Relevancia del efecto de posición serial en el diagnóstico diferencial entre el deterioro cognitivo leve, la demencia de tipo Alzheimer y el envejecimiento normal / Relevance of the serial position effect in the differential diagnosis of mild cognitive impairment, Alzheimer-type dementia, and normal ageing

Los efectos de posición serial son estudiados cuando se memoriza una serie de palabras que excede el span atencional. En sujetos normales son recordadas más frecuentemente las palabras del inicio y final de una lista reflejando el funcionamiento de la memoria episódica a corto y largo plazo. Objetivos: Estudiar el efecto de principio y el de fin de lista en pacientes con deterioro cognitivo leve (DCL) y compararlo con demencia tipo Alzheimer (DTA) y sujetos con envejecimiento normal (SN). Métodos: Fueron evaluados neurológica y neuropsicológicamente 30 pacientes con DTA, 25 con DCL y 20 SN. Se utilizó el Test de aprendizaje auditivo de una lista de palabras de Rey en donde se evaluó el efecto de principio, medio y fin de lista en cada ensayo y su efecto en el recuerdo diferido. Resultados: Los sujetos con DCL mostraron un patrón general de memoria similar a los sujetos con DTA, caracterizado por una reducción en el aprendizaje, olvido acelerado y un claro efecto de fin de lista en el aprendizaje. A nivel del recuerdo diferido mostraron un patrón diferencial recordando palabras de principio y medio más cercano a los normales pero no recordando las finales de la lista como las DTA. Conclusiones: La prueba de aprendizaje de una lista de palabras es una herramienta que nos permite discriminar entre pacientes con DCL y SN. El índice de recencia en el recuerdo diferido es un indicador útil para diferenciar el envejecimiento normal de los pacientes con DCL (AU)

Serial position effects are observed when a person memorises a series of words exceeding his or her attention span. Cognitively normal individuals recall words at the beginning and end of the list more frequently than those in the middle, which reflects the way that short- and long-term episodic memory works. Objective: To study the serial position effect in patients with mild cognitive impairment (MCI) compared to subjects with Alzheimer-type dementia (AD) or normal ageing (NA). Methods: 30 AD, 25 MCI and 20 NA subjects underwent neurological and neuropsychological assessment. The Rey Auditory Verbal Learning Test (RAVLT) was used to study primacy, middle, and recency effects and delayed recall for each group. Results: The general memory pattern of MCI subjects was very similar to that of AD subjects, and was characterised by reduced learning capacity, rapid forgetfulness and clear recency effect in learning. With regard to delayed recall, however, there were differences in performance; MCI subjects’ ability to recall words at the beginning and middle of the list was similar to that of normal subjects, while their memory of words at the end of the list was poor, as in AD subjects. Conclusions: RAVLT is a tool permitting us to distinguish between MCI and NA subjects. The recency index for the delayed recall task is a valid indicator for distinguishing between MCI patients and patients with normal ageing (AU)

Relevance of the serial position effect in the differential diagnosis of mild cognitive impairment, Alzheimer-type dementia, and normal ageing.

UNLABELLED: Serial position effects are observed when a person memorises a series of words exceeding his or her attention span. Cognitively normal individuals recall words at the beginning and end of the list more frequently than those in the middle, which reflects the way that short- and long-term episodic memory works. OBJECTIVE: To study the serial position effect in patients with mild cognitive impairment (MCI) compared to subjects with Alzheimer-type dementia (AD) or normal ageing (NA). METHODS: 30 AD, 25 MCI and 20 NA subjects underwent neurological and neuropsychological assessment. The Rey Auditory Verbal Learning Test (RAVLT) was used to study primacy, middle, and recency effects and delayed recall for each group. RESULTS: The general memory pattern of MCI subjects was very similar to that of AD subjects, and was characterised by reduced learning capacity, rapid forgetfulness and clear recency effect in learning. With regard to delayed recall, however, there were differences in performance; MCI subjects' ability to recall words at the beginning and middle of the list was similar to that of normal subjects, while their memory of words at the end of the list was poor, as in AD subjects. CONCLUSIONS: RAVLT is a tool permitting us to distinguish between MCI and NA subjects. The recency index for the delayed recall task is a valid indicator for distinguishing between MCI patients and patients with normal ageing.

Enhancing a declarative memory in humans: the effect of clonazepam on reconsolidation.

A consolidated memory recalled by a specific reminder can become unstable (labile) and susceptible to facilitation or impairment for a discrete period of time. This labilization phase is followed by a process of stabilization called reconsolidation. The phenomenon has been shown in diverse types of memory, and different pharmacological agents have been used to disclose its presence. Several studies have revealed the relevance of the GABAergic system to this process. Consequently, our hypothesis is that the system is involved in the reconsolidation of declarative memory in humans. Thus, using our verbal learning task, we analyzed the effect of benzodiazepines on the re-stabilization of the declarative memory. On Day 1, volunteers learned an association between five cue- response-syllables. On Day 2, the verbal memory was labilized by a reminder presentation, and then a placebo capsule or 0.25 mg or 0.03 mg of clonazepam was administered to the subjects. The verbal memory was evaluated on Day 3. The volunteers who had received the 0.25 mg clonazepam along with the specific reminder on Day 2, exhibited memory improvement. In contrast, there was no effect when the drug was given without retrieval, when the memory was simply retrieved instead of being reactivated or when short-term memory testing was performed 4 h after reactivation. We discuss the GABAergic role in reconsolidation, which shows a collateral effect on other memories when the treatment is aimed at treating anxiety disorders. Further studies might elucidate the role of GABA in the reconsolidation process associated with dissimilar scenarios. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

Decision-making in Parkinson's disease patients with and without pathological gambling.

BACKGROUND AND PURPOSE: Pathological gambling (PG) in Parkinson's disease (PD) is a frequent impulse control disorder associated mainly with dopamine replacement therapy. As impairments in decision-making were described independently in PG and PD, the objective of this study was to assess decision-making processes in PD patients with and without PG. METHODS: Seven PD patients with PG and 13 age, sex, education and disease severity matched PD patients without gambling behavior were enrolled in the study. All patients were assessed with a comprehensive neuropsychiatric and cognitive evaluation, including tasks used to assess decision-making abilities under ambiguous or risky situations, like the Iowa Gambling Task (IGT), the Game of Dice Task and the Investment Task. RESULTS: Compared to PD patients without gambling behavior, those with PG obtained poorer scores in the IGT and in a rating scale of social behavior, but not in other decision-making and cognitive tasks. CONCLUSIONS: Low performance in decision-making under ambiguity and abnormal social behavior distinguished PD patients with PG from those without this disorder. Dopamine replacement therapy may induce dysfunction of the ventromedial prefrontal cortex and amygdala-ventral striatum system, thus increasing the risk for developing PG.

Addenbrooke's Cognitive Examination validation in Parkinson's disease.

BACKGROUND: There is a clear need for brief, sensitive and specific cognitive screening instruments in Parkinson's disease (PD). OBJECTIVES: To study Addenbrooke's Cognitive Examination (ACE) validity for cognitive assessment of PD patient's using the Mattis Dementia Rating Scale (MDRS) as reference method. A specific scale for cognitive evaluation in PD, in this instance the Scales for Outcomes of Parkinson's disease-Cognition (SCOPA-COG), as well as a general use scale the Mini-mental state examination (MMSE) were also studied for further correlation. METHODS: Forty-four PD patients were studied, of these 27 were males (61%), with a mean (SD) age of 69.5 (11.8) years, mean (SD) disease duration of 7.6 (6.4) years (range 1-25), mean (SD) total Unified Parkinson's Disease Rating Scale (UPDRS) score 37 (24) points, UPDRS III 16.5 (11.3) points. MDRS, ACE and SCOPA-COG scales were administered in random order. All patients remained in on-state during the study. RESULTS: Addenbrooke's Cognitive Examination correlated with SCOPA-COG (r = 0.93, P < 0.0001), and MDRS (r = 0.91 P < 0.0001) and also with MMSE (r = 0.84, P < 0.001). Area under the receiver-operating curve, taking MDRS as the reference test, was 0.97 [95% confidence interval (CI): 0.92-1.00] for ACE, 0.92 (95% CI: 0.83-1.00) for SCOPA-COG and 0.91 (95% CI: 0.83-1.00) for MMSE. Best cut-off value for ACE was 83 points [Sensitivity (Se) = 92%; Specificity (Sp) = 91%; Kappa concordance (K) = 0.79], 20 points for the SCOPA-COG (Se = 92%; Sp = 87%; K = 0.74) and 26 points for MMSE (Se = 61%; Sp = 100%; K = 0.69). CONCLUSION: Addenbrooke's Cognitive Examination appears to be a valid tool for dementia evaluation in PD, with a cut-off point which should probably be set at 83 points, displaying good correlation with both the scale specifically designed for cognitive deficits in PD namely SCOPA-COG, as well as with less specific tests such as MMSE.

Prospective randomized 1-year follow-up comparison of bilateral subthalamotomy versus bilateral subthalamic stimulation and the combination of both in Parkinson's disease patients: a pilot study.

It has been suggested that potential risk of hemiballismus after subthalamotomy makes DBS preferable to ablation for IPD treatment; however, cost and the need for regular electrode control have also been observed as disadvantages to stimulation. The objective was to compare efficacy and safety of different surgical approaches to STN, in a prospective randomized pilot study. Sixteen consecutive IPD patients randomized to receive either: bilateral STN-DBS, bilateral subthalamotomy or unilateral subthalamotomy plus contralateral STN-DBS implantation, and followed for 12 months after surgery. One patient died and was excluded from the analysis. Total and motor UPDRS scores, as well as drug-induced dyskinesias improved significantly at 1 year follow-up, regardless of the procedure administered and without statistically significant differences between treatment modalities. Discrete changes were observed on ACE and MMSE scores. Psychiatric examination of patients subjected to bilateral stimulation and lesion, revealed slight increment in apathy and irritability scores, coinciding with significant deterioration of mentation, behaviour and mood as measured using the UPDRS. One patient presented persistent hemiballismus and required ulterior posteroventral pallidotomy. In this small group of patients, overall motor performance significantly improved after all three procedures, without major differences in outcome. Adverse events were, nevertheless, observed after both ablation and stimulation. The role of bilateral subthalamotomy in patients unable to receive a DBS electrode-implant merits further exploration in a larger series of patients with longer follow-up.

Kinematic evaluation of gestural and repetitive single joint movements of the arm after posteroventral pallidotomy, subthalamotomy or both procedures combined in two Parkinson's disease patients: two case studies.

Two patients with severe Parkinson's disease undergoing partial or complete ablative interruption of basal ganglia (BG) output are presented. One patient who underwent bilateral subthalamotomy, and a second who underwent unilateral posteroventral pallidotomy, followed 7 years later by a bilateral subthalamotomy because of contralateral disease progression, were studied. In addition to the usual clinical evaluation, changes in joint kinematics observed during unconstrained, skilled multi-joint movement and repetitive single joint (RSJ) movement of the wrist were studied. Clinical UPDRS items referred to hand movements contralateral to the procedure, and instrumental measurement of RSJ improved in both patients after either pallidotomy or subthalamotomy. When both BG outflow paths were interrupted as was the case in the second patient (bilateral subthalamotomy after the initial pallidotomy), no added clinical improvement was observed, RSJ even deteriorated slightly. Instrument-based studies for movement alteration detection after simultaneous ablation of the globus pallidus and the subthalamic nucleus of these two patients showed greater sensitivity than clinical evaluation alone. Complex gestural movement performance remained unaffected after partial (subthalamotomy or pallidotomy) or complete interruption of BG outflow (case 2), indicating BG compensatory capacity after total outflow interruption remained intact.

Ictal non-forced grasping behaviour.

Our aim was to investigate whether patients with epileptiform foci in the frontal lobe, as revealed by video EEG (VEEG) analysis, exhibit non-forced grasping behaviour and manipulatory movements during seizures. We retrospectively reviewed ictal videotapes of 30 consecutive patients with frontal and 30 with temporal lobe epilepsy undergoing VEEG for the presence and type of grasping and manipulatory movements. Four of the 30 patients with frontal lobe epilepsy (13%) showed unilateral grasping behaviour, three of whom had whole hand prehension (one with manipulation movements as well) and one pinching movements. In all patients, arm abduction and elevation resembling reaching invariably preceded grasping hand movements. The epileptogenic focus was located in the contralateral and ipsilateral frontocentral region in two and one patient, respectively, and in the ipsilateral orbitofrontal region in another. However, none of the patients with temporal lobe epilepsy showed grasping behaviour. Patients with frontal lobe epilepsy may show non-forced grasping with or without manipulatory finger movements as part of ictal phenomena.

Ictal tachycardia: its discriminating potential between temporal and extratemporal seizure foci.

A wide variety of CNS lesions have been associated with changes in heart rate (HR). However, in epileptic patients their value to lateralize seizure onset remains controversial. This study aims to assess if HR changes associated with partial onset seizures could be useful in lateralizing seizure onset. We analysed HR changes on 100 seizures from 38 consecutive patients (mean age: 27.5 years) admitted for video-EEG telemetry monitoring. We evaluated the R-R interval 30 seconds before the seizure onset and 10, 20 and 120 seconds after the onset. We assessed whether there was a correlation between HR changes and seizure type, left/right differences and different semiological components for each seizure. We recorded 100 seizures. Three non-lateralized seizures were excluded from the analysis; 63/97 (65%) had left hemisphere onset, mainly from the temporal lobe (57.7%). The mean baseline HR was 77 beats per minute Ictal tachycardia (HR: > or = 107.06 beats per minute) was detected in 32 seizures, with ictal onset from the mesial temporal lobe structures in 23/32; 16/32 occurred during the first 10 seconds and 16/32 during the next 20 seconds from the seizure onset independently of the site of origin. Among the different semiological components for each seizure, only dystonic posturing and automatism correlated with HR increments. We did not find bradycardia in our series. Ictal tachycardia occurs most frequently with seizures arising from the mesial temporal lobe and it may not reliably predict the lateralization of seizure onset.

Bilateral pallidotomy for treatment of Parkinson's disease induced corticobulbar syndrome and psychic akinesia avoidable by globus pallidus lesion combined with contralateral stimulation.

OBJECTIVE: Posteroventral pallidotomy (PVP) has proved to be an effective method for the treatment of Parkinson's disease. However, data on bilateral procedures are still limited. To assess the effects of bilateral globus pallidus (GPi) lesion and to compare it with a combination of unilateral GPi lesion plus contralateral GPi stimulation (PVP+PVS), an open blind randomised trial was designed. METHODS: A prospective series of patients with severe Parkinson's disease refractory to medical treatment, and severe drug induced dyskinesias, were randomised either to simultaneous bilateral PVP or simultaneous PVP+PVS. All patients were assessed with the core assessment programme for intracerebral transplantation (CAPIT), and a comprehensive neuropsychological and neuropsychiatric battery both before surgery and 3 months later. RESULTS: The severe adverse effects found in the first three patients subjected to bilateral PVP led to discontinuation of the protocol. All three patients developed depression and apathy. Speech, salivation, and swallowing, as well as freezing, walking, and falling, dramatically worsened. By contrast, all three patients undergoing PVP+PVS had a significant motor improvement. CONCLUSION: Bilateral simultaneous lesions within the GPi may produce severe motor and psychiatric complications. On the other hand, a combination of PVP+ PVS significantly improves parkinsonian symptoms not associated with the side effects elicited by bilateral lesions.

Limb apraxia: cortical or subcortical.

Ideomotor apraxia is defined as a disturbance in timing, sequencing, and spatial organization of gestural movements. Left hemisphere motor dominance reflected by ideomotor apraxia mainly refers to spatially and temporally complex movements performed outside the natural context. While clinicoanatomical studies have failed to unveil a specific lesion correlating with apraxia, white matter damage-interrupting corticocortical and corticosubcortical connections-seems crucial for the deficit to be persistent and severe. Patients with basal ganglia lesions and disorders, such as Parkinson's disease and progressive supranuclear palsy, may exhibit ideomotor apraxia. The putative roles of the basal ganglia in object-oriented action, and therefore in praxis, would include among others (a) the selection of the kinematic parameters and the direction of arm movements, (b) working as an integral part of brain systems involved in timing and representation of action sequences, (c) encoding behavioral context, and (d) working as a subcortical component of the parietofrontal circuits devoted to sensorimotor transformation (e.g., reaching). Several studies suggest that basal ganglia pathology per se may not cause overt apraxia. However, when it is combined with dysfunction of the cortical components of the neural systems involved in sequencing, sensorimotor transformation, and response selection, different types of ideomotor praxis deficits would become clinically manifested.

Detection of Helicobacter pylori in human carotid atherosclerotic plaques.

BACKGROUND AND PURPOSE: Several lines of evidence point toward a relationship between infection and atherosclerotic vascular disease. Thus, infection and inflammation often precede ischemic neurological events. Transient alterations in coagulation and direct arterial invasion by certain microorganisms have been reported. Helicobacter pylori infection is the major cause of peptic ulcer disease and appears to be a risk factor for ischemic cerebrovascular disease. However, in contrast to other chronic infectious agents, H pylori has not been consistently isolated from atherosclerotic lesions. METHODS: We investigated the presence of H pylori in 38 atherosclerotic plaques obtained at carotid endarterectomy by using morphological and immunohistochemical techniques and a highly sensitive polymerase chain reaction method. We performed immunohistochemical detection of intercellular adhesion molecule-1, a marker related to inflammatory cell response. We also examined 7 carotid arteries obtained at autopsy from subjects without carotid atherosclerosis. RESULTS: H pylori DNA was found in 20 of 38 atherosclerotic plaques. Ten of the H pylori DNA-positive plaques also showed morphological and immunohistochemical evidence of H pylori infection. None of 7 normal carotid arteries was positive for H pylori. Intercellular adhesion molecule-1 was expressed in 75% of H pylori-positive plaques and in 22% of H pylori-negative plaques. The presence of the microorganism was associated with male sex but was independent of age, vascular risk factor profile, and prior neurological symptoms. CONCLUSIONS: H pylori is present in a substantial number of carotid atherosclerotic lesions and is associated with features of inflammatory cell response. This study provides additional evidence of the relationship between H pylori infection and atherosclerotic disease.

Mismatch between electrophysiologically defined and ventriculography based theoretical targets for posteroventral pallidotomy in Parkinson's disease.

OBJECTIVES: Over the past few years many reports have shown that posteroventral pallidotomy is an effective method for treating advanced cases of Parkinson's disease. The main differences with earlier descriptions were the use of standardised evaluation with new high resolution MRI studies and of single cell microrecording which can electrophysiologically define the sensorimotor portion of the internal globus pallidus (GPi). The present study was performed on a consecutive series of 40 patients with Parkinson's disease who underwent posteroventral pallidotomy to determine localisation discrepancies between the ventriculography based theoretical and the electrophysiologically defined target for posteroventral pallidotomy. METHODS: The tentative location of the posteroventral GPi portion was defined according to the proportional Talairach system. Single cell recording was performed in all patients. The definitive target was chosen according to the feasibility of recording single cells with GPi cell features, including the presence of motor drive and correct identification of the internal capsule and of the optic tract by activity recording and microstimulation. RESULTS: In all 40 patients the electrophysiologically defined sensorimotor portion of the GPi was lesioned, with significantly improved cardinal Parkinson's disease symptoms as well as levodopa induced dyskinesias, without damage to the internal capsule or optic tract. Significant differences between the localisation of the ventriculography based theoretical versus electrophysiological target were found in depth (p<0.0008) and posteriority (p<0.04). No significant differences were found in laterality between both approaches. Difference ranges were 8 mm for laterality, 6.5 mm for depth, and 10 mm for posteriority. CONCLUSIONS: Electrophysiologically defined lesion of GPi for posteroventral pallidotomy, shown to be effective for treating Parkinson's disease, is located at a significantly different site from the ventriculography based theoretical target.

[Chronic hereditary ataxic polyneuropathy]. / Polineuropatia atáxica hereditaria crónica.

Sensory ataxic polyneuropathies are characterised by the presence of sensory ataxia due to damage to large myelinated sensory fibres, with total or relative preservation of muscle strength, pain and temperature sensation. Hereditary ataxic polyneuropathies are exceptional and very few families with this disorder have been reported so far. We here describe the neurological, electrophysiological and sural nerve biopsy data of four siblings with an ataxic chronic polyneuropathy, starting after age 50. They had an ataxic gait which worsened in darkness, horizontal nystagmus, hypo or areflexia, and severe impairment of limbs' propriocaption. Nerve conduction studies showed absent sensory nerve action potentials in all nerves tested. Somatosensory evoked potentials showed reduced amplitude and prolonged latencies. Sural nerve biopsy showed a severe loss of myelinated and unmyelinated fibres. Symptoms slowly progressed over the years. The recognition of this syndrome is important in the search for the etiology of chronic ataxic neuropathies.

[Neurological complications of renal transplant]. / Complicaciones neurológicas del trasplante renal.

Advances in surgical procedures and new immunosuppressor therapies have improved the outcome of renal grafts. However, these changes have been accompanied by infectious, neoplastic and neurologic complications. The purpose of this study was to determine the incidence of neurologic complications among 542 patients receiving a renal transplant (from living or cadaveric donors) at CEMIC between 1970 and 1996. Neurologic complications occurred in 43 patients (8%) as follows: 8 meningitis (1.5%), 8 acute confusional syndrome (1.5%), 7 encephalitis (1.3%), 7 cerebrovascular accidents (1.3%), 6 convulsions (1.1%), 3 tumors (0.5%), 3 femoral nerve lesion (0.5%), and 1 epidural lipomatosis (0.1%). Etiologic agents most commonly observed in meningitis were: Cryptococcus neoformans, Listeria monocytogenes and Mycobacterium tuberculosis. Major difficulties arose in the diagnosis of encephalitis. Diagnosis of the above complications required clinical astuteness and repeated bacteriologic, serologic and imaging studies.

Disruption of spatial organization and interjoint coordination in Parkinson's disease, progressive supranuclear palsy, and multiple system atrophy.

Patients with basal ganglia diseases may exhibit ideomotor apraxia. To define the nature of the impairment of the action production system, we studied a repetitive gesture of slicing bread by three-dimensional computergraphic analysis in eight nondemented patients with Parkinson's disease in the "on" state, five with progressive supranuclear palsy and four with multiple system atrophy. Two patients with Parkinson's disease and two with progressive supranuclear palsy showed ideomotor apraxia for transitive movements on standard testing. A Selspott II system was used for kinematic analysis of wrist trajectories and angular motions of the shoulder and elbow joints. Patients with Parkinson's disease, progressive supranuclear palsy, and even some with multiple system atrophy exhibited kinematic deficits in the spatial precision of movement and velocity-curvature relationships; in addition, they failed to maintain proper angle/angle relationships and to apportion their relative joint amplitudes normally. Spatial disruption of wrist trajectories was more severe in patients with ideomotor apraxia. We posit that the basal ganglia are part of the parallel parieto-frontal circuits devoted to sensorimotor integration for object-oriented behavior. The severity and characteristics of spatial abnormalities of a transitive movement would therefore depend on the location and distribution of the pathologic process within these circuits.

Limb apraxias: higher-order disorders of sensorimotor integration.

Limb apraxia comprises a wide spectrum of higher-order motor disorders that result from acquired brain disease affecting the performance of skilled, learned movements. At present, limb apraxia is primarily classified by the nature of the errors made by the patient and the pathways through which these errors are elicited, based on a two-system model for the organization of action: a conceptual system and a production system. Dysfunction of the former would cause ideational (or conceptual) apraxia, whereas impairment of the latter would induce ideomotor and limb-kinetic apraxia. Currently, it is possible to approach several types of limb apraxia within the framework of our knowledge of the modular organization of the brain. Multiple parallel parietofrontal circuits, devoted to specific sensorimotor transformations, have been described in monkeys: visual and somatosensory transformations for reaching; transformation of information about the location of body parts necessary for the control of movements; somatosensory transformation for posture; visual transformation for grasping; and internal representation of actions. Evidence from anatomical and functional brain imaging studies suggests that the organization of the cortical motor system in humans is based on the same principles. Imitation of postures and movements also seems to be subserved by dedicated neural systems, according to the content of the gesture (meaningful versus meaningless) to be imitated. Damage to these systems would produce different types of ideomotor and limb-kinetic praxic deficits depending on the context in which the movement is performed and the cognitive demands of the action. On the other hand, ideational (or conceptual) apraxia would reflect an inability to select and use objects due to the disruption of normal integration between systems subserving the functional knowledge of actions and those involved in object knowledge.