Letters to the Editor

transfusion at the age of 32. Sclerosingtreatment had been performed twice foroesophageal varices. She had had noepisodes suggestive of cerebral haemorrhageor hepatic encephalopathy.

Neurological examination was normal.She had no mental impairment orextrapyramidal signs. Ti weighted MRI ofthe brain showed symmetric high signalintensity in the globus pallidus, subthala-mus, cerebral peduncle, substantia nigra,and the periaqueductal region of the mesen-cephalic and upper pontine tegmentum(figure). T2 weighted MRI and brain CTwere normal. Abnormal data in routinelaboratory tests included erythrocyte sedi-mentation rate 44 mm/hour, red bloodcell count 3 240 000/mm3, white bloodcell count 2 200/mm3, and platelets64000/mm3, packed cell volume 27%,haemoglobin 8-8 g/dl, total bilirubin 1-7mg/dl, and raised values in other liver func-tion tests. A test for antihepatitis C virusantibody was positive. Metals in serum were(normal range in parenthesis) iron 45(56-117) ,ug/dl, unsaturated iron bindingcapacity 416 (150-336),g/dl, copper 148(103-159),ug/dl, zinc 48 (61-121) ,ug/dl,and manganese 0 55 (0 1-0 27) ,ug/dI.Whole blood contained 8-33 (0A4-2 0) ,ugmanganese/dl. The patient's orbital paindisappeared spontaneously. She was givenferrous sulphate (320 mg per day), and wasrecommended to avoid manganese richfoods.

Hyperintensity in Ti weighted MRI inthe basal ganglia and in the midbrain teg-mentum was the characteristic MRI findingin our patient. An increased lipid, melanin,and methaemoglobin concentration, orcalcified tissues, and ectopic Schwann cellsin neurofibromatosis may cause similar

MRI changes.4' In our patient, the possibil-ities of raised methaemoglobin, calcifiedlesions, or ectopic Schwann cells were ruledout by normal CTs, no stigmata of neurofi-bromatosis, and no history of stroke.Symmetric hyperintensity of basal ganglia inTI weighted MRI has been reported inpatients with chronic liver diseases andpossible manganese intoxication.2'67 Pujolet al2 reported that on Ti weighted MRI,33 of 45 patients with advanced liver dys-function had symmetric high signal intensityin the globus pallidus. In seven of 11patients who had liver transplants, MRIabnormalities decreased, and disappeared infour patients, suggesting a direct linkagebetween MRI findings and liver dysfunc-tion. Manganese shortens spin lattice relax-ation times via its paramagnetism andincreases signal intensity on TI weightedMRI.3 The high manganese concentrationin whole blood in our patient suggested thatthe changes on MRI may reflect manganeseaccumulation, as postulated in chronichepatopathy.7 Ti hyperintense lesions inthe basal ganglia have not been reported inpatients with Hallervorden-Spatz orWilson's diseases, which result in iron orcopper deposition in the brain, especially inthe basal ganglia.8'" Therefore, we postu-late that the hyperintensity in Ti weightedimages may represent an alteration resultingfrom an accumulation of paramagnetic sub-stances such as manganese, but not suchnon-specific changes as cell loss, necrosis,or glial proliferation. In iron deficiencyanaemia the enteric absorption of iron andmanganese is increased." Thus in ourpatient iron deficiency may have enhancedmanganese absorption, whereas liver dys-function may have resulted in the reductionof manganese excretion.

Axial and coronal Ti weightedMRI (TR 500 ms, TE 15 ms) showing high signal intensity in thebasal ganglia and periaqueductal region of the upper brain stem (arrow).

Several experimental and clinicopatho-logical studies on manganese intoxicationemphasised vulnerability of the basal gan-glia, especially the globus pallidus."l' Thepresent patient showed TI high signalintensity in the tegmentum of the upperbrain stem as well as changes in the basalganglia. The pattern of distribution wasalmost identical to that seen in our previouspatient with manganese intoxication duringtotal parenteral nutrition.6 These two find-ings suggest that the basal ganglia and theperiaqueductal structures in the tegmentumof the upper brainstem may have commonmetabolic characteristics with respect tocertain trace metals.

HIROSHI SAITOAKIKO EJIMA

Department ofNeurology,National Nishitaga Hospital and Department of

Neurology,Institute ofBrain Diseases, Tohoku University

School ofMedicine,1-1 Seiryo-machi, Aoba-ku, Sendai, 980_Japan

Correspondence to: Dr H Saito, Department ofNeurology, National Nishitaga Hospital, 2-11-11Kagitori-honchou, Taihaku-ku, Sendai 982,Japan.

1 Papavasiliou PS, Miller ST, Gotzias GC. Roleof liver in regulating distribution and excre-tion of manganese. Am J Physiol 1966;211:211-16.

2 Pujol A, Graus F, Peri J, Mercader JM,Rimola A. Hyperintensity in the globuspallidus on TI-weighted and inversion-recovery MRI: a possible marker ofadvanced liver disease. Neurology 1991;41:1526-7.

3 Newland MC, Ceckler TL, Kordower JH,Weiss B. Visualizing manganese in the pri-mate basal ganglia with magnetic resonanceimaging. Exp Neurol 1989;106:251-8.

4 Henkelman RM, Watts JF, Kucharczyk W.High signal intensity in MR images of car-cified brain tissue. Neuroradiology 1991;179:199-206.

5 Mirowitz SA, Sartor K, Gado M. High-intensity basal ganglia lesions on Ti-weighted MR images in neurofibromatosis.AJ7NRAmJNeuroradiol 1989;10:1159-63.

6 Ejima A, Imamura T, Nakamura S, Saito H,Matsumoto K, Momono S. Manganeseintoxication during total parenteral nutri-tion. Lancet 1992;339:426.

7 Inoue E, Hori S, Narumi Y, Fujita M,Kuriyama K, Kadota T, Kuroda C. Portal-systemic encephalopathy: Presence of basalganglia lesions with high signal intensity onMR images. Radiology 1991;179:551-5.

8 Cumings JN. Trace metals in the brain and inWilson's disease. J Clin Pathol 1968;21:1-7.

9 Starosta-Rubenstein S, Young AB, Kluin K,Hills G, Aisen AM, Gabrielsen T, BrewerGJ. Clinical assessment of 31 patients withWilson's disease. Arch Neurol 1987;44:365-70.

10 Schaffert DA, Johnsen S, Johnson PC, DrayerBP. Magnetic resonance imaging in patho-logically proven Hallervorden-Spatz disease.Neurology 1989;39:440-2.

11 Mena I, Horiuchi K, Burke K, Cotzias GC.Chronic manganese poisoning: Individualsusceptibility and absorption of iron.Neurology 1969;19:1000-6.

Transient amnestic syndrome afterspontaneous haemorrhage into a hypo-thalamic pilocytic astrocytoma

The aetiology of the syndrome of transientglobal amnesia is unknown.' 2 A relationwith migraine has been proposed and in acase-controlled series, no association wasfound with cerebrovascular disease, but 7%of patients developed epilepsy within oneyear of their first attack.' Controversy existsas to the relation between tumours or struc-tural brain lesions and transient globalamnesia, and in the reported cases the

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(A) CT of the head without contrast obtained 48 hours after clinical recognition of the patient'sacute problem. This shows an area of increased attenuation within the hypothalamus. (B) sagittaland (C) coronal Tl weighted MRI without contrast. These images show an expansile mass centredin the right hypothalamus which extends across the midline and obliterates the floor of the thirdventricle. The mass has a moderately hypointense central portion, and a hyperintense rim.Incidental note is made of a slightly enlarged "partially empty sella" with the pituitary gland havinga concave margin. (D) haematoxylin and eosin stain ( x 60) of the biopsy specimen showing a

biphasic cellular pattern, granule bodies (arrow), and pilloid appearance consistent with a pilocysticastrocytoma.

importance of epilepsy in the pathogenesishas been understated.34 We report a case ofspontaneous haemorrhage into a hypothala-mic pilocytic astrocytoma, presenting withan episode with clinical features suggestiveof transient global amnesia.A 58 year old previously healthy white

woman was found by her husband early one

morning acting strangely. She recognisedher husband, and was not impaired physi-cally or in speech. He described her as look-ing "puzzled," but she was not delayed inher responses, and had normal comprehen-sion to simple commands. She seemedunable to recall the answers given to her lessthan a minute previously, and repetitivelyasked questions such as "what day is it,""where are the kids," and "where are we

going?" There was no abnormal posturingor laughing. By late afternoon she was

slowly improving and by the next morningher memory deficit had resolved, but shewas completely amnestic for the precedingday. She presented for review to her familyphysician the next day, and her examinationwas reported to be normal. A cranial CTshowed a 2-5 cm area of increased attenua-

tion in the hypothalamus, without contrastenhancement (figure (A)). Cranial MRIshowed an expansile mass within the medialaspect of the right hypothalamus, displacingthe third ventricle from right to left, and theoptic chiasm inferiorly (figure (B and C)).This mass had mildly decreased signal

intensity on T 1 weighted images and pro-

foundly decreased signal intensity on T2weighted images consistent with acute

haemorrhage. Carotid angiography was nor-

mal. An open biopsy of the lesion was per-

formed via a subfrontal approach at anotherinstitution. After the operation she hadshort term memory impairment, and shewas referred to our institution for furtherevaluation and treatment recommendations.Review of the histopathology showed a pilo-cytic astrocytoma (figure (D)). The postop-erative memory deficit has shown onlyslight improvement at 12 months follow up.

Subsequent cranial MRI and CT have beenconsistent with resolving haemorrhage.There have been no further transient neuro-

logical episodes suggestive of complex par-

tial or other seizures.Caplan has defined the following strict

criteria for the diagnosis of transient globalamnesia3; (a) the attack onset should havebeen witnessed; (b) dysfunction during theattack should have been limited to repetitivequeries and amnesia; (c) there should havebeen no other major neurological signs or

symptoms; and (d) the memory loss shouldhave been transient, usually lasting hours or

up to one day. The onset of the episode inour patient cannot, however, be reliablydetermined, as the patient either awokefrom sleep with the amnesia or developed itsoon after awakening. This is a not uncom-

mon finding in patients with presumed

transient global amnesia. In the series byMiller et al 2 20 of the 347 episodes oftransient global amnesia were first noted onawakening.

In our patient, the first neurological man-ifestation was a transient global amnesia-like episode, with complete resolutionwithin the time course normally seen withtransient global amnesia. Previous reportsof transient global amnesia in associationwith tumours have been comprehensivelyreviewed by Caplan,34 with reports of pri-mary or secondary tumours involving thetemporal lobe, thalamic region, and in onereport a very large tumour diffusely involv-ing the anterior nucleus of the thalamus andfornix. The mechanism of transient amnes-tic episodes in these patients is uncertain.An epileptic mechanism seems likely inmany cases, with involvement of temporallobe structures, and some of these reportedcases had clear epileptic features with theamnestic event, later developed epilepsy,had focal neurological signs at presentation,or developed focal neurological signs beforethe memory loss resolved. "Transienttumour attacks" may occur in patients withintracranial tumours, and investigations forepilepsy or a vascular cause are often nega-tive.5 One of the cases described by Rosshad features suggestive of transient globalamnesia, but had a right superior homony-mous hemianopia due to a left temporallobe neoplasm.5 The aetiology of the cere-bral disturbance causing the amnesiaremains uncertain. In our case, the tempo-ral lobes were not involved, and there wereno other features at presentation or followup to suggest a diagnosis of epilepsy. Therewas clearly an acute event with haemor-rhage into the tumour, and we believe thatthe resultant sudden mass effect andoedema were responsible for the suddentransient global amnesia through pressureon pathways and structures involved inmemory. The proximity of the pilocyticastrocytoma to the mammillary bodies andtheir connections suggests that local pres-sure in this region from oedema related tothe spontaneous haemorrhage may haveaccounted for the memory impairment.Involvement of the fornix could also haveinterrupted cholinergic inputs from themedial septum to the hippocampus, whichmay be potentially important for learningprocesses.By Caplan's more stringent criteria,3 our

case would not be considered to fulfil all theclinical diagnostic criteria for the diagnosisof transient global amnesia. It does, how-ever, resemble the syndrome sufficiently tocause diagnostic confusion. Transientamnesia can have many causes, includingepilepsy,' cerebrovascular disease,3 andthose associated with tumour,3 4 whateverthe mechanism. Before attributing transientamnesia to transient global amnesia, othermore serious causes must be excluded byappropriate investigation.

ERIC J SORENSONPETER L SILBERT

EDUARDO E BENARROCHDepartment of NeurologyCLIFFORD RJACK

Department of Diagnostic RadiologyJOSEPH E PARISI

Department of PathologNy,Mayo Clinic and Mayo Foundation,

Rochester, Minnesota, USA

Correspondence to: Dr EE Benarroch, Depart-ment of Neurology, Mayo Clinic, Rochester,Minnesota 55905, USA.

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1 Hodges JR, Warlow CP. The aetiology oftransient global amnesia: a case-controlstudy of 114 cases with prospective follow-up. Brain 1990;113:639-57.

2 Miller JW, Petersen RC, Metter EJ, MillikanCH, Yanagihara T. Transient global amne-sia: clinical characteristics and prognosis.Neurology 1987;37:733-7.

3 Caplan LR. Transient global amnesia. In:Vinken P, Bruyn G, Klawans HL, eds.Handbook of clinical neurology. Vol 45,Frederiks JAM, ed: Clinical neuropsychology.Amsterdam: Elsevier, 1985:205-18.

4 Caplan LR. Transient global amnesia: criteriaand classification. Neurology 1986;36:441.

5 Ross RT. Transient tumor attacks. ArchNeurol 1983;40:633-6.

Musical hallucinations associated withpost-thyroidectomy hypoparathyroid-ism and symmetric basal ganglia calci-fications

Bilateral symmetric basal ganglia calcifica-tions most often result from parathyroiddisorders and subsequent imbalances incalcium and phosphorus metabolism.Associated neurological and psychopatho-logical symptoms are, however, controver-sial.'

"Musical hallucinations" are usuallydefined as the hearing of tunes andmelodies without relevant external stimuli.They are reported to be very rare comparedwith verbal hallucinations.2A 63 year old, right handed housewife

with a 40 year history of post-thyroidectomyhypoparathyroidism presented with a

chronic progressive syndrome, with musicalhallucinations, mild intellectual impair-ment, and cerebellar ataxia.

She reported having suddenly startedhearing music about five months beforeadmission. The tunes, which were charac-terised by a stomping rhythm ("that terriblemodern pop music"), did not vary much("like a short tune being played all overagain"). The hallucinations occurred con-tinuously during the daytime, when awak-ing at night, or when talking. Insight intothe character of hallucinations was achievedafter initial deception.

Ear examination showed a mild pan-cochlear perceptive hearing loss due to pres-byacusis, more prominent on the left side.Neurolinguistic and neuropsychologicalexaminations failed to show signs of apha-sia, agnosia, visuospatial disorders, orhemispatial neglect. The patient had an IQof 86 on the Hamburg Wechsler intelli-gence test for adults with low scores on ver-bal scales. Verbal and visual short termmemory were impaired slightly, as mea-sured by the Benton visual retention testand Amthauer (IST 70) test indicatingacquired cognitive deficits of the organictype.

Electrophysiological examinations (EEG,topographical EEG, and acoustically andvisually evoked potentials (AEP; VEP)showed no evidence of epileptic activity orconsistent focal activity. P300, AEP, andVEP latencies were in the normal ranges.

Cranial CT showed dense areas of calcifi-cation predominantly involving the basalganglia (for example, pulvinar thalami,

Cranial CT (unenhanced) with bilateral symmetric and confluent calcifications of dentate nucleus ofthe cerebellum, (A, B) pulvinar of thalamus and striatum (caudate nucleus and putamen), (C) andhemispheric white matter (C, D).

striatum), cerebellar dentate nuclei, andperiventricular white matter (figure).

At admission ECG showed massive pro-longation of the Q-T interval (0-48 ms; fre-quency adapted upper limit: 0-36 ms);ECG was normal on the day of discharge.Complete blood count and all routine labo-ratory tests were in the normal ranges,except serum concentrations of calcium onadmission and discharge of 1-45 and 2-48(normal range 2-0-2 75) mM and inorganicphosphorus concentrations of 6-03 and 1-45(normal range: 0-8-1-5) mM. Twenty fourhour urinary calcium excretion rates on theday of admission and discharge were 0 77and 6-17 (normal range: 3 25-8-25) mMand inorganic phosphorus excretion rateswere 7-3 and 21-7 (normal range: 10-32)mM. Intact parathormone was below thedetection limit (<1 pg/ml; normal range:10-60 pg/ml).The patient initially received 1500 mg

Ca2+ and 4 mg dihydrotachysterol orally perday. Three additional intravenous applica-tions of Ca2+ were given to avoid manifesttetany. The hallucinations started to fadeon day 12 of treatment and dihydrotachys-terol was adjusted to 2 mg per day. Threeweeks after admission the patient was freeof hallucinations. Cerebellar symptoms, andsigns of neuromuscular instability(Chvostek's and Trousseau's signs)improved significantly. Tinnitus and milddeafness remained unchanged three monthslater, the patient had no complaints, andher neurological state was normal on themedication described.The disappearance of the musical halluci-

nations coincided with the normalisation ofserum electrolyte balance. Although elec-trolyte disturbances after hypoparathy-roidism have long been known to causeneuropsychiatric symptoms,3 musical hallu-cinations have not been reported.Two basic theories regarding the patho-

genesis of complex auditory hallucinationshave been proposed.The "perceptual release" theory is based

on the pathogenetic role of the sensoryimpairment. Our patient had had a mildprogressive hearing loss associated with tin-nitus. Despite the disappearance of auditoryhallucinations, however, there was noimprovement in hearing and tinnitus. Thisis not compatible with either the persistentnature of otogenic auditory hallucinationsdue to progressive hearing loss, or withtransient hallucinations of acute otopathicorigin, as no acute lesion could be found.Complex auditory phenomena may alsooccur with lesions of the tegmentum of thepons and lower midbrain; however, CT andAEP failed to disclose a brainstem lesion inour patient.

According to the other pathogenetic con-cept, local metabolic dysfunction might leadto a dissociation of circuits in the associa-tion cortex. In our patient, cranial CTshowed that the principal areas of extensivebilateral calcifications included the stria-tum, the pulvinar thalami, and the cerebel-lar dentate nuclei (figure). Calcifications ofthe dentate nuclei are usually thought toresult in cerebellar ataxia. Medial (internal)pallidal efferents are supposed to inhibitthalamocortical neurons, and an increasedthalamocortical drive to lateral orbitofrontaland anterior cingulate cortex due to lesionsnear the pulvinar thalami might lead toauditory hallucinations.4 There is stillconsiderable controversy regarding a link

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