923 DURAL SINUS THROMBOSIS
Plasma cortisol levels
during dexamethasone adrenal suppression.
administered as 125 mg in rectal foam (n 6, solid Hydrocortisone line) or 20 mg orally (n = 2, broken line). Horizontal broken lines normal range. Mean and SD shown.
SIR,-Your Jan 24 editorial states that: "Anticoagulation is not recommended for other forms [other than cavernous sinus thrombosis] of dural sinus thrombosis and should be used only after careful consideration and exclusion of cortical venous infarction.... The mortality of superior sagittal sinus thrombosis (78 %) must still be considered high". These statements do not correspond to our experience of cerebral venous thrombosis (CVT). Before the introduction of angiography, CVT was diagnosed at necropsy and was therefore thought to be usually fatal. In early angiographic seriesl2 the case fatality rate was 30-50 %, but in later series3,4 it was between 25% and 30%, and in a series of 38 consecutive cases it was only 10%.5 Several reasons may explain this decrease, the main one probably being that it is now possible to diagnose "benign" forms of CVT with few symptoms and spontaneous recovery. Another reason is that septic thrombosis has, since the use of antibiotics, become both far less frequent (4/38 in our series’) and severe. The use of anticoagulants in CVT remains controversial. They are usually considered dangerous because the promote haemorrhage into an already haemorrhagic infarct. However, in some reports, a considerable improvement was observed just after the initiation of heparin,5,6 and in our series of 23 heparin-treated patients there were no deaths, and 19 patients recovered completely.5 It therefore seems that, in the vast majority of patients, anticoagulants are not harmful, and that, in some, they may be life-saving. Although in CVT anticoagulants do carry a risk of increasing intracranial haemorrhage, this risk is probably very low and the benefits outweigh the dangers.
administered rectally. The patients then lay on a bed or sat in a comfortable chair until the end of the study. The foam was retained for at least 6 h by all patients. Blood samples for cortisol estimation were withdrawn from the cannula for up to 6 h. In 2 of the patients, dexamethasone suppression was continued for a further 2 days and blood samples were taken at the same times as on the first day. On the second day, no other form of steroid was given because the object was to confirm adrenal suppression throughout the 6 h. On the third day, these 2 patients received an oral dose of 20 mg hydrocortisone acetate at 0900. The mean values for hydrocortisone absorption are shown in the figure. Plasma cortisol levels increased in all 6 volunteers after rectal foam and exceeded the lower limit of normal in all of the 2, 4, and 6 h samples. In every case, the peak was in the 4 h sample and ranged from 225 to 1020 nmol/1. The absorption profile was similar for all patients. The two subjects who also had samples taken during dexamethasone suppression alone maintained endogenous cortisol levels below 60 nmol/1 throughout the 6 h period of study. Systemic absorption from 125 mg of hydrocortisone in rectal foam was less than that from a 20 mg oral dose (figure). Nevertheless, use of rectal foam does result in a range of physiological cortisol levels not dissimilar to those obtained after the oral dose that is typically used in maintenance therapy for adrenal failure. Clinicians should be aware of the potential for adrenal suppression and steroid adverse effects after hydrocortisone rectal foam, particularly if patients are using the foam chronically. The manufacturers have taken immediate steps to amend the promotional material and data sheet. was
Gastroenterology Unit, Royal Hallamshire Hospital, Sheffield S10 2JF 1. Ruddell
P. A. CANN C. D. HOLDSWORTH
WSJ, Dickinson RJ, Dixon MF, Axon ATR. Treatment of distal ulcerative colitis in relapse: Comparison of hydrocortisone enemas and rectal hydrocortisone foam. Gut 1980; 21: 885-89. 2. Somerville KW, Langman MJS, Kane SP, et al.Effect of treatment on symptoms and quality of life in patients with ulcerative colitis: Comparative tnal of hydrocortisone acetate foam and prednisolone 21-phosphate enemas. Br Med J 1985; 291: 866. 3. Farmer RG, Schumacher OP. Treatment of ulcerative colitis with hydrocortisone enemas: Relationship of hydrocortisone absorption, adrenal suppression and clinical response. Dis Colon Rectum 1970; 13: 355-61.
Neurology Clinic, Hôpital de la Salpétrière, 75651 Paris, France
venous and sinus thrombosis. Clin Neurosurg 1967; 14: 1-24. 2. Weber G. Zerebrale venen und sinus thrombosen. Schweiz Arch Neurol Psychiat 1958; 82: 320-44. 3. Bansal BC, Gupta RR, Prakash C. Stroke during pregnancy and puerperium in young females below the age of 40 years as a result of cerebral venous/venous sinus thrombosis. Jpn Heart 1980; 21: 171-83 J 4. Rousseaux P, Bernard MH, Scharpereel B, Guyot JF. Thrombose des sinus vemeux intra craniens (à propos de 22 cas). Neurochirurgie 1978; 24: 2-6. 5. Bousser M-G, Chiras J, Sauron B, Bories J, Castaigne P. Cerebral venous thrombosis: a review of 38 cases. Stroke 1985; 16: 199-213. 6. Fairbum B. Intracranial venous thrombosis complicating oral contraception: Treatment by anticoagulant drugs. Br Med J 1973; ii: 647
Krayenbuhl HA. Cerebral
VALPROATE INHIBITION OF UREA SYNTHESIS
SiR,—Dr Kamoun and Dr Rabier (Jan 3, p 48) suggest that the hyperammonaemia and inhibited urea synthesis observed after the administration of valproatel may be attributed to reduced synthesis of argininosuccinate. Studies using similar in-vitro preparations or bolus administration of valproate have identified widespread metabolic effects on the liver and kidney.2-5 These techniques are powerful and valuable in the detection of such effects but the importance of the findings must eventually be tested in experiments with replicate clinical therapeutic regimens. Factors which may cause discrepancy between the results of the different approaches include the biochemical effects of the many metabolites of valproate, which will not be present in vitro, and the availability of acetyl-CoA, which may be limiting in vitro but not in the intact organism. Orotate excretion may be used as a marker of carbamoyl phosphate accumulation (see figure), and inhibition at any stage downstream of carbamoyl phosphate synthesis would be expected to increase orotate excretion. This reasoning is supported by studies of genetic defects in this pathway. The administration of valproate decreased orotate excretion, both in our experiments and in a previous clinical study,’ which suggests that the site of inhibition of ureagenesis is not at the synthesis of argininosuccinate. If, however, the supply of aspartate is limited, as suggested by Kamoun and Rabier, the link between accumulation of carbamoyl phosphate and excretion of orotate may be broken, since aspartate is needed for the synthesis of orotate (figure). Citrulline would then be expected to accumulate: this was not detectable in our experiments.