found by endoscopy in 10 of 14 patients. It is often thought that the vomiting in these patients is due to psychogenic disorders, or is a form of self-stimulation or a bid for attention, but this study shows how often oesophageal reflux occurred. The mean age at onset of five years in these children compared with the onset of reflux during the first few months of life among infants of normal intelligence suggests an acquired cause, such as prolonged supine positioning, abdominal compression from scoliosis, or spasticity of the abdominal muscles, causing pressure. As most of the patients had received severe hypoxic injury at birth, it is possible that either damage to the vagal nuclei or local ischaemia of the oesophagus resulted in dysfunction of the oesophageal motor activity and gastro- oesophageal reflux; the same mechanism may apply to physically disabled children. The association of vomiting, anaemia and

recurrent pneumonia should always suggest this diagnosis”.

Disorders of (he aulonornic nervous sysretn Recurrent vomiting occurs in Kiley-Day syndrome” along wi th other evidence of autonomic dysfunction, such as postural hypotension, absent tears and erratic temperature control. Other symptoms and signs include relative indifference to pain, corneal anaesthesia, absence of fungiform papillae on the tongue and poor motor co-ordination. There are definite genetic implications, with an autosomal recessive model of inheritance. The absence of a flare in response to intradermal histamine may heIp diagnosis. Postmortem examination of patients with this syndrome has not been particularly revealing, and no consistent pathological or biochemical findings have been reported2’.

Presumably the vomiting is related to a disturbance of the autonomic nervous system, so other causes of a disturbance of this kind (such as diabetes) will have to be excluded. The orthostatic tilt test and the sural sensory action potential amplitude can be useful in identifying patients with autonomic neuropathy”.

Managetnent Whatever the cause of the attacks of vomiting, urgent measures may have to be taken to counteract dehydration and metabolic disturbances. Certain investi- gations may then be justified, depending on the associated symptoms and signs, however trivial. A careful history can give a clue, such as even a minor head injury which could lead to a subdural haema- toma, the suspicion of which may justify a brain scan; or other mental and physical disabilities may indicate the need to investigate the gastro-intestinal tract. Tests for metabolic disorders or defects in the autonomic nervous system may be needed, such as checking for postural hypotension with the orthostatic tilt test. Obviously, i t is important to avoid un- necessary investigations, but in view of the serious implications of the symptom, i t is important to exclude some of the neurological disorders discussed, and to exclude reflux.

Some of these tests will be needed to

plan rational treatment-in the case of gastro-oesophageal reflux, for example- but in the absence of significant symptoms and signs, a period of careful observation. may suffice to see how the condition develops, and whether the symptoms fit the pattern of cyclic vomiting supported by a positive family history. Only if the diagnosis is reasonably firmly established can the necessary reassurance be given with conviction. In such instances it is not just the child who must be involved, but the whole family.

NF.11. GORDON Hunrlywood, 3 Siyal Road, ZVilmslo w, Cheshire SK9 4AE.

Rejerences I . Hoila. J:., 'Ionato. kl.. Rasurto, C.. Rracarda,

S., Sassi, M.. Lupattelli, M., Picciafuoco. M.. Rallatori. E., Del-F'avero. A . (1993) 'Ondansetron.' European Journal o j Cancer.

2. Runce. K . T.. Tyers, M. B. (1992) 'The role of 5-tiT in postoperative nausea and vomiting. British Journal of Anaesthesia, 69 (Suppl. 1 ) .

3 . Rasser, L. S . (1964) 'Benign paroxysmal vertigo of chi ldhood. A variety of vest ibular neuronitis.' Brain, 87, 141-152.

4. Steinbergm A,, Frank, Y. (1993) Neurological Manifesrarions of Systemic Diseases in Children. New York: Raven Press.

5 . Gee, S. (1882) 'On fitful or recurrent vomiting.' Si. Barttiolonre~v's Hospiral Reports, 18, 1-3.

6. Hoyt. C. S., Stickler, ti. B. (1960) 'A study of 44 children with the syndrome of recurrent (cyclic) vomiting.' Pediatrics, 25, 775-780.

7 . Alac Keith, R. C., Pampiglione. G. (1956) 'The recurrent syndrome in children: clinical an: encephalographic observations in 52 cases. ~IecrroeticephaloRraphy and Clinical Neuro- physiology, 8, I6 I .

8. Reinhart, J . B., Evans, S. L., McFadden, D. L.

29A (SUPPI. I ) , S16-S2I.

S60-S62.

When is a Behavioura I Phenotype Not a Phenotype?

THE answer to the question posed in our title, is regrettably, 'too often'. Here, we refer to behaviour phenotypes as

(1977) 'Cyclic vomiting in children: seen through the psychiatrist's eye.' fediarrics. 59, 37 1-377.

9. Hammond. J . (1974) 'The late sequelae of recurrent vomiting of childhood.' Devehp- mental Medicine and Child h'eurology. 16,

10. Apley. J . , Hale, R. (1973) 'Children with recurrent abdominal pain: how d o they grow up?' Briiisti Medical Journal, 2, 7-9.

1 1 . Rufter. M., Tizard. J.. Whitmore, K. (1970) Educaiion. Itealrh and Behavioiir. London:

15-22.

Longman. I ? . Douglas, E . 1.. ., White, P T. (1971) 'Abdominal

epilepsy: a reappraisal.' Journal o/ Pediarricr, 78. VI-67.

13. Gordon, N. (1964) 'Abdominal epilepsy.' Developmenial Medicme and Child Neurology. 6, 522-523. (Annotation.)

14. tiordon. N . (1989) 'Migraine, epilepsy, post- traumatic syndromes and spreading depression.' Developmental Medicine and Child Neurology. 31, 682-686. (Annofarion. )

IS. Lang, K . (196?) 'On the importance of central nervous system damage in periodic vomiting in childhood.' Monarsschrifr fur Kinderhcilkunde.

16. Carr, J . (1984) 'Gastric malformations and displacements.' I n Forfar, J . 0.. Arneil, G . C. (Eds.) Textbook OJ Paediarrics. 3rd Edn. Edinburgh: Churchill Livingstone, pp. 439-442.

17. Eradod, R . . Baudon, J . J . (1991) 'Severe rumination in infants.' Archives Francaises de

1 11, 161-167.

Pediairie. 48. 253-256. 18. Gisel, E. ti., Patrick, J . (1988) 'Identification of

children with cerebral palsy unaple to maintain a normal nutritional state. Lancer, I ,

19. Sondheimcr. J . .M.. Morris. B. A. (1979) 'Gastroesophageal renux among severel retarded children.' Journal of Pediatrics. 9 2

20. Cadman, D., Richards, J . , t'eldman. W. (1978) 'Gastro-esophageal reflux in severely retarded children.' Developmenral Medicine and Child Neurology, 20, 95-98.

21. Y a w , F., Zussman, W . (19641 'Familial dys- autonomia (Riley-Day syndrome).' Arrhives of Neurology. 10, 459-463.

22. Abraham, R . R.. Abraham, R . M.. Wynn, V. (1986) 'Autonomic and electrophysiological studies in patients with signs and symptoms of diabetic neuropathy.' Electroencephalography and Clinical Neurophysiology, 63, 223-230.

283-285.

7 10-7 14.

behaviours associated with genetic disorders, but the term is sometime

pathology. The recent genetic and psychiatric literature is replete with poorly substantiated reports of putative associ- ations between genetic syndromes and behavioural characteristics. Inaccurate reports lead to unnecessary anxiety on the part of parents, stigmatisation of the affected children, inappropriate use of clinical and laboratory resources, and fruitless research studies.

expanded to include non-genetic brai 1

e

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