J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.1.146 on 1 February 1973. Downloaded from Journal ofNeurology, , and Psychiatry, 1973, 36, 146-151

Sequelae to pneumoencephalography

Y. S. WHITE, D. S. BELL, AND R. MELLICK From the Psychiatric Research Unit, Callan Park Hospital, Rozelle 2039, Australia

SUMMARY Fifty patients were examined clinically and neurologically for seven days after pneumo- encephalography. was present in 78%, neck stiffness in 3400, pyrexia in 38%, vomiting in 340/, tachycardia in 740/, a change in the level of consciousness in 18%, and abnormal neurological signs in 3000. Of the 13 patients with epilepsy, there was an increased frequency of seizures in four, associated with increased EEG epileptiform activity in three. EEG abnormality either appeared or increased in 7400 of cases on the second day after the air study. A mechanism for the production of these sequelae is proposed. It is concluded that these findings indicate that in most cases an organic syndrome follows pneumoencephalography. guest. Protected by copyright. Since its introduction in 1919, pneumoencephalo- METHODS graphy has been observed to produce a wide From a consecutive series of 54 patients undergoing range of side-effects: Bohn (1937), in a study of pneumoencephalography, the 50 to be described were 1,000 cases, reported headache, vomiting, py- followed for a minimum of seven days during which rexia, tachycardia, changes in blood pressure, time there was no other change in their management, stiffness in the neck, and mental confusion. four being omitted for the following reasons: two Changes in the constituents of cerebrospinal because of failed pneumoencephalograms, one Schwab and von because of unavoidable discharge on the day after fluid were reported by Storch pneumoencephalography, and one because of un- (1937), Levinson, Kaplan, and Cohn (1939), avoidable changes in medication in the post-pneumo- Wartenberg (1939), Robertson (1957), Marrack, encephalography period. The ages of the 50 patients Marks, and Couch (1961), Taveras and Wood ranged from 13 to 74 years; 29 were male and 21 (1964), and Dykes and Stevens (1970). Electro- female. All the patients were investigated at the encephalographic (EEG) abnormalities were Psychiatric Research Unit, which provides a neuro- found by Riehl and Ansel (1969) and Hammer logical and neurosurgical service to the psychiatric and Klingler (1969). Alterations in ventricular hospitals of New South Wales. size on radiological examination, present for Forty-four patients were cooperative enough to varying periods after pneumoencephalography, allow pneumoencephalography to be performed http://jnnp.bmj.com/ Robertson under neuroleptanalgesia; after premedication with were observed by (1947), Stallworthy sodium pentobarbitone 100-200 mg, droperidol and Savage (1955), Le May (1967), and Booker, 15-50 mg and fentanyl 75-200 ,tg were administered. Matthews, and Whitehurst (1969). Six patients were uncooperative or medically unwell These observations suggest that in many cases and for this reason were given a general anaesthetic, pneumoencephalography results in sequelae initiated with thiopentone sodium and relaxants and consistent with an organic brain syndrome. We continued after endotracheal intubation with nitrous In these cases the use the definition of the brain oxide/oxygen. latter premedication on September 27, 2021 by will organic syn- used was omnopon and scopolamine or pethidine drome proposed by Lipowski (1967)-that is, a hydrochloride and atropine. state of cerebral insufficiency in which there is The volume of air injected into the ventricles by a reduction in the level of cognition and a the lumbar route varied between 35 and 50 ml. In characteristic slowing of the EEG. Our study 28 cases a sample was obtained was designed to delineate the clinical features of before and after the injection of air and these samples the post-pneumoencephalography syndrome. were examined as soon as possible for protein, glu- 146 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.1.146 on 1 February 1973. Downloaded from Sequelae to pneumoencephalography 147 cose, chloride, and cells. In addition the cerebrospinal gested degenerative cerebellar disease and im- fluid was cultured and its Wassermann reaction proved after the air study, disappearing by the determined. As the results conformed with the seventh day of observation. cerebrospinal fluid changes that have already been In eight patients clouding of consciousness documented in the literature, a single analysis was made of each patient's combined specimens for the occurred or was aggravated after pneumo- rest of the series. encephalography. Confusion or incontinence The patients were kept in bed for three days and was present in four patients for one day and in were interviewed and examined daily for seven days another three confusion together with incontin- after pneumoencephalography. Particular attention ence for three to five days and one patient was paid to headache, nausea, vomiting, pain in the became drowsy. back, fever, level of consciousness, blood pressure, Three EEG records were obtained in each of41 pulse rate, and any changes in the pre-existent cases. In six cases only one record was obtained epilepsy. after the air study. In three either the pre- or post- An EEG was taken on the second and eighth day pneumoencephalography EEG was not done. In after the air study or as close as possible to these 34 cases an EEG abnormality either appeared or time intervals and a blind comparison made be- most tween these and the EEG performed before the pro- increased in the week after the air study. In cedure. During the observation period, changes in cases the abnormalities. were more marked on medication and any other procedure which could the second day and improved or resolved by the have affected the EEG were avoided. eighth. The changes consisted characteristically

A lateral radiograph of the was taken every of a decrease of the order of 1-2 Hz in the fre- guest. Protected by copyright. day until the air bubble in the lateral ventricle was quency of the posterior dominant rhythm and less than 1 cm in width. A smaller air bubble could the appearance or increase to a moderate degree not be measured accurately. The period during of background slow wave activity in the theta which the air over the cortex could be demonstrated and delta range. Eight cases showed no change in the plain film was recorded. in the EEG and in five there appeared to be a decrease in the EEG abnormality. RESULTS Abnormalities with apparent localizing signifi- Headache lasting one to nine days occurred in 39 cance were misleading. In five a focal abnormal- of the 50 patients and vomiting for one to five ity appeared for the first time in the post- days in 17 patients. Nine patients had vomiting pneumoencephalography record, but in four of on the first day only and four of these had these the known cerebral pathology was diffuse omnopon and scopolamine as premedication for and generalized-for example, generalized cere- general anaesthesia. Neck stiffness was found on bral atrophy associated with senile dementia. A examination in 17 patients from the first to the seventh day. Pyrexia was recorded in 19 cases for one to two days, the maximum being 390 C. TABLE 1 One patient with pyrexia of 38° C for four days DURATION AIR DETECTED RADIOLOGICALLY http://jnnp.bmj.com/ was subsequently found to have a thrombosis in AFTER PNEUMOENCEPHALOGRAPHY the deep veins of one leg. A tachycardia of 90/min or greater occurred in 37 patients and Patients with Patients with normal air radiological diagnosis lasted one to four days. In all except three the studies of cerebral atrophy rate was greater than 100/min. Six patients were (n= 20) (n = 30) hypertensive for 1 to 12 hours after the air study Duration Cortical* Ventricular Cortical Ventricular and three became hypotensive during this period. (days) air filling air filling One of the latter had been given parenteral on September 27, 2021 by 1-2 11 3 9 1 chlorpromazine for sedation. In 15 cases, at 3-4 3 7 12 3 one 5-6 0 4 4 9 least of the following neurological signs 7-8 0 4 4 12 appeared in the period from the first to the 9-10 0 1 1 2 11-12 0 0 0 1 seventh day: unequal pupils, expressive dys- 13-14 0 1 0 2 phasia, pyramidal or extrapyramidal system involvement. Nystagmus in one patient sug- * Six patients did not have radiologically detectable air over the cortex. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.1.146 on 1 February 1973. Downloaded from

148 Y. S. White, D. S. Bell, and R. Mellick lateralized EEG abnormality appeared in two headache, neck stiffness, nausea and vomiting, cases, both with generalized cerebral pathology. pyrexia, tachycardia, alteration in the frequency On the other hand, the increase in bilateral EEG of fits, change in the level of consciousness, abnormality obscured the localizing sign in one appearance of neurological signs, and EEG case of temporal lobe epilepsy with a lateralized abnormalities. EEG abnormality. Headache was a common complaint. Robert- The five subjects whose EEGs improved son (1957) claimed that headache is rare after temporarily included a patient with focal pneumoencephalography. Taveras and Wood epilepsy whose focal discharge disappeared (1964) found that the absence of headache after during the week after the air study and a case of pneumoencephalography was related to the epilepsy in which the focal discharge and the presence of cerebral atrophy, but we were unable background slow wave abnormalities persisted to confirm this. unchanged, but the posterior dominant rhythm All patients with neck stiffness also had head- increased in frequency. ache and most of these did not notice any stiff- The pneumoencephalograms revealed that 20 ness. Bohn (1937) and Schwab and von Storch patients had normal air studies and 30 had (1937) suggested that neck stiffness after pneumo- cerebral atrophy. Table 1 shows that cortical and encephalography is associated with an aseptic ventricular air were present for a longer period meningeal reaction resulting from the presence in those who had cerebral atrophy. The one of air in the subarachnoid spaces. patient with an apparently normal pneumo- Pyrexia lasting one to two days has been notedguest. Protected by copyright. encephalogram, who had ventricular air present by Bohn (1937), Le May (1967), and Clark, for 14 days, had had neurosurgical treatment for Wilson a temporal lobe cyst approximately 13 years Obenchain, Hanafee, and (1970). In our previously. series there was no correlation between the There was no significant difference in the presence of pyrexia and the occurrence of neck incidence or duration of headache between those stiffness. patients with normal pneumoencephalograms Nausea and vomiting occurring only on the and those with cerebral atrophy and similarly no first day after the air study was in some cases no difference in incidence of overall EEG abnormal- doubt due to the premedication or the anaes- ity. However, there was significantly less vomiting thetic. Omnopon is well recognized as causing in those with cerebral atrophy. nausea and vomiting in susceptible persons There were 13 patients with epilepsy. Of these, (Dripps, Eckenhoff, and Vandam, 1961): of the one had a decrease in the frequency of seizures six patients given omnopon and scopolamine, for the period of observation and in four the four had vomiting for one day only. Although frequency increased. Three of the latter showed fentanyl may possibly cause vomiting, the other an increase of epileptiform activity in the EEG drugs used in neuroleptanalgesia are antiemetic. When correction was made for those patients recorded on the second day after pneumo- http://jnnp.bmj.com/ encephalography. given general anaesthesia, the absence of vomit- Cerebrospinal fluid examination revealed a ing was significantly more common in those with decrease in the protein concentration of the cerebral atrophy (P < 0-05). We cannot suggest sample taken after the injection of air in 15 out an explanation for this finding. The eight cases of of 28 cases (range 1 to 13 mg%O). In five there was vomiting for periods longer than one day were an increase of 1 to 6 mg%O. There was no change possibly associated with organic cerebral changes in eight. An increase in the number of white after pneumoencephalography. cells in the cerebrospinal fluid after the injection The occurrence of tachycardia in 740% of on September 27, 2021 by of air was found in 14 cases, in seven there was a patients was surprisingly common; in Bohn's decrease, and in seven there was no change. (1937) series of 1,000 patients it was noted in only 3300. The only significant fluctuations in DISCUSSION blood pressure would appear to have been The findings in this study indicate that the com- associated with the anaesthesia or, in one case of mon sequelae of pneumoencephalography are hypotension, with the administration of parent- J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.1.146 on 1 February 1973. Downloaded from Sequelae to pneumoencephalography 149 eral chlorpromazine, which can lower the blood ment of an organic brain syndrome in people pressure (Goth, 1964). aged 50 years and over and in those with cerebral Neurological signs that appeared temporarily damage. All of our eight patients with impair- after the air study were varied and showed no ment of consciousness had one or both of these particular pattern. Only impairment ofconscious- features. In fact seven had cerebral atrophy. ness would seem to have been reported pre- This is also relevant to the findings of Potthoff viously: Hammer and Klingler found this in 29 (1970), who reported the occurrence of a 'psycho- of 92 patients in the 24 hours after pneumo- organic syndrome' occurring after pneumo- encephalography. encephalography in a group of patients with The appearance or increase of EEG abnor- Parkinson's disease, 85.3% of whom were found mality to a mild or moderate degree in 34 of 47 to have cerebral atrophy. cases further confirms the occurrence of cerebral One patient had a transient but striking im- dysfunction after the air study and is consistent provement in her mental state. with previous reports (Hammer and Klingler, 1969; Riehl and Ansel, 1969). An increase in the frequency of epileptic seizures was associated with an increase in EEG epileptiform activity in CASE HISTORY four of five cases, but otherwise the changes in A woman, aged 47 years, a known alcoholic, had been admitted to hospital five months previously in

hepatic coma. She was unable to give any history, guest. Protected by copyright. but was known to have had episodes of delirium tremens in the past. After recovery from the hepatic TABLE 2 coma, she was regarded as suffering from dementia. LEVEL OF CONSCIOUSNESS RELATED TO CEREBRAL ATROPHY Physical examination revealed multiple spider naevi on her face and shoulders, a tender firm hepato- No clouding of Clouding of megaly, evidence of peripheral neuropathy in the consciousness consciousness lower limbs, and bilateral extensor plantar responses. (n = 42) (n =8) She had frequent attacks ofunexplained fever, during which she would become even more confused, but Normal pneumoencephalogram 19 1 Cerebral atrophy as the liver function tests, , and cere- radiological diagnosis 23 7 brospinal fluid showed no abnormality. The EEG on admission showed a low voltage 11 Hz alpha rhythm. Before the air study the patient was hyperactive. Approximately two weeks after admission she had several grand mal seizures and was started on phenytoin sodium 100 mg tds and methylpheno- this series were non-specific. In particular, when barbitone 60 mg tds. Pneumoencephalography was a focal or lateralized abnormality appeared for performed two days later under general anaesthesia the first this did not have time, localizing signifi- after premedication with omnopon and scopolamine. http://jnnp.bmj.com/ cance. In fact, the increase in generalized EEG The air study revealed slight dilatation of the abnormality in one case actually obscured a and excess cortical air over both lateralized epileptiform discharge. Our finding of hemispheres indicative of diffuse cerebral atrophy. false localizing signs in the post-pneumo- For four days after pneumoencephalography the encephalography records is consistent with the patient was more cooperative, answered questions in bulk of the reviewed Riehl and a rational manner, and commented relevantly about literature, by events in Ansel (1969), but contrary to their observations. occurring the ward around her. On the fifth

day after her air study she again reverted to her con- on September 27, 2021 by The presence of cerebral atrophy reduced the fused, noisy, and verbally aggressive behaviour. The likelihood of nausea and vomiting. There was a cerebrospinal fluid examination was normal. trend for cerebral atrophy to be associated with During the period of improvement, her EEG impairment of consciousness (Table 2), but this showed a slight reduction in the frequency of the did not reach the level of statistical significance. alpha rhythm and an appearance of background Lipowski (1967) has noted that, in general, there delta activity of higher amplitude in the left temporal is an increased predisposition to the develop- region. Eight days after the air study long runs of J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.1.146 on 1 February 1973. Downloaded from

150 Y. S. White, D. S. Bell, and R. Mellick spike and wave discharge with a repetition frequency observed by us may be explained by the fact that of one per second appeared, of higher amplitude on the long tracts traversing this zone may also be the right side. affected. The stretching of the basal perforating arteries may lead to headache. The occurrence of a transient improvement in mental state after pneumoencephalography does not seem to have been documented. The altera- We are grateful to Professor L. G. Kiloh for his tion may have been associated with the treat- helpful advice and to the staff of the Psychiatric Research Unit who assisted in the many observa- ment of the epilepsy, but against this is the fact tions required for this study. that the patient reverted to her previous mental state even though the medication remained un- changed. The change in the EEG during the stage of improvement suggested that this patient REFERENCES had been affected by the organic brain syndrome Bohn, S. S. (1937). The reactions of patients to encephalo- graphy. An analysis of one thousand consecutive cases. following pneumoencephalography. Bulletin of the Neurological Institute of New York, 6, 540- About half of the cases examined had a drop 568. in protein concentration in the cerebrospinal Booker, H. E., Matthews, C. G., and Whitehurst, W. R. (1969). Pneumoencephalographic planimetry in neuro- fluid after injection of the air. Similar findings logical disease. Journal of Neurology, Neurosurgery, and have been reported by Schwab and von Storch Psychiatry, 32, 241-248. T. W. N., and Clark, R. A., Obenchain, G., Hanafee, guest. Protected by copyright. (1937), Marrack et al. (1961) and Dykes and Wilson, G. H. (1970). Pneumoencephalography. Com- Stevens (1970). Our finding in 5000 of cases of a parison of complications in 100 pediatric and 100 adult white cell pleocytosis after injection of air is cases. , 95, 675-678. Davidoff, L. M., and Dyke, C. G. (1951). The Normal consistent with reports from Schwab and von Encephalogram, 3rd edn. Lea and Febiger: Philadelphia. Storch (1937), Davidoff and Dyke (1951), Dott, N. M. (1960). Brain, movement and time. British Marrack et al. (1961), and Taveras and Wood Medical Journal, 2, 12-16. Dripps, R. D., Eckenhoff, J. E., and Vandam, L. D. (1961). (1964). Introduction to Anesthesia. The Principles of Safe Practice, In patients with cerebral atrophy both cortical 2nd edn. Saunders: Philadelphia. Dykes, J. R. W., and Stevens, D. L. (1970). Alterations in and ventricular air were present for longer than lumbar cerebrospinal fluid protein during air encephalo- in those with normal pneumoencephalograms. graphy. British Medical Journal, 1, 79-81. The time course of the organic brain syndrome Goth, A. (1964). Medical Pharmacology: Principles and Con- cepts, 2nd edn. Mosby: Saint Louis. and the presence of air in the cerebrospinal fluid Hammer, B., and Klingler, D. (1969). Veranderungen des spaces, particularly that in the ventricles, corre- Ventrikelsystems und des EEGs 24 Stunden nach Pneumen- closely to each other. zephalographie. Wiener medizinische Wochenschrift, 119, sponded 484-488. The mechanism by which the sequelae to Le May, M. (1967). Changes in ventricular size during and pneumoencephalography are produced may be after pneumoencephalography. Radiology, 88, 57-63. Levinson, A., Kaplan, I., and Cohn, D. J. (1939). Changes in explained as the consequence of the abrupt and fluid the brain after the the chemistry of cerebrospinal during encephalo- temporary displacement of graphy. Journal of Laboratory and Clinical Medicine, 25, http://jnnp.bmj.com/ injection of air into the ventricular system. 225-237. Lipowski, Z. J. (1967). Delirium, clouding of consciousness Although the duration of the displacement is and confusion. Journal ofNervous and Mental Disease, 145, short lived, the effect may be prolonged for days 227-255. by arterial spasm (Dott, 1960), which occurs as a Marrack, D., Marks, V., and Couch, R. S. C. (1961). Changes in the lumbar cerebro-spinal fluid during air-encephalo- result of stretching and attenuation of the basal graphy. British Journal of Radiology, 34, 635-639. perforating arteries. The resultant ischaemia Potthoff, P. C. (1970). Psycho-organic syndromes following would affect the diencephalon, the midbrain, the pneumoencephalography in parkinsonian patients. In

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