Cognitive impairment in fatigue and sleepiness associated conditions

Although relating to very different concepts, sleepiness and fatigue are often confounded. However, both fatigue-associated conditions such as the chronic fatigue syndrome (CFS) and sleepiness-associated conditions such as the sleep apnea-hypopnea syndrome (SAHS) are associated with cognitive impairment with impaired attention, concentration and memory performances. Fifteen pure CFS patients, without primary sleep disorders or clinically relevant sleepiness, were compared to 15 untreated SAHS patients, without clinically relevant fatigue, and to 16 healthy controls of similar age. The auditory verbal learning test (AVLT), digit span, digit symbol and finger tapping test (FTT) were used as cognitive and behavioural measures. In addition we assessed daytime EEG spectral power and P300 evoked potentials. With exception for the digit span, all tests showed lower performances in patient groups. Recall on the AVLT did not differ between the two patient groups, but the digit and symbol spans showed more severe impairment in SAHS patients. Psychomotor performance on the FTT presented with slower hit rates in SAHS than in CFS. EEG theta power was highest in CFS patients. P300 latencies and amplitudes did not differ between groups. Fatigue- and sleepiness-associated conditions can both present with significant and objective impairment of cognitive functioning and behavioural motor performance. In our sample cognitive impairment and psychomotor performance were worse when associated to sleepiness in SAHS than with fatigue in CFS.     

Gelastic seizures in ring chromosome 20 syndrome: a case report with video illustration

Although increasingly recognised, ring chromosome 20 (r[20]) syndrome is still diagnosed with delay, sometimes leading to inappropriate presurgical evaluation. The focal, presumed frontal, character of the seizures manifesting with fear and hypermotor behaviour and episodes of non-convulsive status epilepticus (NCSE) are most typical, as well as cognitive impairment with behavioural problems and, sometimes, dysmorphic signs. We present a girl diagnosed at the age of 13 years who suffered from an atypical clinical presentation, with minimal cognitive problems, absence of dysmorphic symptoms, and hypermotor/gelastic seizures. [Published with video sequences].     

Clusterin in neurological disorders: molecular perspectives and clinical relevance

Firstly discovered in rete testis fluid, clusterin is a glycoprotein present in most of the other biological fluids. Several isoforms of clusterin are encoded from a single gene located on chromosome 8 in human species. Among the different isoforms, the secreted form of clusterin is expressed by a variety of tissues, including the nervous system under normal conditions. This form is presumed to play an anti-apoptotic role and seems to be a major determinant in cell survival and neuroplasticity after stroke. In animal models of this pathology, both neuronal and astroglial subpopulations express high levels of clusterin early after the ischemic damage. Recent lines of evidence point also to its possible involvement in neurodegenerative disorders. It is thought that in Alzheimer's disease the association between amyloidogenic peptides and clusterin contributes to limit Aβ species misfolding and facilitates their clearance from the extracellular space. Thus, intercellular and intracellular factors that modulate local clusterin expression in the nervous system may represent potent targets for neurodegenerative disease therapies. In this review we provide a critical overview of the most recent data on the involvement of clusterin in neurodegenerative diseases with special reference to their putative clinical relevance.     

Contribution of orodental status to the intensity of orofacial tardive dyskinesia: an interdisciplinary and video-based assessment

BackgroundTardive dyskinesia (TD) is a neurological motor complication eventually arising in one-third of patients chronically exposed to antipsychotic drugs. Some orodental peripheral factors have been reported to influence TD.ObjectiveTo measure orodental factors such as temporomandibular joint function, static occlusal contacts, and denture condition, and attempt correlations with orofacial TD intensity.MethodsIn this exploratory cross-sectional pilot study, 31 subjects between 30 and 75 years of age were divided in two groups displaying minimal to mild, or moderate to severe orofacial TD, respectively, and underwent a detailed oral, dental, and prosthetic evaluation to capture various aspects of oral health compared between the two groups. Blinded video-based TD ratings along a validated scale were obtained to compare dentulous and edentulous subjects, and contrast TD intensity in complete denture wearers with and without their own prostheses.ResultsNone of the factors examined tightly correlated with orofacial TD intensity. However, edentulism was associated with a higher median orofacial TD rating compared to the dentulous group (p = 0.001). Further, a significant intra-subject difference was observed in the edentulous subjects rated with their own complete dentures in place or not (p = 0.028), the dentures attenuating the mean orofacial ratings by 21.8 ± 7.3%.ConclusionOf all orodental factors considered, only edentulism and complete denture wearing influenced oral TD expression, calling for the close monitoring of the dental status in antipsychotic drug-exposed patients to prevent tooth loss. Further studies to measure the impact of an adequate prosthodontic rehabilitation in edentulous subjects with orofacial TD seem warranted.     

Early ischemic lesions following subarachnoid hemorrhage: common cold remedy as precipitating factor?

A 46-year-old woman presented with tetraplegia contrasting with a relatively preserved consciousness following aneurysmal subarachnoid hemorrhage (SAH). Multiple ischemic lesions were detected by magnetic resonance imaging (MRI), in the absence of vasospasm or signs of increased intracranial pressure. During the weeks before SAH, the patient had repeatedly used a nasal decongestant containing phenylephrine. After coiling of the aneurysm harboured by the right posterior cerebral artery, symptomatic vasospasm developed in the territory of the right middle cerebral artery and required aggressive therapy by intra-arterial infusion of milrinone followed by continuous intravenous administration. Follow-up MRI did not reveal new ischemic lesions. Echocardiography had demonstrated the presence of a patent foramen ovale. At 3 months follow-up, a major motor deficit persisted with akinetic mutism. The mechanisms of multiple early infarction following aneurysmal SAH are still debated, as vasospasm is usually not seen on the first imaging. Among precipitating factors of microvascular vasospasm, vasoactive substances like phenylephrine, may play a significant role.     

Efficient "pop-out" visual search elicits sustained broadband γ activity in the dorsal attention network

An object that differs markedly from its surrounding-for example, a red cherry among green leaves-seems to pop out effortlessly in our visual experience. The rapid detection of salient targets, independently of the number of other items in the scene, is thought to be mediated by efficient search brain mechanisms. It is not clear, however, whether efficient search is actually an "effortless" bottom-up process or whether it also involves regions of the prefrontal cortex generally associated with top-down sustained attention. We addressed this question with intracranial EEG (iEEG) recordings designed to identify brain regions underlying a classic visual search task and correlate neural activity with target detection latencies on a trial-by-trial basis with high temporal precision recordings of these regions in epileptic patients. The spatio-temporal dynamics of single-trial spectral analysis of iEEG recordings revealed sustained energy increases in a broad gamma band (50-150 Hz) throughout the duration of the search process in the entire dorsal attention network both in efficient and inefficient search conditions. By contrast to extensive theoretical and experimental indications that efficient search relies exclusively on transient bottom-up processes in visual areas, we found that efficient search is mediated by sustained gamma activity in the dorsal lateral prefrontal cortex and the anterior cingulate cortex, alongside the superior parietal cortex and the frontal eye field. Our findings support the hypothesis that active visual search systematically involves the frontal-parietal attention network and therefore, executive attention resources, regardless of target saliency.     

Encoding dysfunctions in a dynamic-static paradigm for visuospatial working memory in first-episode psychosis patients: a 2-year follow-up study

Aim: To investigate static and dynamic visuospatial working memory (VSWM) processes in first‐episode psychosis (FEP) patients and explore the validity of such measures as specific trait markers of schizophrenia. Methods: Twenty FEP patients and 20 age‐, sex‐, laterality‐ and education‐matched controls carried out a dynamic and static VSWM paradigm. At 2‐year follow up 13 patients met Diagnostic and Statistical Manual (of Mental Health Disorders) – Fourth Edition (DSM‐IV) criteria for schizophrenia, 1 for bipolar disorder, 1 for brief psychotic episode and 5 for schizotypal personality disorder. Results: Compared with controls, the 20 FEP patients showed severe impairment in the dynamic VSWM condition but much less impairment in the static condition. No specific bias in stimulus selection was detected in the two tasks. Two‐year follow‐up evaluations suggested poorer baseline scores on the dynamic task clearly differentiated the 13 FEP patients who developed schizophrenia from the seven who did not. Conclusions: Results suggest deficits in VSWM in FEP patients. Specific exploratory analyses further suggest that deficit in monitoring‐manipulation VSWM processes, especially involved in our dynamic VSWM task, can be a reliable marker of schizophrenia.     

Ghrelin/obestatin ratio in two populations with low bodyweight: constitutional thinness and anorexia nervosa

Constitutional thinness (CT) and anorexia nervosa (AN) are two categories of severely underweight subjects. Some appetite-regulating hormones display opposite levels in AN and CT. While levels of ghrelin, an orexigenic hormone, fit with the normal food intake in CT, the lack of efficacy of increased ghrelin levels in AN is not clear. Obestatin is a recently described peptide derived from the preproghrelin gene, reported to inhibit appetite in contrast to ghrelin. The aim of this study was to determine whether the circadian profile of obestatin, total and acylated ghrelin levels is different in CT subjects when compared with AN patients. Six-points circadian profiles of plasma obestatin, acylated ghrelin, total ghrelin and other hormonal and nutritional parameters were evaluated in four groups of young women: 10 CT, 15 restricting-type AN, 7 restored from AN and 9 control subjects. Obestatin circadian levels were significantly higher in AN (p<0.0001) while no difference was found between CT and control subjects. Acylated and total ghrelin were found increased in AN. Acylated ghrelin/obestatin and total ghrelin/obestatin were found decreased in AN compared to CT or C subjects (p<0.05). The percentage of acylated ghrelin was found decreased in CT group (p<0.05). The decreased ghrelin/obestatin ratio found in AN might participate in the restraint in nutriment intake of these patients. In contrast, in CT a lower percentage of acylated over total ghrelin might be considered in the aetiology of this condition.