Factors associated with fatigue in CNS inflammatory diseases with AQP4 and MOG antibodies.

OBJECTIVE: Fatigue is a common and disabling symptom amongst people with multiple sclerosis, however it has not been compared across the central nervous system (CNS) inflammatory diseases associated with aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibodies (Ab). We explored the factors associated with fatigue within and across the two diseases, and compared fatigue levels between them. METHODS: We performed a cross-sectional study of 90 AQP4-Ab and 44 MOG-Ab patients. Fatigue was assessed using the Modified Fatigue Impact Scale (MFIS). Clinical, demographic, and psychometric (anxiety, depression, pain) data were used as independent variables. Multivariable linear regression was used to identify significant independent variables associated with fatigue within and across the two diseases. RESULTS: Within AQP4-Ab patients, age (P = 0.002), disease duration (P = 0.004), number of clinical attacks (P = 0.001), disability (P = 0.007), pain interference (P < 0.001), anxiety (P = 0.026), and depression (P < 0.001) were significant independent variables. Interestingly, disease duration had a negative association with fatigue (P = 0.004). Within MOG-Ab patients, pain interference score (P < 0.001) and anxiety (P = 0.001) were significant independent variables. Although fatigue was worse in AQP4-Ab patients compared to MOG-Ab patients (P = 0.008) in all patients as well as in those who ever had transverse myelitis (P = 0.023), this was driven by the differences in age, disability and pain interference rather than antibody subtype itself. INTERPRETATION: Multiple factors, but not the antibody specificity, appear to contribute to fatigue in antibody positive CNS inflammatory diseases. A multifaceted treatment approach is needed to better manage the physical, cognitive, and psychosocial aspects of fatigue in these patients.

Agnosia for bird calls.

The cognitive organisation of nonverbal auditory knowledge remains poorly defined. Deficits of environmental sound as well as word and visual object knowledge are well-recognised in semantic dementia. However, it is unclear how auditory cognition breaks down in this disorder and how this relates to deficits in other knowledge modalities. We had the opportunity to study a patient with a typical syndrome of semantic dementia who had extensive premorbid knowledge of birds, allowing us to assess the impact of the disease on the processing of auditory in relation to visual and verbal attributes of this specific knowledge category. We designed a novel neuropsychological test to probe knowledge of particular avian characteristics (size, behaviour [migratory or nonmigratory], habitat [whether or not primarily water-dwelling]) in the nonverbal auditory, visual and verbal modalities, based on a uniform two-alternative-forced-choice procedure. The patient's performance was compared to healthy older individuals of similar birding experience. We further compared his performance on this test of bird knowledge with his knowledge of familiar human voices and faces. Relative to healthy birder controls, the patient showed marked deficits of bird call and bird name knowledge but relatively preserved knowledge of avian visual attributes and retained knowledge of human voices and faces. In both the auditory and visual modalities, his knowledge of the avian characteristics of size and behaviour was intact whereas his knowledge of the associated characteristic of habitat was deficient. This case provides further evidence that nonverbal auditory knowledge has a fractionated organisation that can be differentially targeted in semantic dementia.

YouTube as a potential learning tool to help distinguish tonic-clonic seizures from nonepileptic attacks.

Medical students are increasingly turning to the website YouTube as a learning resource. This study set out to determine whether the videos on YouTube accurately depict the type of seizures that a medical student may search for. Two consultant epileptologists independently assessed the top YouTube videos returned following searches for eight terms relating to different categories of seizures. The videos were rated for their technical quality, concordance of diagnosis with an epileptologist-assigned diagnosis, and efficacy as a learning tool for medical education. Of the 200 videos assessed, 106 (63%) met the inclusion criteria for further analysis. Technical quality was generally good and only interfered with the diagnostic process in 8.5% of the videos. Of the included videos, 40.6-46.2% were judged to depict the purported diagnosis with moderate agreement between raters (75% agreement, κ=0.50). Of the videos returned after searching "tonic-clonic seizure", 28.6-35.7% were judged to show nonepileptic seizures with almost perfect interrater agreement (92.9% agreement, κ=0.84). Of the videos returned following the search "pseudoseizure", 77.8-88.9% of videos were judged to show nonepileptic seizures with substantial agreement (88.9% agreement, κ=0.61). Across all search terms, 19.8-33% of videos were judged as potentially useful as a learning resource, with fair agreement between raters (75.5% agreement, κ=0.38). These findings suggest that the majority of videos on YouTube claiming to show specific seizure subtypes are inaccurate, and YouTube should not be recommended as a learning tool for students. However, a small group of videos provides excellent demonstrations of tonic-clonic and nonepileptic seizures, which could be used by an expert teacher to demonstrate the difference between epileptic and nonepileptic seizures.

A depth-based head-mounted visual display to aid navigation in partially sighted individuals.

Independent navigation for blind individuals can be extremely difficult due to the inability to recognise and avoid obstacles. Assistive techniques such as white canes, guide dogs, and sensory substitution provide a degree of situational awareness by relying on touch or hearing but as yet there are no techniques that attempt to make use of any residual vision that the individual is likely to retain. Residual vision can restricted to the awareness of the orientation of a light source, and hence any information presented on a wearable display would have to limited and unambiguous. For improved situational awareness, i.e. for the detection of obstacles, displaying the size and position of nearby objects, rather than including finer surface details may be sufficient. To test whether a depth-based display could be used to navigate a small obstacle course, we built a real-time head-mounted display with a depth camera and software to detect the distance to nearby objects. Distance was represented as brightness on a low-resolution display positioned close to the eyes without the benefit focussing optics. A set of sighted participants were monitored as they learned to use this display to navigate the course. All were able to do so, and time and velocity rapidly improved with practise with no increase in the number of collisions. In a second experiment a cohort of severely sight-impaired individuals of varying aetiologies performed a search task using a similar low-resolution head-mounted display. The majority of participants were able to use the display to respond to objects in their central and peripheral fields at a similar rate to sighted controls. We conclude that the skill to use a depth-based display for obstacle avoidance can be rapidly acquired and the simplified nature of the display may appropriate for the development of an aid for sight-impaired individuals.

No evidence for ITD-specific adaptation in the frequency following response.

Neurons sensitive to interaural time differences (ITDs) in the fine structure of low-frequency signals have been found in binaurally responsive auditory nuclei in a wide range of species. The present study investigated whether the frequency following response (FFR) would show evidence for neurons "tuned" to ITD in humans. The FFR is a scalp-recorded measure of sustained phase-locked brainstem activity that has been shown to follow the frequency of low-frequency tones. The magnitude of the FFR often decreases over time for tones of long duration. The present study investigated whether this adaptation effect is ITD specific.The FFR to a 100-ms, 80-dB SPL, 504-Hz target tone was measured for ten subjects. The target was preceded by a 200-ms, 80-dB SPL, 504-Hz adaptor. The target always led by 0.5 ms in the left ear. The adaptor led either in the left ear or in the right ear by 0.5 ms. Stimuli (adaptor + target = pair) were presented in alternating polarity at a rate of 1.81 Hz. We used a "vertical" montage (+Fz, ­ C7, ground = Fpz) for which the FFR is assumed to reflect phase-locked neural activity from rostral generators in the brainstem. The averaged FFR waveforms for each polarity were subtracted, to enhance temporal fine structure responses. The results showed significant adaptation effects in the spectral magnitude of the FFR. However, adaptation was not larger when the adaptor had the same ITD as the target than when the ITD of the adaptor differed from that of the target. Thus, the current data provide no evidence that the spectral magnitude of the scalp-recorded FFR provides a non-invasive indicator of ITD-specific neural activation.

A retrospective diagnosis of epilepsy in three historical figures: St Paul, Joan of Arc and Socrates.

It has been suggested that undiagnosed epilepsy profoundly influenced the lives of several key figures in history. Historical sources recounting strange voices and visions may in fact have been describing manifestations of epileptic seizures rather than more supernatural phenomena. Well-documented accounts of such experiences exist for three individuals in particular: Socrates, St Paul and Joan of Arc. The great philosopher Socrates described a 'daimonion' that would visit him throughout his life. This daimonion may have represented recurrent simple partial seizures, while the peculiar periods of motionlessness for which Socrates was well known may have been the result of co-existing complex partial seizures. St Paul's religious conversion on the Road to Damascus may have followed a temporal lobe seizure which would account for the lights, voices, blindness and even the religious ecstasy he described. Finally, Joan of Arc gave a detailed narrative on the voices she heard from childhood during her Trial of Condemnation. Her auditory hallucinations appear to follow sudden acoustic stimuli in a way reminiscent of idiopathic partial epilepsy with auditory features. By analysing passages from historical texts, it is possible to argue that Socrates, St Paul and Joan of Arc each had epilepsy.

Differences between psychoacoustic and frequency following response measures of distortion tone level and masking.

The scalp-recorded frequency following response (FFR) in humans was measured for a 244-Hz pure tone at a range of input levels and for complex tones containing harmonics 2-4 of a 300-Hz fundamental, but shifted by ±56 Hz. The effective magnitude of the cubic difference tone (CDT) and the quadratic difference tone (QDT, at F(2)-F(1)) in the FFR for the complex was estimated by comparing the magnitude spectrum of the FFR at the distortion product (DP) frequency with that for the pure tone. The effective DP levels in the FFR were higher than those commonly estimated in psychophysical experiments, indicating contributions to the DP in the FFR in addition to the audible propagated component. A low-frequency narrowband noise masker reduced the magnitude of FFR responses to the CDT but also to primary components over a wide range of frequencies. The results indicate that audible DPs may contribute very little to the DPs observed in the FFR and that using a narrowband noise for the purpose of masking audible DPs can have undesired effects on the FFR over a wide frequency range. The results are consistent with the notion that broadly tuned mechanisms central to the auditory nerve strongly influence the FFR.