J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.52.12.1451 on 1 December 1989. Downloaded from

Letters 1451 chronous myoclonic jerks that aItected the excitatory effects, from nervousness and sion to report the case and for reviewing the face and limbs. Tactile and auditory stimuli tremors to agitated delirium, multifocal manuscript. produced generalised myoclonic jerks. myoclonus and seizures, in a group ofcancer DAVID C REUTENS Fundoscopy and pupillary reactions were patients treated with pethidine, correlated EDWARD G STEWART-WYNNE normal and oculocephalic, corneal and gag with the plasma level of norpethidine as well Department ofNeurology, reflexes were present. Muscle tone was as the ratio of norpethidine to pethidine in Royal Perth Hospital, normal. Generalised myoclonic jerks were the plasma.2 GPO Box X2213 Perth, produced when deep tendon reflexes were It is likely that the myoclonus and general- Western Australia 6001 tested. Both plantar responses were flexor. ised convulsions in our patient were related Formal assessment of muscle power, sensa- to norpethidine accumulation. Normal mus- References tion and coordination was not possible. cle tone and marked stimulus sensitivity do General examination revealed third and not usually occur in a phenothiazine (pro- I Szeto HH, Inturrisi CE, Houde R et al. fourth heart sounds and a soft ejection chlorperazine) induced syndrome. In our Accumulation of normeperidine, an active systolic murmur. patient, the effect of uraemia on the metabolite of meperidine, in patients with Initial biochemical investigation showed: threshold for central excitation, resulted in renal failure or cancer. Ann Intern Med 1977; plasma potassium 7-9 mmol/l, bicarbonate lower norpethidine levels producing myo- 86:738-40. 17 mmol/l, urea 47-8 mmol/l, creatinine clonus and seizures compared to the levels 2 Kaiko RF, Foley KM, Grabinski PY et al. required in cancer patients (424-1856 pg/l).' Central nervous system excitatory effects of 1504 umol/l, glucose 7 5 mmol/l, arterial meperidine in cancer patients. Ann Neurol blood pH 7 24, pCO2 43 mm Hg, pO2 104 In both uraemic and norpethidine related 1983;13: 180-5. mm Hg, oxygen saturation 97%. The myoclonus, the involvement of not only the 3 Hochman MS. Meperidine-associated myo- haemoglobin level was 97 g/l and the leuco- distal muscles of the stimulated limb, but clonus and seizures in long term hemodialysis cyte count 10 8 x 109/l. Cardiomegaly was also proximal muscles and other limbs in the patients. Ann Neurol 1983;14:593. present on a chest radiograph. Three sets of myoclonic response to peripheral stimuli, 4 Tang R, Shimomura SK, Rotblatt M. Meperi- blood cultures and a midstream urine suggests that the myoclonus was a reticular dine induced seizures in sickle cell patients. specimen were sterile. rather than a cortical reflex type. The former Hospital Formulary 1980;15:764-72. Three hours of haemodialysis did not has been described in uraemia,5 hypo- 5 Chadwick D, French AT. Uraemic myoclonus: guest. Protected by copyright. natraemia and post an example of reticular reflex myoclonus? J affect the patient's neurological status. A anoxic encephalopathy. Neurol Neurosurg Psychiatry 1979;42:52-5. generalised tonic/clonic convulsion occurred Because of norpethidine's long half life in 6 Jenner P, Pratt JA, Marsden CD. Advances in less than 10 minutes after administration of uraemic patients, neurological abnormalities Neurology, Vol 43: Myoclonus. In: Fahn S et naloxone, 0-2 mg. Recurrent hyperkalaemia may persist for several days after cessation of al, eds. Mechanism ofaction ofclonazepam in (7 5 mmol/l) was treated with oral sodium pethidine. In the presence of renal failure, myoclonus in relation to effects on GABA and resonium. Electroencephalography revealed repeated muscle contraction may result in S-HT. New York: Raven Press, 1986:629-43. generalised theta and delta activity of life threatening hyperkalaemia and urgent 7 Gilbert PE, Martin WR. Antagonism moderate to high amplitude, intermixed with control of myoclonus and seizures becomes of the convulsant effects of heroin, necessary. Clonazepam was very effective in d-propoxyphene, meperidine, normeperidine multifocal spike and sharp waves at a and thebaine by naloxone in mice. J frequency of 1-2 per second. Intravenous this case and is also dramatically effective in Pharmacol Exp Ther 1975;192:538-41. injection of clonazepam, 0 5 mg, resulted in controlling post-anoxic myoclonus, where immediate cessation of myoclonic jerks and diazepam, phenytoin and phenobarbitone reduction of spike and sharp activity. Lower have been ineffective.6 In another reported amplitude semirhythmic 3-4 Hz activity case3 of myoclonus due to presumed appeared. Myoclonus and hyperkalaemia norpethidine toxicity, clonazepam was in- IntrameduHary spinal cord metastasis follow- did not recur. The pethidine level in the effective but the route of administration ing a slowly progressive course plasma stored from the time of admission was not recorded. Naloxone, by completely was < 10 pg/l and the norpethidine level antagonising the depressant effects of Sir: Intramedullary spinal cord metastasis is 114,pg/I. Haemodialysis did not affect the pethidine and norpethidine but only par- a well known but rare complication of can- rate of fall of plasma norpethidine levels tially antagonising the latter's excitatory cer.' In the majority of patients it occurs in which were logarithmically related to time effects,7 may unmask seizure activity when conjunction with widespread systemic dis- (correlation coefficient, r = -0 82; P < used in norpethidine intoxication. From our ease and progresses rapidly.23 We report a http://jnnp.bmj.com/ 005). The elimination half life of the data, norpethidine appears to be difficult to patient in whom the condition was the only metabolite in our patient was 25 hours. remove by dialysis. indication of relapse and whose signs and The initial metabolism of pethidine occurs In uraemic patients requiring narcotic symptoms progressed slowly. in the liver where hydrolysis to pethidinic analgesia, agents such as pethidine and A 54 year old woman was referred to our acid and N-demethylation to norpethidine, dextropropoxyphene with toxic metabolites department because of difficulty in walking, followed by hydrolysis to norpethidinic acid, should be avoided. While morphine and burning sensations in the thighs and low occurs. While repeated administration of codeine may result in unusually severe and backache, slowly progressive over the past pethidine in patients with cancer' 2 or sickle prolonged respiratory depression and seda- year. At the age of 52 an adenocarcinoma of cell anaemia4 may result in norpethidine tion in renal failure, their cautious use at the lung had been detected and a lobectomy on September 28, 2021 by accumulation, more rapid accumulation lower dosage, with careful clinical monitor- of the left lung had been performed. after fewer doses occurs in renal failure. ing, is to be preferred. Examination showed proximal paresis of Norpethidine is a central nervous system the legs, MRC grade 3-4/5, more pronoun- excitant with less potent depressant effects We thank Dr G N Thatcher, Nephrologist at ced on the right side. Distally, the strength than pethidine. The progression of Royal Perth Hospital, for giving his permis- was nearly normal. Superficial pain and J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.52.12.1451 on 1 December 1989. Downloaded from

1452 Letters temperature sensations were disturbed below then declined again. Myelography showed 2 Grem JL, Burgess J, Trump DL. Clinical the level of L2 in both legs. Sensation of recurrence of the tumour. Radiotherapy features and natural history of vibration was impaired below the hip on the induced a second remission for four months intramedullary spinal cord metastases. Cancer on after which she an almost com- 1985;56:2305-14. right side and below the knee the left side. developed 3 Winkelman MD, Adelstein DJ, Karlins NL. Tendon reflexes of the legs were decreased. plete neurological deficit below the level of Intramedullary spinal cord metastases diag- Plantar responses were equivocal. Cerebro- ThlO. nostic and therapeutic considerations. Arch spinal fluid (CSF) contained 8 leukocytes per Intramedullary spinal cord metastasis Neurol 1987;44:526-31. mm3; no tumour cells were found at repeated usually has an abrupt onset.3 Untreated, the 4 Smaltino F, Bernini FP, Santoro S. Com- lumbar punctures. The protein and f,- neurological symptoms evolve within one puterized tomography in the diagnosis of glucuronidase content were increased to res- month to full deficit and more than 80% of intramedullary metastases. Acta Neuro- pectively 1,46 g/l (normal value: 0 20-0 50 the patients die within three months after chirurgica 1980;52:299-303. 5 Murphy KC, Feld R, Evans WK, et al. g/l) and 37 mU/I (normal value: 9-27 mU/l). seeking medical attention.2 Our patient and Intramedullary spinal cord metastases from Myelography on the first occasion did not the few other examples published3'5 show small cell carcinoma ofthe lung. J Clin Oncol show a significant abnormality but three that the condition can follow a slowly 1983;1:99-106. months later showed widening of the spinal progressive course and hence should be 6 Zanten AP van, Twijnstra A, Benthem V van, et cord at level T10-Tl 1. Magnetic resonance included in the differential diagnosis of a al. Cerebrospinal fluid ,B-glucuronidase imaging (MRI) revealed an intramedullary patient with a slowly progressive activities in patients with central nervous lesion with prominent enhancement after myelopathy. system metastases. Clin Chem Acta 1985; intravenous administration of gadolinium As initially in our patient, myelography 147:127-34. (fig). Other metastases were not fails to show an in about 40% of detected and abnormality Since this paper was accepted an additional article describ- an exploratory operation was performed. cases2 and MRI is likely to be superior. ing the value ofgadolinium-enhanced MRI in the diagnosis After laminectomy, a local tuberous en- Patients with intramedullary spinal cord of intramedullary metastases has appeared: Fredericks RK, largement ofthe spinal cord at level T10-Tl 1 metastasis have variable, sometimes virtually Elster A, Walker FO. Gadolinium-enhanced MRI: a superior technique for the diagnosis of intraspinal metas- was found, with diffuse widening of the normal, CSF findings.2 In some patients it tases. Neurology 1989;39:734-6. spinal cord for two centimeters cranially. contains identifiable tumour cells but in such

The dorsal surface of the spinal cord looked cases meningeal carcinomatosis is likely to be guest. Protected by copyright. normal and there were no signs of leptomen- present. The slight elevation of ,B-glucuron- ingeal involvement. After incision, the partly idase content noted in our patient may necrotic intramedullary tumour was also reflect leptomeningeal involvement, Management ofintraventricular haemorrhage removed as radically as possible. The his- although slight elevations ofcerebrospinal ,6- secondary to ruptured arteriovenous malfor- tological appearance of the removed tissue glucuronidase activities occur with paren- mation in a child with Von Willebrand's was identical to that of the lung tumour. The chymal metastases.6 Radiation therapy can disease patient received radiotherapy to the site of be an effective treatment and lead to the metastasis. Strength and sensation in the neurological stabilisation or improvement Sir: We report a case of an adolescent female legs improved. and disappearance of pain.3 Operative treat- who presented with intraventricular For nine months her clinical condition ment has been used rarely3 but, as in our haemorrhage following minor trauma. She remained stable but the strength in her legs patient, can be temporarily beneficial when was diagnosed as having von Willebrand's the condition is slowly progressive. disease but, in addition, had an intraven- JHTM KOELMAN,* tricular arteriovenous malformation. This M DE VISSER,* case emphasises the need to investigate possi- s..,,.,...X .~W JAM KUSTER,t . ble structural abnormalities even in the JJR DREISSEN,$ presence of a known coagulopathy in J VALK,§ patients with intracerebral haemorrhage. PA KOSTER¶f A 13 year old female complained of head- Departments ofNeurology,* ache, nausea, vomiting, stiff neck and Neurosurgery,: Radiology,fJ blurred vision two days after a minor episode Academic Medical Centre, Amsterdam ofhead trauma. CT revealed intraventricular Department ofNeurology,t and subarachnoid haemorrhage. She alsohttp://jnnp.bmj.com/ Elisabeth Gasthuis, Haarlem, reported a history of heavy menstrual flow Department ofRadiology,§ and epistaxis while taking aspirin. Her family Free University Hospital, history was notable for easy bruising and Amsterdam, The Netherlands prolonged bleeding. Apart from meningis- Address for correspondence: Dr JHTM mus, neurological examinations were nor- Koelman, Department of Neurology, mal. Coagulation studies revealed normal Academic Medical Centre, Meibergdreef 9, prothrombin and partial thromboplastin 1005 AZ Amsterdam, The Netherlands. times but a prolonged bleeding time. The diagnosis of type 1 von Willebrand's disease on September 28, 2021 by ...... was ultimately made. Following a bolus of References cryoprecipitate she was placed on a contin- Fig MRI Ti weighted image after I Costigan DA, Winkelman MD. Intramedullary uous cryoprecipitate infusion, titrated to intravenous gadolinium showing intense spinal cord metastasis. J Neurosurg 1985; keep her von Willebrand's factor greater signal intramedullary at T10-TJ . 62:227-33. than 50%.