Diana Caine

Operational criteria for the classification of chronic alcoholics: identification of Wernicke's encephalopathy.

OBJECTIVES: To establish better operational criteria for the diagnosis of Wernickes encephalopathy. Current criteria for diagnosing Wernickes encephalopathy require the presence of three clinical signs (oculomotor abnormalities, cerebellar dysfunction, and an altered mental state), although it has often been reported that most patients do not fulfil all these criteria. METHODS: The clinical histories of 28 alcoholics with neurological and neuropsychological assessments and definitive neuropathological diagnoses were examined to determine clinical signs for use in a screening schedule. Operational criteria were then proposed for differentiating patients with Wernickes encephalopathy alone or in combination with Korsakoffs psychosis or hepatic encephalopathy. The new criteria for Wernickes encephalopathy require two of the following four signs; (1) dietary deficiencies, (2) oculomotor abnormalities, (3) cerebellar dysfunction, and (4) either an altered mental state or mild memory impairment. Reproducibility and validity testing of these criteria were performed on 106 alcoholics screened from a large necropsy sample. RESULTS: Despite rater variability with regard to specific symptoms, within and between rater reliability for diagnostic classification using the criteria retrospectively on patient records was 100% for three independent raters. Validity testing showed that Wernickes encephalopathy was underrecognized only when occurring with hepatic encephalopathy (50% sensitivity). CONCLUSIONS: By contrast with current criteria, the proposed operational criteria show that the antemortem identification of Wernickes encephalopathy can be achieved with a high degree of specificity.

Neuropsychological and neuropathological sequelae of cerebral anoxia: A critical review

Fifty-eight studies of the neuropathological and neuropsychological outcomes of cerebral anoxia were reviewed. Neuropathological reports were examined for the variety, extent, and specificity of lesions resulting from an anoxic event. While most attention has focused on damage to the hippocampus following anoxic brain injury, the review indicated that watershed cerebral cortex and the basal ganglia were both more frequently damaged than the hippocampus. The hippocampus was the sole affected structure in only 18% of reported cases. Neurological, neuropsychological and psychiatric studies were analyzed. Of 67 individual case reports, a memory disturbance was documented in 36 (54%), but a memory disturbance without report of additional cognitive deficits occurred in only 13 (19.4%). Changes in personality and behavior were noted in 31 (46.2%). Visuospatial or, less frequently, visual recognition problems were noted in 21 individual cases (31.3%) reviewed. Memory deficits were found in all 14 group studies reviewed, while in 9 papers changes in behavior or personality were also documented. Six studies also reported visuospatial deficits. Careful reading of the literature reveals a range of cognitive and behavioral changes that reflect very well the neuropathological outcomes of anoxic episodes.

The topography of metabolic deficits in posterior cortical atrophy (the visual variant of Alzheimer’s disease) with FDG-PET

Background:The term “posterior cortical atrophy” (PCA) refers to a clinical syndrome in which higher order visual processing is disrupted owing to a neurodegenerative disorder, the most commonly associated pathology being Alzheimer’s disease. Objective:To map the topography of hypometabolic brain regions in a group of subjects with PCA who had undergone detailed neuropsychological characterisation. Methods:Resting cerebral metabolism was measured with (18F)fluorodeoxyglucose-positron emission tomography (FDG-PET) in patients with PCA (n = 6), typical Alzheimer’s disease (n = 10), and healthy controls (n = 10). The data were analysed using statistical parametric mapping (SPM99) and region of interest techniques. Results:Clinically, the PCA subjects showed predominant visuospatial deficits (including features of Balint’s syndrome) consistent with damage to the dorsal stream of visual processing. Compared with the controls, the PCA group showed marked glucose hypometabolism primarily affecting the posterior cerebral hemispheres (right worse than left). In addition, the PCA group showed two symmetrical areas of hypometabolism in the region of the frontal eye fields. Compared with typical Alzheimer’s disease, the PCA group had selective hypometabolism in the occipito-parietal region (right much worse than left). Conclusions:The neuropsychological and PET findings are consistent with damage predominantly to the dorsal stream of visual processing. Frontal eye field hypometabolism secondary to loss of input from the occipito-parietal region may be the mechanism for the ocular apraxia seen in Balint’s syndrome.

Models of face recognition and delusional misidentification: a critical review.

The “two-route model of face recognition” proposed by Bauer (1984) and adopted by Ellis and Young (1990), has become a widely accepted model in studies of face processing disorders, including both prosopagnosia and the delusional misidentification syndromes. We review the origin and application of the two-route model of face recognition in examining both the neuroanatomical pathways and the cognitive pathways to face recognition. With respect to the neuroanatomy, we conclude that face recognition is subserved by a single pathway, the ventral visual pathway, as there is no evidence to suggest that the dorsal visual pathway is capable of visual recognition or of providing an affective response to familiar stimuli. We demonstrate how operation of the ventral visual pathway and its connections to the amygdala can parsimoniously account for the findings in the literature on prosopagnosia and delusional misidentification syndromes. In addition, we propose a cognitive model of face processing stemming from the work of Bruce and Young (1986). Our model involves two pathways subsequent to the system responsible for face recognition: one pathway to a system containing semantic and biographical information about the seen face, and a second pathway to a system responsible for the generation of an affective response to faces that are familiar. We demonstrate how this cognitive model can explain the dissociations between overt and covert recognition observed in prosopagnosia and the Capgras delusion.

Mirrored-self Misidentification: Two Cases of Focal Onset Dementia

We present two patients in whom the mirror sign, the inability to recognize one’s own reflected image, was a stable and persisting symptom signalling the onset of a progressive dementing illness. Extensive neuropsychological testing was conducted with both patients, with particular emphasis on face processing and the understanding of reflected space. Both patients were also investigated with structural imaging techniques (computed tomography and magnetic resonance imaging). Although the neuroimaging results were not strongly lateralizing for either patient, neuropsychological testing revealed striking right hemisphere dysfunction with relatively intact left hemisphere cognitive function in both patients. Of particular interest was the patients’ dissociation on tests of face processing; one patient, FE, had significant face processing deficits while the other patient, TH, had relatively intact face processing. Further testing with TH revealed striking deficits in his ability to interpret reflected space. The results of the face processing tests are discussed in the context of current models of normal face processing, with particular emphasis on the affective component in face recognition. We propose that a combination of cognitive deficits underlie the mirror sign delusion, including perceptual, affective and reasoning impairments, and also discuss the contributions of cortical and subcortical lesions in these two patients and in delusions in general.

Towards an understanding of delusions of misidentification: Four case studies

Four detailed cases of delusions of misidentification (DM) are presented: two cases of misidentification of the reflected self, one of reverse intermetamorphosis, and one of reduplicative paramnesia. The cases are discussed in the context of three levels of interpretation: neurological, cognitive and phenomenological. The findings are compared to previous work with DM patients, particularly the work of Ellis and Young (1990; Young, 1998) who found that loss of the normal affective response to familiar faces was a contributing factor in the Capgras delusion. The four cases presented suggest that this particular deficit is not a critical factor in the development of other forms of DM.

Visuospatial functions in atypical parkinsonian syndromes

Objectives: Visuospatial deficits have been occasionally reported but never systematically studied in atypical parkinsonian syndromes. The interpretation of existing studies is complicated by the possible influence of motor and frontal executive deficits. Moreover, no attempt has been made to distinguish visuoperceptual from visuospatial tasks. The aim of the present study was to assess visuoperceptual and visuospatial abilities in three atypical parkinsonian syndromes while minimising the influence of confounding variables. Methods: Twenty patients with multiple system atrophy (MSA), 43 with progressive supranuclear palsy (PSP), and 25 with corticobasal degeneration (CBD) as well as 30 healthy age matched controls were examined with the Visual Object and Space Perception Battery (VOSP). Results: Visuospatial functions were intact in MSA patients. PSP patients showed mild deficits related to general cognitive decline and the severity of oculomotor symptoms. The CBD group showed the most pronounced deficits, with spatial tasks more impaired than object based tasks. Performance on object based, but not spatial, tasks was related to general cognitive status. The extent of the visuospatial impairment could not be predicted from disease duration or severity. Conclusion: Visuospatial functions are not consistently impaired in atypical parkinsonian syndromes. The degree and pattern of impairment varies across the diseases, suggesting that the observed deficits could have a different neural basis in each condition. The distinction between the object based (“ventral stream”) and the space oriented (“dorsal stream”) processing might be useful in the interpretation of visuospatial deficits in parkinsonian syndromes, especially in CBD.

Brainstem serotonergic neurons in chronic alcoholics with and without the memory impairment of Korsakoff's psychosis

There are several lines of evidence to suggest that serotonergic neurons in the brain are detrimentally affected by chronic alcohol consumption. The present study aims to quantify pathological changes in brainstem regions containing serotonergic neurons in chronic alcoholics compared to age-matched non-alcoholic controls. An antibody specific for tryp-tophan hydroxylase was used to immunohistochemically demonstrate serotonergic neurons in serial sections of postmortem brainstem. The cases analyzed were divided into four groups on the basis of their clinical and pathological presentation; chronic alcoholics with Wernickes encephalopathy, chronic alcoholics with additional Korsakoffs psychosis, non-alcoholic controls, and a single chronic alcoholic without neurological complications. There was an overall reduction in the number of serotonergic neurons in all alcoholic cases when compared with controls. All brainstem regions were affected, but the largest neuronal loss was found in areas of the medullary and caudal pontine reticular formation (reduced by 80–90%). Alcoholics with Korsakoffs psychosis did not differ in the amount or extent of pathology from the other alcoholic cases analyzed. The data indicate that significant numbers of serotonergic neurons degenerate in chronic alcoholics. Such a loss is likely to have significant clinical consequences.

Heterogeneity of semantic and visuospatial deficits in early Alzheimer's disease.

Staging of visuospatial and semantic deficits in patients with dementia of the Alzheimer type (DAT) was examined. The authors hypothesized that semantic ability would be more impaired in these patients, reflecting predominant temporal pathology early in the disease. However, in the 1st study (n = 26), 3 patients (11.5%) had marked visual but no semantic impairment. This finding was extended in a 2nd study with a 2nd patient sample (n = 21) and more specific tasks. Two patients (9.5%) again had visual but no semantic impairment. These studies confirm that, in patients with DAT presenting with relatively focal deficits, visual deficits sometimes occur before semantic problems. The findings are discussed with regard to the cognitive demands and neuroanatomical underpinning of the tests used and point to the necessity of using cognitively specific tests to enable accurate analysis of deficits in the context of the neuroanatomical basis of impairment.

Posterior cortical atrophy: a review of the literature.

Abstract The past three decades have seen an accumulation of reports of neurodegenerative disease with disruption to visual processing. Disorders of both visuospatial processing and visual recognition have been described, though the former predominate. But the conundrum of posterior cortical atrophy (PCA) is that while the clinical presentation is relatively homogeneous, the nosological status remains something of a puzzle. Many cases coming to pathology have had Alzheimer’s Disease (AD) but in a different distribution from that seen in typical AD (tAD). Patients with non-specific subcortical gliosis and, more occasionally, Creutzfeldt Jacob disease, neither of which have an obvious affinity with PCA, have also been described. On the other hand, no case of PCA has been reported with the pathology of either corticobasal degeneration or dementia with Lewy Bodies, both of which do commonly present with prominent parietal symptomatology.