Investigating Inducible Muscle Overactivity in Acquired Brain Injury and the Impact of Botulinum Toxin A.

OBJECTIVE: To investigate the pattern of change in muscle overactivity during repetitive grasp/release using dynamic computerized dynamometry (DCD; objective 1) and the effect of botulinum toxin A (BTX-A; objective 2). DESIGN: Secondary analysis of an observational cohort study. SETTING: Hospital outpatient spasticity management service. PARTICIPANTS: A convenience sample (N=65), comprising adults with upper motor neuron syndrome affecting the arm after acquired brain injury (ABI; n=38) and participants without ABI (n=27). INTERVENTIONS: After clinical assessment, a subgroup of participants with ABI (n=28) underwent BTX-A injections as part of their spasticity management. MAIN OUTCOME MEASURES: Post hoc DCD data processing extracted the values of minimum force generation between 10 sequential contractions. The pattern of change was analyzed. RESULTS: The ABI injected group exerted greater force at baseline than both other groups (ABI injected=1.04 kg, ABI noninjected=0.74 kg, participants without ABI=0.53 kg; P=.011). After the first contraction, minimum force values increased for all groups and were greatest in the ABI injected group. With subsequent cycles, the group without ABI showed a linear pattern of decreasing force generation, whereas both ABI groups showed a quadratic increasing pattern, which was of greater magnitude in the ABI injected group. After injection, values for the ABI injected group showed a 51% reduction in inducible muscle overactivity (P=.003) to magnitudes similar to those of the ABI noninjected group. CONCLUSIONS: This study showed that hand relaxation deteriorated during repetitive movements in people with spasticity, a feature hypothesized to adversely influence everyday hand function. After BTX-A injection, the magnitude but not the pattern of this inducible muscle overactivity improved.

Altered sexual function after central neurological system trauma is reflective of region of injury; brain vs spinal cord.

OBJECTIVE: To compare and contrast the contributory effects of traumatic brain injury (TBI) and spinal cord injury (SCI) on sexual function and social relationship opportunities, hypothesizing that patterns of change in sexual function would follow etiology. DESIGN: Cross-sectional, case-matched survey of community living individuals with TBI, SCI or both (termed dual diagnosis). PARTICIPANTS: Consecutive sample of participants with TBI (n = 25), SCI (n = 24) and dual diagnosis (n = 28), an average 3.6 years post-rehabilitation discharge. METHODS: Participants were interviewed using a modified version of the 'Sexuality after Spinal Injury Questionnaire.' RESULTS: Almost all respondents (97%) perceived adverse post-injury change in their experience of neurosexual function and/or social relationships. Physiological aspects of sexual function (e.g., erection, orgasm) were most affected by SCI whereas social relationships appeared more affected by TBI. People with dual diagnoses exhibited a combination of features. Participants with SCI (with or without TBI) were significantly more likely to have their concerns about sexual function discussed during rehabilitation than the TBI group. CONCLUSION: TBI and SCI produce predictable impacts upon sexual function following injury, the impact of which were less frequently addressed during inpatient rehabilitation for those with TBI.

External causes of death after severe traumatic brain injury in a multicentre inception cohort: clinical description and risk factors.

Objective: To characterize the clinical profile of patients dying from external causes (EC) following severe traumatic brain injury (TBI). Design and Methods: Data from 2545 patients forming the NSW-BIRP inception cohort discharged from post-acute inpatient rehabilitation between 1 July 1990 and 1 October 2007 were retrospectively reviewed. Standardized mortality ratios (SMRs) were calculated for EC sub-categories. Demographic, clinical and rehabilitation service factors were compared between deaths from EC, deaths from other causes (OC), and non-deceased. Clinical profiles of EC sub-categories were analysed descriptively. Results: Overall, patients with TBI were 5.2x more likely to die from EC relative to the general population. Risk of death was elevated in all EC sub-categories examined, with the largest risks relating to other accidental threats to breathing (SMR = 33.0; 95%CI = 13.79-60.45) and falls (SMR = 14.3; 95%CI = 5.01-28.39). The EC group were younger, more likely to have pre-injury psychiatric histories, less severe injuries, greater functional independence, and die earlier than the OC group. There was considerable heterogeneity in the clinical profiles of patients dying from different EC sub-categories. Conclusions: EC constitutes one of the largest causes of mortality following TBI in patients surviving beyond the post-acute phase. Potential implications for risk modification and prevention of premature and avoidable deaths are discussed.

Incidence of paroxysmal sympathetic hyperactivity following traumatic brain injury using assessment tools.

INTRODUCTION: A consensus statement proposed a diagnostic framework to systematise the identification of paroxysmal sympathetic hyperactivity (PSH) using the PSH-Assessment Measure (PSH-AM). METHODS: This retrospective study identified adult patients with a primary diagnosis of traumatic brain injury and a hospital length of stay >14 days. Based on PSH-AM scores, patients were grouped into 'unlikely', 'possible', or 'probable' PSH. For this study, 'possible' and 'probable' PSH patients were collapsed into a single group (PSH+), and resultant data were compared with 'unlikely' diagnoses (PSH-). PSH-AM data were assessed against clinical diagnoses to establish sensitivity and specificity data. RESULTS: Sixty five patients met inclusion criteria, with 45/65 (69%) categorised as either 'possible' or 'probable' PSH on the PSH-AM. Only 16 of these patients were diagnosed by clinicians. The most common symptoms triggering clinical diagnosis were tachycardia, fever and posturing. Increased respiratory rate, blood pressure or the presence of diaphoresis were not used in diagnosing PSH if the PSH-AM was not utilised. Assuming clinical assessment as the current gold standard, the PSH-AM yielded a sensitivity of 94% and a specificity of 35% when used retrospectively. Patients clinically diagnosed with PSH were discharged 5 days earlier compared to those identified by the PSH-AM. CONCLUSIONS: The recently proposed diagnostic framework may reduce misdiagnosis, length of stay and hospitalisation costs.

Early Fever As a Predictor of Paroxysmal Sympathetic Hyperactivity in Traumatic Brain Injury.

OBJECTIVE: Paroxysmal sympathetic hyperactivity (PSH) is characterized by episodic, hyperadrenergic alterations in vital signs after traumatic brain injury (TBI). We sought to apply an objective scale to the vital sign alterations of PSH in order to determine whether 1 element might be predictive of developing PSH. SETTING/PARTICIPANTS/DESIGN: We conducted an observational study of consecutive TBI patients (Glasgow Coma Scale score ≤12) and monitored the cohort for clinical evidence of PSH. PSH was defined as a paroxysm of 3 or more of the following characteristics: (1) tachycardia, (2) tachypnea, (3) hypertension, (4) fever, (5) dystonia (rigidity or decerebrate posturing), and (6) diaphoresis, with no other obvious causation (ie, alcohol withdrawal, sepsis). MAIN MEASURES: The Modified Clinical Feature Severity Scale (mCFSS) was applied to each participant once daily for the first 5 days of hospitalization. RESULTS: Nineteen (11%) of the 167 patients met criteria for PSH. Patients with PSH had a higher 5-day cumulative mCFSS score than those without PSH (median [interquartile range] = 36 [29-42] vs 29 [22-35], P = .01). Of the 4 components of the mCFSS, elevated temperature appeared to be most predictive of the development of PSH, especially during the first 24 hours (odds ratio = 1.95; 95% confidence interval, 1.12-3.40). CONCLUSION: Early fever after TBI may signal impending autonomic dysfunction.

Effects of concomitant spinal cord injury and brain injury on medical and functional outcomes and community participation.

BACKGROUND: There are limited data on the interactions between concomitant spinal cord injury (SCI) and traumatic brain injury (TBI) in terms of medical, psychological, functional, and community outcomes. OBJECTIVE: To investigate the hypothesis that in addition to SCI-associated sensory-motor impairments, people with dual diagnosis would experience additional TBI-associated cognitive impairments that would have a negative impact on community reintegration. METHODS: Cross-sectional, case-matched study comparing a consecutive sample of participants with dual diagnosis (n = 30) to an SCI group (n = 30) and TBI group (n = 30). Participants who were on average 3.6 years postrehabilitation discharge were interviewed using a battery of standardized outcome measures. RESULTS: Length of rehabilitation stay was significantly longer in SCI and dual diagnosis participants. Fatigue, pain, sexual dysfunction, depression, and sleep disturbances were frequently reported by all groups. Similar levels of anxiety and depression were reported by participants in all groups, however TBI participants reported higher stress levels. All groups achieved mean FIM scores > 100. The dual diagnosis and SCI groups received more daily care and support than TBI participants. Similar levels of community reintegration were achieved by all groups with a high level of productive engagement in work, study, or volunteer activities. CONCLUSIONS: The findings of this study do not support the hypotheses. Postrehabilitation functioning was better than anticipated in adults with dual diagnosis. The contribution of rehabilitation factors, such as longer admission time to develop compensatory techniques and strategies for adaptation in the community, may have contributed to these positive findings.

Contextual influences on employment of people with dual diagnosis: spinal cord injury and traumatic brain injury.

BACKGROUND/AIM: Research into the paid employment of people with spinal cord injury or traumatic brain injury is prevalent; however, little research has examined the factors that may support employment for adults with a concomitant spinal cord injury and traumatic brain injury (dual diagnosis). This study aimed to determine the level of paid employment reported by people with dual diagnosis and to explore contextual factors that supported paid employment. METHODS: This cross-sectional cohort study recruited 30 participants with dual diagnosis from a specialist spinal rehabilitation unit. Interviews were conducted during the first five years post-rehabilitation discharge to determine level of paid employment and contextual factors that supported employment. RESULTS: At interview, 47% of participants were in paid employment. Employment type at interview indicated a shift away from more physically intensive jobs. Employed and unemployed participants reported a high level of social support and reported experiencing few physical or attitudinal barriers in their day to day lives. These environmental factors did not differentiate between employed and unemployed participants (z range = -0.98 to -0.17; P value range = 0.33-0.86). The most common facilitator of employment identified by participants was the personal factor - motivation (93% of employed participants). CONCLUSION: When considering the impact of contextual factors on paid employment for people with a dual diagnosis of spinal cord injury/traumatic brain injury, personal factors may be of greater influence than environmental factors. Study participants experienced few physical or attitudinal barriers and reported highly supportive interpersonal relationships.

Computerised pinch dynamometry in the assessment of adult hand spasticity.

BACKGROUND/AIM: The hand engages with the environment through the grasp, stabilisation, manipulation and release of objects during everyday tasks, activities and routines. Upper motor neuron syndrome following acquired brain injury may negatively impact hand function, reducing strength, range of motion and motor control. It is important for clinicians to reliably measure such impacts, particularly for the impact of intervention and to monitor change in performance over time. Therefore, the aim of this study was to investigate the test-retest reliability and construct validity of Dynamic Computerised pinch Dynamometry for measuring fine hand motor performance following acquired brain injury. METHODS: The Dynamic Computerised pinch Dynamometry protocol was completed by 36 community dwelling adults and 27 healthy adults using a simulated pinch and release task in lateral and pincer grip positions. Measurements were conducted over two testing occasions approximately five weeks apart. Dynamic Computerised pinch Dynamometry output was evaluated to determine the test-retest reliability and construct validity of the measure. RESULTS: Test-retest reliability scores using Kendall coefficient of concordance ranged from W = 0.61-0.94. Dynamic Computerised pinch Dynamometry discriminated between participants with and without acquired brain injury (z = 4.97-6.50, P < 0.05) and between the affected and non-affected hand of participants with acquired brain injury (z = 3.37-5.22, P < 0.001). CONCLUSIONS: Dynamic Computerised pinch Dynamometry in both lateral and pincer positions had fair to excellent test-retest reliability, and had good construct validity for discrimination between participants with and without acquired brain injury as well as between the affected and non-affected hand of participants with acquired brain injury.

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. DESIGN, PATIENTS AND SETTING: Inception cohort study of 2545 adults consecutively discharged from one of three metropolitan tertiary, post-acute inpatient rehabilitation services of the New South Wales Brain Injury Rehabilitation Program from 1 January 1990 to 1 October 2007 after inpatient rehabilitation for primary TBI. MAIN OUTCOME MEASURE: Survival status at 1 October 2009. RESULTS: 258 deaths were recorded in this sample, yielding a standardised mortality ratio of 3.19 (95% CI, 2.80-3.60). Risk of death remained elevated above societal norms for at least 8 years after discharge from rehabilitation. Mortality risk was increased by: functional dependence at discharge; age at injury; pre-injury drug and alcohol misuse; pre-injury epilepsy; and discharge to an aged care facility. The risk of death from external causes, and respiratory system and nervous system disorders was six to seven times higher, and the risk of death from disorders of the digestive system, and mental and behavioural disorders was five times higher in adults with severe TBI than in the general population. CONCLUSIONS: People who survive to discharge from inpatient rehabilitation following a severe TBI were found to have a sustained increase in risk of death for eight years post discharge. Various demographic and injury-related variables selectively increase mortality risk and may be modifiable in order to reduce the observed increase in mortality.

Clinical assessment of hand motor performance after acquired brain injury with dynamic computerized hand dynamometry: construct, concurrent, and predictive validity.

OBJECTIVE: To assess the construct, concurrent, and predictive validity of dynamic computerized hand dynamometry. DESIGN: Prospective correlational study between dynamometry and functional upper limb performance. SETTING: Hospital outpatient spasticity clinics. PARTICIPANTS: Adults with upper motor neuron syndrome affecting the upper limb after acquired brain injury (ABI) (n=38; median age, 50 y; range, 18-81 y) and healthy adult control participants (n=27; median age, 37 y; range, 22-62 y). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Dynamic computerized dynamometry elements of hand performance (isometric force, force velocity, isometric grip work, contraction and relaxation duration) and the Action Research Arm Test. RESULTS: Motor elements of hand performance objectively measured by the dynamic computerized dynamometry protocol achieved moderate to good validity when correlated with standardized measures of functional hand performance. Dynamic computerized dynamometry identified clear differences in hand performance between participants with and without ABI. Within the ABI group, dynamic computerized hand dynamometry achieved fair to moderate predictive validity with regards to whether a participant would be referred for botulinum toxin A injections. CONCLUSIONS: This study provides support for the construct, concurrent, and predictive validity of the dynamic computerized dynamometry protocol.

Test-retest reliability of computerised hand dynamometry in adults with acquired brain injury.

BACKGROUND/AIM: The ability to objectively and reliably measure hand performance over time is critical to monitor patient performance and evaluate treatment efficacy. Current spasticity measures are subjective in nature and fail to capture the complexity of the multi-faceted upper motor neuron syndrome. This study examined the test-retest reliability of dynamic computerised hand dynamometry for simultaneously measuring multiple aspects of positive and negative features of the upper motor neuron syndrome during an active grasp and release task. METHODS: Community-living adults with upper motor neuron syndrome following acquired brain injury attending metropolitan spasticity clinics for management of upper limb spasticity (N = 36; mean age 50 years ±15) and control participants (N = 27, mean age 40 years ±12) completed a computerised hand dynamometry protocol across two testing occasions 5 weeks apart. Objective measurement of Isometric Force, Cycle Duration and Isometric Grip Work, Force Velocity, was completed during a repeated grasp and release test protocol with a computerised hand dynamometer to evaluate the reliability and reproducibility of hand performance. RESULTS: Kendall Coefficient of Concordance W scores ranged from W = 0.69-0.98 for motor elements of grasp and release, including Isometric Force, Cycle Duration, Isometric Grip Work and Force Velocity. CONCLUSIONS: The investigated dynamic computerised hand dynamometry protocol showed fair/good to excellent levels of test-retest reliability in control participants and in subjects with upper motor neuron syndrome following acquired brain injury.

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.

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.

Patterns of agitated behaviour during acute brain injury rehabilitation.

OBJECTIVE: To monitor daily shift-by-shift changes in agitated behaviour during adult brain injury rehabilitation. DESIGN: A prospective, descriptive study. METHODS: Eight participants were monitored daily for up to 28 days. The Agitated Behaviour Scale (ABS) evaluated behaviour during three nursing shifts (morning, afternoon, night). Severity of agitation, peak intensity and concomitant behaviours were calculated. Shift differences and patterns of behavioural changes were analysed. RESULTS: Four hundred and seven recordings were taken with the ABS. All participants demonstrated multiple agitated behaviours (between 3-13 concomitant behaviours per person); the most common behaviours were representative of the ABS Disinhibition sub-scale. Weekly peak intensity ranged from 14-55 on the ABS. Mean ABS scores were highest during the afternoon shift and lowest at night. Improved cognition was associated with resolving agitated behaviour; while persistent agitated behaviour was associated with low levels of cognition. Minimal agitated behaviour was observed in participants who emerged from post-traumatic amnesia. CONCLUSIONS: Agitated behaviour during acute brain injury rehabilitation has a complex clinical presentation. High levels of agitation observed during the afternoon shift may be associated with low levels of structured activities available at that time, higher levels of environmental stimuli during visiting times and increased cognitive fatigue. Lower cognitive ability was related to consistently higher levels of agitated behaviour and vice-versa.

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.

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.

Cost Effectiveness of Long-Term Incobotulinumtoxin-A Treatment in the Management of Post-stroke Spasticity of the Upper Limb from the Australian Payer Perspective.

BACKGROUND: In Australia, the reimbursement of botulinum neurotoxin-A (BoNT-A) on the Pharmaceutical Benefits Scheme for the treatment of moderate to severe spasticity of the upper limb following a stroke (PSS-UL) is restricted to four treatment cycles per upper limb per lifetime. This analysis examined the cost effectiveness of extending the treatment beyond four treatments among patients with an adequate response to previous treatment cycles. METHODS: A Markov state transition model was developed to perform a cost-utility analysis of extending the use of incobotulinumtoxin-A beyond the current restriction of four treatment cycles among patients who have shown a successful response in previous treatment cycles ('known responders'). The Markov model followed patients in 12-weekly cycles for 5 years, estimating the proportion of patients with or without response over this period in each of the modelled treatment arms. Post hoc analysis of an open-label extension phase study informed the Markov model. The perspective of the analysis was the Australian healthcare system, meaning only direct healthcare costs were included. Utility values by response status were derived from EQ-5D data from a published double-blind, placebo-controlled study. The primary outcome measure was the incremental cost per quality-adjusted life-year (QALY). Univariate and probabilistic sensitivity analyses were conducted. RESULTS: The open-label extension study data demonstrated the probability of treatment response after four injections was greater among 'known responders' than those without prior response. The incremental cost per QALY gained of continued use of incobotulinumtoxin-A beyond the current restriction of four treatments was A$59,911. CONCLUSION: Limiting BoNT-A treatment to four cycles per patient per lifetime is likely to be suboptimal in many patients with PSS-UL. Treatment response beyond four cycles is highest among known responders, and allowing such patients to continue treatment beyond four cycles appears cost effective.

The excitatory:inhibitory ratio model (EIR model): An integrative explanation of acute autonomic overactivity syndromes.

Numerous medical conditions present with acute and severe autonomic and muscular overactivity. These syndromes include Neuroleptic Malignant Syndrome, Serotonin Syndrome, Dysautonomia (or paroxysmal sympathetic storms) following acquired brain injury, Autonomic Dysreflexia, Parkinsonian-Hyperpyrexia Syndrome, Malignant Catatonia, intrathecal baclofen withdrawal, Malignant Hyperthermia, Stiff Man Syndrome and Irukandji Syndrome. In their worst forms, each of these syndromes are relatively rare, are treated by different medical specialties and show widely varying pathophysiology. Most are considered to be medical emergencies and share significant mortality rates. Previous authors have noted similarities between some of these conditions, prompting the suggestion that a single common mechanism may underlie their clinical presentation. However, the development of such an integrative model has not occurred. This paper presents a short review of the clinical syndromes, grouped by the location of pathology and mechanism of action. From this background, an integrative framework termed the excitatory:inhibitory ratio (EIR) model is presented. The EIR model consists of two inter-related networks operating at spinal and brainstem levels. The model is evaluated against pre-clinical scientific research, known pathways, each disorder's pathophysiology (where this is known) and variable severity, and used to explain the reasons behind the efficacy of current treatment regimes. Circumstantial evidence for an expanded aetiology for Malignant Hyperthermia is provided and generic treatment strategies for a number of other conditions are suggested. Finally, minor modifications to this model provide a basis to begin to explain less severe, regional "overlap" syndromes.

Long-term mortality trends in functionally-dependent adults following severe traumatic-brain injury.

PRIMARY OBJECTIVE: To investigate mortality trends in functionally dependent adults following traumatic brain injury (TBI). METHODS: Data for 966 consecutive admissions to a specialist TBI rehabilitation service were reviewed. Details for 69 subjects who were functionally dependent at rehabilitation discharge were cross-referenced against the State Government Death Register. The observed mortality rate was compared to an equivalent population sample derived from Australian Life Tables. RESULTS: Twenty-five subjects (36%) were deceased at an average 10.5 years post-injury (SD 5 years; range 1.7-18.8 years). The observed numbers of deaths far exceeded the expected population figure (1.9) for the same period (1989-2007) yielding a standardized mortality rate of 13.2. Mortality trends suggested a bimodal distribution, with more deaths in the first 5 years post-injury followed by no further deaths until 9 years post-injury. CONCLUSIONS: Mortality in this functionally-dependent group was significantly associated with age, male sex and degree of disability at discharge. The bimodal distribution of mortality data suggests different contributory mechanisms to early vs. late mortality in this group.