Spread of dystonia in patients with idiopathic adult-onset laryngeal dystonia.

BACKGROUND AND PURPOSE: Adult-onset laryngeal dystonia (LD) can be isolated or can be associated with dystonia in other body parts. Combined forms can be segmental at the onset or can result from dystonia spread to or from the larynx. The aim of this study was to identify the main clinical and demographic features of adult-onset idiopathic LD in an Italian population with special focus on dystonia spread. METHODS: Data were obtained from the Italian Dystonia Registry (IDR) produced by 37 Italian institutions. Clinical and demographic data of 71 patients with idiopathic adult-onset LD were extracted from a pool of 1131 subjects included in the IDR. RESULTS: Fifty of 71 patients presented a laryngeal focal onset; the remaining subjects had onset in other body regions and later laryngeal spread. The two groups did not show significant differences of demographic features. 32% of patients with laryngeal onset reported spread to contiguous body regions afterwards and in most cases (12 of 16 subjects) dystonia started to spread within 1 year from the onset. LD patients who remained focal and those who had dystonia spread did not show other differences. CONCLUSIONS: Data from IDR show that dystonic patients with focal laryngeal onset will present spread in almost one-third of cases. Spread from the larynx occurs early and is directed to contiguous body regions showing similarities with clinical progression of blepharospasm. This study gives a new accurate description of LD phenomenology that may contribute to improving the comprehension of dystonia pathophysiology.

Effect of aliskiren and carvedilol on expression of Ca(2+)/calmodulin-dependent protein kinase II δ-subunit isoforms in cardiac hypertrophy rat model.

CONTEXT: The critical role of CaMKIIδ isoforms in cardiac hypertrophy is well documented. OBJECTIVE: This study was aimed to investigate the possible inhibitory effects of aliskiren (ALS) and/or carvedilol (CAV) on CaMKIIδ isoforms expression in experimental cardiac hypertrophy. MATERIALS AND METHODS: Male Wistar albino rats were subcutaneously injected with isoproterenol (ISO) (5 mg/kg/day) for 4 weeks to induce cardiac hypertrophy. Hypertrophied rats were daily treated with either ALS (10 mg/kg) and/or CAV (10 mg/kg). At the end of the treatment, rats were killed; blood and hearts were collected for assessing different biochemical parameters. RESULTS: ISO treatment significantly increased heart weight to body weight (HW/BW) ratio, serum creatine kinase MB (CK-MB) and troponin T (Tn-T) levels, and plasma renin activity (PRA) as compared to control rats. Additionally, ISO treatment produced a significant increase in the expression of myocardial CaMKIIδ2 and CaMKIIδ3 that were associated with significant elevation in myocardial caspase-3 protein expression. Histopathological examination of rats exposed to ISO treatment showed severe myocardial cell degeneration. ALS and/or CAV treatment significantly reduced the altered HW/BW ratio, serum CK-MB and Tn-T levels, PRA, and caspase-3 protein expression in hypertrophied rats, with maximal improvement in the combination group. These biochemical findings were supported by the histopathological examination of the heart tissue. Additionally, treatment with ALS and CAV significantly inhibited ISO-induced increase in CaMKIIδ2 and CaMKIIδ3 expression levels. DISCUSSION AND CONCLUSION: The present study indicated that ALS and CAV treatment ameliorated ISO-induced hypertrophy via inhibiting the expression and the activity of CaMKIIδ isoforms and the associated myocardial apoptosis.

Sex-related differences in olfactory function and evaluation of possible confounding factors among patients with Parkinson's disease.

The role of specific sex-related patterns in olfactory dysfunctions of Parkinson's disease (PD) patients is unclear. The aim of this study was to assess the presence of specific sex-related patterns in olfactory dysfunctions excluding the possibility of confounding effects in patients with Parkinson's disease. One hundred and sixty-eight participants (99 PD patients and 69 controls) were enrolled and evaluated using Sniffin' Sticks Extended test (SSET). There was no significant sex difference in the control group for the SSET parameters. By contrast, in the PD group male patients scored significantly lower on odor discrimination (OD), identification (OI), and Threshold-Discrimination-Identification (TDI) score than females. On multivariable linear regression analysis, the only significant predictors of TDI score were sex and apathy. Among PD patients, men showed a significantly greater impairment compared to women in OI, OD and TDI score, but not in odor threshold (OT). These findings highlighted the possible role of sex differences in the development of associated PD non-motor symptoms.

Hippocampal atrophy is the critical brain change in patients with hypoxic amnesia.

Anoxia is considered a good model for studying amnesia. However, not all individuals who experience anoxic events develop memory problems. Moreover, the question still remains about whether, after anoxia, damage is limited to the hippocampus in patients with amnesia and without other significant cognitive deficits. Here we investigated brain damage in a selected sample of adults affected exclusively by an amnesic syndrome after an anoxic episode. The cerebral MR images of these patients were submitted to visual inspection, volumetric measurements of the mesial temporal structures following manual segmentation, and to Voxel-Based Morphometry of the whole brain. We studied five anoxic patients and thirty-three well-matched healthy subjects. Our aim was to: (a) quantify regional atrophic changes associated with chronic anoxic damage compared to control subjects (Group Comparison Analysis); (b) identify regions of common abnormality across all patients (Conjunction Analysis in the VBM); (c) investigate whether measures of regional volume reduction correlated with neuropsychological memory scores; (d) compare the results obtained with visual inspection and ROI analyses with those obtained with VBM. We found that anoxic patients presented a significant reduction of gray matter volume in the hippocampus bilaterally compared to healthy subjects. The only common atrophic region across all patients was the hippocampus bilaterally. Correlation analysis showed only a trend between the Prose immediate free recall test and the left hippocampus. Our findings confirm that the hippocampus is very sensitive to damage stemming from anoxia. Patients with hypoxic amnesia may present damage in other brain regions, but only hippocampal atrophy is common in all of them.

Reduced oxygen due to high-altitude exposure relates to atrophy in motor-function brain areas.

BACKGROUND AND PURPOSE: At high altitudes barometric pressure is reduced and, thus, less oxygen is inhaled. Reduced oxygen concentration in brain tissue can lead to cerebral damage and neurological and cognitive deficits. The present study was designed to explore the effects of high-altitude exposure using a quantitative MRI technique, voxel-based morphometry. METHODS: We studied nine world-class mountain climbers before (baseline) and after (follow-up) an extremely high-altitude ascent of Everest and K2. We investigated the effects of repeated extremely high-altitude exposures by comparing mountain climbers' scans at baseline with scans of 19 controls. In addition, we measured the effects of a single extremely high-altitude expedition by comparing mountain climbers' scans at baseline and follow-up. RESULTS: A region of reduced white matter density/volume was found in the left pyramidal tract near the primary (BA 4) and supplementary (BA 6) motor cortex when mountain climbers at baseline were compared with controls. Further, when mountain climbers' scans before and after the expedition were compared, a region of reduced grey matter density/volume was found in the left angular gyrus (BA 39). CONCLUSION: These findings suggest that extremely high-altitude exposures may cause subtle white and grey matter changes that mainly affect brain regions involved in motor activity.

Bilateral damage to the mammillo-thalamic tract impairs recollection but not familiarity in the recognition process: a single case investigation.

Focal damage confined to the hippocampus may result in recognition deficits characterized by a dissociation between impaired recollection and preserved familiarity. Here, we report a single case of an amnesic patient with bilateral damage to the anterior part of the thalamus, who presented with a neuropsychological profile suggesting such a dissociation. We hypothesized that this focal damage involved the so-called Delay and Brion's circuit, which has been theorized to subserve episodic memory processes, but at a different anatomical level than in patients with hippocampal lesions. Using two independent experimental paradigms (remember/know and confidence receiver operating characteristics [ROC]) and recruiting a sex- and age-matched group of healthy controls, we demonstrated that this patient's recognition deficits were due to a selective impairment of recollection with a normal familiarity process. The patient underwent an ad hoc brain MRI study, and a quantitative analysis of his MR images was performed. Tissue damage extended bilaterally to the mammillo-thalamic tract, with complete preservation of the medio-dorsal thalamic nuclei. Our findings support the idea that the same functional specialization hypothesized for the different sub-regions of the mesial temporal lobe might also extend to the thalamus. This case will be discussed in light of its implications in support of recent theories, which regard recollection and familiarity as independent processes associated with different neural circuits.

Episodic memory impairment in patients with Alzheimer's disease is correlated with entorhinal cortex atrophy. A voxel-based morphometry study.

The aims of this study were to investigate the pattern of cortical atrophy and the relationships between memory performances and the brain regions in Alzheimer's Disease (AD). optimized voxel-based morphometry (VBM) was applied to the MRI brain images of 18 probable AD and 18 healthy subjects (HS). Patients performed verbal and visuo-spatial episodic and shortterm memory tests. Contrasting of AD group with HS, and anatomobehavioural correlations were carried out in order to identify regional atrophic changes and neuro-cognitive aspects in AD group. We found evidence of gray matter (GM) volume reduction in AD in the medial temporal, parietal and frontal areas bilaterally and in the left anterior thalamic nuclei. Performance on the episodic memory delayed recall tests co-varied with GM volume in the left entorhinal cortex. The pattern of cortical atrophy likely reflects the heterogeneous level of dementia severity in our AD group. The anatomical region affected in the left hemisphere indicates a sufferance at multiple levels of the Polysynaptic Hippocampal Pathway, which is involved in declarative memory. Findings on the entorhinal cortex and the delayed memory scores support the role of the entorhinal cortex in episodic memory. Damage to the entorhinal cortex, deafferenting the hippocampus from neocortical inputs, interferes with episodic memory consolidation in AD patients.

Cognitive and behavioural predictors of progression rates in Alzheimer's disease.

Cognitive and functional decline in Alzheimer's disease (AD) may show different, yet correlated, rates of progression. Over a 2-year period we investigated the predictive role of neuropsychological and behavioural variables on the cognitive and functional decline of 43 patients with AD. Slow and fast decliners were defined on the basis of cognitive and functional indexes of disease progression. We found that cognitive decline was predicted by diffuse cognitive impairment and functional progression by visuospatial deficits. Psychotic symptoms predicted faster disease progression in both cognitive and functional dimensions.

Visual repetition priming for words relies on access to the visual input lexicon: evidence from a dyslexic patient.

In this study we tested the hypothesis that visual repetition priming for words depends upon the accessibility of lexical units in the visual input lexicon. For this purpose, we investigated a dyslexic patient, A.M., whose neuropsychological performances suggested an impaired access to the lexical route of reading. According to the predictions, Experiments 1 and 2 demonstrated deficient priming in tests involving the visual presentation of words (Word Identification and Stem Completion). In Experiment 3, we demonstrated that A.M.'s deficient priming was specific for visually presented words, in that the auditory presentation elicited a normal priming effect (auditory Stem Completion). These data are discussed in the light of a theoretical framework suggesting a fractionation of the modalities by which repetition priming can be elicited, each mediated by a particular memory subsystem.

Lexical and conceptual components of stem completion priming in patients with Alzheimer's disease.

This study evaluated the hypothesis of dissociation between normal lexical but deficient conceptual repetition priming in patients with Alzheimer's disease (AD). For this purpose, we administered to patients with AD and age-matched normal controls the Stem Completion task. In Experiment 1, the level of word processing during study was manipulated by requiring subjects to count vowels (graphemic condition) or generate meanings (semantic condition) of target words. In Experiment 2, the presentation modality was varied during the study to obtain an intramodal and crossmodal repetition priming. Probably due to a floor effect of performance in the graphemic condition, in Experiment 1, AD patients exhibited lower priming than normal controls for the semantically processed words but comparable priming for the graphemically processed ones. In contrast, in Experiment 2, AD patients were poorly primed both in the intra- and crossmodal conditions. Results question the hypothesis of a lexical/conceptual dissociation in the repetition priming exhibited by AD patients and call for other explicative hypotheses of the dissociation between normal and deficient forms of repetition priming in degenerative dementia.

Word-list forgetting in young and elderly subjects: evidence for age-related decline in transferring information from transitory to permanent memory condition.

This study aimed at investigating different memory components involved in word list forgetting by young and elderly healthy individuals. For this purpose, we analyzed in 55 young (age range 20-35) and 50 aged (age range 60-80) healthy subjects the memory decay passing from the fifth immediate to the delayed recall trial of the Rey's Auditory Learning task as a function of the position of the words in the list. Young and elderly groups displayed the same forgetting rate for words recalled from the primacy and mid-list tracts of the serial position curve. However, memory loss for the recency positions was disproportionately larger in the elderly than in the young group. These data demonstrate that aged subjects rely on short-lived memory processes in immediate recall of terminal list items more extensively than young subjects and, as a consequence, a larger proportion of words become inaccessible to them following a delay.

Forgetting from long-term memory in dementia and pure amnesia: role of task, delay of assessment and aetiology of cerebral damage.

This study investigated the hypothesis that memory disordered patients suffer of an exalted forgetting rate from long-term memory within the first few minutes following acquisition. For this purpose, we administered to groups of Alzheimer's (AD), Multi-infarct demented (MID), pure amnesic and age-matched normal controls a test involving immediate and 15-min delayed word-list recall and a modified version of the Huppert and Piercy's procedure (1978) assessing yes/no Recognition for pictures at 90 sec, 10 min, 1 hr and 24 hr delay intervals. Results showed an abnormal immediate/delayed performance decline for the word-list recall in AD and pure amnesic patients. In the same period, however, their Recognition score in the Huppert and Piercy's procedure decayed at normal rate. In the following intervals (1 hr and 24 hr), both groups disclosed abnormal forgetting slopes. Vascular demented patients, by contrast, disclosed fully normal forgetting rates both on the word-list recall and on the Huppert and Piercy's procedure. These findings are discussed in the light of cognitive mechanisms and neuroanatomical structures presumably underlying memory consolidation.

Different components in word-list forgetting of pure amnesics, degenerative demented and healthy subjects.

This study investigated the contribution of different components of the serial position curve to the accelerated forgetting rate displayed by amnesic and degenerative demented patients in word-list recall. For this purpose, we analyzed immediate and 15 min delayed recall performances on Rey's 15-word learning task of 16 pure amnesic, 15 Alzheimer's demented and 81 healthy subjects. Results documented that in all groups most forgetting occurred at the expense of terminal items of the word list. Nevertheless, both amnesic and demented patients showed a disproportionately larger memory loss on the recent part of the serial position curve than healthy subjects. Finally, amnesics (but not AD patients) suffered from a significantly larger forgetting rate for primacy items than normal controls. These data demonstrate that a critical deficit in memory disordered patients is represented by a failure in transferring information from a transitory memory status to a more durable storing condition. At least in amnesic patients, our results also suggest "true" long-term forgetting, presumably due to decay or to the intervening inaccessibility of previously stored memory representations.

A callosal disconnection syndrome of vascular origin.

OBJECTIVE: To study the after-effects of a selective lesion of the corpus callosum on the capacity in transferring spatial information on arm posture derived from kinesthesia and vision. DESIGN: Neuropsychological and psychophysical evaluations of a patient with callosal damage. SETTING: Institute of Neurology, University of "Tor Vergata", Rome, Italy and Research Centre, IRCCS "S. Lucia", Rome, Italy. PATIENT: P.V., a 59 years old man suffering from a vascular lesion of the left half of corpus callosum and left callosal radiations. MEASURES: Sensori-motor and cognitive tasks. Exo- and egocentric pointing abilities tasks. RESULTS: Impairments due to a disconnection between the two cerebral hemispheres were pointed out. About pointing abilities, errors were greater when each hand pointed to the remembered location of the other hand. Errors decreased dramatically with eyes open for right hand pointing to remembered location of left and right hand, and left hand pointing to remembered location of left hand. Open eyes left hand pointing to remembered location of right hand remained as poor as with eyes closed. CONCLUSIONS: The results appear compatible with the following network: visual information from striate and extrastriate cortex is passed forward to parietal cortex bilaterally (even in PV due to the splenium sparing). Kinesthetic information from parietal cortex of left and right hemisphere converge on a single visuokinesthetic center, lateralized to the left hemisphere. Information about limb position in three-dimensional space is then encoded in body-centered coordinates and passed forward to motor and premotor cortex in the frontal lobe. These frontal regions are those disconnected in PV.

Cognitive function in multiple sclerosis: a subcortical pattern of neuropsychological impairment?

In order to evaluate cognitive impairment in multiple sclerosis (MS) neuropsychological tests were administered to 25 patients with clinically definite disease. Four (16%) showed diffuse cognitive impairment, whereas the others, compared with controls showed a specific deficit on tests known to be sensitive to frontal lobe damage. These results are interpreted in the light of current hypotheses relating to subcortical contributions in cognition.

White matter damage along the uncinate fasciculus contributes to cognitive decline in AD and DLB.

This study investigates the patho-physiological implications of the uncinate fasciculus (UF) in the two most common forms of dementia, namely Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Forty-five consecutive patients diagnosed with either probable AD or DLB, and 16 individuals with amnesic mild cognitive impairment (a-MCI) were investigated using diffusion tensor MRI. Thirteen healthy subjects (HS) were also studied as controls. In each subject, the UF was bilaterally reconstructed by probabilistic tractography. From each UF, macroscopic volume and correspondent fractional anisotropy (FA) (an index of microscopic white matter integrity) were derived for the whole tract, and for the frontal and temporal portion of the UF. No significant between-group volumetric differences were found. In contrast, FA values from the UF were reduced bilaterally in patients with dementia (either AD or DLB) compared to HS. In addition, patients with AD showed reduced FA values compared to those with a-MCI. No significant FA difference was found between AD and DLB patients, nor between a-MCI and HS. Finally, in all patients, UF FA values were associated with neuropsychological scores at tests exploring memory and executive functions. This study indicates that the UF is remarkably damaged in patients at the stage of dementia, independently from the diagnostic form. Moreover, this UF damage seems to be driven by temporal involvement in AD, for which a prodromal stage (a-MCI) is defined.

Prospective memory in thalamic amnesia.

The contribution of the thalamus to the functioning of prospective memory (PM) is currently unknown. Here we report an experimental investigation of the performance of two patients with bilateral infarcts in the anterior-mesial regions of the thalami on an event-based PM paradigm. One patient, G.P., had a pervasive declarative memory impairment but no significant executive deficit. The other patient, R.F., had a memory deficit limited to verbal material with associated behavioral abnormalities (inertia and apathy); she performed poorly on tests of executive functions. Although both patients performed poorly on the PM task, a qualitative analysis of performance revealed different mechanisms at the base of their impaired PM. G.P. had reduced declarative memory for target words compared with normal controls; but, unforgotten words were normally able to elicit his recall of the prospective intention. Conversely, R.F.'s declarative memory for target words was as accurate as that of normal controls, but she presented a dramatically reduced ratio between the number of target words she recalled and the number of times she activated the prospective intention on the PM task, suggesting that her deficit consisted of difficulty in activating the intention despite normal declarative memory for the target events. In conclusion, results of the present study demonstrate that thalamic structures have an important role in PM processes. They also document that damage to the anterior-mesial regions of the thalami affects PM abilities by two different mechanisms, respectively based on the relative disruption of declarative memory or executive processes functioning, which, in turn, is related to the specific intrathalamic structures involved by the lesions. Indeed, while G.P.'s pervasive declarative memory deficit was underlain by bilateral involvement of the mammillo-thalamic tract, R.F.'s executive and behavioral abnormalities were likely related to bilateral damage of the midline, intralaminar, and medio-dorsal nuclei.

Gross anatomy of the corpus callosum in Alzheimer's disease: regions of degeneration and their neuropsychological correlates.

BACKGROUND/AIMS: Differences in the gross shape of the corpus callosum (CC) and its subregional areas were investigated on brain MRI of patients with probable Alzheimer's disease (AD) and age- and gender-matched healthy normal control subjects. The AD patients differed from the normal control subjects in terms of a more convex shape and a reduced area of the CC. METHODS: As for the comparisons of the subregional areas of the CC, we adapted a splitting method which takes into account the modification of the global shape of the CC, and we implemented it by normalizing the CC, to avoid the bias introduced by the observed callosal shape variability. RESULTS: The application of this method unveiled that the regional CC reductions were located in the anterior and posterior third of the CC, i.e. where small myelinated fibers are more frequent. None of the neuropsychological scores collected at the time of the MRI investigation of AD could predict a regional and/or overall callosal area reduction. The only measure that correlated with area of the isthmus of the CC was the MMSE that was administered to all participants. CONCLUSIONS: This latter result may be used as an in vivo indicator of the progress of neocortical disintegration in AD.

Verbal and spatial memory spans in Alzheimer's and multi-infarct dementia.

This study aimed to explore verbal and spatial memory spans in Alzheimer's (AD) and multi-infarct (MID) demented patients. For this purpose, we administered the forward and backward versions of the Digit Span and of the Corsi test to 18 AD, 18 MID and 26 controls. Results revealed a normal forward verbal span but reduced backward verbal and forward and backward spatial spans in both demented groups. These data are discussed in the light of the Working Memory model. It is argued that the normal verbal forward span is sustained by a normally functioning Articulatory Loop. The deficient processing resources of the Central Executive, on the other side, are responsible for the reduced extension of the other memory spans. The possible anatomical substrate of short-term memory impairment in dementia, as well as alternative interpretations of memory span performance in demented patients are discussed.

Recency effect in Alzheimer's disease: a reappraisal.

This study investigated the hypothesis that discrepant results regarding the recency effect in Alzheimer's disease (AD) patients are due to the different scoring procedures used by various authors and/or to the different number of terminal items attributed to the recency part of the curve. Our results indicate that the last two processed words are available to AD patients for recall, just as they are to controls. Words processed slightly earlier are less available to AD patients than to controls, presumably because of the accelerated forgetting rate in demented patients.