44 Orrell, James-Galton, Stevens, Rossor

Cerebral achromatopsia as a presentation ofTrousseau's syndrome

RichardW Orrell, Merle James-Galton, John M Stevens, Martin N Rossor

St Mary's Hospital,Praed Street, London,UKDepartment ofNeurologyRW OrrellMN RossorDepartment ofNeuroradiologyJM Stevens

Department ofClinicalNeuropsychology, TheNational Hospital,Queen Square,London, UKM James-Galton

Correspondence toDr RichardW Orrell,Academic Unit ofNeuroscience, Charing CrossHospital, Fulham PalaceRoad, London W6 8RF, UK

Accepted 11 August 1994

SummaryA 67-year-old man developed a suddenonset of achromatopsia. Magnetic reson-ance imaging showed occipital lobeinfarction. Repeated episodes of neuro-logical deficit referable to the posteriorcirculation initially suggested an embolicsource, but subsequently proved to be dueto a coagulopathy related to a carcinomaof the bladder. This has implications forthe management of patients presentingwith achromatopsia, and progressive orrecurrent neurological episodes, and inparticular the use of anticoagulation inthis situation.

Keywords: cerebral achromatopsia, Trousseau's syn-drome, bladder carcinoma, disseminated intravascularcoagulation

Introduction

'Cerebral achromatopsia is a syndrome inwhich the patient loses the ability to see coloursafter cortical damage. This loss may be com-plete or partial, and it may or may not beaccompanied by other visual defects'."2 Wedescribe a case of this unusual but readilyrecognisable clinical syndrome, and its associa-tion with a paraneoplastic coagulopathy.

Case report

A 67-year-old man was travelling as a front seatpassenger in a car when he experienced asudden brilliant flash of white throughout hisvision, followed by a kaleidoscope effect, withcriss-cross lines and bright colours. Theexperience lasted about 20 seconds, and he wasleft with some fogginess of vision, and was onlyable to see images in black and white. Threeweeks previously he had experienced an epi-sode of weakness in the right hand, lasting fortwo days, but otherwise had no previousneurological symptoms. Over a period of twoweeks there was some improvement in hisvision, but persistence of the loss of colourvision.

Eighteen months previously he had present-ed with haematuria. Cystoscopy demonstrateda multifocal transitional cell carcinoma on theleft wall of the bladder which was in the earlyinvasive stage. This was being controlled byrepeated cystoscopy and fulguration. He hadischaemic heart disease, with occasionalangina, had coronary artery by-pass grafting

four years previously, and had been taking300 mg aspirin daily.On examination he appeared well, with a

regular pulse, blood pressure 160/100 mmHgnormal heart sounds, and no carotid bruits.Neurological examination was normal, but forabsent colour vision and a partial righthemianopia. Visual acuity was 6/18 bilaterally.Two weeks after the onset of visual distur-

bance he developed a sudden onset of uppermotor neurone weakness in the right arm andface, with reduced sensation in the right arm,following a bout of heavy coughing. Investiga-tion at this time demonstrated normal fullblood count, erythrocyte sedimentation rate,prothrombin time, serum urea and electrolytes,and glucose. Treponemal serology wasnegative. Chest radiograph was normal. Com-puted tomographic (CT) scan of the brainshowed an area of presumed recent infarctioninvolving the left occipital lobe and posteriorpart of the temporal lobe. Magnetic resonance(MR) scan the next day showed bilateraloccipital lobe infarction, mainly below thecalcarine fissure (see figures). MR angiographyshowed the posterior circulation to be normal,with no evidence of basilar artery thrombosis.Doppler examination of the carotid arteriesshowed a 30% internal carotid stenosis on theright, and 55% on the left. There was noclinical or electrocardiographic evidence of anarrhythmia, and an echocardiogram showed noevidence of a cardiac source of emboli.

NEUROPSYCHOLOGICAL ASSESSMENTA detailed neuropsychological assessment wascarried out at the time of the original visualdeficit. On the Wechsler Adult IntelligenceScale (Revised) he obtained a verbal IQ of 128.3There was no evidence of generalised intellec-tual impairment. Recognition memory for ver-bal material was excellent, he scored in thesuperior range on the Warrington RecognitionMemory for words.4

Test of primary visual function were per-formed. Reading acuity on the Ffookes sym-bols test was 6/18. Shape discrimination waswithin normal limits.5 Shape detection on theVOSP (Visual Object and Space Perception)figure-ground was unimpaired.6 Colour dis-crimination was severely impaired. He wasunable to pick out any numbers on the Ishiharatest. He had great difficulty on the Farnsworth100-Hue test, error score 784.78 There was noevidence of visual disorientation; he was able to

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Cerebral achromatopsia

Figure 1 MRI, 1.5 Tesla, with Gadolinium enhance-ment, showing features of bilateral occipital lobe infarc-tion, more marked on the left

count scattered dots accurately, missing onlythose which fell within his visual field defect.

Tests of higher visual processing from theVOSP6 were performed. He was completelyunable to see any form of a letter on theIncomplete Letter task. His performance onthe Silhouettes test was very poor (4/30). Onthe Progressive Silhouettes test he was slow toidentify the objects even when complete. Healso made errors of identification of simple linedrawings of objects. He showed some degree ofprosopagnosias, being able to identify only 1/12Famous Faces and he complained of difficultyin recognising people.The interpretation ofhis neuropsychological

assessment is that the only elements of corticalblindness present were a severe achromatopsiaand a mild impairment ofacuity. In addition hehad an aperceptive agnosia. The degree ofimpairment of his primary visual processingwas insufficient to account for his poor perfor-mance on tests of visual object processing.

PROGRESSIn view of the recurrent episodes of neuro-logical deficit, which were felt to be possiblyembolic, he was started on an infusion ofheparin at 10 000 units over 24 hours, withcaution because of the haemorrhagic nature ofthe infarct, and his previous haematuria. Theright arm weakness resolved over three days,with a residual mild right facial weakness. Hewas commenced on warfarin anticoagulationwith careful control.Two weeks later, having developed mild

haematuria and having discontinued the war-farin himself, he was found wandering at night,aphasic and agitated. He had a left upper motorfacial weakness, and a progressive left hemi-plegia. He had complete cortical blindness,with small pupils, absent gag reflex, and briskjaw jerk. CT scan at this stage showed extensivebilateral occipital infarction. He was againcommenced on a heparin infusion, and over a

Figure 2 MRI, coronal section of the brain, showingfeatures of bilateral occipital lobe infarction, mainlybelow the calcarine fissure

period of weeks had some recovery of vision inthe left homonymous fields, but remaineddrowsy, and the heparin was discontinued.Within two weeks he developed a deep vein

thrombosis of the right leg, with gangrenousareas in the toes, and as there was somerecovery in his conscious level, heparin wasrecommenced. Within three months of theinitial presentation of visual disturbance hedeveloped significant haematuria, with furtherevidence of disseminated intravascular coagu-lation (DIC). Over a period of one week thecoagulopathy progressed. This failed to re-spond to treatment with platelets and freshfrozen plasma and he died peacefully.Post-mortem examination showed the cause

of death to be a pulmonary embolus, with athrombosed right external iliac vein. There wasa stage 4 bladder carcinoma, invading throughthe bladder wall into the perivesical fat, with aright hydronephrosis and hydroureter. His-tology showed an ulcerated poorly differenti-ated transitional cell carcinoma extending intothe perivesicular fat, and lymphatic channelinvasion. There was no evidence of metastaticspread. On examining the brain, there werebilateral basal occipital infarcts and bilateralparietal infarcts, all being recent, with signs ofcolliquative necrosis. Additional infarcts werepresent in the kidney and spleen, with gang-renous infarction of the right forefoot and toesof the left foot. There was no evidence of anembolic source in the heart or great vessels.

Discussion

Cerebral achromatopsia has been recognisedfor many years, with debate over the existenceof a specific cortical colour centre. Clinicalevidence links the anterior inferior part of theoccipital lobe with colour perception in man.Bilateral lesions at this site may cause achroma-

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46 Orrell, James-Galton, Stevens, Rossor

topsia with preservation of primary visualfunction.9 A unilateral lesion will causehemiachromatopsia. Animal studies, and morerecently functional positron emission tomo-graphy studies in man,'0 have shown an area inthe lingual and fusiform gyri ofman, equivalentto area V4 in the macaque monkey, whichappears to function as a centre for colourvision.' More recently, further experimentalevidence in the monkey has cast doubt on areaV4 being the centre for cortical registration ofcolour. " Monkeys appear to show the oppositepattern of deficit to humans, with preservedcolour discrimination, but impairment ofshapediscrimination.

Cerebral achromatopsia must be distin-guished from other syndromes of impairedcolour vision (see box). The description by thepatient we report, of the world appearing to bein black and white ('as if watching a black andwhite television') is typical. The Farnsworth100-Hue Test7'8 assesses the ordering ofchromatically graded coloured discs, and ischaracteristically abnormal in achromatopsia.The assessment of central achromatopsia canbe especially difficult when the deficit is limitedto a quadrant or hemifield, as it may spare theregions near fixation.'2Most cases ofcerebral achromatopsia are due

to cerebral infarction caused by cerebrovas-cular disease or embolic phenomena,9 and arebilateral, although some cases of homonymoushemiachromatopsia have been reported.'3-'8Cerebral achromatopsia has also been reportedas a rare manifestation of migraine. 9 Fineemboli occluding the penetrating branches ofthe calcarine artery at its termination will causeappropriate infarction, whilst larger emboli,and basilar artery occlusion, lead to preserva-tion of the colour centre of the visual cortex asthe blood supply is preserved by superficialbranches of the posterior and middle cerebralarteries in this area.20 MR angiography wouldappear to be the investigation of choice.The association of thrombosis and cancer is

well recognised, although the precise mechan-isms remain uncertain. Arnand Trousseau first

Impaired colour vision

* achromatopsia = cannot see colour* agnosia = loss of colour knowledge* anomia = inability to name colour

described the association of a thrombotic state,especially a superficial migratory thrombo-phlebitis, with neoplasia in 1865. Morerecently it has been recognised that phlebitis isone ofmany manifestations ofthe coagulopathyassociated with neoplasia.21'22 The cause islikely to be multifactorial, including plateletactivation by the tumour cells, procoagulantproduction by activated macrophages, anddirect tumour cell procoagulant production.23Thrombosis is found in around 150% of all casesof malignancy, especially pancreatic car-

24cinoma.Many patients with a chronic DIC will not

show excessive bleeding, and diffuse throm-bosis may be the only clinical manifestation. Inchronic, or low grade, DIC associated withmalignancy, many laboratory parameters ofhaemostasis may be within normal limits, ordifficult to interpret.24'25 The coagulopathy mayresolve with treatment of the underlyingcancer, especially prostatic carcinoma. Patientswith cancer may be resistant to anticoagulanttherapy, with thrombotic episodes continuing,but warfarin and heparin may have somebenefit on both the laboratory measures of thecoagulopathy, and the clinical features. Themain problem, as in this patient, may bebleeding from the tumour, and also the risk ofintracerebral haemorrhage with pre-existingcerebral lesions. Aspirin and dipyridamolehave been suggested as an alternative for bothprophylaxis of extension of thrombi, and long-term prophylactic therapy.24 Other manifesta-tions of the thrombotic coagulopathy seen inthis patient include infarction ofthe kidney andspleen, digital arterial thrombosis leading togangrene, and deep vein thrombosis with pul-monary embolism.26

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