17q21.31 duplication causes prominent tau-related dementia with increased MAPT expression.

To assess the role of rare copy number variations in Alzheimer's disease (AD), we conducted a case-control study using whole-exome sequencing data from 522 early-onset cases and 584 controls. The most recurrent rearrangement was a 17q21.31 microduplication, overlapping the CRHR1, MAPT, STH and KANSL1 genes that was found in four cases, including one de novo rearrangement, and was absent in controls. The increased MAPT gene dosage led to a 1.6-1.9-fold expression of the MAPT messenger RNA. Clinical signs, neuroimaging and cerebrospinal fluid biomarker profiles were consistent with an AD diagnosis in MAPT duplication carriers. However, amyloid positon emission tomography (PET) imaging, performed in three patients, was negative. Analysis of an additional case with neuropathological examination confirmed that the MAPT duplication causes a complex tauopathy, including prominent neurofibrillary tangle pathology in the medial temporal lobe without amyloid-ß deposits. 17q21.31 duplication is the genetic basis of a novel entity marked by prominent tauopathy, leading to early-onset dementia with an AD clinical phenotype. This entity could account for a proportion of probable AD cases with negative amyloid PET imaging recently identified in large clinical series.

[Evaluation of temporality semantic knowledge in normal aging and in mild and moderate stages of Alzheimer's disease]. / Évaluation des connaissances sémantiques de la temporalité au cours du vieillissement normal et de la maladie d'Alzheimer aux stades légers à modérés, étude préliminaire.

OBJECTIVE: Episodic and semantic processes are involved in temporality used in daily life. Episodic memory permits one to place an event on the time axis, while semantic memory makes us aware of the time segmentation and its symbolic representation. Memory of the knowledge connected to the passing of time is materialized on the calendar and can be seen symbolically on the dial of a clock. In AD, semantic memory processes are preserved longer than processes related to episodic memory. We wonder whether the specific field of knowledge about time is altered during AD. METHODOLOGY: We validated a specific evaluation with a control group (354 healthy subjects). Then we applied this battery to assess AD patients to appreciate the feasibility of this tool for this population. We then compared 22 AD patients with a control group matched for age, sex and educational level. Our clinical scale of temporal semantic knowledge consists of four parts: (a) hour reading with a.m. and p.m. hours; (b) using a clock: 12 clock faces with the hour numbers already placed: the patient draws hour and minute hands for various hours; (c) temporal segmentation: exploration of the knowledge on daytime scale and of the calendar; (d) time duration estimation: calculate how long the interview has lasted after indicating the time of its beginning and its end, then the time between 10.40 to 12.00. RESULTS: While age and educational level had an influence on all the scores, in the two groups control and patients, gender did not. Temporal segmentation, independent of the cultural level, revealed the best acquired knowledge in our control population. All the scores differentiated patients from control subjects. The temporal semantic knowledge correlated with the AD severity seemed to be correlated with the attention, verbal comprehension, and some components of executive functions, but was not related to the clock drawing test result. Depression did not have any influence on this scale in our AD group. DISCUSSION: The temporal semantic knowledge clinical scale shows differential alterations, notably in hour reading and using a clock, and less in temporal segmentation. CONCLUSION: Temporal semantic knowledge is altered in AD. The diagnosis and follow-up of these alterations allow professionals and caregivers to consider adaptations of the patient's environment according to their needs.

[Significance of the blink reflex in the Wallenberg syndrome]. / Apports du réflexe trigémino-facial dans l'étude du syndrome de Wallenberg.

The blink reflex was studied in 38 cases with lateral medullary lesions (Wallenberg syndrome). Twenty-one blink reflexes were abnormal. The most common abnormality is an afferent delay in the late reflex on the side of the lesion with a normal early reflex. This abnormality is not pathognomonic of the Wallenberg syndrome. The physiopathogeny is discussed.

[Central neurologic forms of Waldenström's disease. Bing-Neel syndrome. 3 cases]. / Formes neurologiques centrales de la maladie de Waldenström. Syndrome de Bing-Neel. Trois cas.

Three cases of central nervous system involvement in Waldenström's macroglobulinemia (Bing Neel's syndrome) are reported. Such cases are unusual and have a poor prognosis. One patient received chemotherapy including BCNU, cyclophosphamide, vincristine, melphalan and prednisolone, which was followed by a dramatic improvement. The pathogenesis of Bing Neel's syndrome is discussed.

[Parkinson disease and cognitive evoked potentials]. / Maladie de Parkinson et potentiels évoqués cognitifs.

Long latency auditory evoked potentials were recorded in 50 patients with Parkinson's disease, some case were also investigated by the Rapid Evaluation of Cognitive Functions test (RECF) and Trail Making A test (TMA). Latencies of P2, N2 and P300 waves were longer in the parkinsonian group than in a control group matched for age. Latencies of N2 and P300 waves were correlated significantly with scores for RECF and TMA presumed to be sensitive to organic brain lesions. On the other hand no significant correlation was found between RECF and P1 and P2 latencies. In addition, correlation was lacking between Verbal Automatism test scores, presumed to be resistant to organic brain lesions, and P300 wave latencies. Cognitive evoked potential (CEP) latency increases with age in normal subjects. In the parkinsonian group the coefficient of correlation between these two factors was lower but still significant. The parkinsonian patients with dementia as defined by DSM III criteria, or an RECF score of less than 46, showed longer N2 and P300 latencies but no significant difference in N1 and P2 latencies. In contrast, comparison of P300 and N2 wave latencies in depressed and non-depressed parkinsonian patients failed to show any significant difference. The bilateral akinetic forms had marked lengthening of P300 wave latencies and a lower TMA score. Neither the duration of the disease, type of treatment, duration of L-Dopa therapy significantly influenced the latency of cognitive event-related potentials.

[Neurological toxicity of amiodarone. 5 case reports]. / Toxicité neurologique de l'amiodarone. A propos de cinq observations.

Five patients developed neurological adverse effects as they were treated with amiodarone for 2 to 18 months. The daily maintenance dose did not exceed 400 mg. The neurological manifestations included tremor, ataxia, peripheral neuropathy, dyskinesia, myoclonic jerks, extrapyramidal hypertony, and altered mental status. These side effects resolved within 3 days to 3 months after amiodarone withdrawal. Advanced age, renal failure, diabetes mellitus, and alcoholism seemed to be risk factors for development of amiodarone neurotoxicity. Both peripheral and central nervous systems are involved in these amiodarone-induced complications.

[Exploration of visual memory by functional MRI]. / Exploration de la mémoire visuelle par l'IRM fonctionnelle.

PURPOSE: The aim of our study was to evidence the location of the cortical area triggered by visual memory tasks by he mean of functional magnetic resonance imaging examination (fMRI). METHODS: Twelve healthy volunteers underwent fMRI examination on a 1.5 Tesla magnet with echoplanar imaging sequence during figurative and non-figurative memory tasks. An area was considered to be activated if at least 10 contiguous voxels activation was noted. Activated areas were defined for both tasks and the brain mapping was realized according to Talairach atlas. RESULTS: For all examinations a bilateral activity was evidenced (area 17 and 18). In addition, a frontal activation was also noted in 83% of the cases for both tasks. However, frontal activation was bilateral in 9/10 cases for the figurative task and 6/10 cases for the non-figurative task. CONCLUSION: FMRI was able to evidence activation of cerebral areas during visual memory tasks in all our study cases. Frontal activation was not discriminative of figurative or non figurative memory. This might be probably explain by inappropriate non-figurative tests. FMRI should allow a better knowledge of memory mechanisms as well as an enhancement of functional cerebral mapping before surgery.

Event-related auditory evoked potentials and multiple sclerosis.

Long latency event-related auditory evoked potentials, particularly the P300 wave, constitute an objective electrophysiological index of cognitive function. For this reason, these potentials have been studied in a series of 101 patients with multiple sclerosis (MS), classified according to McAlpine's criteria into definite, probable and possible cases. The patients were also classified as depressed or non-depressed according to the DSM-III and Research Diagnostic Criteria. They were also subjected to a battery of psychometric tests. In the patient population the N200 and P300 latencies were increased, as were the P200 latencies, when compared with a control population. This electrophysiological pattern had previously been observed in other conditions characterised by subcortical lesions. Partial correlations (at constant disease duration) between the disability score and the cognitive deficit were found to be significant. Patients with an increased P300 latency had a greater disability and the P300 latency was significantly correlated with the duration of the illness. The N200 and P300 latencies were increased in depressed MS subjects, but this increase did not reach the level of significance. Depression was more frequent in the more severely handicapped patients. This suggests that the origin of the depression seen in multiple sclerosis is only partly organic, and that it is one of the factors contributing to the subcortical cognitive deficit in multiple sclerosis. Progressive forms of the disease exhibited the most profound cognitive deficit, and the most marked increase in P300 latency.

[Cognitive evoked potentials at the stages II and III of human immunodeficiency virus infection]. / Potentiels évoqués cognitifs aux stades II et III de l'infection par le virus de l'immunodéficience humaine.

Neuropsychological and psychometric investigations have sometimes attested to and sometimes denied the existence of cognitive perturbations during the early phases of human immunodeficiency virus (HIV) infection (stages II and III of the CDC classification): strictly asymptomatic seropositivity or generalized lymphadenopathy. Therein lies the basis of the debate concerning the neurotropism of the virus and its deleterious effects on the central nervous system (CNS). We hoped to contribute to the resolution of this discussion by recording late evoked auditory potentials, which are composed of two types of components: exogenous responses attesting to the reception of stimuli by specific sensory areas of the CNS, regardless of their informative value for the subject; and endogenous responses that occur later, appearing when the subject is required to distinguish between different stimuli, for example, counting high-pitched sounds randomly distributed among low-pitched ones. The latter responses, which have been most extensively studied for wave P300, are associated with cognitive functions, and alterations of the evoked cognitive potentials have been observed during the course of demential syndromes of various origins. Fifteen individuals were subjected to the protocol for recording long-latency, evoked auditory potentials. These studies were completed by a battery of psychometric tests, two methods for evaluating depression and an assessment of the anxiety level. The results showed a significant lengthening of the latency of wave P300 in the seropositive subjects. This prolongation also affected one of the exogenous components, i.e., wave P2. In addition, their intelligence quotients, regardless of whether the IQ explores the so-called crystallized component or the fluid component of intelligence, were not significantly different from those of the general population.(ABSTRACT TRUNCATED AT 250 WORDS)