Letters to the Editor 91

syphilis were negative in the blood and the a role in the aetio-pathogenesis ofALS in our 3 Chen L. Neurofibrillary change on Guam. Arch J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.1.91 on 1 January 1991. Downloaded from patient. It is interesting that another case of Neurol 1981;38:16-8. cerebrospinal fluid (CSF). He was HIV 4 Forno LS, O'Flanagan TJ. Amyotrophic lateral negative. CSF protein was 0-25 g/l and there Guam type ALS has also been reported sclerosis of the Guam type in a U.S. veteran. were no cells or oligoclonal bands. Serum before in an American serviceman who had Neurology 1973;23:876-80. was raised at 199 "exposure" on Guam.4 In contrast to our 5 Hoffman PM, Robins DS, Oldstone MBA et al. creatine phosphokinase IU/ Humoral immunity in Guamanians with L. EMG demonstrated normal motor and case, however, the latter patient had nigral amyotrophic lateral sclerosis and parkinson- sensory conduction velocities, fibrillation and depigmentation and many NFTs. These ism-dementia. Ann Neurol 1981;10:193-6. fasciculation potentials and positive sharp changes could be due to the more protracted 6 Kurtzke JF, Beebe GW. Epidemiology of course of his illness which spanned over 12 amyotrophic lateral sclerosis: 1. A case-con- waves. Voluntary units were generally small trol comparison based on ALS death. in amplitude and there was gross excess of years. Neurology 1980;30:453-62. long duration polyphasic units with either a Our patient was HLA Bw 35 antigen 7 Hoigne R, Hopf B, Sonntag R. Penicillins, full or slightly reduced interference pattern in positive. The incidence of this HLA antigen cephalosporins and tetracycline. In: Dukes MNG, ed. Meyler's side effects of drugs. 9th all muscles tested. The findings were consis- was found to be significantly increased in ed, Oxford: Excerpta Medica, 1980:418-9. tent with the diagnosis of ALS. patients with Guamanian type ALS.' 8 Gale AN. Insect-sting encephalopathy. Br Med The patient's condition continued to There was a history of concussion and a J 1982;284:20-1. road traffic accident in our patient 17 and 13 9 Schoene WC, Carpenter S, Behan PO, Gesch- deteriorate gradually until he died from bron- wind N. "Onion bulb" formation in the chopneumonia seven years after the onset of years before clinical presentation with ALS. central and peripheral nervous system in his symptoms. At necropsy on naked-eye Although a history of mechanical trauma or association with multiple sclerosis and hyper- examination there was obvious atrophy of surgical operations was found to be two to trophic polyneuropathy. Brain 1977;100: 755-73. virtually all the skeletal muscles. The fresh three times more common in patients with 10 Goldstein NP, Rucker W, Woltman HW. brain was externally normal. The spinal cord MND than in matched controls,6 it is unlikely Neuritis occuring after insect stings. JAMA showed extreme atrophy of the ventral roots that trauma had played an important role in 1960;173:1727-30. this patient because of the long latent period 11 Wolfgang JS, Graeber MB, Kreutzberg GW. at all levels but there were no abnormalities Peripheral nerve lesion produces increased externally. Histological examination of between his injuries and the onset of ALS. levels of MHC antigens in the CNS. J numerous skeletal muscles and of the tongue ALS in our patient was preceded by a Neuroimmunol 1989;21:117-23. revealed partial denervation. Sections from bizarre intermittent illness which at the the cerebral hemispheres, from all levels of beginning was thought to be psychiatric in the brain stem and from the spinal cord origin. However, the patient did not have a showed poor myelination of the cortical, past or family history of psychiatric disease pontine and cortico-spinal bundles and some nor did he have a personality disorder. Fur- reduction in anterior horn cells. There was no thermore, these symptoms did not respond neuronal abnormality in the basal ganglia. to adequate psychiatric measures including Multiple sections from the cerebral cortex treatment with anxiolytics, breathing into a and various levels of the spinal cord did not paper bag and psychotherapy. The patient's show neurofibrillary tangles or senile symptoms were therefore almost certainly plaques. The findings were typical of ALS. organic in nature and are probably a hyper- Fatigue and melatonin in Parkinson's There was severe haemorrhagic broncho- sensitivity reaction to penicillin. In fact, disease pneumonia and bronchitis but no abnor- intermittent symptoms lasting weeks or malities in other organs. months which are similar to those in our Fatigue is a major, although often neglected Our patient had undisputed generalised patient occasionally result from penicillin symptom of Parkinsonism. This is influenced ALS. The clinical course was chronic and hypersensitivity7 and they are known as to some extent by circadian factors, including progressive and was characterised by features pseudoallergic reactions or Hoigne's syn- sleep benefit, diurnal changes in levodopa of pseudobulbar palsy, a combination of drome. Our patient almost certainly had metabolism, dopamine receptor sensitivity, upper and lower motor neuron signs, wide- Hoigne's syndrome which was followed by and monoamine oxidase activity.' spread fasciculations and the absence of sen- ALS two to three months later. In normal subjects, one of many factors sory signs. The EMG was diagnostic of ALS The association between MND and ana- that influences fatigue may be changes in and the necropsy findings were typical of this phylaxis has not been reported before. melatonin rhythmicity.2 The use in Parkin- condition. However, we are aware of another patient son's disease of the decarboxylase inhibitor Interestingly, the patient resided in Guam who had developed ALS shortly following a benserazide, which reduces 5-hydroxytryp- for one year seven years before the onset ofhis severe anaphylactic shock (J Lewis, personal tamine and melatonin concentration in the http://jnnp.bmj.com/ symptoms. The clinical course of his illness communication). Other neurological disor- rodent pineal3 may therefore indirectly affect was that of "pure" ALS without features of ders are sometimes precipitated by hypersen- fatigue mechanisms. We have investigated Parkinsonism or dementia. This is compat- sitivity reactions. Gale reported two cases of Parkinsonian disability, plasma melatonin ible with the diagnosis of Guam type ALS as extrapyramidal disease following insect levels and urinary 6-hydroxy melatonin sul- the latter is clinically indistinguishable from stings.8 Demyelinating diseases9 and peri- phate (aMT6s) as an index of the evening ALS occurring elsewhere in the world.' Al- pheral neuritis'" have also been reported melatonin rise in untreated subjects and fol- though the pathological features of ALS on following anaphylactic reactions. Like lowing levodopa and benserazide treatment. Guam frequently consist of diffuse neuronal trauma, anaphylaxis might trigger ALS or Eighteen subjects with idiopathic Parkin- loss and neurofibrillary tangles (NFTs) in the alternatively, accelerate the progression of son's disease were studied, 11 males, seven on October 5, 2021 by guest. Protected copyright. cerebrum (especially the hippocampus) and latent disease. A recent study has demon- females, aged 42-81 (mean 64 years) with a cerebellum, in addition to degeneration of strated that non-specific injury outside the mean duration of symptoms of nine years motor neurons and pyramidal tracts, CNS, for example, transection ofa peripheral (range 2-28). None had on/off fluctuations. neuronal loss and the presence of NFTs are nerve, induces strong expression of MHC Twelve had a stable r.esponse across the day, not a sine qua non for the diagnosis of this class 1 and to a lesser extent class 2 antigens in six progressive fatigue. Six subjects were condition. In a recent study2 NFTs and CNS neurons." One can postulate a similar studied untreated and one week following neuronal loss in the hippocampus were found mechanism for the role of anaphylaxis in benserazide 50 mg orally four times daily, the in only 46% of patients with Guamanian ALS. remainder taking- levodopa 2 g daily (n = 5); ALS, whilst 4% of these patients exhibited P 0 BEHAN and levodopa 1700 mg daily plus benserazide A M 0 BAKHEIT 380 mg daily (n = 7). motor neuron and cortico-spinal tract degen- Glasgow University Department ofNeurology, eration only. The absence of NFTs and Institute of Neurological Sciences, Samples for plasma melatonin assay were neuronal loss therefore does not preclude the Southern General Hospital, obtained by indwelling venous catheters at diagnosis of Guamanian ALS in our patient. Glasgow G51 4TF three hourly intervals over a 24 hour period. Furthermore, the diagnostic significance of Four, six hourly consecutive urinary collec- NFTs in Guamanian ALS is not clear since tions were carried out during the same 24 these are present in 56-69% ofthe apparently hour period. Plasma melatonin concentration healthy indigenous population of Guam.3 1 Tandan R, Bradley WG. Amyotrophic lateral and urinary 6-hydroxy-melatonin sulphate sclerosis: Part 1. Clinical features, pathology as An environmental risk factor(s) for and ethical issues in management. Ann Neurol was assayed by radioimmunoassay des- developing Guamanian ALS has long been 1985;18:271-80. cribed by Fraser et alt and Arendt et al ' suspected and is supported by the dramatic 2 Rodgers-Johnson P, Garruto RM, Yanagihara respectively. R, et al. Amyotrophic lateral sclerosis and Peak melatonin concentrations in recent change in the incidence of ALS on parkinsonism-dementia on Guam: A 30 year plasma Guam with Westernisation.2 It is possible evaluation of clinical and neuropathologic six untreated subjects with Parkinson's that such an environmental factor had played trends. Neurology 1986;36:7-13. disease showed wide interindividual variation 92 Letters to the Editor

(range 29-65 pg/ml). Benserazide 200 mg and radiological improvement with cortico- J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.1.91 on 1 January 1991. Downloaded from orally did not reduce mean peak plasma steroids is nonspecific and there may con- melatonin levels or alter urinary aMT6s tinue to be a need to recourse to biopsy in excretion. Peak levels and time of peak level cases of this type. were similar to values in normal, healthy BRF LECKY young laboratory staff. Mean peak plasma Department ofNeurology N JEYAGOPAL melatonin levels and mean urinary aMT6s ETS SMITH excretion were slightly lower in levodopa- Department ofNeuroradiology benserazide treated than in untreated PM FOY Department ofNeurosurgery patients with Parkinson's disease (p > 0 1). Walton Hospital, Liverpool Parkinsonian disability scores (King's College rating scale), presence or absence of diurnal fatigue, peak plasma melatonin and Correspondence to: Dr Lecky, Regional Depart- ment of Neurology, Walton Hospital, Liverpool urinary aMT6s concentrations showed no L9 1AE, UK. significant correlation. The pineal gland from three patients (91 and 70 year old females, 78 year old male) 1 Van der Velden M, Bots GTAM, Endtz LJ. with Lewy body associated Parkinson's dis- Cranial CT in multiple sclerosis showing a ease, treated with levodopa-decarboxylase mass effect. Surg Neurol 1979;12:307-10. inhibitor combinations, were examined 2 Sagar HJ, Warlow CP, Sheldon PWE, Esiri Pineal histopathology was MM. Multiple sclerosis with clinical and microscopically. radiological features of cerebral tumour. unremarkable, with cells containing brown Figure Contrast enhanced CT scan showing enhancing lesions. JNeurol Neurosurg Psychiatry 1982;45:802-8. se-cretory granules; there were no intracyto- multiple ring-like 3 Gutling E, Landis T. CT ring sign imitating plasmic Lewy bodies. tumour, disclosed as multiple sclerosis by MRI: A Case Report. J Neurol Neurosurg Plasma melatonin and urinary 6-hydroxy Psychiatry 1989;52:903-6. melatonin sulphate concentrations in 4 Morimoto T, Nagan H, Sano N, et al. A case of untreated and levodopa-decarboxylase multiple sclerosis with multi ring-like and inhibitor treated subjects with Parkinson's butterfly-like enhancement on computerised disease are within the normal range as deter- een months previously she had developed tomography. Brain Dev 1955;7:43-5. mined in normal healthy young subjects, and paraesthesia and numbness of the right face it is worth noting that the pineal structure is and arm, with incomplete recovery and four normal in Parkinsonian patients. Therefore months previously blurring of vision of the benserazide inhibits melatonin synthesis in left eye with complete recovery. the rodent but not in humans with the Abnormal findings were an ataxic gait, conventional doses used in the treatment of VAR 6/18, bilateral optic disc pallor and Parkinson's disease. ataxia ofthe right limbs with an extensor right PHS CRITCHLEY plantar response. Visual evoked responses Atypical meningitis complicating a GP MALCOLM showed considerably prolonged latencies penetrating head injury PN MALCOLM from each eye. Cranial CT showed a small left WR GIBB was treated bacterial genus bacillus contains J ARENDT* frontal enhancing lesion. She The JD PARKES with high dose intravenous methylpredniso- predominantly saprophytic organisms with University Department ofNeurology, lone with marked improvement. low pathogenicity for humans with the excep- King's College School ofMedicine and Dentistry, She was re-admitted ten months later with tion of the anthrax bacillus. These organisms and Institute ofPsychiatry, London Department ofBiochemistry,* a five month history ofincreasing ataxia, right may rarely be responsible for serious local (Division of Clinical Biochemistry), hemiparesis and expressive speech difficulty. and disseminated infections with a significant University of Guildford, Surrey. Examination showed expressive dysphasia mortality. To our knowledge there have been and dysarthria. There was moderate impair- only 11 documented cases in which bacillus Correspondence to: Dr GP Malcolm, c/o Professor ment of cognitive function. Visual acuities subtilis has been implicated in such infections. Symon, Institute of Neurology, National Hospital were 6/60. There was a bilateral internuclear We present a previously unrecorded compli- for Nervous Diseases, Queen Square, London WC1N 3BG, UK ophthalmoplegia and right facial weakness. cation of a penetrating head injury in which a http://jnnp.bmj.com/ The right hemiparesis was severe and joint patient survived a self-inflicted crossbow bolt position sense was absent in the right foot. injury but developed a meningitis secondary 1 Marsden CD, Parkes JD. "On and Off"; Cranial CT showed multiple ring enhancing to the introduction of bacillus subtilis spores variability and response swings in Parkinson's disease. In: Clifford-Rose F, Capildeo R, eds. lesions (fig). The lumbar cerebrospinal fluid from the bolt itself. Research progress in Parkinson's disease. (CSF) pressure was 33 cms of water and the A 24 year old man with a long history of (Progress in Neurology series). London: Pit- CSF protein was elevated at 64 mg/100 ml depressive illness and drug abuse was admit- man Medical, 1981:265-74. with on immunofixation. ted having been found in his bathroom with a 2 Arendt J, Bojkowski C, Folkard S, et al. Some equivocal results effects of melatonin and the control of its CSF contained 5 WBC per mm3, mostly crossbow by his side and a crossbow bolt secretion in humans. In: Photoperiodism, lymphocytes. An HIV antibody test was protruding from his left temporal region. On on October 5, 2021 by guest. Protected copyright. melatonin, and the pineal (Ciba Foundation negative. examination he was conscious and orientated Symposium). London: Pitman, 1985: vol 117, 266-83. There was rapid deterioration with drowsi- with no focal neurological signs and the flight 3 Arendt J, Ho AK, Laud C, et al. Differential ness, dysphagia and weakness of the left arm. feathers of the bolt were visible in the left effect of benserazide (Ro4-4602) on the con- Because of doubt about the radiological diag- temporal region. Skull radiographs showed centration on indoleamines in rat pineal and in midline hypothalamus. Br JPharmac 1981;72:157-62. nosis, and the rarity of dysphasia in multiple the metal tip of the bolt lying the 4 Fraser S, Cowen P, Franklin M, Franey C, sclerosis, a CT guided biopsy of the left (fig la). Arendt J. Direct radioimmunoassay for frontal lobe was carried out. The histology The bolt was removed by a left temporal melatonin in plasma. Clin Chem 1983;29: showed and no evidence of craniectomy with a perioperative dose of a 396-7. demyelination 5 Arendt J, Bojkowski C, Franey C, Wright J, malignancy. She was treated with high dose broad spectrum antibiotic. The entry point Marks V. Immunoassay of 6-hydroxy- intravenous methylprednisolone for five days was anterior to the left middle meningeal melatonin sulphate in human plasma and and cyclosporin 10 mg/kg for five months artery and the tract was fully explored and urine: Abolition of the urinary 24-hour rhythm with atenolol. J Clin Endocrin Metab with marked improvement. Six months later irrigated. The immediate post-operative 1985;60: 1166-73. speech and limb power were normal and she period was uneventful. On the fifth post- was able to stand and walk a few steps with operative day the patient developed a pyrexia assistance. The CT appearances improved. but with no evidence of meningism. Lumbar Enhancing lesions with mass effect have puncture showed no evidence oforganisms, a previously been reported in multiple sclero- polymorph count of 180/ml, a lymphocyte Cerebral CT lesions in multiple sclero- SiS.1-3 We are aware of only two reports of count of 10/ml, a red cell count of 5000/ml, a sis mimicking multiple metastases multiple lesions of this type24 and the florid protein level of 4700 mg/l with a marked radiological appearance in our case seems globulin increase, and a cerebrospinal fluid A 38 year old right handed woman was exceptional. The radiological differential (CSF) glucose of 3-8 mmol/l. Computerised admitted with blurred vision of the right eye diagnoses include abscesses, tumours and tomography (CT) scan showed the bolt tract and incoordination of the right limbs. Eight- vascular lesions. The short term clinical extending to the frontal horn ofthe left lateral