KIF1A-related disorders in children: A wide spectrum of central and peripheral nervous system involvement.

KIF1A-related disorders (KRD) were first described in 2011 and the phenotypic spectrum has subsequently expanded to encompass a range of central and peripheral nervous system involvement. Here we present a case series demonstrating the range of clinical, neurophysiological, and radiological features which may occur in childhood-onset KRD. We report on all the children and young people seen at a single large tertiary centre. Data were collected through a retrospective case-notes review. Twelve individuals from 10 families were identified. Eight different mutations were present, including four novel mutations. Two patients displayed a very severe phenotype including congenital contractures, severe spasticity and/or dystonia, dysautonomia, severe sensorimotor polyneuropathy and optic atrophy, significant white matter changes on brain MRI, respiratory insufficiency, and complete lack of neurodevelopmental progress. The remaining 10 patients represented a spectrum of severity with common features including a movement disorder with spasticity and/or dystonia, subtle features of dysautonomia, sensory axonal neuropathy, varying degrees of optic atrophy and of learning and/or behavioural difficulties, and subtle or absent-but sometimes progressive-changes in white matter on MRI. Epilepsy was common among the more severely affected children. This case series demonstrates that KRD comprise a range of neurological disorders, with both the milder and the more severe forms combining central and peripheral (including autonomic) nervous system deficits.

The Association between Arterial Stiffness, Initial Stroke Severity, and 3-Week Outcomes in Patients with Ischemic Stroke.

OBJECTIVES: Vascular compliance is emerging as a useful cardiovascular risk factor. The aim of this study was to investigate the association between arterial stiffness and stroke severity at presentation and 3 weeks. METHODS: Forty two patients with acute ischemic stroke (55% male, mean age 71 years) were recruited over 15-months. Stroke subtypes were classified into lacunar circulation infarct (LACI), partial anterior circulation infarct (PACI), and posterior circulation infarct (POCI). Arterial stiffness was measured by QKD (defined as the time interval between the appearance of the Q wave [Q] on the ECG and the arrival of the diastolic Korotkoff [K] sound over the brachial artery in diastole [D]; QKD It is measured in milliseconds) using 24-hour ambulatory blood pressure (BP) and electrocardiogram monitoring. The measured QKD values were then corrected for a heart rate of 60 bpm and a systolic BP of 100 mm Hg (QKD100-60). Stroke severity was assessed on admission and at 3 weeks using the National Institutes of Health Stroke Scale (NIHSS). RESULTS: Regression analysis for all patients showed a weak non-significant correlation between arterial stiffness and stroke severity. However, on performing subgroup analysis using Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, we found that in large-artery atherosclerosis, arterial stiffness predicted stroke severity significantly at baseline (r = .45, b = .093, P = .04), but not significant for cardio embolism or small-artery occlusion subtypes. QKD100-60 and stroke severity were not significantly associated in week 3. There was no difference in NIHSS scores at weeks 0 and 3, or in QKD100-60 between LACI, PACI, and POCI, or dipper versus non-dippers and reverse dippers. CONCLUSION: Further research is needed to explore the association between QKD and stroke severity.

The relationship between dipping profile in blood pressure and neurologic deficit in early acute ischemic stroke.

Blood pressure (BP) in healthy individuals exhibits a diurnal variation, with a nighttime dip of 10%-20%. A persistently high nighttime BP is associated with increased cardiovascular morbidity. The effects of diurnal BP variations on the neurologic deficit in acute stroke at presentation and in the first few weeks poststroke are unclear. We hypothesized that persistently elevated BP results in poor outcome. Patients with an acute ischemic stroke presenting within 48 hours of onset underwent 24-hour ambulatory monitoring of systolic, diastolic, and mean BP. There were a total of 35 patients (16 males; mean age, 74 ± 14 years). The percentage change between mean day and night BP classified patients into dippers (> 10% change), nondippers (0-10% change), or reverse-dippers (< 0% change). The Scandinavian Stroke Scale (SSS) and the National Institute of Health Stroke Scale (NIHSS) were assessed on admission, at week 1, and at week 3. The relationship between neurologic score and dipping classification was analyzed using analysis of variance and analysis of covariance, with age and baseline score as covariates. Based on both the SSS and NIHSS, the reverse-dippers had the lowest neurologic scores at baseline, week 1, and week 3, followed by the nondippers. The dippers performed the best in comparison. No significant differences in demographics and/or other BP characteristics among the groups that could account for these differences in outcome were noted. A reverse-dipping profile in diastolic BP was associated with poor neurologic state at baseline and weeks 1 and 3 compared with both dippers and nondippers.

Human brain structure predicts individual differences in preconscious evaluation of facial dominance and trustworthiness.

Social cues conveyed by the human face, such as eye gaze direction, are evaluated even before they are consciously perceived. While there is substantial individual variability in such evaluation, its neural basis is unknown. Here we asked whether individual differences in preconscious evaluation of social face traits were associated with local variability in brain structure. Adult human participants (n = 36) monocularly viewed faces varying in dominance and trustworthiness, which were suppressed from awareness by a dynamic noise pattern shown to the other eye. The time taken for faces to emerge from suppression and become visible (t2e) was used as a measure of potency in competing for visual awareness. Both dominant and untrustworthy faces resulted in slower t2e than neutral faces, with substantial individual variability in these effects. Individual differences in t2e were correlated with gray matter volume in right insula for dominant faces, and with gray matter volume in medial prefrontal cortex, right temporoparietal junction and bilateral fusiform face area for untrustworthy faces. Thus, individual differences in preconscious social processing can be predicted from local brain structure, and separable correlates for facial dominance and untrustworthiness suggest distinct mechanisms of preconscious processing.

Unconscious evaluation of faces on social dimensions.

It has been proposed that two major axes, dominance and trustworthiness, characterize the social dimensions of face evaluation. Whether evaluation of faces on these social dimensions is restricted to conscious appraisal or happens at a preconscious level is unknown. Here we provide behavioral evidence that such preconscious evaluations exist and that they are likely to be interpretations arising from interactions between the face stimuli and observer-specific traits. Monocularly viewed faces that varied independently along two social dimensions of trust and dominance were rendered invisible by continuous flash suppression (CFS) when a flashing pattern was presented to the other eye. Participants pressed a button as soon as they saw the face emerge from suppression to indicate whether the previously hidden face was located slightly to the left or right of central fixation. Dominant and untrustworthy faces took significantly longer time to emerge (T2E) compared with neutral faces. A control experiment showed these findings could not reflect delayed motor responses to conscious faces. Finally, we showed that participants' self-reported propensity to trust was strongly predictive of untrust avoidance (i.e., difference in T2E for untrustworthy vs neutral faces) as well as dominance avoidance (i.e., difference in T2E for dominant vs neutral faces). Dominance avoidance was also correlated with submissive behavior. We suggest that such prolongation of suppression for threatening faces may result from a passive fear response, leading to slowed visual perception.