FOCAL SEIZURE DISORDER COMPLICATING IODOPHENDYLATE MYELOGRAPHY

312

days at 0°C to fasting subjects. An hour after administration the subjects were questioned as to the taste characteristics of the drink and given the opportunity, by means of an openended question, to report any other sensation they might have experienced. All materials provoked some post-ingestional symptoms, and symptoms of burning, tightness, or pain in the chest, neck, face, or arms or numbness were reported in response to coffee (6 subjects), spiced tomato juice (6), and the 2% MSG solution (2). These results indicate that MSG is not unique in provoking the so-called Chinese restaurant syndrome symptoms and support the notion that these symptoms reflect a more general sensitivity. In the light of the negative results reported by Gore and Salmon it would be interesting to test these everyday dietary materials on their subjects. A negative finding in a U.K. population would direct attention to the special characteristics of the U.S. test subjects. Orange juice, coffee, and spiced tomato juice provoke oesophageal pain in patients with oesophag3tis,2 and a local dietary habit, drinking hot tea, has been implicated in the resophageal lesions of Northern Iran.3 Perhaps the Chinese restaurant syndrome is no more than a manifestation of a common low-grade oesophagitis brought on by American dietary habits. Department of Physiology, Medical Center,

George Washington University, Washington, D.C. 20037, U.S.A.

RICHARD A. KENNEY

PARALYSIS OR SEDATION FOR CONTROLLED VENTILATION? SIR,-A retrospective study of 50 patients who had received controlled ventilation at the Royal Sussex County Hospital, Brighton, has revealed some disturbing information. 48 (96%) had received muscle relaxants for ventilation, sometimes as the only agent used to control ventilation, even though most were also prescribed sedatives, usually opiates, to be given as required. There appeared to be insufficient reliance on opiates for sedation of patients, and even when they were used muscle relaxants were usually given simultaneously. Despite our formal teaching to the contrary, many intensive therapy unit (ITU) staff still regard muscle relaxants as sedative or even analgesic agents because a "quiet" patient is achieved. They may also be worried about addiction (unnecessarily) or about alterations in the patient’s hxmodynamic state. Donald and Shovelton5 have vividly recounted the horrors of being intubated and awake, and, if asked, more patients might admit to this. Nurses are now specifically instructed to give opiates (or other sedatives) in as large doses as are required to sedate patients and allow them to be adequately ventilated. The only limitation to the dose that may be given is an untoward reaction or an unsatisfactory hsemodynamic state. One patient in the survey received a total of 1194 mg phenoperidine over eleven days, and 21% of the patients received between 6 and 10 mg phenoperidine per hour, with

FOCAL SEIZURE DISORDER COMPLICATING IODOPHENDYLATE MYELOGRAPHY

SIR,-Residual iodophendylate (’Pantopaque’) after myelohas been implicated in the production of adhesive arachnoiditis and dysfunction of nervous tissue in close contact with the residual contrast substance.1-3 We have seen a patient who had a focal seizure disorder which developed 4 months after a myelogram and who had residual iodophendylate at a site fitting in with the motor distribution of her seizures. A 30-year-old, right-handed woman presented in October, 1978, with intermittent twitching of the left side of her face, affecting the corner of her mouth and partly closing her left eye. The episodes lasted for 30 min to 1 h, occurred several times daily, and had been a problem for 3 months. Subsequently, focal motor seizures developed affecting the left side of her face, her neck, and her left arm. She often lost consciousness and after these attacks she was disoriented, drowsy, and agitated. Physical examination after seizure activity revealed a mild left hemiparesis with relative left-sided hypsesthesia and an extensor plantar response on the left. She had a history of familial scoliosis which had been causing leg and back pain. On Feb. 9, 1978, she had had a cervical myelogram with iodophendylate. The myelogram was normal, but several small droplets of contrast material were retained within the cranium. The patient then had a TlO-Ls spinal fusion and Harrington rod procedure. There was no history of head injury, previous seizures, or paroxysmal disorders. Her family history was negative for epilepsy. In November, 1978, a radionuclide brain scan and EEG were normal. Skull X-rays disclosed a 2 mm round opacity in the right middle fossa thought to represent retained iodophendylate. A computerised tomogram (CT) was normal except for a high-density particle corresponding to the opacity seen on skull X-ray (figure). A cerebral arteriogram localised the opa-

graphy

1. Davies FL. Effect of unabsorbed contrast media on the central nervous system. Lancet 1956; ii: 747-48. 2. Mason MS, Raaf J. Complications of pantopaque myelography. J Neurosurg 1962; 17: 302-11. 3. Tabadden. Unusual complications of iophendylate injection myelography.

Arch Neurol 1973; 29: 435-36.

serious hxmodynamic consequences. Muscle relaxants should be added only if sedation proves inadequate because of falling blood-pressure or if a sleeping patient is not synchronising with the ventilator. The overuse of muscle relaxants is, I suspect, a common practice in ITUs. no

Department of Anæsthesia, King’s College Hospital, London SE5 9RS

C. M. H. MILLER

JONES

2. Price SF, Smithson KW, Castell DO. Food sensitivity in reflux esophagitis. Gastroenterology 1978; 75: 240-43. 3. Crespi M, et al. Oesophageal lesions in Northern Iran: A pre-malignant condition? Lancet 1979; ii: 217-20. 4. Donald I. A doctor’s personal recollections of second-time cardiac valve replacement. Scott Med J 1976; 21: 49-57. 5. Shovelton DS. Reflections on an intensive therapy unit. Br Med J 1979; i: 737-38.

Residual contrast material

as seen on

CT

scan.

313 but was otherwise normal. An EEG obtained after seizure activity demonstrated voltage attenuation and slowing of the dominant rhythm. Lumbar puncture was unsuccessful because of the spinal fusion. This patient’s focal motor seizures have persisted and have not responded to anticonvulsants (phenytoin, phenobarbitone, carbamazepine, primidone, clonazepam, valproic acid). The focal motor seizures now affect only her face; more severe seizures affecting face, neck, and arm with loss of consciousness occur every 5-10 days. Neurological examination during her periods of relative seizure freedom is normal. She is now taking phenytoin and carbamazepine. The focal motor seizures began some 4 months after a cervical myelogram. Residual contrast could be identified as a small droplet of high density on CT scan, skull X-ray, and cerebral angiogram. Its location accorded with the nature of her seizures. Focal epilepsy in primates can be produced with aluminium oxide cream in the subarachnoid space.4 Seizures appeared 2-8 months later, were usually of focal onset in the contralateral face and arm, and once established, recurred spon-

city to the right sylvian cistern,

taneously. The alumina

cream

focus is

morphologically

characterised

by neuronal depopulation and astrocytic gliosis. The histological changes from retained iodophendylate have been studied experimentally. Clarke et al. (ventriculography in dogs) demonstrated inflammatory lesions in the ventricular walls with erosion by a granulomatous lesion into the underlying parenchyma. Jakobsen6 (myelography on rats) noted inflammatory lesions within 4-30 days which persisted throughout the 120-day study. The reaction was accentuated around nerve roots and blood vessels. Spinal capillaries demonstrated endothelial proliferation. Gray matter of the spinal cord contained many shrunken and vacuolated cells with surrounding gliosis. Neuronal loss was seen as early as 8 days after myelography. The brains showed signs of degeneration with nerve cell loss in the hippocampus and basal ganglia. Suspicion that retained iodophendylate may have caused our patient’s focal seizures arises from the anatomical location of the contrast substance and the tendendy of this material to produce lesions morphologically similar to those seen in experiments with topically applied convulsant metals. Department of Neurology, Letterman Army Medical Center, San Francisco, California 94129, U.S.A.

MICHAEL K. GREENBERG STEPHEN C. VANCE

PROSTAGLANDIN E AND SCHIZOPHRENIA

SiR,-The finding by Dr Mathe and his colleagues (Jan. 5,

16) of higher levels of immunoreactive prostaglandin E (PGE) in the cerebrospinal fluid of schizophrenics than in that of healthy controls is of great interest. Mathe et al. need not have been so sceptical about the significance of their results; despite their statement to the contrary, there is direct evidence relating excess PGE with the production of a schizophreniap.

like condition. In 1964I described a cataleptic state of long duration in animals following intracerebroventricular injection of minute doses of prostaglandins of the E series. Main and I then suggested2 that faulty prostaglandin metabolism leading to excess 4. Ward AA.

Topical convulsant metals. In: Purpura DP, Penry JK, Tower DB, Woodbury DM, Walter RD, eds. Experimental models of epilepsy: A manual for the laboratory worker. New York: Raven Press, 1972: 15-26. 5. Clarke RG, Milhorat TH, Stanley WD, Di Chiro G. Experimental pantopaque ventriculography. J Neurosurg 1971; 34: 387-95. 6. Jakobsen JK. On the side-effects of contrast media for myelography. Acta Pathol Microbiol Scand A 1973; 81: 323-36. 1. Horton EW. Actions

of prostaglandins E1, E2 and E3 on the central nervous system. Br J Pharmacol 1964; 22: 189-92. 2. Horton EW, Main IHM. Differences in the effects of prostaglandin F2&agr;, a constituent of cerebral tissue, and prostaglandin E1 on conscious cats and chicks. Int J Neuropharmacol 1965; 4: 65-69.

account for the catalepsy associated with mental illnesses in man. This suggestion was prompted by the striking resemblance to human catalepsy of a condition which could be induced in animals by small amounts of a substance known to be a natural constituent of the brain. This hypothesis has been re-stated more elegantly by Feldberg3 who has also suggested how it might be tested-namely, by a clinical trial of a non-steroidal anti-inflammatory drug in schizophrenics. These drugs block prostaglandin biosynthesis4 and so could reduce the CSF levels of PGE to normal. The results of Mathe et al. indicate that such a trial is most certainly worthwhile. I would, however, sound two notes of caution. First, before and during the trial CSF prostaglandin levels must be monitored to check that the inhibitor is given in sufficient dosage to lower prostaglandin levels. Secondly, a lack of improvement in the clinical condition of patients during such therapy, despite the lowering of CSF PGE levels, need not negate the hypothesis completely. The non-steroidal drugs block the biosynthesis of all prostaglandins, but it may be an imbalance between the production of different prostaglandins that is the mechanism at fault in schizophrenia. A positive result, on the other hand, could be of great significance not only in treatment but also in supporting the hypothesis of prostaglandin involvement in schizophrenia.

PGE2 in the brain might well

Department of Pharmacology, University of Edinburgh, Edinburgh EH8 9JZ

E. W. HORTON

GLYCINE IN ACUTE MANAGEMENT OF ISOVALERICACIDÆMIA

SiR,—Isovalericacidaemia, an inherited disorder of leucine metabolism due to a deficiency of isovaleryl CoA dehydrogenase, manifests with periodic episodes of ketoacidosis, pancytopenia, and high levels of isovaleric acid (IVA), 3-hydroxyisovaleric acid (3-HIVA), and isovalerylglycine. These episodes are usually started by an increased catabolic state. The clinical manifestations seem to be the result of the accumulation of IVA, and between the clinical episodes the patients are symptom-free and IVA is removed and detoxified as isovalerylglycine.5 Krieger and Tanakasuggested using high doses of glycine to treat and prevent acute episodes, and they reported promising results in one patient. Cohn et al. reported that glycine seemed to have helped in the acute management of two babies with this disease. We too have observed the beneficial effects of glycine in a patient with isovalericacidoemia. This 3 year 3 month old mentally retarded female had been admitted several times to the D.I.F. National Institute of Paediatrics with severe ketoacidosis. Isovalericacidsemia was diagnosed during one of these admissions. The ketoacidosis proved resistant to conventional measures. The most recent episode was triggered by an intercurrent tonsilitis. On admission the patient was comatose, ketoacidotic, had gastrointestinal bleeding, the characteristic "sweaty feet" odour, and prothrombin time longer than 1 min. Because of the vomiting, glycine was administered rectally at a dose of 175 mg/kg diluted in 10 ml water. In a couple of hours the vomiting and tachypnaea disappeared. The patient became less soporific and responded well to stimuli. Some biochemical changes are summarised in the figure. The PaC02 increased and the urine became ketone negative. 3.

Feldberg W. Possible association of schizophrenia with a disturbance of prostaglandin metabolism: a physiological hypothesis. Psychol Med 1976;

6: 359-69. 4. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature 1964; 231: 232-35. 5. Tanaka K, Isselbacher KJ. The isolation and identification of n-isovalerylglycine from urine of patients with isovaleric acidemia. J Biol Chem 1967; 242: 2966-72. 6. Krieger I, Tanaka K. Therapeutic effects of glycine in isovaleric acidemia. Pediat Res 1976; 10: 25-29. 7. Cohn RM, Yudkoff M, Rothman R, Segal S. Isovaleric acidemia: Use of glycine therapy in neonates. N Engl J Med 1978; 299: 996-99.