25
however, no investigation based on these findings is available for diagnosis, although this area is under review." Abnormalities in the saliva of CF patients have not proved
consistently useful for diagnostic purposes in children or adults during conventional assessment for CF .12 Certainly no attempt has been made to use any of these techniques in the diagnosis of CF in immature newborn babies in whom both prematurity and its attendant problems may produce secondary cellular abnormalities and prevent accurate diagnosis. Other tests such as immunoreactive trypsin assay13 lack reference data and therefore when abnormal may also simply reflect the problems of prematurity rather than CF. Of the
techniques presently being developed for use in prenatal diagnosis, those which reflect abnormal gut function do not offer any hope of separating primary disease from secondary manifestations.14,15 The genetic basis of CF is steadily being unravelled16 and this work may eventually resolve the diagnostic difficulties in very premature infants. Meanwhile, when a sick baby presents with a clinical picture of gastrointestinal dysfunction, arrangements should be made for the storage of blood (for subsequent DNA analysis) if death becomes inevitable, so that pathological findings may at some point in the future be related to genotype. From the cases reported to date it seems clear that abnormal gut function may not dominate the clinical picture, and therefore storage of blood on a wider scale until postmortem results are available may be necessary to achieve adequate data. If the preterm infant who dies already has an affected older sibling, then it may be possible to confirm or refute the diagnosis by means of current
genetic techniques.
SACRAL ROOT STIMULATION FOR BLADDER CONTROL THE major therapeutic application of electrical stimulation began when Melzack and Wall presented their theory of the gate control of pain in 1965.1 Before this time, accounts of the use of electrical stimulation in the treatment of disease (dating back to the 1 st century) were of historical interest and amusement only. Publication of the gate control theory led to many trials of the effect of peripheral nerve and subsequently spinal cord stimulation for the control of intractable pain. As a result of this type of stimulation, effects on other neurological functions were demonstrated and shown to be related to physiological responses, particularly in patients with spasticity, impaired bladder control, or peripheral vascular disease. This kind of stimulation produces a worthwhile result in about 70% of patients and has a physiological basis, but it is still essentially empirical in the sense that its use is based on observation rather than on a well-established theoretical system. 11. Williamson PS, Fowles DC, Weinberger M. Electrodermal potential and conductance
clinically discriminate between cystic fibrosis and control patients. Pediatr Res 1985; 19: 810-14. 12. Wiesmann UN, Boat TF, di Sant Agnese P. Flow-rates and electrolytes in minor-salivary-gland saliva in normal subjects and patients with cystic fibrosis. Lancet 1972; ii: 510-12. 13.Heeley AR, Heeley ME, Richmond SNJ. The value of blood trypsin measurement by RIA in the early diagnosis of cystic fibrosis. In: Albertini APG, Crosignani PG, eds. Progress in perinatal medicine.Oxford: Excerpta Medica, 1983: 95-203. 14. Brock DJH. Amniotic fluid alkaline phosphatase isoenzymes in early prenatal diagnosis of cystic fibrosis.Lancet 1983; ii: 941-43. 15.Brock DJM, Bedgood G, Barron L, Hayward C. Prospective prenatal diagnosis of cystic fibrosis. Lancet 1985; i: 1175-78. 16.Farrall M, Law H-Y, Rodeck CM, et al. First-trimester prenatal diagnosis of cystic fibrosis with linked DNA probes.Lancet 1986; i: 1402-05. 1.Melzack R, Wall PD.Pain mechanisms: a new theory.Science 1965; 150: 971-79. measurements
Sacral anterior root stimulation is in a different category. It is one of the few uses of electrical stimulation of the nervous system which is not directly based on Melzack and Wall’s original paper. In a series of reports, Brindley and his co-workers have demonstrated specific stimulation with
specific results-ie, stimulation is applied
to nerve roots
which control bladder function. The latest study by this group2 describes 50 patients with sacral anterior root stimulator implants. Follow-up ranged from 1 to 9 years. Of the 49 patients still alive, 39 were pleased with the treatment and had no reservations, 6 were pleased but had reservations, and 4 were dissatisfied. In all, about 125 patients have had implants carried out at the Maudsley Hospital or other centres. The procedure makes use of an ingenious set of electrodes in which are trapped the left and right sacral roots from S2 to S5 (in most cases). From the stimulator electrodes, platinum wires run to a radio receiver which activates the implant. The radio receiver is implanted subcutaneously and activated by a pulse-generating device (carried by the patient) to stimulate bladder emptying. In all patients it was shown preoperatively that the detrusor had a surviving efferent nerve supply. In the original animal experiments, by which the procedure was developed, it was intended that the stimulator should be used for continuous activation of the rhabdosphincter to assist continence, but in the human series only one patient used continuous rather than intermittent sphincter activation. In some cases it may be necessary to cut the posterior roots when the implant is inserted to prevent reflex emptying action of the bladder (where the bladder is working reflexly but inefficiently) from interfering with the proper functioning of the stimulator. Of the 50 patients reported, 31 became continent night and day, and another 5 became continent at night. 4 of 7 patients had reversal of ureteric reflux with stimulation. Residual bladder volume was decreased and there was also a reduction in the number of symptomatic urinary infections and in bladder trabeculation. Of the 38 male patients, 26 have been able to achieve penile erection by means of the implant but the quality of the erection tends to deteriorate with time, in contrast to micturition, where the result often improves with time. Most of these implant-driven erections are used for sexual intercourse. Complications of the implant have been minor-pain in some patients, cerebrospinal fluid leakage, damage to nerve roots, and postoperative urinary infections during urodynamic studies. Autonomic dysreflexia has been noted in only 1 patient since the original 50 patients were reported. The main, and usually the only, indication for sacral anterior root stimulation is for control of micturition; in this it is remarkably successful, partly by lowering the residual volume of urine and partly by raising the bladder capacity. One difficulty with poor bladder function is development of reflux which may ultimately result in serious kidney damage. Sacral root stimulation generally has a beneficial effect on reflux. Failure of bladder control is perhaps the single most distressing symptom in medicine with far-reaching medical and social implications. Whilst any person may eventually come to terms with a wheelchair existence nobody can accept failure of bladder control. Brindley and his coworkers have made a considerable advance in this difficult and neglected area. 2.
Brindley GS, Polkey CE, Rushton DN, Cardozo L. Sacral anterior root stimulator for bladder control in paraplegia the first 50 cases. J Neurol Neurosurg Psychiatry 1986, 49: 1104-14.