1442 Letters to the Editor J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.11.1442 on 1 November 1994. Downloaded from nerve palsy were present. Perimetry showed recognition of this "non-apoplectic" mode (pH 6-0) with a 30% methanol gradient. full visual fields and visual acuity was 6/9 in of presentation allows prompt neurosurgical Standards of aspartate, glutamate, taurine, both eyes. Magnetic resonance imaging management, hopefully averting permanent and alanine in concentrations of 9, 90, and showed appreciable tumour recurrence. ophthalmoplegia and the possibility of life 900 pmol (Wakojunyaku, Tokyo, Japan) Foci of haemorrhage were evident through- threatening upward extension of the pitu- were measured every eight to 12 CSF sam- out the lesion, which was compressing both itary mass, while permitting definitive treat- ple analyses to obtain calibration curves. cavernous sinuses, although there was no ment of the underlying adenoma. The retention time was identified from the chiasmal compression. A further endonasal DOMINIC THOMPSON standard chromatograms and the area was MICHAEL POWELL transphenoidal hypophysectomy was per- Department ofSurgical Neurology, used for the calculation of CSF amino acid formed. Overtly haemorrhagic and necrotic The National Hospitalfor Neurology neurotransmitters. We estimated the maxi- pituitary adenoma was identified at opera- and Neurosurgery, mal error of the glutamate concentration to Queen Square, London, UK tion and later verified histologically. Two OLIVER FOSTER be 30% in some of our samples based on months after this procedure the left third Department ofNeurology, the data reported by Ferrarese et al.4 We nerve palsy had begun to resolve. The Middlesex Hospital, London, UK expressed the results as mean (SD) and Haemorrhage within pituitary adenomas compared the concentrations between 1 Brougham M, Heusner AP, Adams RD. is a common finding either at the time of Acute degenerative changes in adenomas of patients and control subjects by Mann- operation or on subsequent histopathologi- the pituitary body with special reference to Whitney U test. cal examination and is often subclinical.23 It pituitary apoplexy. J Neurosurg 1955;7: Symptomatic cerebral vasospasm was has been suggested that in cases of subclini- 421-39. defined with transcranial Doppler and, 2 Mohr G, Hardy J. Haemorrhage, necrosis, cal haemorrhage, tissue necrosis is an and apoplexy in pituitary adenomas. Surg together with neurological deficits, was uncommon finding whereas it is common in Neurol 1982;18:181-9. graded as mild, moderate, or severe. The those presenting with clinical apoplexy. 3 Wakai S, Fukishima T, Teramoto A, Sano K. outcome was assessed at three months after minor haemorrhage within vascu- Pituitary apoplexy: Its incidence and clinical to the Repeated significance. Y Neurosurg 1981;55: 187-93. subarachnoid haemorrhage according lar adenomas probably accounts for the 4 Onesti ST, Wiseniewski T, Post KD. Clinical Glasgow outcome scale. The patients were clinically occult group, whereas swelling versus subclinical pituitary apoplexy: pre- divided into two groups; good outcome, if secondary to ischaemic oedema or haemor- sentation, surgical management, and out- the Glasgow outcome score showed good come in 21 patients. Neurosurgery 1990; rhagic infarction in an adenoma which has 26:980-6. recovery or moderately disabled, and poor outgrown its blood supply, is proposed as 5 Rovitt RL, Fein JM. Pituitary apoplexy: a outcome, if it showed severely disabled or the more likely sequence of events in cases review and reappraisal. Y Neurosurg 1972; dead. The amino acid neurotransmitters of clinical apoplexy.4 The second mecha- 37:280-8. were compared between the two groups by nism seems to have been responsible for the Student's t test. three cases presented here, where extensive Patients and normal controls were com- necrosis was uniformnly seen. The absence pared. Mean values of glutamate, aspartate, of severe headache, obtundation, and and alanine increased some threefold (p < altered visual acuity accords with the find- 0-05). The taurine increased 1-7-fold but ing that whereas ophthalmoplegia is com- Excitotoxic amino acid neurotrans- the difference was not significant. Five patible with an alert state, defects in visual mitters are increased in human patients made a good recovery, one was acuity are more often associated with cerebrospinal fluid after subarachnoid moderately disabled, two severely disabled, impaired consciousness.5 haemorrhage and two died of delayed ischaemia due to The mortality and morbidity of untreated vasospasm (table). Differences in amino classical pituitary apoplexy is high, whereas Experimental evidence' suggests a role for acid neurotransmitter concentrations were the results of expedient surgical intervention glutamate neurotoxicity in many neurode- compared between those who had good for pituitary apoplexy are generally good. generative disorders, but few clinical studies outcomes and those with poor outcomes. Misdiagnosis of pituitary apoplexy even in have been conducted to substantiate this Concentrations of the amino acid neuro- its more typical presentation is common, hypothesis.23 We have measured excitatory transmitters tended to be higher in the poor however, and it is therefore important that and inhibitory amino acid neurotransmitters outcome group, but these differences were those involved in the initial evaluation of including glutamate, aspartate, taurine, and not significant. patients are aware of the variability in clini- alanine in human CSF in the acute stage of Persson et al evaluated the cortical extra- cal presentation and the need for early and subarachnoid haemorrhage in relation to cellular glutamate concentration in a patient appropriate radiological evaluation. clinical outcome. with severe subarachnoid haemorrhage by a Magnetic resonance imaging combines high The study protocol was approved in microdialysis method5 and found a 25-fold http://jnnp.bmj.com/ diagnostic accuracy with excellent anatomi- advance by the local ethics committee and increase in glutamate, aspartate, and taurine cal detail particularly in the coronal plane informed consent was obtained from a rela- under conditions of energy perturbation as (figure). tive. Ten patients who had a subarachnoid indicated by the simultaneously measured The case for urgent surgical decompres- haemorrhage due to a ruptured cerebral lactate:pyruvate ratio and suggested that a sion in the presence of obtundation and aneurysm were included in this study massive accumulation of glutamate and actual or threatened visual loss is generally (table) and their ruptured aneurysm was aspartate in the extracellular space may supported. In the alert patient presenting clipped within 48 hours of ictus. A ventricu- contribute to neuronal injury in subarach- with ophthalmoplegia in the absence of lar catheter was placed, CSF was intermit- noid haemorrhage.5 We measured concen- visual field deficit or impaired acuity the tently drained to maintain the intracranial trations of amino acids in the ventricular on September 26, 2021 by guest. Protected copyright. surgical role is less clearly defined and many pressure below 20 mm Hg, and CSF sam- CSF, which can be regarded as a pool into advocate conservative management in this ples were collected from day 3 to day 8 after which substances diffuse from the extra- instance. Steroid treatment and close clini- the haemorrhage and for at least two days cellular space. As the amino acids were cal observation is certainly associated with after operation. Samples were deproteinised diluted in the CSF in the ventricles, their spontaneous improvement in some cases, and stored at -80°C until analysis. Control concentrations in the extracellular space although there do not seem to be any reli- CSF samples were collected and stored in may be higher than those measured in the able predictive criteria on which such the same way from patients without neuro- CSF. patients can be identified. The clinical logical disorders who underwent spinal taps The concentration of extracellular gluta- course is unpredictable and the possibility for spinal anaesthesia. mate that is toxic to neurons is poorly of rapid deterioration with blindness or The CSF samples were diluted 10 times defined particularly as any such effects are death must be borne in mind and weighed with distilled water and 30,l aliquots were enhanced by compromising energy genera- against the surgical alternative. The used. Amino acids were measured three tion.6 In vitro experiments with cultured transphenoidal approach in experienced times for each CSF sample by high perfor- neurons have suggested that concentrations hands is extremely well tolerated and mance liquid chromatography with an elec- of 5-100 ,umol/l glutamate are toxic to neu- surgery ensures immediate decompression trochemical detector (ECD-100; EICOM, rons.' Olney et al reported that direct injec- of the parasellar structures and affords the Kyoto, Japan) after a 4-6 mm (diameter) x tion of 500 nmol (as 11l of a 500 mmol/l opportunity to obtain tissue for histological 150 mm reverse phase precolumn glutamate solution over five minutes) into evaluation to aid subsequent management. (Eicompak, MA-50DS, EICOM, Kyoto, the rat striatum was necessary to cause Extraocular muscle palsies may occur as Japan) derivatisation procedure with o- delayed local neuronal degeneration.3 The the sole manifestation of infarction or phthaldialdehyde and ethylmercaptan.