The Influence of Family History of Neurodegenerative Disease on Adolescent Concussion Outcomes.

Evidence suggests that factors associated with a family history of neurodegenerative disease (fhNDD) may influence outcomes following a concussion. However, the relevance of these findings in adolescent populations has not been fully explored. Therefore, the present study sought to evaluate the relationship between fhNDD and neurological outcomes following an adolescent concussion. Data from a local pediatric concussion clinic were used to compare adolescents with (n = 22) and without (n = 44) an fhNDD. Clinical symptom burden, emotional health, cardio-autonomic function, and cognitive performance were assessed at initial (~2 weeks) and follow-up (~5 weeks) post-injury evaluations. Cardio-autonomic function was assessed at rest and during isometric handgrip contraction (IHGC). Results indicated no significant group differences in emotional health or cognitive performance. Across evaluations, those with an fhNDD exhibited greater somatic symptom severity, alterations in HRV at rest, and early blunted cardio-autonomic reactivity during IHGC compared to those without an fhNDD. These findings suggest that positive fhNDD is negatively associated with clinical symptomology and cardio-autonomic functioning following an adolescent concussion. Further, these findings encourage clinicians to utilize a comprehensive neurological evaluation to monitor concussion recovery. Future studies should look into exploring the role of specific neurodegenerative processes and conditions on concussion outcomes in adolescents.

Predictive Value of Subacute Heart Rate Variability for Determining Outcome Following Adolescent Concussion.

Objective assessments of concussion recovery are crucial for facilitating effective clinical management. However, predictive tools for determining adolescent concussion outcomes are currently limited. Research suggests that heart rate variability (HRV) represents an indirect and objective marker of central and peripheral nervous system integration. Therefore, it may effectively identify underlying deficits and reliably predict the symptomology following concussion. Thus, the present study sought to evaluate the relationship between HRV and adolescent concussion outcomes. Furthermore, we sought to examine its predictive value for assessing outcomes. Fifty-five concussed adolescents (12-17 years old) recruited from a local sports medicine clinic were assessed during the initial subacute evaluation (within 15 days postinjury) and instructed to follow up for a post-acute evaluation. Self-reported clinical and depressive symptoms, neurobehavioral function, and cognitive performance were collected at each timepoint. Short-term HRV metrics via photoplethysmography were obtained under resting conditions and physiological stress. Regression analyses demonstrated significant associations between HRV metrics, clinical symptoms, neurobehavioral function, and cognitive performance at the subacute evaluation. Importantly, the analyses illustrated that subacute HRV metrics significantly predicted diminished post-acute neurobehavioral function and cognitive performance. These findings indicate that subacute HRV metrics may serve as a viable predictive biomarker for identifying underlying neurological dysfunction following concussion and predict late cognitive outcomes.

Increased pulse wave velocity in persons with spinal cord injury: the effect of the renin-angiotensin-aldosterone system.

Increased pulse wave velocity (PWV), a marker of cardiovascular disease (CVD), has been reported in otherwise healthy individuals with spinal cord injury (SCI) compared with age-matched uninjured controls. Due to decentralized descending sympathetic vascular control, individuals with injuries above T6 are prone to orthostatic hypotension and, as a result, depend on the renin-angiotensin-aldosterone system (RAAS) to maintain orthostatic blood pressure (BP). The purpose of this study was to determine resting PWV, a noninvasive surrogate of central arterial stiffness, in individuals with cervical (C4-T1; n = 11) and thoracic (T6-T12; n = 11) SCI, compared with age-matched controls (controls; n = 11). Next, our aim was to describe group differences in BP, plasma norepinephrine (NE), and renin response to head-up tilt (HUT). Finally, we sought to determine the relationship between PWV and the orthostatic change in BP, NE, and the plasma renin during HUT among the groups. PWV was significantly increased in both cervical (8.81 ± 1.91 m/s) and thoracic (7.36 ± 1.58 m/s) SCI compared with the controls (5.53 ± 0.95 m/s; P < 0.05). The change from supine to 60° HUT in BP and NE was significantly reduced and change in plasma renin was significantly increased in the cervical group compared with the thoracic and control groups. Group affiliation and change in plasma renin were significant predictors of PWV (R2 = 0.63, P = 0.001). These data suggest that dependency on the RAAS for orthostatic BP maintenance may be associated with increased PWV and risk of CVD in the SCI population.NEW & NOTEWORTHY Our novel findings suggest that increased arterial stiffness in individuals with SCI may be due to greater dependency on the RAAS to maintain hemodynamic stability during an orthostatic challenge. Asymptomatic orthostatic hypotension can occur in persons with SCI during transition from the supine to the seated position and during other upright activities of daily living; however, it is seldom addressed by clinicians.

Visceral adiposity in persons with chronic spinal cord injury determined by dual energy X-ray absorptiometry.

OBJECTIVE: To determine visceral adipose tissue (VAT) volume (VATvol) by dual energy X-ray absorptiometry (DXA) in spinal cord injured (SCI) and able-bodied (AB) participants and to explore the relationships between VATvol and routine anthropometric measures. METHODS: Sixty-three subjects with SCI and 126 healthy male AB controls were stratified as low risk [LR: waist circumference (WC) < 102 cm] and moderate to high risk (MHR: WC ≥ 102 cm) for identification of risk for cardiometabolic disease: AB-LR, SCI-LR, AB-MHR, and SCI-MHR. Anthropometrics and standard body composition measurements by DXA with analysis to derive VATvol were performed. RESULTS: Comparison of the four subgroups demonstrated the highest subcutaneous adipose tissue volume (SATvol) in the AB-MHR group (P < 0.01), and the highest VATvol in the SCI-MHR group (P < 0.01). Furthermore, when compared to the AB group, participants with SCI had a 27% increase in VATvol for every centimeter increase in WC and a 20% increase in VATvol for every unit increase in BMI. CONCLUSIONS: Because cutoff values for the routine surrogate measures of adiposity underestimate visceral adiposity in persons with SCI, the risk of adverse metabolic consequences would also be underestimated, which necessitates adjustment of the these cutoff values or, preferably, to perform its direct measurement.

Orthostatic effects of midodrine versus L-NAME on cerebral blood flow and the renin-angiotensin-aldosterone system in tetraplegia.

OBJECTIVE: To compare responses to head-up tilt (HUT) in individuals with chronic tetraplegia after midodrine hydrochloride (10 mg) versus nitro-L-arginine methyl ester (L-NAME, 1 mg/kg) administration. DESIGN: Prospective comparative drug trial. SETTING: Veterans Affairs medical center. PARTICIPANTS: Participants (N=7) were studied during 3 laboratory visits: no drug, midodrine (administered orally 30 min before HUT), and L-NAME (infused over a 60-min period). INTERVENTIONS: Anti-hypotensive agents, midodrine, and L-NAME. MAIN OUTCOME MEASURES: Mean arterial pressure (MAP), cerebral blood flow (CBF), and markers of the renin-angiotensin-aldosterone system (RAAS, plasma renin and serum aldosterone) were measured in the supine position at baseline (BL) and during a 45° HUT maneuver. Data were compared between BL and the average of 3 assessments collected during HUT. RESULTS: Orthostatic MAP and CBF were increased with the midodrine and L-NAME groups compared with the no drug trial and the relationship between the change in MAP and CBF was significant (r=0.770; P<0.001). Both L-NAME and midodrine appeared to suppress the post-HUT RAAS response compared with no drug. CONCLUSIONS: Increasing orthostatic blood pressure with L-NAME or midodrine appears to increase CBF and suppress the RAAS during HUT in persons with tetraplegia, although more data are needed to confirm these preliminary findings.

Orthostatic responses to nitric oxide synthase inhibition in persons with tetraplegia.

OBJECTIVES: To determine the effects of 1.0 mg/kg nitro-L-arginine methyl ester (L-NAME) on orthostatic mean arterial pressure (MAP), serum aldosterone, and plasma renin concentrations in persons with chronic tetraplegia compared with nonspinal cord-injured controls. DESIGN: Prospective placebo-controlled intervention study. SETTING: James J. Peters Veterans Affairs Medical Center. PARTICIPANTS: Patients (n=5) with tetraplegia and controls (n=7) participated. The groups were matched for age, height, and weight; the average duration of injury in the tetraplegia group was 22+/-14 years. INTERVENTION: Subjects with tetraplegia visited the laboratory twice, receiving placebo on day 1 and L-NAME (1.0 mg/kg) on day 2. The agents were infused via an intravenous catheter over 60 minutes with the patient in the supine position. Data were collected during the infusion and then during head-up tilt to 45 degrees for 30 minutes. Control subjects visited the laboratory once for placebo infusion and the head-up tilt maneuver. MAIN OUTCOME MEASURE: Orthostatic MAP. RESULTS: Orthostatic MAP was reduced after placebo infusion in subjects with tetraplegia compared with controls (69+/-11 vs 89+/-9 mmHg, respectively; P<.01) and compared with L-NAME infusion (90+/-16 mmHg; P<.01). Orthostatic MAP did not differ when comparing the tetraplegia group with controls after L-NAME infusion. Orthostatic aldosterone levels were increased after placebo compared with L-NAME infusion in persons with tetraplegia; plasma renin levels did not differ among the groups. CONCLUSIONS: These data suggest that nitric oxide synthase inhibition may have clinical potential for treatment of orthostatic hypotension in persons with chronic tetraplegia.

Cold face test in persons with spinal cord injury: age versus inactivity.

INTRODUCTION: Persons with spinal cord injury (SCI) reflect a model of precocious aging and inactivity; as such, these individuals manifest well-appreciated cardiovascular abnormalities. We aimed to determine the influence of inactivity in persons with SCI, and the influence of age in healthy controls, on cardiovascular autonomic responses to the cold face test (CFT). METHODS: Subjects recruited (n = 42) included 18 controls: 10 young (25 +/- 2 years) and 8 old (50 +/- 6 years), and 24 subjects with chronic SCI: 17 with tetraplegia (C3-C8 44 +/- 7 years) and 7 with paraplegia (T5-T10 36 +/- 8 years). Heart rate (HR) and blood pressure were collected continuously: 2-min pre-CFT, 1-min CFT and 2-min post-CFT. Time-frequency (wavelet) analysis of HR (HFln) was used as an estimate of vagal cardiac modulation. RESULTS: The HR response to the CFT differed significantly among the SCI group (4.1 +/- 8.8 bpm) and the young (-7.7 +/- 5.9 bpm; P \ 0.001) and old (-6.8 +/- 10.7 bpm; P \ 0.01). The HFln response was reduced in the SCI (0.01 +/- 1.59) as compared with the young controls (1.50 +/- 1.50; P \ 0.05), but was not different from the old controls (0.69 +/- 1.39). The bradycardia did not differ among the young and old controls; however, the vagal response was attenuated in the old compared with the young. These data suggest that age does not significantly alter the heart rate response to the CFT, but attenuates the vagal response. CONCLUSION: In the SCI group, the paradoxical heart rate response to facial cooling and the lack of vagal activation suggest that abnormal autonomic cardiovascular reflexive control may result from profound inactivity and/or from the spinal cord injury per se.

Effect of hypotensive challenge on systemic hemodynamics and cerebral blood flow in persons with tetraplegia.

INTRODUCTION: Individuals with tetraplegia have impaired central control of sympathetic vascular modulation and blood pressure (BP); how this impairment affects cerebral blood flow (CBF) is unclear. OBJECTIVES: To determine if persons with tetraplegia maintain CBF similarly to able-bodied controls after a hypotensive challenge. METHODS: Seven individuals with chronic tetraplegia and seven age-matched, non-SCI control subjects underwent a hypotensive challenge consisting of angiotensin-converting enzyme (ACE) inhibition (1.25 mg enalaprilat) and 45 degrees head-up tilt (HUT). Heart rate (HR), low frequency systolic BP variability (LFsbp), brachial mean arterial pressure (MAP) and middle cerebral artery CBF were measured before and after the challenge. Group differences for the baseline (BL) to post-challenge response were determined by repeated measures ANOVA. RESULTS: HR did not differ between the groups in response to the hypotensive challenge. LFsbp response was significantly reduced in the tetra compared to the control group (-38 +/- 51 vs. 72 +/- 93%, respectively). MAP did not differ between the groups at BL but was significantly lower in the tetra compared to the control group post-challenge (55 +/- 13 vs. 71 +/- 9 mmHg, respectively); the percent change in MAP was significantly greater in the tetra than in the control group (-29 +/- 14.1 vs. -13 +/- 9%, respectively). However, CBF did not differ between the groups at baseline or post-challenge; the percent change in CBF post-challenge was not different between the tetra and control groups (-29 +/- 13.2 vs. -23 +/- 10.3%, respectively). INTERPRETATION: Despite impaired sympathetic vasomotor and BP control, CBF in persons with tetraplegia was comparable to that of control subjects during a hypotensive challenge.