Do we know how to diagnose epilepsy early in Alzheimer's disease?

Epilepsy is an increasingly recognized comorbidity in Alzheimer's disease (AD). First described as generalized in dementia patients, epileptic AD patients are nowadays fully described in earlier stages of the disease (with mild or subjective cognitive impairment). At such early stages, patients may present not only with generalized seizures, but also with focal seizures (commonly localized in the frontal or temporal lobe). Thus, partial or generalized epilepsy is part of the semiological spectrum of AD that should be borne in mind at all stages of disease to ensure early identification and prevent the risk of repeated seizures (such as accidents, injury, progression of cognitive impairment). This review of the available (and still growing) literature shows that there are already sufficient data to inform physicians on seizure semiology, and on the diagnostic value of electroencephalography and brain imaging. Taken together, these tools can help to rapidly identify epilepsy in AD patients. Nevertheless, epilepsy diagnosis can be challenging, and test medication is sometimes necessary. Some cerebrospinal fluid biomarkers (or their ratios) may also prove to be good predictors of seizures in AD, but further studies are needed. Epilepsy in AD patients is frequently pharmacosensitive, and a good response can be obtained with standard doses of antiepileptic drugs. For all these reasons and based on our review of the literature, it appears that, at present, the diagnosis of epilepsy in AD is not only possible at any stage of the disease, but also to be recommended to improve the patient's prognosis.

Exploring anterograde memory: a volumetric MRI study in patients with mild cognitive impairment.

BACKGROUND: The aim of this volumetric study was to explore the neuroanatomical correlates of the Free and Cued Selective Reminding Test (FCSRT) and the Delayed Matching-to-Sample-48 items (DMS-48), two tests widely used in France to assess verbal and visual anterograde memory. We wanted to determine to what extent the two tests rely on the medial temporal lobe, and could therefore be predictive of Alzheimer's disease, in which pathological changes typically start in this region. METHODS: We analysed data from a cohort of 138 patients with mild cognitive impairment participating in a longitudinal multicentre clinical research study. Verbal memory was assessed using the FCSRT and visual recognition memory was evaluated using the DMS-48. Performances on these two tests were correlated to local grey matter atrophy via structural MRI using voxel-based morphometry. RESULTS: Our results confirm the existence of a positive correlation between the volume of the medial temporal lobe and the performance on the FCSRT, prominently on the left, and the performance on the DMS-48, on the right, for the whole group of patients (family-wise error, P < 0.05). Interestingly, this region remained implicated only in the subgroup of patients who had deficient scores on the cued recall of the FCSRT, whereas the free recall was associated with prefrontal aspects. For the DMS-48, it was only implicated for the group of patients whose performances declined between the immediate and delayed trial. Conversely, temporo-parietal cortices were implicated when no decline was observed. Within the medial temporal lobe, the parahippocampal gyrus was prominently involved for the FCSRT and the immediate trial of the DMS-48, whereas the hippocampus was solely involved for the delayed trial of the DMS-48. CONCLUSIONS: The two tests are able to detect an amnestic profile of the medial temporal type, under the condition that the scores remain deficient after the cued recall of the FCSRT or decline on the delayed recognition trial of the DMS-48. Strategic retrieval as well as perceptual/attentional processes, supported by prefrontal and temporo-parietal cortices, were also found to have an impact on the performances. Finally, the implication of the hippocampus appears time dependent, triggered by a longer delay than the parahippocampus, rather than determined by the sense of recollection or the encoding strength associated with the memory trace.

[Cognitive and affective theory of mind in Lewy body dementia: A preliminary study]. / Théorie de l'esprit cognitive et affective dans la démence à corps de Lewy : une étude préliminaire.

INTRODUCTION: 'Theory of Mind' refers to the ability to attribute mental states, thoughts (cognitive component) or feelings (affective component), to others. This function has been studied in many neurodegenerative diseases; however, to our knowledge no studies investigating theory of mind in dementia with Lewy Bodies (DLB) have been published. The aim of our study was to search theory of mind deficits in patients with DLB. METHODS: Seven patients with DLB (DLB group), at the stage of mild dementia or mild cognitive impairments, and seven healthy elderly adults (control group) were included in the study. After a global cognitive assessment, we used the Faux Pas Recognition test to assess the cognitive component of theory of mind, and the Reading the Mind in the Eyes test for the assessment of affective component. RESULTS: We found a significant difference between the two groups for the Faux Pas test with an average score of 35.6 for the DLB group and 48.3 for the control group (P=0.04). Scores were particularly low in the DLB group for the last question of the test concerning empathy (42.9% versus 85%, P=0.01). There was not a significant difference between the two groups for the Reading the Mind in the Eyes test (P=0.077). DISCUSSION: This preliminary study showed early impairments of theory of mind in the DLB. The cognitive component seems more affected than the affective component in this pathology. This pattern is consistent with the pattern found in Parkinson's disease, but differs from other neurodegenerative diseases as Alzheimer's disease or frontotemporal lobe dementia. These patterns may help to differentiate DLB from these diseases. Further study is needed to confirm these results and to compare with other dementias.

[Syndrome of transient epileptic amnesia and epileptic amnesic syndrome: the same entity?]. / Le syndrome of transient epileptic amnesia et l'epileptic amnesic syndrome sont-ils une même entité ?

A chronic subjective cognitive impairment can be symptomatic of temporal lobe epilepsy (TLE); it is thereby frequently reversible with the use of antiepileptic monotherapy. In this field, two distinct syndromes have been described: the Epileptic Amnesic Syndrome (EAS) and the Syndrome of Transient Epileptic Amnesia. Their diagnostic criteria have much in common but identification of STEA is based only on transient amnesic attacks. On the contrary, EAS takes into account subtle temporal lobe seizures. Here, we report a case where chronic cognitive disturbances were combined with very limited temporal lobe seizures while amnesic attacks were lacking. Antiepileptic drug treatment led to normalization of cognitive function. The criteria of STEA were not applicable because of the lack of transient amnesia in the patients' medical history. Considering brief episodes of flashbacks and abdominal pain as possibly seizure-related, the criteria of EAS were more operative: they allowed proper investigation to confirm TLE in our patient.

[French guidelines on the use of repetitive transcranial magnetic stimulation (rTMS): safety and therapeutic indications]. / Recommandations françaises sur l'utilisation de la stimulation magnétique transcrânienne répétitive (rTMS) : règles de sécurité et indications thérapeutiques.

During the past decade, a large amount of work on transcranial magnetic stimulation (TMS) has been performed, including the development of new paradigms of stimulation, the integration of imaging data, and the coupling of TMS techniques with electroencephalography or neuroimaging. These accumulating data being difficult to synthesize, several French scientific societies commissioned a group of experts to conduct a comprehensive review of the literature on TMS. This text contains all the consensual findings of the expert group on the mechanisms of action, safety rules and indications of TMS, including repetitive TMS (rTMS). TMS sessions have been conducted in thousands of healthy subjects or patients with various neurological or psychiatric diseases, allowing a better assessment of risks associated with this technique. The number of reported side effects is extremely low, the most serious complication being the occurrence of seizures. In most reported seizures, the stimulation parameters did not follow the previously published recommendations (Wassermann, 1998) [430] and rTMS was associated to medication that could lower the seizure threshold. Recommendations on the safe use of TMS / rTMS were recently updated (Rossi et al., 2009) [348], establishing new limits for stimulation parameters and fixing the contraindications. The recommendations we propose regarding safety are largely based on this previous report with some modifications. By contrast, the issue of therapeutic indications of rTMS has never been addressed before, the present work being the first attempt of a synthesis and expert consensus on this topic. The use of TMS/rTMS is discussed in the context of chronic pain, movement disorders, stroke, epilepsy, tinnitus and psychiatric disorders. There is already a sufficient level of evidence of published data to retain a therapeutic indication of rTMS in clinical practice (grade A) in chronic neuropathic pain, major depressive episodes, and auditory hallucinations. The number of therapeutic indications of rTMS is expected to increase in coming years, in parallel with the optimisation of stimulation parameters.

[Sepsis associated encephalopathy]. / Encéphalopathie associée au sepsis.

The sepsis associated encephalopathy (SAE) is a common cause of delirium, accompanied by hyperthermia or not. It is defined as a diffuse cerebral dysfunction induced by the systemic response to the infection without clinical or laboratory evidence of direct infectious involvement of the central nervous system. It is, thus, a diagnosis of exclusion. The pathogenic mechanisms underlying SAE are now better understood: it involves, at least, an intense inflammation of the central nervous system and a major impairment of the blood brain barrier. At the present time, clinical, biological and radiological characteristics of SAE have been sufficiently described to ensure rapid identification, but prognosis remains severe. Proper management requires treatment as early as possible of the infectious site and accompanying systemic inflammatory response. When appropriately conducted, minimal consequences or complete recovery can be expected.

[Love and neurology]. / Amours et neurologie.

INTRODUCTION: Love is a complex emotional state which is difficult to define. Considering anthropological studies, this feeling can now be divided into three distinct behaviors: lust, attraction for a specific partner and conjugal or filial attachment. STATE OF ART: For each, recent findings have contributed to identify specific neuronal networks which are interconnected as shown by common activation of limbic and paralimbic systems. A major role of arginine/vasopressin and oxytocin has also been pointed out for mate choice and attachment promotion. In the field of neurology, studies about pathologies of love are sparse and mainly focused on sexual disorders. Pathologies of attachment like autism and borderline personality are beginning to be identified. PERSPECTIVES: Future investigations would yield a better understanding of this complex emotional state and a better detection of new pathologies related to a major affective disability. CONCLUSION: Neurosciences have contributed to highlight mechanisms involved in love.

[Apathy or depression? Do you have a nose for it? Four case reports of paramedian frontal tumors]. / Apathie ou dépression ? Une question de nez ? Illustration par quatre cas de tumeurs frontales paramédianes.

We report four cases of patients with clinically isolated apathy which was mistaken for depression even though they were suffering from voluminous brain tumors. These cases remind us that rigorous clinical analysis is essential: searching for signs of organic origin or psychiatric etiology is fundamental to avoid an incorrect diagnosis. In particular, these four patients displayed anosmia, an uncommon symptom for patients suffering from depression. In addition, brain imaging is important to correctly identify the most prudent medical and/or surgical management strategy. In this short discussion, we propose an algorithm for the clinical diagnosis of apathy.

Acute limbic encephalitis and glutamic acid decarboxylase antibodies: a reality?

Limbic encephalitis (LE) associated with glutamic acid decarboxylase antibodies (GAD-Ab) is rare. We describe a 30-year-old male with acute LE and GAD-Ab, with follow-up during 2 years of cognitive status including verbal episodic memory, number of seizures recorded by high-resolution video-EEG, brain MRI, 2-[18F]-fluoro-2-deoxyglucose PET and GAD-Ab titres. Treatment with corticosteroids, IV immunoglobulins, immunosuppressors and antiepileptic drugs resulted in improved memory status, disappearance of seizures and decreased GAD-Ab titres. Review of the other cases of literature and this case is in favour of the existence of autoimmune LE associated with GAD-Ab and supports the link between memory, temporal seizures and possibly GAD-Ab titres.

[Is there a bridge between migraine and familial mesial temporal lobe epilepsy?]. / Migraines et épilepsies temporales mésiales familiales : quel est le lien ?

Numerous reviews have emphasized the links between certain types of epilepsy and migraine. Historically, Gowers was one of the first, in 1907, to have drawn attention to a possible relationship between migraine headache and epilepsy in a period when no additional examination was available. In the last two decades, progress in molecular biology, electrophysiology, and neuro-imaging has enabled a better approach to the fundamental elements underlying the interrelationship between these two nosological domains. During this same time, a new term "channelopathy" has appeared in the literature. This term groups together affections involving a dysfunction of ion channels. In this article, the links between the different types of migraine and familial mesial temporal lobe epilepsy are illustrated by two case reports. This association does not appear to occur at random but would undoubtedly depend on a common genetic substratum, leading to a direct comorbidity. These occasional recurring symptoms would lie within the framework of a more general concept of "Primary Brain Channelopathies".

[Recurrent ischemic strokes revealing Lyme meningovascularitis]. / Une méningovascularite infectieuse de Lyme révélée par des accidents ischémiques cérébraux successifs.

INTRODUCTION: Infectious vascularitis is an unusual cause of ischemic stroke (IS). We report a case of Lyme meningovascularitis complicated with multiple IS. CASE REPORT: A 64-year-old man, without any cardiovascular risk factor, was admitted for a right hemiparesia with a left thalamic hypodensity on the initial cerebral CT scan. No cause for this presumed IS could be identified. Later, the patient developed cognitive impairment and a bilateral cerebellar syndrome. Multiple infarcts and multiple intracranial stenosis were seen on cerebral MRI with magnetic resonance angiography (MRA). Cerebrospinal fluid tests showed meningitis and positive Lyme serology with an intrathecal specific anti-Borrelia antibody index. Antibiotic treatment was followed by good biological and partial clinicoradiological outcome. CONCLUSION: The diagnosis of Lyme neuroborreliosis should be entertained as a possible cause of IS in highly endemic zones.

Sensitivity optimization of the scanning microdeformation microscope and application to mechanical characterization of soft materials.

In this article we present the study of the sensitivity optimization of our system of micromechanical characterization called the scanning microdeformation microscope. The flexural contact modes of vibration of the cantilever have been modeled. We discuss the matching between the cantilever stiffness and the contact stiffness which depends on the sample material. In order to obtain the best sensitivity, the stiffnesses must be the closest one to each other. Because the length of the cantilever directly affects its stiffness, the cantilever geometry can be optimized for different materials. We have validated this study with measurements on a soft material the polydimethylsiloxane with a cantilever optimized for materials of Young's moduli of some megapascals. Experimental results obtained with two different samples have shown the high sensitivity of the method for the measurement of low Young's moduli and have been compared with nanoindentation and dynamic mechanical analysis results.

Piezoelectric and optical setup to measure an electrical field: application to the longitudinal near-field generated by a tapered coax.

We propose a new setup to measure an electrical field in one direction. This setup is made of a piezoelectric sintered lead zinconate titanate film and an optical interferometric probe. We used this setup to investigate how the shape of the extremity of a coaxial cable influences the longitudinal electrical near-field generated by it. For this application, we designed our setup to have a spatial resolution of 100 microm in the direction of the electrical field. Simulations and experiments are presented.

Sensitive ultrasonic vibrometer for very low frequency applications.

Ultrasonic measurement of distance is a well-known low cost method but only a few vibrometers have been developed because sensitivity, spatial resolution, and bandwidth are not high or wide enough for standard laboratory applications. Nevertheless, compared to optical vibrometers, two interesting properties should be considered: very low frequency noise (0.1 Hz to 1 kHz) is reduced and the long wavelength enables rough surfaces to be investigated. Moreover, the ultrasonic probe is a differential sensor, without being a mechanical load for the vibrating structure as usual accelerometers based on contacting transducers are. The main specificity of the presented probe is its ultralow noise electronics including a 3/2 order phase locked loop which extracts the phase modulation related to the amplitude of the detected vibration. This article presents the main useful physical aspects and details of the actual probe. The given application is the measurement of the vibration of an isolated optical bench excited at very low frequency with an electromagnetic transducer.

Near-infrared thermography using a charge-coupled device camera: application to microsystems.

Using near-infrared thermography microscopy and a low-cost charge-coupled device (CCD) camera, we have designed a system which is able to deliver quantitative submicronic thermal images. Using a theoretical model based on Planck's law and CCD sensor properties allowed us to determine a minimal theoretical detection temperature and an optimal temperature sensitivity of our system. In order to validate this method, we show a good relationship between a theoretical study and a thermal measurement of a microsample.

Finite element analysis of the behavior of the Scanning Microdeformation Microscope.

The Scanning Microdeformation Microscope, as many other scanning probe microscopes developed in the last years, is a kind of ac force microscope using the near-field acoustic interaction. The heart of the system is an electromechanical oscillator made of a silicon cantilever, a diamond or sapphire tip, associated with a bimorph piezoelectric transducer and a specific amplifier. The specificity of the system is the way of detection of the oscillation frequency performed electrically through the admittance of the piezoelectric transducer. In this paper, we describe the technique of detection involved in the microscope. A modelling of the complete behavior of the electromechanical oscillator performed with the finite element method (FEM) (of simulation) is presented. A comparison between experimental and theoretical behavior shows a very good agreement.