1411THE LANCET

While awake, she looked healthy and no jerks were seen. There wasno laboratory evidence of meningitis, lacticacidosis, aminoaciduria,hypogylcaemia, hypocalcaemia, or intrauterine infection. Neithercranial computed tomography (CT) nor electroencephalographyshowed any abnormality. The jerking movements continueddespite treatment with several anticonvulsants. At 1 month of age,the bilaterally synchronous jerks were replaced by more

asynchronous myoclonic jerks, which affected the arms, legs, head,and trunk erratically. We suspected myoclonic encephalopathy ofinfancy, despite the absence of opsoclonus.3 Ultrasonographyshowed a round mass (18 x 18 mm) in the left adrenal gland.Abdominal CT also showed a mass with fine calcification, and thepresumptive diagnosis was neuroblastoma. There was no evidenceof metastasis. The myoclonus disappeared at 3 months of age, andover the next 6 months she was observed without any therapeuticintervention. Abdominal ultrasonography done every monthshowed no change in tumour size. Laparotomy at 10 monthsrevealed rosette-fibrillary types of neuroblastoma involving the leftadrenal gland and lymph nodes at the left renal hilus. These werecompletely removed. Her postoperative course was uneventful, buther motor development was slightly retarded: she sat at 8 monthsand walked at 18 months of age. Cranial magnetic resonanceimaging at the age of 18 months showed incomplete myelination ofsubcortical white matter.Neonatal sleep myoclonus and neuroblastoma are rare, but they

can coexist. Furthermore, the myoclonus disappeared before thetumour was removed. Despite these findings, a possible relationbetween myoclonus and neuroblastoma cannot be ruled out. Thetumour was clinically silent and remained unchanged for 6 months,which suggests that it might have been present at birth. Withoutultrasonography, it might have remained undetected. Hence, it ispossible that neuroblastoma is unrecognised in some neonates withclusters of myoclonic jerks during sleep. In addition, neurologicalmanifestations sometimes result from the remote action of

neoplasms. In children, the most well-known paraneoplasticsyndrome is myoclonic encephalopathy, which often complicatesneuroblastoma.3 However, our patient did not have opsoclonus orclinical deterioration. Her myoclonic jerks were similar to thepolymyoclonia of myoclonic encephalopathy of infancy, but theydisappeared spontaneously without steroid therapy. Although it isuncertain whether our patient has a newly identified paraneoplasticsyndrome, the possible association of neonatal myoclonus with anoccult neoplasm should be carefully investigated.

Department of Paediatrics,Nagoya University School of Medicine,Showa-ku, Nagoya 466, Japan

KOSABURO ASOKAZUYOSHI WATANABETAMIKO NEGOROKEIZO HORIBE

Department of Paediatric Surgery,Nagoya University School of Medicine

YOSHIO WATANABETAKASHI UMEDA

Department of Paediatrics,Nagoya First Red Cross Hospital SUNAO FURUNE

1. Commission on Classification and Terminology of the International League againstEpilepsy. Proposal for revised classification of epilepsies and epileptic syndromes.Epilepsia 1989; 30: 389-99.

2. Daoust-Roy J, Seshia SS. Benign neonatal sleep myoclonus: a differential diagnosis ofneonatal seizures. Am J Dis Child 1992; 146: 1236-41.

3. Lott I, Kinsborne M. Myoclonic encephalopathy of infants. In: Fahn S, et al, eds.Advances in neurology: myoclonus, vol 43. New York: Raven Press, 1986: 127-36,665.

Sensitisation to peanut and vitamin D oilypreparations

SiR,—In a recent case of anaphylactic shock after ingestion ofpeanut butter, the history indicated that peanut oil in vitamin Dpreparations taken during the first two years of life was the onlypossible method of sensitisation. Peanut sensitisation by peanut oilin infant formulae has also been reported.’ We have done aprospective analysis of peanut cutaneous reactivity according to thetype of vitamin D supplementation in early infancy.A skin prick test with peanut antigen was done in 122 children

aged between 7 and 60 months (mean [SD] 37 [14-4]) referred tothe paediatric allergy unit. During the first two years of life 40 of

these children received appropriate doses of vitamin D free frompeanut oil (group A), and 72 had vitamin D in preparations thatcontained peanut oil: 28 a daily dose (group B), and 44 a monthlydose (group C). A positive skin prick test, defined as a weal greaterthan 3 mm, was found in 5% in group A, 32-1% in group B, and25% in group C:

Group A Group B Group CChildren tested 40 28 44

Allergic children 27 20 30Positive peanut skin test 2(5%) 9(32-1%) 11(25%)

The odds ratio of B versus A was 9 00 (p < 0003) and of C versus Awas 6-33 (p < 001). No significant difference was found betweengroups B and C.

Sensitisation to peanut is widely acknowledged to play a role inatopic dermatitis and is a major factor in life-threateninganaphylactic reactions.2 Traces of proteins in the peanut oil of someinfant formulae are thought to be the sensitising factor.1 The samesensitising process is suggested in children treated with vitamin D inpreparations made partly of peanut oil. Although cutaneoussensitisation is not synonymous with clinical reactivity to peanut butmerely indicates a risk, our data suggest the need to avoid allmedications containing peanut oil in infancy.

H&ocirc;pital Saint-Vincent-de-Paul,75674 Paris, France

GUY DE MONTISDOMINIQUE GENDRELMARTINE CHEMILLIER-TRUONGCHRISTOPHE DUPONT

1. Moneret-Vautrin DA, Hatahet R, Kanny G, Ait-Djafer Z. Allergenic peanut oil inmilk formulas. Lancet 1991; 338: 1149.

2. Yunginger JW, Squillace DL, Jones RT, Helm RM. Fatal anaphylactic reactionsinduced by peanuts. Allergy Proc 1989; 10: 249-54.

Primary central nervous system lymphomaand brain biopsy in AIDS

SIR,-In an editorial1 on brain biopsy for intracranial masslesions, you say that inability to treat a central nervous system(CNS) lymphoma argues against regular use of brain biopsy inpatients with late-stage AID S. At our centre, a prospective study onthe role of brain biopsy in the diagnosis and treatment of intracranialmass lesions in patients with AIDS is ongoing.We enrolled, from Oct 1, 1991 to March 31, 1993, 56 patients

with brain mass lesions. All were treated with an antitoxoplasmaempirical regimen for 3-4 weeks. 30 were considered as havingtoxoplasmic encephalitis because of response to therapy. The other26 were selected for potential brain biopsy; indication was in allcases a poor clinical and/or radiological response to antitoxoplasmatherapy. In 13 (50%) biopsy could not be done because ofcontraindicatons or refusal. 13 had brain biopsy (8 stereotactic and 5ultrasound guided), and 12 (92%) had a final diagnosis (7 primaryCNS lymphoma, 3 progressive multifocal leukoencephalopathy, 1mycotic abscess, 1 tuberculous abscess). Only minimum bleedingconfined to the tumour bed occurred in 1 patient. Of the 7 patientswith primary CNS lymphoma (3 immunoblastic, 3 large cell, and 1lymphoblastic according to WF) 6 received whole-brain irradiation(cobalt-60, opposed lateral portals, 40-44 Gy). 5 completed a fullcourse and were clinically stabilised. 3 showed a partial radiologicalresponse, and 2 a stable lesion (computed tomography). Weobserved clinical and radiological progression in only 1 patient, withdeath occurring 28 days after biopsy and before completion ofradiotherapy.We retrospectively compared the 7 patients with biopsy-proven

CNS lymphoma to the 7 patients with a necropsy-diagnosedcerebral lymphoma observed at our centre during 1986-90. Thetwo groups were similar for age, sex, CD4 count, previous AIDSdiagnosis, time from onset to presumptive diagnosis, severity ofneurological status, white cell count, haemoglobin, and time oftreatment with antiretroviral drugs. Patients with a biopsy-confirmed diagnosis had significantly longer survival from onset ofneurological symptoms, with an estimated median survival time(EMST) of 233 days compared with 73 days in necropsy-provenpatients (p = 0-0002, logrank test). This result was confirmed bycalculating survival from presumptive diagnosis (221 vs 9 days,

1412 THE LANCET

p = 0005). As an indirect measure of quality of life, we calculatedthe ratio of days of hospital stay to survival time from presumptivediagnosis in biopsy-proven (69%) and in necropsy-proven (100%)patients (relative risk 0-69,95% CI 066-0-72). Cerebral lymphomawas the cause of death in 6 of 7 (86%) necropsy-proven and in 2 of 4(50%) biopsy-proven patients (2-25, 043-117). Stratifying the 7biopsy-proven patients according to Karnofsky performance status(KPS), we observed significantly longer survival for patients with aKPS equal or above 50 (EMST 147 days) compared with those witha score below 50 (9 days, p = 0-008). Survival in patients with anAIDS diagnosis at biopsy or within 1 year (EMST 147 days) wassimilar to that in patients with an AIDS-defining event occurringearlier than 1 year (113 days).

In our experience brain biopsy was safe and accurate. Theabsence of biopsy-diagnosed cerebral toxoplasmosis suggests that aprolonged empirical therapy could allow good selection of patientsfor invasive procedures. As reported, in patients with CNSlymphoma a biopsy-proven diagnosis and radiotherapy prolongsurvival and improve quality of life. However, this observation isprobably true only for patients with a good KPS at biopsy. Webelieve that your opinion that brain biopsy should be reserved forCNS mass lesions in patients with a good quality of life is valid.Brain biopsy in patients with a low performance status should bedone only in selected cases. Unlike recent reports in our experiencea previous AIDS-defining event did not worsen survival. Anegative expectation about the outcome of therapy was a majordeterminant for the lack of accrual of these patients in prospectiveclinical trials.’ Correct definition of selection criteria and thedemonstration of survival benefits in selected subgroups couldimprove the acceptance of this procedure by patients and bymedical teams.

Clinic of Infectious Diseases,Catholic University,00168 Rome, Italy

ANDREA ANTINORIADRIANA AMMASSARIRITA MURRIMARIO TUMBARELLOLUIGI ORTONA

Institute of Neurosurgery,Catholic University, Rome

MASSIMO SCERRATIROMEO ROSELLI

Department of Radiotherapy,Catholic University, Rome GIAMPIERO AUSILI CEFARO

1. Editorial. Brain biopsy for intracranial mass lesions in AIDS. Lancet 1992; 340: 1135.2. Baumgartner JE, Rachlin JR, Beckstead JH, et al. Primary central nervous system

lymphomas: natural history and response to radiation therapy in 55 patients withacquired immunodeficiency syndrome. J Neurosurg 1990; 73: 206-11.

3. Chappel ET, Guthrie BL, Orenstein J. The role of stereotactic biopsy in themanagement of HIV-related focal brain lesions. Neurosurgery 1992; 30: 825-29.

4. Galetto G, Levine A. AIDS-associated primary central nervous system lymphoma.JAMA 1993; 269: 92-93.

Fatal drug-induced pancreatitis in HIV

SiR,&mdash;Increases in pancreatic enzymes in HIV patients is

common; severe pancreatitis, however, is rare.1 Drugs (didanosine,pentamidine, anticonvulsants) or HIV-related disease, such ascytomegalovirus (CMV), mycobacteriosis, cryptosporidiosis, ortumours are reported causes.2 We have observed fatal pancreatitiscaused by co-trimoxazole in an HIV patient with pre-existingamylasaemia.A 42-year-old woman had heterosexually acquired HIV. She was

on anticonvulsant prophylaxis with valproic acid for many years forgenuine epilepsy (figure). Because of an asymptomatic increase inpancreatic enzymes, attributed to valproic acid, ultrasound andnuclear magnetic resonance (NMR) of the pancreas were done andshowed no abnormalities. Antiviral therapy with didanosine forHIV-related encephalopathy and inhaled pentamidine prophylaxiswere started. During didanosine treatment, pancreatic enzymesfurther increased without symptoms (figure), so the drug wasstopped after 3 months. The raised enzymes persisted.

She was referred to our hospital with Pneumocystis carinii

pneumonia. High-dose intravenous co-trimoxazole 320/1600 wasstarted four times a day and valproic acid was tapered; nocorticosteroids were given. Serum amylase at entry was 869 U/Land serum lipase over 1400 U/L. 10 days later she developed severe

Pancreatic enzymes.

Left-hand y-axis=serum amylase (0-0), normal=115 U/L;right-hand y-axis=serum lipase (N&mdash;&mdash;N), normal=2a0 U/L.US=ultrasound.

epigastric pain and serum amylase rose to 2600 U/L. Ultrasoundand computed tomography showed severe haemorrhagic andnecrotising pancreatitis.

Despite appropriate medical therapy, she died 2 days later.

Necropsy revealed acute haemorrhagic pancreatitis with fattynecrosis, pancreatogenic ascites, and secondary intramural bowelbleeding. HIV-encephalopathy and P carinii pneumonia wereconfirmed. CMV, mycobacteriosis, and neoplasms were excluded.

Sulphonamides are pancreatotoxic agents and in our case there islittle doubt that the sulphonamide moiety of co-tromoxazole wasresponsible for the fatal outcome.3 The increase in pancreasenzymes was probably drug-induced, since this is a well-knownside-effect of valproic acid and didanosine.4,5

Medical Clinic,Univerity Hospital,CH-8091 Zurich, Switzerland

RES JOSTCLAUDIA STEYFRANCO SALOMON

1. Murthy UK, DeGregorio F, Oates RP, Blair DC. Hyperamylasemia in patients withthe acquired immunodeficiency syndrome. Am J Gastroenterol 1992; 87: 332-36.

2. Bonacini M. Pancreatic involvement in human immunodeficiency virus infection.J Clin Gastroenterol 1991; 13: 58-64.

3. Antonow DR. Acute pancreatitis associated with trimethoprim-sulfamethoxazol AnnIntern Med 1986; 104: 363-65.

4. Mallory A, Kern F. Drug-induced pancreatitis. Balli&egrave;res Clin Gastroenterol 1988; 2:293-307.

5. Cooley PP, Kunches LM, Saunders CA. Once daily administration of

2’3’dideoxyinosine (ddI) in patients with the acquired immunodeficiencysyndrome or AIDS-related complex: results of phase I trial. N Engl J Med 1990;322: 1340-45.

Frequency of craniosynostosis inYorkshire, UK

SiR,&mdash;Our impression is that the number of cases of

craniosynostosis has recently increased among infants born in theYork and Selby areas of Yorkshire. 16 such infants born betweenSeptember, 1990, and November, 1992, have been seen at YorkDistrict Hospital, with diagnoses of either simple primarycraniosynostosis or a syndrome with craniosynostosis as a feature.During this period there were about 7600 children born to residentsof the area. Typical published incidence for all forms ofcraniosynostosis varies between 1 in 1900 and 1 in 4000 births,!which indicates that no more than 4 cases would be expectedin children bom during the above period: 16 is significantlyhigher than this (p<0-01 by Poisson distribution for rare

events).To clarify whether this increase was limited to the York and Selby

areas, we examined the Regional Information System (RI S) data forYorkshire for 1988-89 to 1991-92 inclusive. These data show a