Caroline Hommet

Olfaction: A potential cognitive marker of psychiatric disorders

Cognitive deficits are well documented in psychiatric disorders, particularly in schizophrenia and depression. Cognitive activity roots in perceptions. However, research on sensorial alterations in psychiatric conditions has mainly focused on visual or auditory processes and less on olfaction. Here, we examine data on olfactory deficits in psychiatric patients using a systematic review of recent publications. Schizophrenic patients are mainly characterized by no reliable change in odour sensitivity and by a deficit in odour identification, recognition and discrimination. Depressed patients principally exhibit a deficit in the hedonic aspects of this perception, even if, in some case, alterations in sensitivity or identification are also found. Changes in odour perception are also found in dementia and in some neurodegenerative disease, but in this case alterations concern all aspects of the sensorial experience (detection threshold, identification and recognition). Taken together, these data indicate that olfactory abnormalities might be a marker of psychiatric conditions, with a specific pattern for each disease.

Region-Specific Hierarchy between Atrophy, Hypometabolism, and β-Amyloid (Aβ) Load in Alzheimer's Disease Dementia

Gray matter atrophy, glucose hypometabolism, and β-amyloid Aβ deposition are well-described hallmarks of Alzheimers disease, but their relationships are poorly understood. The present study aims to compare the local levels of these three alterations in humans with Alzheimers disease. Structural magnetic resonance imaging, 18F-fluorodeoxyglucose positron emission tomography (PET), and 18F-florbetapir PET data from 34 amyloid-negative healthy controls and 20 demented patients with a high probability of Alzheimers disease etiology (attested using neuroimaging biomarkers as recently recommended) were analyzed. For each patient and imaging modality, age-adjusted Z-score maps were computed, and direct between-modality voxelwise comparison and correlation analyses were performed. Significant differences in the levels of atrophy, hypometabolism, and Aβ deposition were found in most brain areas, but the hierarchy differed across regions. A cluster analysis revealed distinct subsets of regions: (1) in the hippocampus, atrophy exceeded hypometabolism, whereas Aβ load was minimal; (2) in posterior association areas, Aβ deposition was predominant, together with high hypometabolism and lower but still significant atrophy; and (3) in frontal regions, Aβ deposition was maximal, whereas structural and metabolic alterations were low. Atrophy and hypometabolism significantly correlated in the hippocampus and temporo-parietal cortex, whereas Aβ load was not significantly related to either atrophy or hypometabolism. These findings provide direct evidence for regional variations in the hierarchy and relationships between Aβ load, hypometabolism, and atrophy. Altogether, these variations probably reflect the differential involvement of region-specific pathological or protective mechanisms, such as the presence of neurofibrillary tangles, disconnection, as well as compensation processes.

Gait analysis in demented subjects: Interests and perspectives

Gait disorders are more prevalent in dementia than in normal aging and are related to the severity of cognitive decline. Dementia-related gait changes (DRGC) mainly include decrease in walking speed provoked by a decrease in stride length and an increase in support phase. More recently, dual-task related changes in gait were found in Alzheimer’s disease (AD) and non-Alzheimer dementia, even at an early stage. An increase in stride-to-stride variability while usual walking and dual-tasking has been shown to be more specific and sensitive than any change in mean value in subjects with dementia. Those data show that DRGC are not only associated to motor disorders but also to problem with central processing of information and highlight that dysfunction of temporal and frontal lobe may in part explain gait impairment among demented subjects. Gait assessment, and more particularly dual-task analysis, is therefore crucial in early diagnosis of dementia and/or related syndromes in the elderly. Moreover, dual-task disturbances could be a specific marker of falling at a pre-dementia stage.

Language in benign childhood epilepsy with centro-temporal spikes abbreviated form: Rolandic epilepsy and language

Although Benign Childhood Epilepsy with Centrotemporal Spikes (BECTS) has a good prognosis, a few studies have suggested the existence of language disorders relating to the interictal dysfunction of perisylvian language areas. In this study, we focused on language assessment in 16 children aged 6-15 currently affected by BECTS or in remission. An important proportion of children showed moderate or more severe language impairment. The most affected domains were expressive grammar and literacy skills. We found linguistic deficits during the course of epilepsy but also persistent deficits in children in remission, suggesting possible long-term effects. Our results support the hypothesis that BECTS may be associated with impairment to language and suggest the possibility of a direct link between epileptic activity and language development, and the existence of long-term consequences.

Molecular Imaging of Microglial Activation in Amyotrophic Lateral Sclerosis

There is growing evidence of activated microglia and inflammatory processes in the cerebral cortex in amyotrophic lateral sclerosis (ALS). Activated microglia is characterized by increased expression of the 18 kDa translocator protein (TSPO) in the brain and may be a useful biomarker of inflammation. In this study, we evaluated neuroinflammation in ALS patients using a radioligand of TSPO, 18F-DPA-714. Ten patients with probable or definite ALS (all right-handed, without dementia, and untreated by riluzole or other medication that might bias the binding on the TSPO), were enrolled prospectively and eight healthy controls matched for age underwent a PET study. Comparison of the distribution volume ratios between both groups were performed using a Mann-Whitney’s test. Significant increase of distribution of volume ratios values corresponding to microglial activation was found in the ALS sample in primary motor, supplementary motor and temporal cortex (p = 0.009, p = 0.001 and p = 0.004, respectively). These results suggested that the cortical uptake of 18F-DPA-714 was increased in ALS patients during the “time of diagnosis” phase of the disease. This finding might improve our understanding of the pathophysiology of ALS and might be a surrogate marker of efficacy of treatment on microglial activation.

Reading ability and processing in Duchenne muscular dystrophy and spinal muscular atrophy

We analysed the reading abilities and processing of 21 children with Duchenne muscular dystrophy (DMD), 11 matched children suffering from spinal muscular atrophy (SMA) and 42 children receiving normal education. The principal result observed was that the DMD children exhibited a reading age which was significantly lower than the SMA children compared with their chronological age. These learning disabilities were not related to a deficit in non‐verbal performance intelligence, but psycholinguistic evaluation showed a deficit in verbal intelligence, especially in the Similarities and Arithmetic WISC‐R subtests, in phonological abilities, oral word repetition, and in digit span score. The results for the DMD children were heterogeneous, and ranged from normal to greater or lesser involvement. In an attempt to clarify the nature of this reading impairment in DMD children, the three groups (DMD, SMA, and normal control children) were tested by reading aloud a list of single words and non‐words. The DMD children were significantly impaired in reading non‐words, suggesting reading disability similar to dysphonetic dyslexia, the most frequent subtype of developmental dyslexia. These results are discussed in the light of psychometric data available for our DMD population and in the light of previous studies. The practical consequences of diagnosis on rehabilitation are very important. The precise description of the cognitive deficits seen in DMD is of value for future clinical and genetic studies.

Sleep and brain lesions: a critical review of the literature and additional new cases

We present a comprehensive review of sleep studies performed in patients with brain lesions complemented by 16 additional personal selected cases and by discussion of the corresponding animal data. The reader is cautioned about the risk of establishing an erroneous correlation between abnormal sleep and a given disorder due to the important inter and intra variability of sleep parameters among individuals. Salient points are stressed: the high frequency of post-stroke sleep breathing disorders is becoming increasingly recognised and may, in the near future, change the way this condition is managed. Meso-diencephalic bilateral infarcts induce a variable degree of damage to both waking and non-REM sleep networks producing and abnormal waking and sometimes a stage 1 hypersomnia reduced by modafinil or bromocriptine, which can be considered as a syndrome of cathecholaminergic deficiency. Central pontine lesions induce REM and non-REM sleep insomnia with bilateral lateral gaze paralysis. Bulbar stroke leads to frequent sleep breathing disorders. Polysomnography can help define the extent of involvement of various degenerative diseases. Fragmented sleep in Parkinsons disease may be preceded by REM sleep behavioural disorders. Multiple system atrophies are characterised by important sleep disorganization. Sleep waking disorganization and a specific ocular REM pattern are often seen in supra-nuclear ophtalmoplegia. In Alzheimer patients, sleep perturbations parallel the mental deterioration and are possibly related to cholinergic deficiency. Fronto-temporal dementia may be associated with an important decrease in REM sleep. Few narcoleptic syndromes are reported to be associated with a tumour of the third ventricle or a multiple sclerosis or to follow a brain trauma; all these cases raise the question whether this is a simple coincidence, a revelation of a latent narcolepsy or, as in non-DR16/DQ5 patients, a genuine symptomatic narcolepsy. Trypanosomiasis and the abnormal prion protein precociously after sleep patterns. Polysomnography is a precious tool for evaluating brain function provided it is realised under optimal conditions in stable patients and interpreted with caution. Several unpublished cases are presented: one case of pseudohypersomnia due to a bilateral thalamic infarct and corrected by modafinil, four probable late-onset autosomal recessive cerebellar ataxias without sleep pattern anomalies, six cases of fronto-temporal dementia with strong reduction in total sleep time and REMS percentage on the first polysomnographic night, one case of periodic hypersomnia associated with a Rathkes cleft cyst and four cases of suspected symptomatic narcolepsy with a DR16-DQ5 haplotype, three of which were post-traumatic without MRI anomalies, and one associated with multiple sclerosis exhibiting pontine hyper signals on MRI.

Outcome at adulthood of the continuous spike-waves during slow sleep and Landau-Kleffner syndromes

Summary:  Purpose: The aim of this study was to determine the clinical, social, and/or professional and cognitive outcomes in adulthood of the continuous spike–waves during slow sleep (CSWS) and Landau–Kleffner syndromes, which are two rare epileptic syndromes occurring in children.

Epilepsy and Dementia in the Elderly

Epilepsy is a frequent condition in the elderly; however, it remains a relatively understudied condition in older adults with dementia. The diagnosis of a seizure is particularly difficult and is most often based on questions to the caregiver. Epilepsy in dementia has significant consequences on the prognosis of the underlying dementia: it can result in a worsening of cognitive performance, particularly in language, as well as a reduction in autonomy, a greater risk of injury and a higher mortality rate. In this review, management strategies are recommended for the clinician. The presence of pre-existing Alzheimer’s disease does not exempt the clinician from ruling out other symptomatic causes of seizures. Anti-epileptic drugs (AED) should be started only after the diagnosis has been clearly established, when the risk of recurrence is high, and with monotherapy whenever possible. Although few data are available, the more recent AED offer significant advantages over the older medications in this context.

Emergent EEG in clinical practice.

OBJECTIVE Emergency situations require a rapid and precise diagnostic approach. However, the exact role and value of the electroencephalogram (EEG) in emergent conditions have yet to be clearly defined. Our objective was to determine why clinicians order an emergency EEG, to assess to what extent it helps establish a correct diagnosis and to evaluate the result it has on subsequent patient management. METHODS We studied all successive emergency EEGs ordered during a 3-month period in our institution. We analyzed the reasons why each EEG was ordered and interviewed the prescribing clinicians in order to determine the impact the result of the EEG had on the diagnosis and subsequent therapeutic management. RESULTS We prospectively studied a total of 111 consecutive recordings. The main reasons for ordering an emergent EEG were: suspected cerebral death (21%), non-convulsive status epilepticus (19.7%), subtle status epilepticus (14%) and follow-up of convulsive status epilepticus (11.2%). In 77.5% of the cases the clinicians considered that the EEG contributed to making the diagnosis and that it helped confirm a clinically-suspected diagnosis in 36% of the cases. When subtle status epilepticus (SSE) or non-convulsive status epilepticus (NCSE) was suspected, the diagnosis was confirmed in 45% and 43.3% of the cases, respectively. In 22.2% of the requests involving follow-up of convulsive status epilepticus after initial treatment, the EEG demonstrated persistent status epilepticus. It resulted in a change in patient treatment in 37.8% of all the cases. When the EEG helped establish the diagnosis, patient treatment was subsequently modified in 46.6% of the cases. CONCLUSIONS This prospective study confirms the value of an emergent EEG in certain specific clinical contexts: the management of convulsive status epilepticus following initial treatment or to rule out subtle status epilepticus. An emergent EEG can also be ordered if one suspects the existence of non-convulsive status epilepticus when a patient presents with mental confusion or altered wakefulness after first looking for the specific signs suggesting this diagnostic hypothesis. SIGNIFICANCE After 50 years of development and use in daily practice, the EEG remains a dependable, inexpensive and useful diagnostic tool in a number of clearly-defined emergency situations.