Capturing the ghost in the machine: a process for development and validation of measures of phenomenal consciousness in delirium.

BACKGROUND: Delirium has conventionally been considered a disorder of consciousness. Alertness and arousal are used as surrogates in clinical practice but are insufficient for the purposes of a more dimensional assessment of consciousness. We present a process of development and validation of candidate measures of phenomenal consciousness that could be applied to the diagnosis of delirium. METHODS: First, a narrative review of available instruments in the fields of phenomenal consciousness, including prereflective consciousness, the phenomenal-sensed experience and reflective thought, was undertaken. Eligibility of tools in the context of applicability to delirium was based upon objectivity in test interpretation and the requirement for tester administration. Second, where there was a gap in suitable cognitive tools, new items were derived using the silent generation technique. A process of face and construct validity using a diverse panel of experts was performed, and readability was evaluated. RESULTS: 814 articles were screened from the literature review. Fourteen candidate tools were reported from the three domains of phenomenal consciousness. One of these met the eligibility criteria for a delirium assessment. Fifty-seven new tests of phenomenal consciousness were identified. After a process of item reduction, a total of 26 individual tests were identified. After content validity, 22 of the 26 items were retained. The scale average content validity index was 0.89. The agreement between raters was between 80% and 97%. 100% of responses for face validity were rated as positive. Flesch Reading Ease Score was 91.6 (very easy to read). CONCLUSIONS: Candidate measures of phenomenal consciousness are described, and early validity studies are promising.

Genotype, extrapyramidal features, and severity of variant ataxia-telangiectasia.

OBJECTIVE: Variant ataxia-telangiectasia is caused by mutations that allow some retained ataxia telangiectasia-mutated (ATM) kinase activity. Here, we describe the clinical features of the largest established cohort of individuals with variant ataxia-telangiectasia and explore genotype-phenotype correlations. METHODS: Cross-sectional data were collected retrospectively. Patients were classified as variant ataxia-telangiectasia based on retained ATM kinase activity. RESULTS: The study includes 57 individuals. Mean age at assessment was 37.5 years. Most had their first symptoms by age 10 (81%). There was a diagnostic delay of more than 10 years in 68% and more than 20 years in one third of probands. Disease severity was mild in one third of patients, and 43% were still ambulant 20 years after disease onset. Only one third had predominant ataxia, and 18% had a pure extrapyramidal presentation. Individuals with extrapyramidal presentations had milder neurological disease severity. There were no significant respiratory or immunological complications, but 25% of individuals had a history of malignancy. Missense mutations were associated with milder neurological disease severity, but with a higher risk of malignancy, compared to leaky splice site mutations. INTERPRETATION: Individuals with variant ataxia-telangiectasia require malignancy surveillance and tailored management. However, our data suggest the condition may sometimes be mis- or underdiagnosed because of atypical features, including exclusive extrapyramidal symptoms, normal eye movements, and normal alpha-fetoprotein levels in some individuals. Missense mutations are associated with milder neurological presentations, but a particularly high malignancy risk, and it is important for clinicians to be aware of these phenotypes. ANN NEUROL 2019;85:170-180.

Machine learning and clinical neurophysiology.

Clinical neurophysiology constructs a wealth of dynamic information pertaining to the integrity and function of both central and peripheral nervous systems. As with many technological fields, there has been an explosion of data in neurophysiology over recent years, and this requires considerable analysis by experts. Computational algorithms and especially advances in machine learning (ML) have the ability to assist with this task and potentially reveal hidden insights. In this update article, we will provide a brief overview where such technology is being applied in clinical neurophysiology and possible future directions.

Measuring TMS stimulus/response characteristics from both hemispheres simultaneously for proximal and distal upper limb muscles.

The different types of magnetic stimulators available commercially permit preferential activation of an area of cortex confined to one hemisphere. Stimulating bilaterally may be a desirable means, however, of obtaining information from each hemisphere simultaneously at rest or during a motor task. The aims of this study were to validate and optimize this method by comparing the biophysical and the physiologic features of biphasic with monophasic stimulation from a circular coil. Five (three male, four right-handed) healthy adults were studied. Relaxed proximal and distal upper limb muscles were activated using a 13-cm outer diameter circular coil centered at the vertex. Motor evoked potentials (MEPs) were recorded simultaneously and bilaterally from the abductor pollicis brevis and from the biceps. Stimulators were used to generate different induced pulse waveforms (biphasic or monophasic), which were calibrated in volts. Stimulus-response (S/R) curves were then constructed by adjusting the intensity of stimulation in 10% increments. The datasets were then modeled using a linear function. Biphasic stimulation, with the first phase of coil current being counterclockwise when viewed from above, produced comparable S/R curves to monophasic stimulation with no significant difference in grouped data ( > 0.5 for abductor pollicis brevis and > 0.07 for biceps). Individually there was a tendency for biphasic MEPs to be larger in amplitude compared with monophasic MEPs. Bilateral stimulation produced MEPs of comparable shape and latency with the biphasic protocol. Right- and left-side S/R curves can be constructed simultaneously from selected proximal and distal upper limb muscles groups by using a centered circular coil delivering a biphasic pulse.

Acquisition and expression of proximal and distal upper limb stimulus-response curves to transcranial magnetic stimulation.

Motor cortex stimulus-response (S/R) curves are an indication of cortical excitability and are of relevance to topographical mapping. The aims of this study were to compare two different methods of collecting data to construct a S/R curve for transcranial magnetic stimulation (TMS) in the upper limbs, to identify reliable summary statistics for the S/R curve, and to determine whether S/R curves predicted motor threshold. Motor evoked potentials (MEP) were obtained from biceps brachii (BB) and abductor pollicis brevis (APB) muscles at rest with a circular coil centered at the vertex. Motor threshold was determined using a validated protocol. MEPs were obtained with 1% increments in intensity or from the average of five trials at 5% increments. The S/R relationships were fitted to linear, S-shaped, and Boltzmann functions. A linear function determined from the average of five trials accurately summarized our data (r2 from 0.6 to 0.9, P < 0.05, n = 8, for right APB and from 0.6 to 0.9, P < 0.05, n = 8 for right BB). The X-axis intercept of the line determined using these methods fell between the upper and lower limits of motor threshold in all eight subjects. We propose that MEP values obtained at intervals of 5% averaged over five trials, fitted to a linear function provides a practical means of assessing the S/R characteristics of TMS for proximal and distal upper limb muscles.