Melissa T. Nott

A review of paroxysmal sympathetic hyperactivity after acquired brain injury.

Severe excessive autonomic overactivity occurs in a subgroup of people surviving acquired brain injury, the majority of whom show paroxysmal sympathetic and motor overactivity. Delayed recognition of paroxysmal sympathetic hyperactivity (PSH) after brain injury may increase morbidity and long‐term disability. Despite its significant clinical impact, the scientific literature on this syndrome is confusing; there is no consensus on nomenclature, etiological information for diagnoses preceding the condition is poorly understood, and the evidence base underpinning our knowledge of the pathophysiology and management strategies is largely anecdotal. This systematic literature review identified 2 separate categories of paroxysmal autonomic overactivity, 1 characterized by relatively pure sympathetic overactivity and another group of disorders with mixed parasympathetic/sympathetic features. The PSH group comprised 349 reported cases, with 79.4% resulting from traumatic brain injury (TBI), 9.7% from hypoxia, and 5.4% from cerebrovascular accident. Although TBI is the dominant causative etiology, there was some suggestion that the true incidence of the condition is highest following cerebral hypoxia. In total, 31 different terms were identified for the condition. Although the most common term in the literature was dysautonomia, the consistency of sympathetic clinical features suggests that a more specific term should be used. The findings of this review suggest that PSH be adopted as a more clinically relevant and appropriate term. The review highlights major problems regarding conceptual definitions, diagnostic criteria, and nomenclature. Consensus on these issues is recommended as an essential basis for further research in the area. ANN NEUROL 2010;68:126–135

The incidence of dysautonomia and its relationship with autonomic arousal following traumatic brain injury

Primary objective: To determine the incidence of autonomic arousal vs. Dysautonomia following traumatic brain injury (TBI) in an Intensive Care Unit (ICU) setting and to prospectively evaluate these groups against injury severity and outcome variables. Research design: Prospective observational group comparison (cohort) study of consecutive ICU admissions to a major trauma hospital over a 2-year period. Main outcomes and results: Eighty-nine of 113 subjects met inclusion and exclusion criteria, with consent gained for 79 subjects (61 male, 18 female: 89% of potential subjects). During the first 7 days post-injury, elevated autonomic parameters were almost universal in the sample (92%), predominantly hypertension and tachycardia. Nineteen of 79 subjects (24%) were autonomically aroused on day 7 (that is, had elevated heart rate, respiratory rate, blood pressure and temperature). Dysautonomia was diagnosed on day 14 post-injury in six of 79 subjects (8%) using previously published criteria. Autonomically aroused subjects had significantly more severe injuries, poorer outcomes and greater estimated costs than non-aroused subjects. Furthermore, Dysautonomic subjects within the autonomically aroused group had significantly worse outcome and, excluding early deaths, a greater period of hospitalization and higher estimated costs. Conclusions: The 8% incidence of Dysautonomia during ICU admission was in broad agreement with previous research. While day 7 autonomic arousal indicated a greater degree of injury, the diagnosis of Dysautonomia provided additional prognostic information. A coordinated multi-centre research effort into this condition appears appropriate.

Agitation following traumatic brain injury: An Australian sample

Purpose: Agitation following traumatic brain injury (TBI) is perceived to limit the achievement of rehabilitation goals. The aims of this study were: (1) To examine the nature and incidence of agitation during TBI rehabilitation in an Australian sample; and (2) To explore the relationship between agitation and functional outcomes after TBI. Method: Retrospective medical record review of 80 participants admitted for rehabilitation following TBI. Outcome data collected at discharge, 6 and 24 months post-discharge, included length of stay, duration of post-traumatic amnesia (PTA), community integration, functional independence and life satisfaction. Results: Seventy per cent of patients demonstrated agitation during rehabilitation for an average of 32 days. Agitated patients experienced longer PTA duration, increased length of stay and reduced functional independence, specifically cognitive function, at discharge. These differences between agitated and non-agitated participants did not appear to persist and were not evident at follow-up 6 and 24 months post-discharge. Longer duration of agitation was associated with delayed PTA emergence, longer rehabilitation stay and reduced functional independence at discharge and follow-up. Conclusions: A large proportion of patients with TBI experience agitation. Presence of agitation seems to limit rehabilitation gains at discharge. Longer duration of agitation is associated with persisting limitations to functional independence.

Late mortality after severe traumatic brain injury in New South Wales: a multicentre study

Objectives: To determine the long‐term mortality pattern of adults with severe traumatic brain injury (TBI), and to identify the risk factors associated with death in this group.

Paroxysmal sympathetic hyperactivity after acquired brain injury: A review of diagnostic criteria

Primary objective: To evaluate the development and usage of diagnostic criteria for paroxysmal sympathetic hyperactivity (PSH) following acquired brain injury (ABI), then comparatively analyse published criteria. Research design: Systematic literature review. Methods and procedures: Literature published in English language prior to 30 November 2008 was reviewed for dysautonomic syndromes following ABI, characterized by simultaneous paroxysmal autonomic hyperactivity and motor over-activity. Main outcome and results: Sixty papers presenting 349 cases of PSH were identified, with a further 21 papers providing additional information regarding the condition. Only 27 of these 81 papers (33%) utilized diagnostic criteria. There were nine novel or substantially modified diagnostic criteria sets, which were analysed further. Criteria showed strong agreement on core clinical features of PSH—heart rate (HR), blood pressure, respiratory rate, temperature, sweating, and motor hyperactivity. Most criteria sets utilized a polythetic diagnostic system and all but one indicated severity thresholds, e.g. HR >120 beats per minute. Two papers specified a minimum episode frequency and four papers required a minimum syndrome duration. Conclusions: Of necessity, diagnostic criteria have been developed ad hoc. The differences between criteria complicate both clinical diagnosis and the process of comparing research cohorts. These findings demarcate the need for a single set of PSH diagnostic criteria and provide the substrate for scientific consensus.

Diagnosing Dysautonomia After Acute Traumatic Brain Injury: Evidence for Overresponsiveness to Afferent Stimuli

OBJECTIVE To differentiate between traumatic brain injury (TBI) subjects with normal and elevated autonomic activity by quantifying cardiac responsivity to nociceptive stimuli and to determine the utility of heart rate variability (HRV) and event-related heart rate changes in diagnosing dysautonomia. DESIGN Prospective cohort study. SETTING Intensive care unit in a tertiary metropolitan trauma center. PARTICIPANTS Adults (N=27) with TBI recruited from 79 consecutive TBI admissions comprising 16 autonomically aroused and 11 control subjects matched by age, sex, and injury severity. INTERVENTIONS None. MAIN OUTCOME MEASURES Immediate: pattern of autonomic changes indexed by HRV and event-related heart rate after nociceptive stimuli. Six months: length of stay, Glasgow Coma Scale, and Disability Rating Scale. RESULTS Heart rate changes (for both HRV and event-related heart rate) were associated with the diagnostic group and 6-month outcome when evaluated pre- and poststimulus but not when evaluated at rest. When assessed on day 7 postinjury, the comparison of HRV and heart rate parameters suggested an overresponsivity to nociceptive stimuli in dysautonomic subjects. These subjects showed a 2-fold increase in mean heart rate relative to subjects with sympathetic arousal of short duration (16% vs 8%), and a 6-fold increase over nonaroused control subjects. Data suggest that post-TBI sympathetic arousal is a spectrum disorder comprising, at one end, a short-duration syndrome and, at the other end, a dramatic, severe sympathetic and motor overactivity syndrome that continued for many months postinjury and associated with a significantly worse 6-month outcome. These findings suggest that it is not the presence of reactivity per se but rather the failure of processes to control for overreactivity that contributes to dysautonomic storming. CONCLUSIONS This study provides empirical evidence that dysautonomic subjects show overresponsiveness to afferent stimuli. Findings from this study suggest an evidence-driven revision of diagnostic criteria and a simple clinical algorithm for the improved identification of cases.

Towards an understanding of sex differences in functional outcome following moderate to severe traumatic brain injury : a systematic review

Background and aim: A clear understanding of the impact sex differences play in clinical traumatic brain injury (TBI) outcome remains elusive. Animal research suggests that females have better functional outcomes following TBI than males. Therefore, this paper aims to systematically review all studies that have examined sex differences in functional outcome measures following moderate to severe TBI in humans. It was predicted that women would exhibit better functional outcome than men. Methods: A predefined study selection criteria was adopted to screen studies eligible for inclusion. A comprehensive and systematic search of various databases, up to the end of April 2007, was undertaken. Two independent reviewers screened studies for eligibility. Selected studies were assessed for methodological quality. Results: 13 studies were included. Because of the heterogeneity of the functional outcome measures and lack of appropriate statistical information, a qualitative analysis was performed. More than half of the papers were considered high quality. Strong evidence was found to suggest that women do not have better functional outcome than men following moderate to severe TBI. Conclusion: The results of this review are contrary to the suggestions from animal literature. Consideration of factors such as the woman patient’s hormonal status at the time of injury and other sources of heterogeneity such as age and injury severity should be addressed in future prospective studies.

Effectiveness of a group anger management programme after severe traumatic brain injury

Primary objective: This study examined the effectiveness of a group approach to the treatment of anger management difficulties for people with severe traumatic brain injury (TBI). Research design: Repeated-measures design with convenience sampling. Method and procedure: Participants were community living clients of a tertiary brain injury service. The group programme consisted of 12 weekly sessions based on a cognitive behavioural therapy (CBT) model, with modifications to incorporate compensations for TBI-related cognitive impairment. Treatment effectiveness was measured using the State-Trait Anger Expression Inventory (STAXI), at pre-treatment, post-treatment and follow-up. Main outcomes and results: The programme was completed by 52 people across nine groups over the years 1998–2006 and 31 of these attended a follow-up session. Completion of the programme was associated with significant decreases in self-reported frequency with which anger was experienced (STAXI Trait Anger) and frequency of expression of anger (Anger Expression-Out), as well as a significant increase in reported attempts to control feelings of anger (Anger Control); changes were maintained at follow-up assessment. Conclusions: A group CBT approach shows promise as an effective community-based treatment for anger control issues after severe TBI. Future research directions should include a wait-list control group and objective rating of anger expression.

Reliability of the Perceive, Recall, Plan and Perform System of Task Analysis: A criterion‐referenced assessment

OBJECTIVE To conduct preliminary examination of the rater and test-reliability of the Perceive, Recall, Plan and Perform (PRPP) System of Task Analysis, an ecological measure designed to assess task-embedded information processing capacity during occupational therapy assessment of confused and agitated adults following traumatic brain injury. METHODS Occupational therapists observed and scored client performance using the PRPP System of Task Analysis. Correlational analysis and measures of agreement were performed to determine interrater and intrarater reliability. Test procedures were examined for reliability and internal consistency. RESULTS Interrater and test reliability considered three factors: therapists, clients and tasks. A moderate level of interrater reliability was achieved between trained therapists (intraclass correlation coefficient (ICC) = 0.60). Test procedures were highly reliable (ICC = 0.88). Across two measurement occasions, therapists showed a tendency towards harder rating on the second test occasion (-4.5%; 95% confidence interval for: -10.67% → 3.17%). CONCLUSION The findings of this study support the use of criterion-referenced tests in the area of occupational performance measurement. Occupational therapists achieved moderate interrater reliability when measuring the performance of adults with brain injury on various activities of daily living. Test procedures were found to be highly reliable in measuring the occupational performance of adults demonstrating confusion and agitation typical to the stage of post-traumatic amnesia following head injury.

Dysautonomia after Severe Traumatic Brain Injury Evidence of Persisting Overresponsiveness to Afferent Stimuli

Baguley IJ, Heriseanu RE, Nott MT, Chapman J, Sandanam J: Dysautonomia after severe traumatic brain injury: Evidence of persisting overresponsiveness to afferent stimuli. Objective:To differentiate between dysautonomic and nondysautonomic subjects with acquired brain injury by measuring sympathetic reactivity after a nociceptive clinical procedure and to determine the utility of heart rate variability as an indicator of sympathetic overresponsivity in dysautonomic subjects. Design:This case-controlled study recruited subjects with acquired brain injury (mean, 5 yrs postinjury) attending a hospital-based outpatient clinic, comprising seven dysautonomic subjects with traumatic brain injury, eight nondysautonomic traumatic brain injury subjects, and 11 nondysautonomic subjects with nontraumatic acquired brain injury. Sympathetic reactivity after nociceptive stimuli (limb assessment and botulinum toxin injection for spasticity management) was compared among groups. Results:Sympathetic overactivity in dysautonomic subjects was evident across all physiologic parameters, whereas nondysautonomic subjects demonstrated limited reactivity. Heart rate variability measures of the balance between sympathetic and parasympathetic cardiac control showed a significant elevation in response to nociceptive stimuli, a response not observed in either nondysautonomic group. This sympathetic overactivity showed a normalizing tendency with increasing time postinjury. Conclusions:This study found persistent sympathetic overactivity in response to nociceptive stimuli in dysautonomic subjects (mean, 5 yrs postinjury). This significantly extends the duration over which such sympathetic overactivity has been quantified in this group, contributing to the accumulating empirical evidence that dysautonomic paroxysms result from sympathetic overresponsiveness. Given that sympathetic overactivity has now been observed from day 7 through 5 yrs postinjury, quantitative evaluation of patients for overresponsiveness to stimuli should be added to current diagnostic procedures at all stages of recovery.