412 J Neurol Neurosurg Psychiatry 2001;71:412–418 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.71.3.412 on 1 September 2001. Downloaded from cell, antithryroid, antigliadin, and anti- the basal ganglia and thalami. Immunohisto- endomysial antibodies, serum electrophore- chemistry for prion protein (PRP KG9 LETTERS TO sis, immunoglobulins, bone marrow aspirate, 1:150, monoclonal antibody, courtesy of the and trephine. Several EEGs showed diVuse CJD surveillance centre in Edinburgh) THE EDITOR slowing of background rhythms. showed prominent staining in the plaques Postmortem neuropathological and histo- and diVusely in the neuropil of cerebral and logical examination confirmed the diagnosis cerebellar cortices. The olfactory tract of vCJD. In addition, there was evidence of showed prominent and diVuse staining for bronchopneumonia. Sections of brain (brain prion protein (PrP) associated with vacuola- New variant Creutzfeldt-Jakob disease weight 1322 g) showed extensive tissue tion (fig 1). presenting with loss of taste and smell involvement with prominent neuronal loss, It is diYcult to determine the precise cause astrocytosis, spongiform change, and numer- of our patient’s olfactory and gustatory Abnormalities of smell and taste have been ous Kuru-type plaques, including florid dysfunction. There were significant his- described in some neurodegenerative dis- plaques. These changes were seen in the cor- topathological changes in the basal forebrain eases including Alzheimer’s dementia, idio- tices of frontal, parietal, temporal, and where both taste and smell are represented.2 pathic Parkinson’s disease, Huntington’s cho- occipital lobes, basal ganglia, thalami, periv- Deposits of prion were, however, also found rea, KorsakoV’s syndrome, Pick’s disease, the entricular grey matter, brain stem, olfactory in many other parts of the brain involved in parkinsonian dementia complex of Guam, areas of the cerebrum, and the cerebellar cor- the neural processing of these senses. and amyotrophic lateral sclerosis.1 Hyposmia tex. Spongiform change and plaques were Changes were particularly prominent in the and hypogeusia are a feature of normal aging most prominent in the cortical regions and olfactory tract. Our patient illustrates that our but they have not been recorded as a promi- cerebellum. Plaques were particularly dense understanding of the clinical range of vCJD nent early feature in previous reports of vari- in the molecular and granular layers of the remains incomplete. Loss of taste and smell ant Creutzfeldt-Jakob disease (vCJD).2–5 We cerebellar cortex. Neuronal loss, gliosis, and are not at all specific to vCJD. These describe a patient with vCJD whose first spongiform change were most conspicuous in symptoms can have many causes including symptoms included deficits of taste and smell. At the time of his initial neurological assessment, this 54 year old ceramic tiler had a 12 month history of loss of taste and smell, anxiety, low mood, and unusually short tem- per. He first became aware that something was wrong when he lost the ability to diVerentiate the taste of tea from that of beer. Loss of taste and personality change pro- gressed gradually. He began to crave vanilla ice cream although he had never liked sweet foods in the past. He became fearful of leav- ing his house. Six months into his illness he became increasingly sleepy. On average he copyright. would sleep for 12 hours a day although he could sleep for 20 hours at a time. He devel- oped slurred speech, unsteady gait, upper limb tremor, and impotence. Neither the patient nor his wife noticed any change in his memory. On examination the patient had scanning dysarthria. His abbreviated mini mental test score was 7/10 (unable to remember an address, give his age, or name the year). He had a staring look with limitation of upgaze. Limb tone was increased with brisk tendon reflexes, ankle clonus, and bilaterally extensor http://jnnp.bmj.com/ plantar responses. There was mild upper limb ataxia and severe ataxia of gait. Although spi- nothalamic sensation was intact, joint posi- tion sense was impaired in both lower limbs. Olfactory testing disclosed evidence of im- paired smell detection and recognition. The patient thought that he could smell some- thing when tested with lavender and tar essence but was unable to recognise or on September 26, 2021 by guest. Protected describe the smell. Over the next 4 months the patient deteriorated rapidly with progressive ataxia, confusion, and agitation. He developed myo- clonic jerks 2 weeks before dying of bron- chopneumonia 16 months after the onset of his first symptoms. Our investigations in vivo supported a diagnosis of vCJD (suggestion of high signal within the thalamus on T2 weighted cranial MRI, negative immunoassay for 14–3–3 pro- tein but raised S100b protein in the CSF (0.91 ng/ml, reference range <0.38 ng/ml), no known mutations in the prion protein gene, methionine homozygous at codon 129). DiVerential diagnoses were excluded by nor- mal or negative full blood count, erythrocyte Figure 1 Bottom: normal (control) olfactory tract of a 61 year old man showing no prion protein sedimentation rate, B12, folate, thyroid func- (PrP) deposition after immunostaining with PrP.Top:olfactory tract showing vacuolation and tion tests, treponemal serology, antinuclear prominent diVuse staining for PrP.PrP plaques and spongioform changes were also found in other factors, glucose, antineuronal, antiPurkinje parts of the olfactory system, the cortex, basal ganglia, cerebellum, and brain stem. www.jnnp.com J Neurol Neurosurg Psychiatry 2001;71:412–418 413 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.71.3.412 on 1 September 2001. Downloaded from other neurodegenerative disorders. However, subjects, in addition to normal healthy Although according to the classic literature the diagnosis of vCJD should be considered if control subjects. the patients with writer’s cramp often have hypogeusia and hyposmia are accompanied Twelve consecutive patients with writer’s obsessive personality features,2 the present by changes of personality and other, more cramp who visited the dystonia outpatient study is the first to confirm the clinical find- “typical” features of vCJD. clinic of the Department of Neurology at ing using objective psychometric measures. M REUBER Kyoto University from May 1998 to Decem- The disease control group consisted of A S N AL-DIN ber 1998, were evaluated with the Yale- patients with peripheral nerve lesions, who Department of Neurology, Pinderfields General Brown obsessive-compulsive scale (Y- had discomfort in writing comparable with Hospital, Aberford Road, Wakefield WF1 4DG, UK BOCS). All patients had been treated with the patients with writer’s cramp in this study, 3 A BABORIE muscle aVerent block for more than 3 who were treated with muscle aVerent block. 3 A CHAKRABARTY months. As a consequence, their writing dis- Thus the current result does not support the Department of Neuropathology, General Infirmary at abilities were moderately improved. All of idea that physical distress and social disability Leeds, Great George Street, Leeds LS1 3EX, UK them could write their names in four to six due to writing impairment is the main cause Correspondence to: Dr A S N Al-Din Chinese characters at the time of assessment. of the obsessive-compulsive features of pa- A disease control group consisted of seven tients with writer’s cramp, but supports the patients with carpal tunnel syndrome, three notion that writer’s cramp and obsessive- 1 Mesholam RI, Moberg PJ, Mahr RN, et al. compulsive symptoms would develop due to Olfaction in neurodegenerative disease: a meta- with cervical spondylotic radiculopathy, one analysis of olfactory functioning in Alzheimer’s with chronic inflammatory demyelinating common pathophysiological mechanisms. and Parkinson’s diseases. Arch Neurol polyneuropathy, and one with myasthenia However, it should be noted that our patients 1998;55:84–90. gravis. All these patients showed disabilities with writer’s cramp had been under the treat- 2 SchiVman SS. Taste and smell losses in normal ment for more than 3 months and the aging and disease. JAMA 1997;278:1357–62. in finger movements due to peripheral nerve 3 Will RG, Zeidler M, Stewart GE, et al. Diagno- lesions of an upper limb, and were recruited duration of disease was relatively short. In sis of new variant Creutzfeldt-Jakob disease. from the outpatient clinic of the Department most cases of writer’s cramp without treat- Ann Neurol 2000;47:575–82. ment, it is known that writing disability is 4 Allroggen H, Dennis G, Abbott RJ, et al.New of Neurology at Kyoto University. A healthy variant Creutzfeldt-Jakob disease: three case control group, age and sex matched to the extremely severe, causing a significant eVect reports from Leicestershire. J Neurol Neurosurg writer’s cramp group, consisted of oYce on their lifestyle. The present result does not Psychiatry 2000;68:375–8. clerks or secretaries of Kyoto University and deny the possibility that the condition could 5 Zeidler M, Stewart GE, Barraclough CR, et al. cause abnormal psychopathology in writer’s New variant Creutzfeldt-Jakob disease: neuro- Shiga University. None of the subjects had logical features and diagnostic tests. Lancet received antidepressive or neuroleptic medi- cramp. 1997;350:903–7. cation for at least 6 months before the study. Recent studies reported abnormal meta- None of the subjects had a history of any psy- bolic activity in basal ganglia together with frontal