John Radcliffe Hospital, Oxford OX3 9DU. Keywords: Prader-Willi syndrome ... 4 Jeffcoate WJ, Laurance BM, Edwards CRW, BesserGM. Endocrine functonin the ...
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to an agent like clozapine might be prophylactic. The latter agent has been shown to have minimal central
antidopaminergic effects4 and would therefore be expected to produce much fewer extrapyramidal side-effects. Acknowledgnent: We gratefully acknowledge support from the South African Medical Research Council.
References 1 Levinson DF, Simpson GM. Serious nonextrapyramidal adverse effects of neuroleptics: sudden death, agranulocytosis, and hepatotoxicity. In: Meltzer HY, ed. Psychopharmacology, the third generation of progress. New York: Raven, 1987:1431-36
Guillain-Barre syndrome in a patient with hairy cell leukaemia
S C Tayal MD MRCPI D S Rowbotham MBBS S K Bansal FRCP Department of Medicine for the Elderly, Ryhope General Hospital, Sunderland SR2 OLY Keywords: Guillain-Barr6 syndrome; hairy cell leukaemia; autoimmunity; lymphocyte subpopulations
Hairy cell leukaemia (HCL) is a chronic form of leukaemia that predominantly affects middle aged men. Neurological complications have been reported in only 5% of patients, mainly due to infections' or leukaemic infiltration2 of the central nervous system. We describe a patient with Guillain-Barre syndrome (GBS) associated with HCL which, to our knowledge, has not been described in the literature. Case report A 78-year-old retired miner was admitted with a 2-week history of progressive weakness of limbs, constipation and retention of urine. There was no preceding history of viral illness. He was on captopril 25 mg twice daily and hydrochlorothiazide 5 mg daily for hypertension. On examination he was heavily built, apxial and had a blood pressure of 170/85 mmHg. Cardiovascular, respiratory and abdominal examination were all normal. Neurological examination revealed higher functions and cranial nerves to be unaffected. Muscular fasciculations were pret in all limbs, with power grade 3/5 proximally and 4/5 distally. There was generalized areflexia and both plantars were equivocal. Sensation was intact. Laboratory data: haemoglobin 14.1 g/dl, whole blood count 10.2x 19/L with lymphocytes 4.78x 1(AL, platelets 216x109/L, erythrocyte sedimentation rate 10mm/h-and peripheral blood smear showed abnormal moonuclear cells. Biochemical results showed plasma sodium 121 mmol/l, potassium 3.05 mmol/l, urea, creatinine and glucose were normal. The CSF was clear, sterile with normal-cell conts8 and a protein level of 1.1 g/l and JgG of 0.1 gll. Monospot test was negative, viral titres were insignificant and blood culture sterile. Bone marrow emnation showed malignant lymphoproliferative morphology suggestive of hairy cell leukaemia. Whole blood count cell markers in theperipheral blood confirmed B cell monoclonal proliferation (CD22activated B cells 96%, CD19-pre B cells 71% and lambda 80%) and a reactive T cell subpopulation (CD4-OKT4 24% and CD8-OKT8 4%). Electromyography and nerve conduction studies were reported as showing severe motor and sensory
-2 Flaherty JA, Lahmeyer HW. Laryngeal-pharyngeal dystonia as a possible-cause of asphyxia with haloperidol treatment. Am J Psychiatry 1978;135:1414-15 3 Leestma JE, Koenig KL. Sudden death and phenothiazines. Arch Gen Psychiatry 1968;18:137-48 4 Baldessarini RJ. Drugs and the treatment of psychiatric disorders. In: Gilman A, Goodman LS, Rall TW, Murad F, eds. Goodman and Gilman's the pharmacological basis of therapeutics, 7th edn, New York: MacMillan, 1985:387-445
(Accepted 23 March 1990)
peripheral neuropathy with predominant demyelination and a degree of secondary axonal degeneration. Treaitment was commenced with subcutaneous interferon 3 million IU three times a week for 2 weeks and intravenous methylprednisolone 500 mg daily for 3 days. The illness was complicated by deep vein thrombosis, multiple pulmonary emboli and supraventricular -tachycardia. The patient died of progressive respiratory failure 4 weeks after admission. Postmortem examination cofirmed the diagnosis of GBS. The infla tory infiltrate was predominantly perivascular in an epineural and extrafascicular distribution and showed a heterogeneous mixture of mononuclear inflammatory cells. mmimunoperoxidase studies for immunoglobulin light chains showed a polyclonal staining pattern. There was no evidence of direct leukaemia/lymphomatous infiltration on the nerves. Discussion
Both GBS and HCL are very uncommon diseases making a chance association unlikely. Cases of GBS may have an underlying cause other than previous viral infection; for example Hodgkin's disease, neoplasms, metabolic disease and a variety of endocrine conditions3. However, GBS has not been reported previously either as the presenting feature or as a complication of HCL. GBS is8an immunologically-mediated disease caused by a delayed hypersensitivity reaction provoked, in a manner not yet understood, by antecedent viral infection or other conditions. Under certain circumstan, partial and perhaps transient immunosuppression could serve as one contributing factor in triggering GBS4. In a proportion of patients with GBS alterations in peripheral blood lymphocyte subpopulations have been described'. These include an increased helper/suppressor T-cell ratio due to a reduction in'the OK0P (suppressor cells) subpopulation. B cell and OKT4 (helper cells) populations remained normal. In our patient there was a predominant neoplastic B cell population. The reactive T cell population showed a helper/suppressr ratio of 6: 1 (normal 2: 1) due to loss of OKT8 cells. Thus depreaion of these'OK8 cells in GBS'might permit the development of autoimmunity to myelin igens and so play an important role in pathogenesis. The m anismn whereby HCL was associated r cells ratio is not with this abnormal T-helper and s clear.- However it is likely that the development:of GBS in this patient reflects an effect of tICL upon the immune status of the patient.
Acknowledgment Our thanks to Dr P Ince, Consultant Neuropathologist, General Hospital, Newcastle-Upon-Tyne,for reviewing the hitology and advice.
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References 1 Kimmel DW, Hermann HC, ONeill BP. Neurolgical comlicati of hairy cell leukaemia. Arch Neurol 1984;41:202-3
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Journal of the Royal Society of Medicine Volume 84 April 1991 2 Wolfe DW, Scopelliti JA, Boselli BD. Leukaemic meningitis in a patient with hairy cell leukaemia. Cancer 1984;54:1085-8 3 Hughes RAC, Winer JB. Guillain-Barr6 syndrome. In: Matthews WB, Glaser GH, eds. Recent advances in clinical neurology, vol. 4. Edinburgh: Churchill Livingstone, 1984:19-43 4 Phanthumchinda K, Intragumtornchai T. Guillain-Barrn syndrome and optic neuropathy in acute leukaemia. Neurology 1988;38: 1324-6
(Accepted 2 April 1990)
Anaesthesia and the Prader-Willi syndrome
Discussion
J W Mackenzie MRCP FFARCS Nuffield Department of Anaesthetics, John Radcliffe Hospital, Oxford OX3 9DU Keywords: Prader-Willi syndrome; obesity; anaesthesia
A syndrome of obesity, short stature, cryptorchidism and mental retardation with hypotonia in the neonatal period was first described by Prader, Labhart and Willi in 19561. It is a rare syndrome (1 in 15 000 live births)2, but in the last 4 years the author has witnessed anaesthesia in two cases.
Case reports Case 1 A 2-year-old boy presented for correction ofventral curvature of micropenis. He also had cryptorhidism; the syndrome had been suspected soon after birth because of hypotonia and poor feeding, even now the child only weighed 10 kg. Premedication comprised trimeprazine 15 mg, plus parenteral morphine 2.5 mg with glycopyrrolate 50,pg. Fasting glucose was 7.5-9 mmol/l. An inhalational iduction was performed without difficulty using halothane. Laryngoscopy was normal and atracurium 5 mg was used to facilitate intubation. Isoflurane 0.5-1% in nitrous oxide and oxygen was used to maintain anaesthesia. A caudal epidural was performed to provide postoperative analgesia and residual neuromuscular blockade was promptly antagonized with neostigmine and glycopyrrolate. Blood glucose remained at 7.5-9 mmolV, and subsequent progress was uneventful. Case 2 The second case took place at another teaching hospital in 1985; he was aged 18 but had a mental age of 6 and weighed 212 kg. His thighs were so bulky that walking necessitated circumduction of each leg, also sitting down to attend to personal hygiene had become difficult. It was proposed to remove some of this excess tissue from one thigh. Day-time solemnence was not present, but sleep was attended by continuous snoring. Right bundle-branch block was present on the electrocardiogram, and haematocrit was normal. Premedication consisted of intramuscular papaveretum 20 mg and scopolamine 0.4 mg. Anaesthesia was conducted by the consultant who had dealt with the patient 2 years previously for a similar procedure, and elected again to use halothane in nitrous oxide and oxygen for induction with maintenance of anaesthesia breathing spontaneously. Laryngoscopy was not attempted. Postoperatively, emergence was slow and accompanied by snoring. Although no complications were documented, wound healing and mobilization were slow.
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5 Hughes RAC, Aslan S, Gray IA. Lymphocyte subpopulations and suppressor cell activity in acute polyradiculoneuritis (Guillain-Barr6 syndrome). Clin Exp Immunol 1983;51: 448-54
A partial deletion of chromosome 15 is a marker for the Prader-Willi syndrome (PWS)3. The associated hypogonadism suggests a hypothalamic lesion. During phase I infants characteristically suckle poorly and prolonged nasogastric feeding may be necessary, the cough reflex is weak and episodes of asphyxia may occur. Phase II begins at 3-5 years of age when hyperphagia ensues and extreme obesity develops. Other features include acromicria with micropenis, micrognathia, high-arched palate, scoliosis and dislocation of the hip. Cardiac conduction defects have been noted and convulsions are common in those with PWS. A reduced tendency to vomit is attributed to the hypothalamic lesion2. Glucose intolerance or frank diabetes are found in obese individuals4 and both hypothermia and hyperthermia have been reported in response to operative stress'6 . No cases of PWS have been referred for investigation at Leeds malignant hyperpyrexia centre (Ellis FR, personal communication) so the relationship to malignant hyperpyrexia remains uncertain. Muscle biopsy has revealed fatty infiltration of type II (fast-twitch) fibres2, which may account for the hypotonia, but contacture tests have not been reported. Patients present for anaesthesia to undergo orchidopexy, orthopaedic surgery, dental surgery, squint correction, cleft lip and palate repair or surgery for obesity later in life7. Life expectancy can now reach the fifth decade if extreme obesity is avoided. Therefore careful assessment, attention to glycaemic control and body temperature, combined with judicious use of muscle relaxants in phase I of the condition, with measures to reduce risks due to the obesity characteristic of phase II are likely to result in an uneventful outcome following anaesthesia in Prader-Willi syndrome5,8.
References
Labhsrt A, Willi H. Ein syndrom von Adipositas, Kleinwuchs, Kryptorchismus und Oligophrenie nach Myatonieartigem Zustand in Neugenborenenalter. Schweiz Med Wochenschr 1956;86:1260-1 Seoond Annual Pader-Willi syndrome scientafic conference, 1987. Am J Med Genet 1987;28:779-924 Ledbetter DH, Riccardi VM, Airhart SD, Strobel RJ, Keenan BS, Crawford JD. Deletions of chromosome 15 as a cause of the Prader-Willi syndrome. N Engl J Med 1981;304:325-30 Jeffcoate WJ, Laurance BM, Edwards CRW, Besser GM. Endocrine functon in the Prader-Willi yndrome. Clin Endocinol 1980;12:81-9 Yamashita M, Koishi K, Yamaya R, Tsubo T, Matsuki A, Oyama T. Anaesthetic considerations in the Prader-Willi syndrome: report of four cases. Can Anaesthetists Soc J 1983; 2:179-84 Mayhew JF, Taylor BT. A in Prader-Willi Syndrome. Can Anaesthetists Soc J 1983;5:565-6 Touquet VLR, Ward MWN, Clark CG. Obesity surgery in a patient with the Prader-Willi syndrome. Br J Surg 1983; 70:180-1 Palmer SK, Atlee JL. Anethetic managent of the Prader-Willi syndrome. Anesthesiology 1976;44:161-3
1 Prader A,
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(Accepted 18 April 1990)
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