Multiparameter MR imaging in the 6-OPRI variant of inherited prion disease.

BACKGROUND AND PURPOSE: Inherited prion diseases represent over 15% of human prion cases and are a frequent cause of early onset dementia. The purpose of this study was to define the distribution of changes in cerebral volumetric and microstructural parenchymal tissues in a specific inherited human prion disease mutation combining VBM with VBA of cerebral MTR and MD. MATERIALS AND METHODS: VBM and VBA of cerebral MTR and MD were performed in 16 healthy control participants and 9 patients with the 6-OPRI mutation. An analysis of covariance consisting of diagnostic grouping with age and total intracranial volume as covariates was performed. RESULTS: On VBM, there was a significant reduction in gray matter volume in patients compared with control participants in the basal ganglia, perisylvian cortex, lingual gyrus, and precuneus. Significant MTR reduction and MD increases were more anatomically extensive than volume differences on VBM in the same cortical areas, but MTR and MD changes were not seen in the basal ganglia. CONCLUSIONS: Gray matter and WM changes were seen in brain areas associated with motor and cognitive functions known to be impaired in patients with the 6-OPRI mutation. There were some differences in the anatomic distribution of MTR-VBA and MD-VBA changes compared with VBM, likely to reflect regional variations in the type and degree of the respective pathophysiologic substrates. Combined analysis of complementary multiparameter MR imaging data furthers our understanding of prion disease pathophysiology.

Physeal injuries in children's and youth sports: reasons for concern?

A systematic review of the literature on the frequency and characteristics of sports related growth plate injuries affecting children and youth in organised sport was carried out. Both acute and chronic physeal injuries related to participation in sports have been reported to occur, although injury incidence data are somewhat limited. Of particular concern is the growing number of stress related physeal injuries, including those affecting the lower extremities. Although most physeal injuries appeared to resolve with treatment and rest, there is also evidence of growth disturbance and deformity. Possible injury risk factors and countermeasures are discussed, and suggestions for directing future research provided.

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.

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 ((18)F)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.

Neuropsychological and quantitative oculometric study of a case of sporadic Creutzfeldt-Jakob disease at predementia stage.

A quantitative assessment of eye movements and a detailed neuropsychological profile were conducted at predementia stage in a patient who later had histological confirmation of sporadic Creutzfeldt-Jakob disease (CJD). The patient was a middle aged man who presented with abnormal eye movements and poor balance. Neuropsychological deficits suggested orbito-mesial dysfunction, resembling progressive supranuclear palsy. Oculometry showed accurate but dramatically slowed saccades, with normal pursuit movements. Neuropsychology and quantitative oculometry may be of value in the differential diagnosis and earlier detection of dementia-akinetic-rigid syndromes; in particular, because of the highly stereotyped nature of saccades, routine quantitative oculometry can reveal significant impairment at a very early stage in some cases and could thus facilitate earlier diagnosis.

Does gymnastics training inhibit growth of females?

OBJECTIVE: The increasingly dominant performance of smaller-sized female gymnasts and increased magnitude of training beginning at an early age have prompted public and medical concerns, especially from an auxological perspective. The objective of this review is to determine if gymnastics training inhibits growth of females. DATA SOURCES: An extensive research of MedLine (PubMed interface) along with cross-referencing was conducted using the Text and MeSH words "gymnastics" in combination with "growth," "maturation," "body height," "body weight," and "growth plate." Our analysis is limited to English articles only. STUDY SELECTION: All published studies that included data related to the research questions were included. MAIN RESULTS: Although data from three historical cohort studies indicate that female gymnasts are short even before they begin training, clinical reports and cohort studies do suggest that some female gymnasts experience attenuated growth during training followed by catch-up growth during periods of reduced training or retirement. There is conflicting evidence whether the "catch-up" is complete. There were no studies reporting prevalence or incidence of inadequate growth. Three cohort studies provide evidence of reduced growth but training was not partitioned from other confounding factors in the gymnastics environment. Although there is a paucity of studies examining the link of dietary practices with diminished growth in female gymnasts, a review of related dietary literature indicates the potential for insufficient energy and nutrient intake among female gymnasts. CONCLUSIONS: Elite level or heavily involved female gymnasts may experience attenuated growth during their years of training and competition followed by catch-up growth during reduced training schedules or the months following retirement. However, a cause-effect relation between gymnastics training and inadequate growth of females has not been demonstrated.

Object orientation agnosia: a failure to find the axis?

A dissociation between the ability to recognize misoriented objects and to determine their orientation has been reported in a small number of patients with vascular lesions. In this article, we describe a 57-year-old man with probable Alzheimer' s disease who shows the same dissociation. Neuroimaging findings indicated marked hypometabolism in the posterior cortical regions, particularly the postero-superior parietal lobes. Clinically, the patient had good object recognition accompanied by severely impaired spatial abilities. The experimental investigations comprised a variety of tasks in which he identified misoriented objects, evaluated the orientation of single objects, or discriminated the orientation of simultaneously presented items. Results revealed that his object recognition was independent of orientation and was largely mediated by salient features. With respect to orientation judgements, the patient displayed a profound inability to judge the orientation of nonupright objects, but remarkably intact (though largely implicit) knowledge of the upright orientation. Strikingly, his orientation judgements were also more accurate for upside-down objects than for other orientations (i.e., 90 degrees ). We interpret these results as evidence that judgements about object orientation are facilitated when the orientation of the principal axis of the object matches that of an internal representation. We propose that the inability to determine other orientations may be due to the failure of an "axis-finding" mechanism implemented in the posterior parietal lobes, that translates between object-centered and eye-centered coordinates appropriate for guiding visual scanning.

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.

Right medial thalamic lesion causes isolated retrograde amnesia.

Pervasive retrograde amnesia without anterograde memory impairment has rarely been described as a consequence of circumscribed brain damage. We report this phenomenon in a 33 yr-old, right-handed man (JG) in association with the extension in the right thalamus of a previously small, bilateral thalamic lesion. JG presented with a dense amnesia for autobiographical material more than a few years old, with some sparing of recent memories. Furthermore, he was completely unable to recognise famous people or world events. Many other aspects of semantic knowledge were intact and there was no evidence of general intellectual impairment, executive dysfunction or loss of visual imagery. Magnetic resonance imaging revealed an acute lesion in the right thalamus and two small, symmetrical, bilateral non-acute thalamic lesions. Follow-up neuropsychological assessment indicated a stable pattern of impaired retrograde and spared anterograde memory over 18 months and psychiatric assessments yielded no evidence of confabulation, malingering or other symptoms to suggest psychogenic amnesia. JG's profile indicates that the division of declarative memory into just two categories - episodic and semantic - is inadequate. Rather, his case adds to the growing body evidence to suggest that world knowledge pertaining to people and events is stored or accessed similarly to autobiographical information and differently from other types of more general factual knowledge. We hypothesize that the right mediodorsal thalamic nucleus and immediately surrounding regions comprise the central processing mechanism referred to by McClelland (Revue Neurologique, 150 (1994) 570) and Markowitsch (Brain Research Review, 21 (1995) 117) as responsible for inducing and co-ordinating the recall of these sorts of cortically stored memory engrams.

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.

Severe anterograde amnesia with extensive hippocampal degeneration in a case of rapidly progressive frontotemporal dementia.

Frontotemporal dementia (FTD) is usually characterized as a spectrum of relatively slowly progressive disorders with largely focal frontal or temporal presentations. The development of clinical and research criteria for discriminating FTD from Alzheimer's disease has relied, in part, on the relative preservation of episodic memory in FTD. We present a patient with FTD who, in addition to the more typical behavioural and language deficits, had a profound anterograde amnesia at the time of diagnosis. Neuroimaging confirmed atrophy of frontal and temporal lobes bilaterally, most marked in the anterior left temporal region. At post-mortem, non-Alzheimer pathology resulting in devastating cell loss was revealed in the hippocampi, as well as in the frontal and temporal cortex, thus providing neuroanatomical corroboration of the episodic memory deficit. Progression of the disease was extraordinarily rapid, with just 2 years between reported onset and time of death. This case demonstrates that the pattern of FTD may include severe anterograde amnesia as a prominent and early consequence of the disease.

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.

Degeneration of anterior thalamic nuclei differentiates alcoholics with amnesia.

The specific neural substrate underlying the amnesia in alcoholic Korsakoff's psychosis is poorly defined because of the considerable brain damage found in many non-amnesic alcoholics, particularly those with Wernicke's encephalopathy. Using operational criteria to identify alcoholics with and without Korsakoff's psychosis, we have shown that many of the cortical and subcortical regions involved in the encoding and retrieval of episodic memory are either unaffected (hippocampus) or damaged to the same extent (prefrontal cortex and the cholinergic basal forebrain) in both amnesic and non-amnesic alcoholics. In the present study we analysed the diencephalic regions involved in episodic memory to determine the neural substrate for the amnesia observed in alcoholic Korsakoff's psychosis. The number of neurons in spaced serial sections containing the hypothalamic mamillary nuclei and the anterior and mediodorsal thalamic nuclei was estimated using unbiased stereological techniques. Neurodegeneration of the hypothalamic mamillary nuclei and the mediodorsal thalamic nuclei was substantial in both non-amnesic and amnesic alcoholics with Wernicke's encephalopathy. However, neuronal loss in the anterior thalamic nuclei was found consistently only in alcoholic Korsakoff's psychosis. This is the first demonstration of a differentiating lesion in alcoholic Korsakoff's psychosis and supports previous evidence that degeneration of thalamic relays are important in this memory disorder.

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.

Effect of strength training on orthostatic hypotension in older adults.

PURPOSE: This preliminary study attempted to identify the frequency of orthostatic hypotension (OH) in community dwelling older adults who volunteered to participate in an 8-week, heavy-resistance, strength-training program. It also assessed the effect of the strength-training program on OH. METHODS: From a larger study (n = 53) on high-resistance strength training in older adults (mean age 71.4 +/- 6.6 years), a subset of subjects (n = 24), mean age 71.0 +/- 5.8 years, was evaluated who met at least one criterion for OH. All subjects were tested for resting blood pressures (BP) and heart rates (HR) in the supine, sitting, and standing positions. Also noted was their response to orthostatism in rising from a cot after 10 minutes and rising from a chair after 5 minutes. The subset was not different from the overall group in gender ratio, age, or effect of medication on BP. The treatment was an 8-week strength-training program at 80% of their one repetition maximum. RESULTS: Significant changes (P < 0.05) were shown in supine diastolic BP (+3.2 mm Hg), sitting systolic BP (-3.9), and standing HR (+4.9 beats per minute). In response to the orthostatic challenge, significant (P < 0.05) improvements were shown in systolic BP (+9.7 mm Hg), diastolic BP (+4.7), and HR (+3.2 beats per minute) for the rise from chair, and in diastolic BP (+6.7 mm Hg) rise from the cot. CONCLUSIONS: These data show that OH is not uncommon (45%) in community dwelling older adults. A strength training program in older adults has little effect on resting BP, but elicits a positive adaptation to an orthostatic challenge.

Does repetitive physical loading inhibit radial growth in female gymnasts?

OBJECTIVE: Stress-related injuries to the distal radius have been noted in female gymnasts with potential for resultant premature closure and abnormal growth at this site. The purpose of this study was comprehensively to review and critically to appraise the available literature to examine the evidence related to this question: does repetitive physical loading inhibit growth of the radius in female gymnasts? DATA SOURCES: MEDLINE and SPORT Discuss were searched from 1975 to the present by using "gymnast" in combination with injury, growth plate, epiphyseal, and ulnar variance. Additional references were retrieved from the bibliographies of the retrieved articles. STUDY SELECTION: All descriptive and analytic studies that included data related to stress-related injuries affecting the distal radius of competitive female gymnasts were included. Conclusions regarding the effects of gymnastics training on radial growth of female gymnasts were limited to data from case reports, clinical series, cross-sectional studies, and descriptive cohort studies. Data from relevant experimental animal studies also were included. DATA EXTRACTION AND SYNTHESIS: In reviewing the literature, particular attention was paid to the relative strengths of the different study designs. From these data, information associated with growth inhibition at the distal radius was examined. MAIN RESULTS: The descriptive research reviewed included clinical, cross-sectional, and cohort studies that establish the existence of stress-related injuries affecting one or more constituent parts of the epiphyseal-physeal-metaphyseal (EPM) complex of the distal radius, symptomatic ulna-radial-length difference (URLD), and distal radius physeal arrest among female gymnasts. Five cross-sectional studies showed radiographic abnormalities consistent with distal radius physeal-stress reaction in 10-85% of gymnasts studied. Two cross-sectional studies indicated "abnormal" positive URLD in 8-20% of wrists radiographed. Four cross-sectional studies showed significant correlations between training intensity and URLD, suggesting a dose-response relation. Three cross-sectional studies indicate greater URLD in gymnasts compared with nongymnasts. Radiographic evidence of distal radius physeal arrest involving physically immature female gymnasts is presented in four studies (two clinical series, one cross-sectional, and one descriptive cohort). In animal studies, prolonged physical training has also been shown to inhibit or stop growth in weight-bearing long bones. However, there were no rigorous studies (i.e., randomized control trials or analytic cohorts) examining the question. CONCLUSION: The results of this critical review of the scientific literature support the plausibility of stress-related distal radius physeal arrest with secondary URLD. However, the strength of evidence is inadequate to be conclusive.

The nucleus basalis (Ch4) in the alcoholic Wernicke-Korsakoff syndrome: reduced cell number in both amnesic and non-amnesic patients.

BACKGROUND: The cholinergic nucleus basalis (Ch4) is an exclusive site of neurofibrillary degeneration in alcoholic patients with Wernicke's encephalopathy. AIM: To test the hypothesis that the loss of Ch4 neurons contributes to the memory disorder, Korsakoff's psychosis, commonly seen in Wernicke's encephalopathy. METHODS: Magnocellular basal forebrain neurons were quantified in alcoholic patients with Wernicke's encephalopathy, both with and without Korsakoff's psychosis, and neurologically asymptomatic alcoholic and non-alcoholic controls. Because amnesic and non-amnesic patients with Wernicke's encephalopathy share common periventricular lesions, both thiamine deficient groups as well as alcoholic patients with no neurological complications were included to determine the lesion specific to memory impairment. RESULTS: Ch4 cell number did not differ significantly between alcoholic and non-alcoholic controls and there was no correlation between cell number and lifetime alcohol intake. However, Ch4 cell number in all groups was significantly correlated with the volume of its major projection target, the cerebral cortex. Ch4 cell number in the non-amnesic Wernicke's encephalopathy group was significantly below controls (24%), with cell number in patients with Korsakoff's psychosis 21% below controls. There was considerable overlap in cell number between groups. On discriminant analysis, there was significantly greater cell loss in three non-amnesic patients with Wernicke's encephalopathy than in some patients with Korsakoff's psychosis. The nonamnesic patient with the greatest cell loss was impaired on attentional tasks. CONCLUSION: Whereas neurons in the nucleus basalis are at risk in thiamine deficient alcoholic patients, cell loss is minor and does not account for the profound memory disorder.