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New variant Creutzfeldt-Jakob disease presenting with loss of taste and smell
  1. M REUBER,
  2. A S N AL-DIN
  1. Department of Neurology, Pinderfields General Hospital, Aberford Road, Wakefield WF1 4DG, UK
  2. Department of Neuropathology, General Infirmary at Leeds, Great George Street, Leeds LS1 3EX, UK
  1. Dr A S N Al-Din
  1. A BABORIE,
  2. A CHAKRABARTY
  1. Department of Neurology, Pinderfields General Hospital, Aberford Road, Wakefield WF1 4DG, UK
  2. Department of Neuropathology, General Infirmary at Leeds, Great George Street, Leeds LS1 3EX, UK
  1. Dr A S N Al-Din

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Abnormalities of smell and taste have been described in some neurodegenerative diseases including Alzheimer's dementia, idiopathic Parkinson's disease, Huntington's chorea, Korsakoff's syndrome, Pick's disease, the parkinsonian dementia complex of Guam, and amyotrophic lateral sclerosis.1 Hyposmia and hypogeusia are a feature of normal aging but they have not been recorded as a prominent early feature in previous reports of variant Creutzfeldt-Jakob disease (vCJD).2-5 We describe a patient with vCJD whose first 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 temper. He first became aware that something was wrong when he lost the ability to differentiate the taste of tea from that of beer. Loss of taste and personality change progressed gradually. He began to crave vanilla ice cream although he had never liked sweet foods in the past. He became fearful of leaving his house. Six months into his illness he became increasingly sleepy. On average he would sleep for 12 hours a day although he could sleep for 20 hours at a time. He developed 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 plantar responses. There was mild upper limb ataxia and severe ataxia of gait. Although spinothalamic sensation was intact, joint position sense was impaired in both lower limbs. Olfactory testing disclosed evidence of impaired smell detection and recognition. The patient thought that he could smell something when tested with lavender and tar essence but was unable to recognise or describe the smell.

Over the next 4 months the patient deteriorated rapidly with progressive ataxia, confusion, and agitation. He developed myoclonic jerks 2 weeks before dying of bronchopneumonia 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 protein 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). Differential diagnoses were excluded by normal or negative full blood count, erythrocyte sedimentation rate, B12, folate, thyroid function tests, treponemal serology, antinuclear factors, glucose, antineuronal, antiPurkinje cell, antithryroid, antigliadin, and antiendomysial antibodies, serum electrophoresis, immunoglobulins, bone marrow aspirate, and trephine. Several EEGs showed diffuse slowing of background rhythms.

Postmortem neuropathological and histological examination confirmed the diagnosis of vCJD. In addition, there was evidence of bronchopneumonia. Sections of brain (brain weight 1322 g) showed extensive tissue involvement with prominent neuronal loss, astrocytosis, spongiform change, and numerous Kuru-type plaques, including florid plaques. These changes were seen in the cortices of frontal, parietal, temporal, and occipital lobes, basal ganglia, thalami, periventricular grey matter, brain stem, olfactory areas of the cerebrum, and the cerebellar cortex. Spongiform change and plaques were most prominent in the cortical regions and cerebellum. Plaques were particularly dense in the molecular and granular layers of the cerebellar cortex. Neuronal loss, gliosis, and spongiform change were most conspicuous in the basal ganglia and thalami. Immunohistochemistry for prion protein (PRP KG9 1:150, monoclonal antibody, courtesy of the CJD surveillance centre in Edinburgh) showed prominent staining in the plaques and diffusely in the neuropil of cerebral and cerebellar cortices. The olfactory tract showed prominent and diffuse staining for prion protein (PrP) associated with vacuolation (fig 1).

Figure 1

Bottom: normal (control) olfactory tract of a 61 year old man showing no prion protein (PrP) deposition after immunostaining with PrP. Top: olfactory tract showing vacuolation and prominent diffuse staining for PrP. PrP plaques and spongioform changes were also found in other parts of the olfactory system, the cortex, basal ganglia, cerebellum, and brain stem.

It is difficult to determine the precise cause of our patient's olfactory and gustatory dysfunction. There were significant histopathological changes in the basal forebrain where both taste and smell are represented.2 Deposits of prion were, however, also found in many other parts of the brain involved in the neural processing of these senses. Changes were particularly prominent in the olfactory tract. Our patient illustrates that our understanding of the clinical range of vCJD remains incomplete. Loss of taste and smell are not at all specific to vCJD. These symptoms can have many causes including other neurodegenerative disorders. However, the diagnosis of vCJD should be considered if hypogeusia and hyposmia are accompanied by changes of personality and other, more “typical” features of vCJD.

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