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Introduction: Positional changes in intracranial pressure (ICP) have been described in humans when measured over minutes or hours in a static posture, with ICP higher when lying supine than when sitting or standing upright. However, humans are often ambulant with frequent changes in position self-generated by active movement. Research question: We explored how ICP changes during movement between body positions. Material and methods: Sixty-two patients undergoing clinical ICP monitoring were recruited. Patients were relatively well, ambulatory and of mixed age, body habitus and pathology. We instructed patients to move back and forth between sitting and standing or lying and sitting positions at 20 s intervals after an initial 60s at rest. We simultaneously measured body position kinematics from inertial measurement units and ICP from an intraparenchymal probe at 100 Hz. Results: ICP increased transiently during movements beyond the level expected by body position alone. The amplitude of the increase varied between participants but was on average ∼5 mmHg during sit-to-stand, stand-to-sit and sit-to-lie movements and 10.8 mmHg [95%CI: 9.3,12.4] during lie-to-sit movements. The amplitude increased slightly with age, was greater in males, and increased with median 24-h ICP. For lie-to-sit and sit-to-lie movements, higher BMI was associated with greater mid-movement increase (β = 0.99 [0.78,1.20]; β = 0.49 [0.34,0.64], respectively). Discussion and conclusion: ICP increases during movement between body positions. The amplitude of the increase in ICP varies with type of movement, age, sex, and BMI. This could be a marker of disturbed ICP dynamics and may be particularly relevant for patients with CSF-diverting shunts in situ.

Axial symptoms emerge in a significant proportion of patients with Parkinson's disease (PD) within 5 years of deep brain stimulation (STN-DBS). Lowering the stimulation frequency may reduce these symptoms. The objectives of the current study were to establish the relationship between gait performance and STN-DBS frequency in chronically stimulated patients with PD, and to identify factors underlying variability in this relationship. Twenty-four patients treated chronically with STN-DBS (>4 years) were studied off-medication. The effect of stimulation frequency (40–140 Hz, 20 Hz-steps, constant energy) on gait was assessed in 6 sessions spread over 1 day. Half of the trials/session involved walking through a narrow doorway. The influence of stimulation voltage was investigated separately in 10 patients. Gait was measured using 3D motion capture and axial symptoms severity was assessed clinically. A novel statistical method established the optimal frequency(ies) for each patient by operating on frequency-tuning curves for multiple gait parameters. Narrowly-tuned optimal frequencies (20 Hz bandwidth) were found in 79% of patients. Frequency change produced a larger effect on gait performance than voltage change. Optimal frequency varied between patients (between 60 and 140 Hz). Contact site in the right STN and severity of axial symptoms were independent predictors of optimal frequency (P = 0.009), with lower frequencies associated with more dorsal contacts and worse axial symptoms. We conclude that gait performance is sensitive to small changes in STN-DBS frequency. The optimal frequency varies considerably between patients and is associated with electrode contact site and severity of axial symptoms. Between-subject variability of optimal frequency may stem from variable pathology outside the basal ganglia.

Purpose: Rapid reach-to-grasp balance-recovery reactions play a critical role in preventing falls. Recent young-adult studies suggest these reactions may be guided using stored visuo-spatial information from the central field, and that peripheral vision may also play an important role. This study used gaze recordings to examine the visual control of reach-to-grasp reactions in older adults. Methods: A motion platform was configured to simulate a “real-life” environment that included a handrail. Subjects performed an activity that required walking to the end of the platform, which was triggered to move suddenly and unexpectedly as they approached the handrail. Twelve healthy older adults (64-79 years old) were tested and compared to 12 healthy young adults (22-30 years old) tested as part of another study. Results: Older adults were more than twice as likely as young adults to react to the platform perturbation by grasping the handrail (10/12 versus 4/12), despite being much less likely to visually fixate the handrail after entering the new environment. Grasping errors were remarkably common (5/10 older, 2/4 young), but there was no consistent relationship to the preceding gaze behavior. Conclusion: Older adults were highly dependent on using a handrail to recover balance, but commonly failed to direct overt visual attention to the rail after entering the unfamiliar environment. The failure to fixate the rail required the reaching movement to be guided using peripheral vision. Further research is needed to determine whether grasping errors can be prevented via interventions that either attract overt attention to the handrail or improve processing of peripheral-field information.

Homozygous familial hypercholesterolemia (HoFH) is an ultra-rare inherited condition that affects approximately one in 300,000 people. The disorder is characterized by extremely high, life-threatening levels of low-density lipoprotein (LDL) cholesterol from birth, leading to significant premature cardiovascular morbidity and mortality, if left untreated. Homozygous familial hypercholesterolemia is severely underdiagnosed and undertreated in the United States (US), despite guidelines recommendations for universal pediatric lipid screening in children aged 9–11. Early diagnosis and adequate treatment are critical in averting premature cardiovascular disease in individuals affected by HoFH. Yet, an unacceptably high number of people living with HoFH remain undiagnosed, misdiagnosed, and/or receive a late diagnosis, often after a major cardiovascular event. The emergence of novel lipid-lowering therapies, along with the realization that diagnosis is too often delayed, have highlighted an urgency to implement policies that ensure timely detection of HoFH in the US. Evidence from around the world suggests that a combination of universal pediatric screening and cascade screening strategies constitutes an effective approach to identifying heterozygous familial hypercholesterolemia (HeFH). Nevertheless, HoFH and its complications manifest much earlier in life compared to HeFH. To date, little focus has been placed on the detection of HoFH in very young children and/or infants. The 2023 Updated European Atherosclerosis Society Consensus Statement on HoFH has recommended, for the first time, broadening pediatric guidelines to include lipid screening of newborn infants. Some unique aspects of HoFH need to be considered before implementing newborn screening. As such, insights from pilot studies conducted in Europe may provide some preliminary guidance. Our paper proposes a set of actionable measures that states can implement to reduce the burden of HoFH. It also outlines key research and policy gaps that need to be addressed in order to pave the way for universal newborn screening of HoFH in the US.

Sitosterolemia is a rare atherogenic sterol storage disease with variability in its presentation requiring a high degree of clinical suspicion. We present 8 cases of sitosterolemia from an Amish kindred that, despite a background of decreased genetic and lifestyle variability, still had markedly variable presentations. (Level of Difficulty: Advanced.)

Objectives: To measure case detection and response time of severe pediatric dyslipidemia, defined as non-high-density lipoprotein cholesterol (HDL-C) ≥190 mg/dL on the initial screening panel. Although low adherence to guidelines recommending universal pediatric lipid screening is well-documented, it is unknown how clinicians respond to pediatric lipid screening results suggestive of severe dyslipidemia. Study design: This study is a single-institution, retrospective review of patients 0-18 years of age with initial lipid panels completed from January 1, 2010, to June 30, 2018. A chart review was conducted on all patients with non-HDL-C ≥190 mg/dL to determine indication(s) for the initial lipid panel, specialty of ordering clinician, type of action taken to an abnormal result (repeat laboratory tests, treatment, and/or referral), time from result to clinician action, and diagnosis. Results: There were 16 860 initial lipid panels that met the inclusion criteria; 178 (1.1%) had non-HDL-C ≥190 mg/dL, indicating severe dyslipidemia. The most common indication for screening was universal screening (52%). For all lipid panels with non-HDL ≥190 mg/dL, a clinician action was documented for 47% within 7 days and 69% within 30 days. No follow-up action was documented in 18 (9%). A clinical diagnosis of familial hypercholesterolemia was the most common diagnosis, in 24% of patients. Conclusions: The majority of lipid panels with non-HDL-C ≥190 mg/dL had some action documented, although the actions varied. Universal screening was the most common indication for testing, clarifying its significance in identifying severe dyslipidemia. Further education and improved management protocols may help responses to severe dyslipidemia in children at high risk for premature cardiovascular disease.