J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.48.11.1186 on 1 November 1985. Downloaded from

Letters 1186 amyotrophic lateral sclerosis. J Neurol Sci were hypoactive in the four limbs. Planter complicated by metabolic disorders. One 1972; 16:201-7. responses were flexor. patient had azotaemia and hyponatraemia. 7Steinke J, Tyler HR. The association of amyto- Laboratory values at the time of semi- Another showed hyperglycaemia. These rophic lateral sclerosis and carbohydrate coma included: serum osmolality, three cases suggest the possibility that the intolerance: A clinical study. Metabolism 410 mosmolkg; blood glucose, 827 mg/dl; metabolic disorders might cause or play a 1964; 13: 1376-81. serum sodium, 172 mmol/l; serum potas- part in opsoclonus. 8 Shahani B, Davies-Jones GAB, Russell R. has. Motor neurone disease. Further evidence for sium, 4-1 mmolVl; serum calcium, The anatomic basis of opsoclonus an abnormality of nerve metabolism. J 11-3 mEg/l; serum chloride, 115 mmolIl; not yet been determined. The frequent Neurol Neurosurg Psychiatry 1971; 34: BUN, 66 mg/dl; creatinine, 1-2 mg/dl; association of opsoclonus with ataxia and 185-91. arterial blood pH, 7-49; Pao,, 49 mm Hg; occasional necropsy findings in the cerebel- Paco2 45 mm Hg; SGOT, 194 IU (normal, lum support the suggestion that opsoclonus Accepted 5 April 1985 12 to 34 IU); SGPT, 228 IU (normal, 5 to is a sign of cerebellar involvement.2 Evi- 29 IU); alkaline phosphatase, 19-0 U dence from a limited number of cases sug- (normal, 3 to 13 U); and serum ammonia, gests, however, the involvement of brain- normal. Urine showed glucoseuria without stem in at least some cases of opsoclonus.2 ketones. An EEG demonstrated diffuse Our case revealed no pathologic changes in slowing in the delta and theta range. the brain, including cerebellum and brain- Treatment with insulin and intravenous stem. Opsoclonus in hyperosmolar nonketotic fluid replacement was instituted. The Many mechanisms may be responsible patient soon became responsive to verbal for opsoclonus.2 A metabolic basis seems coma stimuli. Opsoclonus and myoclonus disap- most likely in our case. Histochemical Sir: Opsoclonus is the term used to peared within 24 hours of the therapy, studies of brain have been performed describe rapid, irregular and chaotic eye which brought the serum osmolality level rarely with opsoclonus5 and hyperosmolar to 362 mosmol/kg, blood glucose value to coma.6 Ross and Zeman- carried out his- movements that occur in all directions. with This phenomenon has been associated with 340 mg/dl and serum sodium level to toenzymatic study in a patient opso-

Theguest. Protected by copyright. encephalitis, neuroblastoma, remote car- 164 mg/dl. Four days after initiation of the clonus and bronchogenic carcinoma. therapy, her mental state was almost nor- authors described definitely decreased suc- cinomas, demyelinating disease, intoxica- in the tions, thalamic haemorrhage, hemispheric mal and the osmolality was controlled be- cinate dehydrogenase activity glioblastoma, Friedreich ataxia and hyd- tween 310 and 340 mosmol/kg. The blood dentate nucleus. They suggested a possible sugar was between 100 and 200 mg/dl and relation between the opsoclonus and the rocephalus.' We describe a patient in nucleus. hyperosmolar nonketotic coma with opsoc- serum electrolytes were normal. However, biochemical change in the dentate lonus. We believe that this is the first report renal and liver function deteriorated Ziegels6 reported that plasma hypertonicity disorders. acutely. Seven days after initiation of the diminished the same enzyme activity in the of opsoclonus in metabolic the rat but did A 64-year-old woman was admitted for therapy, the patient became comatose and ependymal epithelium of pain died. Postmortem examination was per- not investigate the activity in the dentate evaluation of right upper abdominal can be and fever. On admission, neurological formed. She was found to have an nucleus. Although no conclusion examination was normal. Vital signs were adenocarcinoma in the tail of the pancreas drawn from these two reports, we speculate body temperature with multiple metastasis to the liver. The that hyperosmolality may induce a normal except for in the dentate nu- 38-4°C. The fever of unknown cause per- macroscopic and microscopic examination biochemical alteration of the failed to reveal any structural lesion in the cleus which causes opsoclonus. sisted after admission. A CT scan NODA liver revealed multiple space occuping brain. SHOSAKU with anti- case with carcinoma of pancreas AKIRA TAKAO lesions. The patient was treated Our HIROAKI ITOH biotics and steroid hormone. Four weeks developed opsoclonus and unresponsive- obtunded. Her when the patient had nonketotic HIROTOSHI UMEZAKI after admission she became ness Department of Neurology, skin was dry. The next day she was semi- hyperglycaemic hyperosmolality. The eye Hospital, comatose. She showed appropriate with- movements and alteration in consciousness Kyushu-Kosei-Nenkin hyperosmo- 2-1-1 Kishinoura, drawal of the limbs to painful stimuli but resolved with correction of the Yahata-Nishiku, could be http://jnnp.bmj.com/ was unresponsive to verbal commands. The lar state. No structural lesion Kitakyushu 806, pupils were of normal size and responded demonstrated in the brain at necropsy. briskly to light. A striking finding was the Although opsoclonus may occur with Japan presence of opsoclonus. Continuous, rapid remote effects of carcinomas,2 its appear- References and chaotic ocular saccades were noted ance is not transient as in our case. This with irregular myoclonic jerks in the face indicates that the opsoclonus was due to Rivner MH, Jay WH, Green JB, Dyken PR. Opsoclonus in Hemophilus influenzae and four limbs. The eye movements were the hyperosmolar nonketotic coma. 1982;32:661-3. the first report of a meningitis. Neurology (NY) conjugate and mainly in the horizontal This appears to be 2 Cogan DG. Opsoclonus. ln: Vinken PJ, Bruyn plane but with rotary and vertical compo- patient with opsoclonus in metabolic disor- GW, eds. Handbook of Clinical Neurology. nents. Ice water caloric stimuli transiently ders. However, Keane et a13 reportec Amsterdam: Elsevier, 1978, Vol 34. 611-5. on September 26, 2021 by produced conjugated deviation of both opsoclonus in a case with a unilateral glio- Keane JR, Devereaux MW. Opsoclonus associ- eyes toward the irrigated ear and opso- blastoma who had greatly elevated serunr ated with an intracranial tumor: a clonus stopped during the deviation. The glucose and urea nitrogen values. The clinicopathologic case report. Arch Oph- with transient s thalmol 1974;92:443-5. eye movements persisted unchanged author4 also described opsoclona thalamic lids open and closed. Deep tendon reflexes in two cases with thalamic haemorrhagce 4Keane JR. Transient opsoclonus with J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.48.11.1186 on 1 November 1985. Downloaded from

Letters 1187 hemorrhage. Arch Neurol 1980;37:423-4. pletely without any side-effect. pain.'" Although our experience is limited, Ross AT, Zeman W. Opsoclonus, occult car- Patient 3 was a 21-year-old female with it suggests that the agent may be safe and cinoma and chemical pathology in dentate common migraine. There was no family effective in rapidly aborting migraine nuclei. Arch Neurol 1967; 17:546-51. history of headache. The patient's throb- attacks. 'Ziegels J. Histochemical study of choroid plex- uses, ependymal epithelium and subcommis- bing headache began at the age of 13, were SHOSAKU NODA sural organ in experimental conditions. Acta moderate, on the right side, lasting about HIROAKI ITOH Neurol Belg 1975;75:24-30. 12 hours, occurring approximately once HIROTOSHI UMEZAKI per month. Associated symptoms were Department of Neurology, Accepted 10 May 1985 nausea and photophobia. She was referred Kyushu-Kosei-Nenkin Hospital, to our clinic 3 hours after an attack started. 2-1-1 Kishinoura, Yahata-Nishiku, One vial of the aspirin was injected. About Kitakyushu 806, Japan Successftul treatment of migraine attacks 10 minutes after the injection, the YASUO FUKUDA with intravenous injection of aspirin headache disappeared completely with Department of Internal Medicine, mild light-headedness. Sasebo General Hospital, Sir: Aspirin is occasionally used for Aspirin is a potent inhibitor of platelet 10-3 Shimazicho, prophylaxis' and treatment2 of migraine aggregation5 and prostaglandin synthesis.6 Sasebo 857, Japan attacks. Ross-Lee et at2 reported that oral If taken in the early stage of migraine administration of aspirin was usually or attacks, it may be of benefit by inhibiting sometimes effective in aborting acute platelet aggregation which is thought to be attacks in 42 of 61 patients with migraine. the initial biochemical event of the They also studied plasma levels in patients attacks.' At a later stage in the attacks, treated with aspirin and indicated that aspirin may inhibit prostaglandin forma- there was a general correlation between tion and help relieve pain. Prostaglandin better relief from pain and higher plasma appears to play a part in migraine aspirin levels.3 headache.' The pain of migraine attacks in guest. Protected by copyright. Intravenous aspirin (DL-lysine-acetyl- our three patients disappeared within 15 References salicylate; Venopirin®) has been available minutes after the intravenous administra- in Japan since 1983. One vial of the agent tion of The 'O'Neill BP, Mann JD. Aspirin prophylaxis in aspirin. pain persisted in migraine. Lancet 1978;2: 1179-81. contains 497 mg of aspirin. We used the Ross-Lee's patients for about 2 hours fol- 2 Ross-Lee L, Eradie MJ, Tyrer JH. Aspirin aspirin in three patients and succeeded in lowing oral administration of aspirin before treatment of migraine attacks: clinical promptly terminating migraine attacks. there was beneficial effect. The rapid effect observations. Cephalalgia 1982;2:71-6. Patient 1 was a 23-year-old male with of our treatment was remarkable. The 3 Ross-Lee L, Heazewood V, Tyrer JH, Eradi classical migraine. His grandfather and effect may be attributed to the prompt MJ. Aspirin treatment of migraine attacks: mother had recurrent headache. The inhibition of prostaglandin because the plasma drug level data. Cephalalgia patient's throbbing headache began at the severe headache was established when the 1982;2:9-14. age of 19. Attacks were preceded by scintil- agent was used. Imagawa T, Motoyama Y, Inahara H, Watanabe R. Acetylsalicyclic acid and lating scotoma which were severe, on the Zuker et alP studied effect of different salicyclic acid plasma levels after intraven- left side, lasting about 12 hours, occurring concentrations of aspirin on human ous and oral administration of Venopirin'; approximately once per month. Associated platelets. They indicated that over 28 ug/ in human. Clinical Report (Jpn) symptoms were nausea and vomiting. He ml of aspirin was required to inhibit the 1978; 12:17-22. was referred to our clinic 4 hours after an platelet aggregation promptly. Intravenous Weiss HJ. Platelet physiology and abnormality attack started because ergotamine tartrate injection of 497 mg of aspirin in humans of platelet function. New Engl J Med was of little help. The pain was severe and produced high concentration in plasma of 1975;293:531-41. 6 required bed rest. One vial of the aspirin one Smith JB, Willis AL. Aspirin selectively 80,ug/ml within minute; after 5 inhibits prostaglandin production in human was injected. About 15 minutes after the minutes the concentration was 37 ,ug/ml.4 platelets. Nature 197 1;231:235-7. injection, the headache disappeared com- While peak plasma concentration of about 7 Lance JW. Mechanism and Management of pletely without any side-effect. 14 ,ug/ml was reached 20 minutes following Headache, 4th ed. London: Butterworths, Patient 2 was a 56-year-old female with oral administration of the same dose of 1982:162-5. http://jnnp.bmj.com/ common migraine. Her parents and aspirin.4 Cyclooxygenase is an enzyme in O Zucker MB, Peterson J. Effect of acetyl- brother had recurrent headache. The the synthesis of prostaglandin. Inhibition of salicyclic acid, other nonsteroidal anti- patient's throbbing headaches began at the the enzyme activity was studied in animals inflammatory agents, and dipyridamole on age of 20, and were on after human platelets. J Lab Clin Med moderate, the right intravenous and oral administration 1970;76:66-75. side, lasting about 12 hours, occurring of aspirin (10 mg/kg).9 Marked inhibition Imagawa T, Shimahara S, Watanabe R. Inhibi- approximately once per month. Oral was observed 5 minutes after the injection. tion and acetylation of cyclooxygenase in administration of aspirin and dialminate However, the inhibition was not detected microsome fraction of rabbit renal medulla usually had beneficial effect. She was refer- until 30 minutes after the oral administra- after intravenous and oral administration of on September 26, 2021 by red to our clinic 2 hours after an attack tion. These findings seem to be the basis of aspirin. Jap J Clin Exp Med (Jpn) started, because oral aspirin and dialminate the rapid relief. 1983; 60: 3779-84. were of no help. The pain was severe and Side-effects were slight and mainly 0 Momose T. The effect of Venopirink on post- required bed rest. One vial of the aspirin restricted to nausea and perspiration in 5 of operative pain. Med Postgrad (Jpn) 1984;22: 105-13. was injected. About 15 minutes after the 75 patients who were treated with the injection, the headache disappeared com- intravenous aspirin for postoperative Accepted 16 February 1985.