SPEECH THERAPY FOR STROKE PATIENTS

644 LACTICACIDOSIS OF THIAMINE DEFICIENCY

SIR,-Dr Campbell’s article on severe lacticacidosis of thiamine deficiency (Aug 25, p 446) is a timely reminder of an often missed or at least mismanaged condition. The suggestion that thiamine could cure this condition is a practical application of medical schoolboy biochemistry whereby the end-point of the Embden-Meyerhof pathway (pyruvate) enters the Krebs cycle only if the cofactor, in this

case a

thiamine-dependent

enzyme, is available. If it is not,

pyruvate is diverted into the lactate pathway. Since alcoholics

are

notoriously thiamine depleted it makes sense to include thiamine in any acidotic condition in

an alcoholic. For rapid diagnosis, the anion gap-(Na+ K)-(C1’ + HC03 -) -which detects unknown acids, which may be presumed to be lactate if above 15-20 mmol/1, is a useful emergency tool.]Iadopted thiamine treatment in 1977, in all patients with severe acidosis in Brisbane, Australia, where I too saw this condition for the first time in alcoholics. Unlike Campbell none of my patients were aboriginals but they did tend to present after an unusually heavy drinking bout, and were diabetic or manifested a high blood glucose during their acute illness.

Chester Beatty Laboratories, Institute of Cancer Research, London SW3 6JB

A. G. DALGLEISH

RD, Woods HF. Clinical and biochemical aspects of lactic acidosis. Oxford: Blackwell, 1976.

1. Cohen

THIAMINE DEFICIENCY AS CAUSE OF HEPATORENAL SYNDROME

neurotransmitter theory. However, thiamine deficiency also radically affects many central neurotransmitters.9 I can find no explicit description of hepatorenal syndrome which includes any satisfactory account of measured biochemical thiamine status, or of the effect of high-dose parenteral thiamine. Some critical reexamination of the launching-pad might seem indicated. In Campbell’s study the frequent presence of functional anuria or oliguria, with raised liver enzyme levels and/or advanced alcoholic liver disease in fourteen patients, means (by that many if not most had hepatorenal syndrome. As in rarely reported cases of

definition6)

recovery,1O general improvement coincided with improvement in renal function but could not be directly attributed to it. At this hospital we have similar data on Whites, some with biopsy-proven alcoholic liver disease. It is in the interests of patient survival to put thiamine deficiency "top of the list" as a stress factor in hepatorenal syndrome. And this spontaneous

should still be done even when metabolic acidosis is absent, when caloric intake or loading has been abundant and the physical appearance is one of obesity, where clinical markers such as cranial nerve palsy or lateralised footdrop are absent or not immediately recognisable, and irrespective of the exact degree of biochemical and histological liver injury and of whether low-dose thiamine supplements are already being administered. Department of Chemical Pathology, Clwyd Hospital, Rhyl, Clwyd LL18 5UJ Glan

1. Blacket 2.

SiR,-Dr Campbell’s account of beri-beri in the outback (Aug 25, p 446) is an absorbing challenge. I agree that metabolic, cardiovascular, and renal manifestations of thiamine deficiency are commonly misinterpreted. However, experience at this hospital accords with Blacket and Palmer’s findings in metropolitan Australia,l that cardiovascular thiamine deficiency is common enough also in Whites. Blankenhorn’s clinical criteria for beri-beri2 were formulated before the advent of tests such as the erythrocyte transketolase assay. As applied to haematology, in terms only of equivalent haemodynamic stress, such criteria would probably restrict the diagnosis of anaemia to "pure" dietary cases with haemoglobin levels below 3 g/dl. The result is complacency. Data published on groups whose susceptibility to biochemical thiamine deficiency is now confirmed, such as those with liver disease,3,4 tend to give inadequate information on thiamine status and replacement measures, at the same time elaborating new and "untreatable" syndromes for which acute or acute-on-chronic thiamine deficiency would be a sufficient explanation. For instance, the functional renal failure syndrome of liver disease (hepatorenal syndrome) is commonly perceived as carrying a hopeless prognosis.5,6 Death is often sudden or preceded by cardiovascular collapse.’ It was overlooked by Tristani and Cohnthat, after plasma volume expansion, two groups of patients with hitherto apparently different values for certain haemodynamic indices merge into one group with values indistinguishable from those of alcoholic beriberi (see table). Some modern accounts of hepatorenal syndrome would propel reader and patient alike into the upper stratosphere of falseCOMPARISON BETWEEN

STUART H. ANDERSON

3.

RB, Palmer AJ. Haemodynamic studies in high output bell-beri. Br Heart J 1960; 22: 483-501. Blankenhorn MA, Vilter CF, Scheinker IM, Austin RS. Occidental beriberi heart disease. JAMA 1946; 131: 717-26. Rossouw JE, Labadarios D, Krasner N, Davis M, Williams R. Red blood cell and the effect of thiamine supplementation in patients with Scand J Gastroenterol 1978; 13: 133-38. Labadarios D, Rossouw JE, McConnell JB, Davis M, Williams R. Thiamine deficiency in fulminant hepatic failure and effects of supplementation. Int J Vit Nutr Res 1977;

transketolase

activity

chronic liver disease.

4.

47: 17-22. 5. Hecker R, Sherlock S. Electrolyte and circulatory changes in terminal liver failure. Lancet 1956; ii: 1121-25. 6. Conn HO. A rational approach to the hepatorenal syndrome. Gastroenterology 1973; 65: 321-40. 7. Tristani FE, Cohn JN. Systemic and renal hemodynamics in oliguric hepatic failure: effect of volume expansion. J Clin Invest 1967; 46: 1894-1906. 8. Barratt-Boyes BG, Wood EH. Cardiac output and related measurements and pressure values in the right heart and associated vessels, together with an analysis of the hemodynamic response to the inhalation of high oxygen mixtures in healthy Clin Med 1958; 51: 72-90. subjects. Lab J 9. Plaitakis A, Hwang EC, van Woert MH, Szilagyi PIA, Berl S. Effect of thiamin deficiency on brain neurotransmitter systems. Ann NY Acad Sci 1982; 378: 367-81 10. Goldstein H, Boyle JD. Spontaneous recovery from the hepatorenal syndrome. N Engl J Med 1965, 272: 895-98.

SPEECH THERAPY FOR STROKE PATIENTS

SIR,-The difficulties of proving the null hypothesis are noted by Dr Steiner (June 23, p 1413) with respect to the Nottingham speech therapy trial (June 2, p 1197). It is an uphill task, as disbelievers in the reality of extrasensory perception, extraterrestrial visitations, or come to that, the efficacy of any specific form of healing have found to their cost. Nevertheless, it is a tribute to the importance of an idea to think it worth disproving. It is not the case, however, as Judith Williams and her colleagues assert (June 23, p 1413), that a large

(A) HYPERDYNAMIC FUNCTIONAL RENAL FAILURE SYNDROME

OF LIVER DISEASE AND

(B) ALCOHOLIC BERI-BERI, WITH

RESPECT TO THREE IMPORTANT HAEMODYNAMIC VARIABLES

"Before" and "after" refer to plasma volume repletion. *A, and A, (from Tristani and Cohn’) are cases ofhyperdynamlc functional renal syndrome of liver disease; B (from Blacket and (from Barratt-Boyes and Wood’ and :A. C. Guyton’s Textbook of Physiology 1966). t Renal plasma flow figures (assumed effective), divided by (0’9x0 -55).

Palmer’) are cases of

alcoholic beri-beri; and C are controls

645

sample favours the null hypothesis:

on the contrary, the danger is that it can lead to.a small difference of no practical importance being statistically significant. Small-scale studies have been donel°2 and have likewise failed to find positive evidence for the efficacy of speech therapy. At the same time, the measures were sufficiently sensitive to reveal significant differences over periods of 8 weeks (treated patients) and 4 weeks (untreated patients) in moderately and severely aphasic patients. The challenge remains to demonstrate improvement over and above the effects of spontaneous recovery or of non-specific responses to treatment. I find puzzling the enthusiasm your correspondents show for single-case studies. I, for one, pace Dr Howard (June 23, p 1413) would challenge the interpretation of a causal connection when improvement follows language therapy. When improvement does not follow, does the therapist infer that the therapy caused the lack of improvement? And will he or she consider it as important to report? Unless the negative instances are counted and tested statistically there is no chance of falsifying the hypothesis that therapy produces improvement. A further problem is that there is little hope of discovering and none of demonstrating from a singlecase study which features of a complex treatment were or will be effective: this too depends on well thought-out clinical trials. At present such indications as occur of individual differences in the 3 pattern of recovery could be subsumed under a severity dimension, which in itself is sufficient to imply that specific skills will be absent at predictable points, though not necessarily that they can be reintroduced by retraining. In sum, the negative results of the Nottingham trial can only be set aside by positive ones collected by equally rigorous methods. The onus is on those who wish to do the setting aside to provide the alternatives.

Department of Psychology, Bedford College, London NW14NS

MARY J. PICKERSGILL

1. Lincoln NB, Pickersgill MJ, Hankey AI, Hilton CR. An evaluation of operant training and speech therapy in the language rehabilitation of moderate aphasics. Behav Psychother 1982; 10: 162-78 2. Lincoln NB, Pickersgill MJ. The effectiveness of programmed instruction with operant training in the language rehabilitation of severely aphasic patients. Behav Psychother 1984; 12: 237-48. 3 Pickersgill MJ, Lincoln NB Prognostic indicators and the pattern of recovery of communication in aphasic stroke patients J Neurol Neurosurg Psychiatry 1983; 46:

130-39.

TOPICAL CHOLESTEROL TREATMENT OF RECESSIVE X-LINKED ICHTHYOSIS and Hpyert found a better response to treat10% cholesterol cream than with a conventional 10% urea cream in the local treatment of patients with recessive X-linked ichthyosis (RXLI). Their clinical study was prompted by the discovery ofa reduced epidermal cholesterol/cholesterol sulphate ratio in RXLI due to the basic steroid sulphatase (STS) deficiency. In a double-blind, prospective, half-side trial of 6 weeks’ duration, we have compared the clinical effect ofa 1007o cholesterol cream with the same cream basis without cholesterol. Unlike Lykkesfeldt and Hoyer, we compared creams that differed only in cholesterol content; the cream basis was identical to that used by these workers cream basis DLS (Dansk Laegemiddel Standard). 11male patients with typical RXLI (9 adults aged 21-69, median 58 years, and 2 children aged 5-8 years) were assigned to the study. In all patients the diagnosis of RXLI was confirmed by the virtual absence of STS activity in peripheral leucocytes (the STS measurements were kindly performed by Dr Lykkesfeldt). In all patients the scaly lesions of the extremities were completely symmetrical on entry to the study, and their intensity and extension to anterior and posterior aspects of upper arms, forearms, thighs, and lower legs was recorded on a scale from 0 to 3 as done by Lykkesfeldt and H<2(yer. The patients were randomised to treatment with a 10% cholesterol cream twice daily on the skin of the arm and leg on one side and the same cream-basis without cholesterol on the other side. The preparation of creams, blinding, and randomisation were performed at the Hospital Pharmacy. Patients were examined every 2 weeks. In the individual patient one treatment was judged to be

SIR,-Lykkesfeldt

ment

with

a

superior to the other treatment if a greater reduction of the original obtained in one or more areas treated with this cream than in the symmetrical areas treated with the other cream. The trial was stopped after 6 weeks. The patients were blinded as to the composition of creams compared. However, a difference in consistency of the creams was noticed by some of the patients. The observers were completely unaware of which cream had been used since no remnants of cream were apparent at the assessments. All patients completed the study. The preferences were as follows: cholesterol cream superior to cream basis, 1;cream basis superior to cholesterol cream, 1; no difference, 9. In all patients some improvement was recorded on both sides. However, in only 1 patient, a boy of 5 years, the ichthyosis disappeared completely. Thus, the response to local treatment might be age-dependent and the considerably lower median age of the patients studied by Lykkesfeldt and H0yer should be taken into consideration. Our investigation emphasises the importance of the cream basis in the local treatment of ichthyosis. Further clinical studies are needed to establish whether the addition of cholesterol has any beneficial effect on RXLI. scores was

Department of Dermatology;

HANS HENNING IBSEN FLEMMING BRANDRUP

and Hospital Pharmacy, Odense University Hospital,

DK-5000 Odense C, Denmark

1. Lykkesfeldt G, Høyer H. Topical cholesterol ichthyosis. Lancet 1983; ii: 1337-38.

BIRGITTE SECHER treatment

of

recessive

X-linked

FALSE POSITIVE CREATINE KINASE TEST IN HYPOTHYROID MALE AT RISK FOR DUCHENNE MUSCULAR DYSTROPHY

SIR,-The early detection of Duchenne muscular dystrophy (DMD) is important if the birth of a second affected son, before the diagnosis is established in the first, is to be avoided.’ Population screening for DMD has been advocated either by testing all boys not able to walk by 18 months of age for raised creatine kinase,2or by neonatal screening of all male births.3We here draw attention to a possible cause of false positive results in newborn screening. The propositus was the grandson of an obligatory carrier of DMD. His 16-year-old mother was at 50% prior risk of being a carrier-no tests of carrier detection had previously been done because of parental refusal. A raised TSH concentration (255 mU/1) was determined at 11 days of age through the Welsh Regional Screening Programme for Congenital Hypothyroidism. Thyroid function tests confirmed the diagnosis. A 123scan showed no detectable thyroid tissue. The infant was clinically normal. Since the infant was at high risk for DMD, serum creatine kinase (CK) was also measured. The value at age 17 days was strikingly high (995 IU/1). The concentrations of CK and thyroid hormones were measured serially following thyroxine replacement (see table): Within three months the CK was normal. A slightly increased serum CK is common in primary hypothyroidism in adults; in some individuals the increase is considerable.4 The isoenzyme involved (MM) is of somatic muscle origin, and the increased levels return to normal with thyroxine replacement. CK in normal newborn babies may be raised in cord blood, but the levels return to the normal range by the time screening samples are taken (6-10 days). Infants with DMD show a persistent increase in serum CK. The CK result in the present case, with his high prior risk, would have been sufficient to suggest a diagnosis of DMD—a distressing revelation, if it had been made, to a SERIAL MEASUREMENTS OF THYROID HORMONES AND CK

*Treatment started with 1-thyroxine 10 g/kg/day Normal ranges are shown m parentheses-