Paroxysmal sympathetic hyperactivity during neurorehabilitation for severe acquired brain injury: current Scandinavian practice and Delphi consensus recommendations.

OBJECTIVES: To document current practice and develop consensus recommendations for the assessment and treatment of paroxysmal sympathetic hyperactivity (PSH) during rehabilitation after severe acquired brain injury. DESIGN: Delphi consensus process with three rounds, based on the Guidance on Conducting and REporting DElphi Studies (CREDES) guidelines, led by three convenors (the authors) with an expert panel. Round 1 was exploratory, with consensus defined before round 2 as agreement of at least 75% of the panel. SETTING: A working group within the Nordic Network for Neurorehabilitation. PANEL PARTICIPANTS: Twenty specialist physicians, from Sweden (9 participants), Norway (7) and Denmark (4), all working clinically with patients with severe acquired brain injury and with current involvement in clinical decisions regarding PSH. RESULTS: Consensus was reached for 21 statements on terminology, assessment and principles for pharmacological and non-pharmacological treatment, including some guidance on specific drugs. From these, an algorithm to support clinical decisions at all stages of inpatient rehabilitation was created. CONCLUSIONS: Considerable consensus exists in the Nordic countries regarding principles for PSH assessment and treatment. An interdisciplinary approach is needed. Improved documentation and collation of data on treatment given during routine clinical practice are needed as a basis for improving care until sufficiently robust research exists to guide treatment choices.

Investigating cognitive reserve, symptom resolution and brain connectivity in mild traumatic brain injury.

BACKGROUND: A proportion of patients with mild traumatic brain injury (mTBI) suffer long-term consequences, and the reasons behind this are still poorly understood. One factor that may affect outcomes is cognitive reserve, which is the brain's ability to maintain cognitive function despite injury. It is often assessed through educational level or premorbid IQ tests. This study aimed to explore whether there were differences in post-concussion symptoms and symptom resolution between patients with mTBI and minor orthopedic injuries one week and three months after injury. Additional aims were to explore the relationship between cognitive reserve and outcome, as well as functional connectivity according to resting state functional magnetic resonance imaging (rs-fMRI). METHOD: Fifteen patients with mTBI and 15 controls with minor orthopedic injuries were recruited from the emergency department. Assessments, including Rivermead Post-Concussion Questionnaire (RPQ), neuropsychological testing, and rs-fMRI scans, were conducted on average 7 days (SD = 2) and 122 days (SD = 51) after injury. RESULTS: At the first time point, significantly higher rates of post-concussion symptoms (U = 40.0, p = 0.003), state fatigue (U = 56.5, p = 0.014), and fatigability (U = 58.5, p = 0.025) were observed among the mTBI group than among the controls. However, after three months, only the difference in post-concussion symptoms remained significant (U = 27.0, p = 0.003). Improvement in post-concussion symptoms was found to be significantly correlated with cognitive reserve, but only in the mTBI group (Spearman's rho = -0.579, p = .038). Differences in the trajectory of recovery were also observed for fatigability between the two groups (U = 36.5, p = 0.015). Moreover, functional connectivity differences in the frontoparietal network were observed between the groups, and for mTBI patients, functional connectivity differences in an executive control network were observed over time. CONCLUSION: The findings of this pilot study suggest that mTBI, compared to minor orthopedic trauma, is associated to both functional connectivity changes in the brain and concussion-related symptoms. While there is improvement in these symptoms over time, a small subgroup with lower cognitive reserve appears to experience more persistent and possibly worsening symptoms over time. This, however, needs to be validated in larger studies. TRIAL REGISTRATION: NCT05593172. Retrospectively registered.

Longitudinal changes in functional connectivity in speech motor networks in apraxia of speech after stroke.

Objective: The cerebral substrates of apraxia of speech (AOS) recovery remain unclear. Resting state fMRI post stroke can inform on altered functional connectivity (FC) within cortical language networks. Some initial studies report reduced FC between bilateral premotor cortices in patients with AOS, with lowest FC in patients with the most severe AOS. However, longitudinal FC studies in stroke are lacking. The aims of the present longitudinal study in early post stroke patients with AOS were (i) to compare connectivity strength in AOS patients to that in left hemisphere (LH) lesioned stroke patients without a speech-language impairment, (ii) to investigate the relation between FC and severity of AOS, aphasia and non-verbal oral apraxia (NVOA) and (iii) to investigate longitudinal changes in FC, from the subacute phase to the chronic phase to identify predictors of AOS recovery. Methods: Functional connectivity measures and comprehensive speech-language assessments were obtained at 4 weeks and 6 months after stroke in nine patients with AOS after a LH stroke and in six LH lesioned stroke patients without speech-language impairment. Functional connectivity was investigated in a network for speech production: inferior frontal gyrus (IFG), anterior insula (aINS), and ventral premotor cortex (vPMC), all bilaterally to investigate signs of adaptive or maladaptive changes in both hemispheres. Results: Interhemispheric vPMC connectivity was significantly reduced in patients with AOS compared to LH lesioned patients without speech-language impairment. At 6 months, the AOS severity was associated with interhemispheric aINS and vPMC connectivity. Longitudinal changes in FC were found in individuals, whereas no significant longitudinal change in FC was found at the group level. Degree of longitudinal AOS recovery was strongly associated with interhemispheric IFG connectivity strength at 4 weeks. Conclusion: Early interhemispheric IFG connectivity may be a strong predictor of AOS recovery. The results support the importance of interhemispheric vPMC connection in speech motor planning and severity of AOS and suggest that also bilateral aINS connectivity may have an impact on AOS severity. These findings need to be validated in larger cohorts.

Cognitive Reserve, Early Cognitive Screening, and Relationship to Long-Term Outcome after Severe Traumatic Brain Injury.

The objective was to investigate the relationship between early global cognitive functioning using the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS) and cognitive flexibility (Trail Making Test (TMT), TMT B-A), with long-term outcome assessed by the Mayo-Portland Adaptability Index (MPAI-4) in severe traumatic brain injury (sTBI) controlling for the influence of cognitive reserve, age, and injury severity. Of 114 patients aged 18-65 with acute Glasgow Coma Scale 3-8, 41 patients were able to complete (BNIS) at 3 months after injury and MPAI-4 5-8 years after injury. Of these, 33 patients also completed TMT at 3 months. Global cognition and cognitive flexibility correlated significantly with long-term outcome measured with MPAI-4 total score (rBNIS = 0.315; rTMT = 0.355). Global cognition correlated significantly with the participation subscale (r = 0.388), while cognitive flexibility correlated with the adjustment (r = 0.364) and ability (r = 0.364) subscales. Adjusting for cognitive reserve and acute injury severity did not alter these relationships. The effect size for education on BNIS and TMT scores was large (d ≈ 0.85). Early screenings with BNIS and TMT are related to long-term outcome after sTBI and seem to measure complementary aspects of outcome. As early as 3 months after sTBI, educational level influences the scores on neuropsychological screening instruments.

Monthlong Intubated Patient with Life-Threatening COVID-19 and Cerebral Microbleeds Suffers Only Mild Cognitive Sequelae at 8-Month Follow-up: A Case Report.

OBJECTIVE: To elaborate on possible cognitive sequelae related to COVID-19, associated cerebrovascular injuries as well as the general consequences from intensive care. COVID-19 is known to have several, serious CNS-related consequences, but neuropsychological studies of severe COVID-19 are still rare. METHODS: M., a 45-year-old man, who survived a severe COVID-19 disease course including Acute Respiratory Distress Syndrome (ARDS), cerebral microbleeds, and 35 days of mechanical ventilation, is described. We elaborate on M's recovery and rehabilitation process from onset to the 8-month follow-up. The cognitive functions were evaluated with a comprehensive screening battery at 4 weeks after extubation and at the 8-month follow-up. RESULTS: Following extubation, M. was delirious, reported visual hallucinations, and had severe sleeping difficulties. At about 3 months after COVID-19 onset, M. showed mild to moderate deficits on tests measuring processing speed, working memory, and attention. At assessments at 8 months, M. performed better, with results above average on tests measuring learning, memory, word fluency, and visuospatial functions. Minor deficits were still found regarding logical reasoning, attention, executive functioning, and processing speed. There were no lingering psychiatric symptoms. While M. had returned to a part-time job, he was not able to resume previous work-tasks. CONCLUSION: This case-study demonstrates possible cognitive deficits after severe COVID-19 and emphasizes the need of a neuropsychological follow-up, with tests sensitive to minor deficits. The main findings of this report provide some support that the long-term prognosis for cognition in severe COVID-19 may be hopeful.

Recovery of Apraxia of Speech and Aphasia in Patients With Hand Motor Impairment After Stroke.

Objective: Aphasia and apraxia of speech (AOS) after stroke frequently co-occur with a hand motor impairment but few studies have investigated stroke recovery across motor and speech-language domains. In this study, we set out to test the shared recovery hypothesis. We aimed to (1) describe the prevalence of AOS and aphasia in subacute stroke patients with a hand motor impairment and (2) to compare recovery across speech-language and hand motor domains. In addition, we also explored factors predicting recovery from AOS. Methods: Seventy participants with mild to severe paresis in the upper extremity were assessed; 50% of these (n = 35) had left hemisphere (LH) lesions. Aphasia, AOS and hand motor assessments and magnetic resonance imaging were conducted at 4 weeks (A1) and at 6 months (A2) after stroke onset. Recovery was characterized in 15 participants showing initial aphasia that also had complete follow-up data at 6 months. Results: All participants with AOS and/or aphasia had LH lesions. In LH lesioned, the prevalence of aphasia was 71% and of AOS 57%. All participants with AOS had aphasia; 80% of the participants with aphasia also had AOS. Recovery in aphasia (n = 15) and AOS (n = 12) followed a parallel pattern to that observed in hand motor impairment and recovery correlated positively across speech-language and motor domains. The majority of participants with severe initial aphasia and AOS showed a limited but similar amount of recovery across domains. Lesion volume did not correlate with results from behavioral assessments, nor with recovery. The initial aphasia score was the strongest predictor of AOS recovery. Conclusion: Our findings confirm the common occurrence of AOS and aphasia in left hemisphere stroke patients with a hand motor impairment. Recovery was similar across speech-language and motor domains, even in patients with severe impairment, supporting the shared recovery hypothesis and that similar brain recovery mechanisms are involved in speech-language and motor recovery post stroke. These observations contribute to the knowledge of AOS and its relation to motor and language functions and add information that may serve as a basis for future studies of post stroke recovery. Studies including neuroimaging and/or biological assays are required to gain further knowledge on shared brain recovery mechanisms.

An observational study of trait and state fatigue, and their relation to cognitive fatigability and saccade performance.

AIM: Different fatigue measurements and their relation to saccadic functions were investigated in 15 patients with a mild traumatic brain injury (mTBI) and 15 orthopedic controls. MATERIALS & METHODS: State fatigue was measured with the Fatigue Severity Scale and trait fatigue with the question on fatigue in the Rivermead Post Concussion Questionnaire and fatigability as decreased performance over time on a neuropsychological measure. RESULTS: Patients with an mTBI scored significantly higher in state fatigue and showed more fatigability compared with the orthopedic controls. Among patients with mTBI, state fatigue correlated with prosaccade latency and cognitive fatigability, while trait fatigue correlated with anxiety and antisaccade latency and variability. CONCLUSION: This pilot study indicates that saccade measurements might, in the future, be useful in the understanding of fatigue and in the search for prognostic factors after mTBI.

Emotional reserve and prolonged post-concussive symptoms and disability: a Swedish prospective 1-year mild traumatic brain injury cohort study.

OBJECTIVE: Prolonged post-concussive symptoms (PCS) affect a significant minority of patients withmild traumatic brain injury (mTBI). The aetiology is multifactorial depending on preinjury as well as peri-injury and postinjury factors. In this study, we examine outcome from an emotional reserve perspective. DESIGN: Prospective cohort study. SETTING: Patients were recruited from three emergency departments in major university hospitals in Stockholm, Sweden. Follow-up data were collected in an outpatient setting at one of the recruiting hospitals. PARTICIPANTS: 122 patients with a history of blunt head trauma (aged 15-65 years; admitted for mTBI within 24 hours after trauma (Glasgow Coma Scale score of 14-15, loss of consciousness <30 min and/or post-traumatic amnesia <24 hours). Exclusion criteria were other significant physical injury and other major neurological disorder, including previous significant head injury. PROCEDURE: Recruitment in three emergency departments. Initial assessments were made within 1 week after the injury. Patients were mailed the follow-up questionnaires 1 year postinjury. OUTCOME MEASURES: A psychiatric assessment was performed at 1 week post injury. The participants also completed a personality inventory, measures of psychological resilience, depression, anxiety and post-traumatic symptoms. One-year outcome was measured by the Rivermead Post Concussion Symptoms and the Rivermead Head Injury Follow-Up questionnaires. RESULTS: The psychiatric assessment revealed more symptoms of anxiety, depression and post-traumatic symptoms in the acute stage for patients who later developed PCS.After 1 year, 94 participants were still in the programme (male/female 57/37) and 12% matched the extended criteria for PCS (≥3 symptoms and ≥2 disabilities). PCS patients reported more preinjury and concurrent psychiatric problems, lower level of functioning before the injury and experienced more stress. They showed higher somatic trait anxiety, embitterment, mistrust and lower level of psychological resilience than recovered participants. CONCLUSION: Intrapersonal emotional reserve shape the emergence and persistence of PCS after mTBI.

Longitudinal changes in oculomotor function in young adults with mild traumatic brain injury in Sweden: an exploratory prospective observational study.

OBJECTIVES: To assess (1) whether visual disturbances can be demonstrated with objective measures more often in patients with mild traumatic brain injury (mTBI) than in orthopaedic controls and non-injured controls, (2) whether such objectively demonstrated disturbances change over time and (3) whether self-reported visual symptoms after mTBI correlate with objectively measurable changes in visuomotor performance. DESIGN: A prospective, controlled, observational study, with assessments planned 7-10 and 75-100 days after injury. SETTING: Emergency department of a general hospital in Sweden. PARTICIPANTS: 15 patients with mTBI, 15 patients with minor orthopaedic injury, 15 non-injured controls, aged 18-40 years. OUTCOME MEASURES: Visual examination, including assessment of visual acuity, accommodation, eye alignment, saccades and stereoacuity. Symptom assessment using Convergence Insufficiency Symptoms Survey (CISS) and Rivermead PostConcussion Symptoms Questionnaire. RESULTS: Assessments were performed 4-13 and 81-322 days after injury (extended time frames for logistical reasons). No statistically significant difference was found between the mTBI and control groups regarding saccade performance and stereoacuity at any time point. The accommodative amplitude was significantly lower in the mTBI group compared with non-injured controls at baseline. 6 out of 13 patients with mTBI had accommodative insufficiency at follow-up. Near point of convergence in the mTBI group was receded at baseline and improved statistically significantly at follow-up. At baseline, patients with mTBI had significantly higher CISS score than orthopaedic and non-injured controls. For patients with mTBI, the CISS score correlated with fusional vergence. CONCLUSION: There were some transient measurable visual changes regarding convergence in patients with mTBI during the subacute period after the injury. Our findings of persistence of accommodative insufficiency in a considerable proportion of patients with mTBI suggest that this visual function should not be overlooked in clinical assessment.

Behavioural problems in the first year after Severe traumatic brain injury: a prospective multicentre study.

OBJECTIVE: To investigate the occurrence of behavioural problems in patients with severe traumatic brain injury during the first year after injury and potential associations with outcome. An additional post hoc objective was to analyse the frequency of behaviours with need for intervention from staff. DESIGN AND SETTING: In a prospective population based cohort study 114 patients with severe traumatic brain injury were assessed at three weeks, three months and one year after injury. MAIN MEASURES: Assessments included clinical examination and standardised instruments. Agitation was assessed with the Agitated Behaviour Scale, the course of recovery by the Rancho Los Amigo Scale and outcome by Glasgow Outcome Scale Extended. RESULTS: Agitation were most common at 3 weeks post injury and 28% ( n=68) of the patients showed at least one agitated behaviour requiring intervention from staff. Presence of significant agitation at 3 weeks after injury was not associated with poor outcome. At 3 months agitation was present in 11% ( n=90) and apathy in 26 out of 81 assessed patients. At 3 months agitation and apathy were associated with poor outcome at one year. CONCLUSIONS: Most agitated behaviours in the early phase are transient and are not associated with poor outcome. Agitation and apathy are uncommon at three months but when present are associated with poor outcome at one year after injury. In the early phase after a severe traumatic brain injury agitated behaviour in need of interventions from staff occur in a substantial proportion of patients.

No effect of an early intervention after mild traumatic brain injury on activity and participation: A randomized controlled trial.

OBJECTIVE: To evaluate measures of activity, participation and quality of life 3 months after mild traumatic brain injury and the effect of an early intervention for patients with an estimated high risk for problems after mild traumatic brain injury. PATIENTS: Consecutive patients attending the emergency room with mild traumatic brain injury. DESIGN: Randomized controlled trial. METHODS: Patients reporting < 3 symptoms after 10 days were considered to have a low risk for prolonged problems. Patients with ≥ 3 symptoms (high-risk patients) were randomized to a visit to a physician or treatment-as-usual. Data on self-reported limitations in activity, restrictions in participation, and quality of life were collected for all patients at 3 months. RESULTS: At 3 months post-injury, low-risk patients reported good quality of life and significantly fewer problems in everyday life compared with high-risk patients. The intervention had no effect on activity, participation or quality of life. CONCLUSION: Patients who report few symptoms early after mild traumatic brain injury are likely to have a good outcome regarding activity and participation. The intervention offered in this study, focusing on reassurance of a good outcome and treatment of comorbidities, had no effect.

Subacute complications during recovery from severe traumatic brain injury: frequency and associations with outcome.

BACKGROUND: Medical complications after severe traumatic brain injury (S-TBI) may delay or prevent transfer to rehabilitation units and impact on long-term outcome. OBJECTIVE: Mapping of medical complications in the subacute period after S-TBI and the impact of these complications on 1-year outcome to inform healthcare planning and discussion of prognosis with relatives. SETTING: Prospective multicentre observational study. Recruitment from 6 neurosurgical centres in Sweden and Iceland. PARTICIPANTS AND ASSESSMENTS: Patients aged 18-65 years with S-TBI and acute Glasgow Coma Scale 3-8, who were admitted to neurointensive care. Assessment of medical complications 3 weeks and 3 months after injury. Follow-up to 1 year. 114 patients recruited with follow-up at 1 year as follows: 100 assessed, 7 dead and 7 dropped out. OUTCOME MEASURE: Glasgow Outcome Scale Extended. RESULTS: 68 patients had ≥1 complication 3 weeks after injury. 3 weeks after injury, factors associated with unfavourable outcome at 1 year were: tracheostomy, assisted ventilation, on-going infection, epilepsy and nutrition via nasogastric tube or percutaneous endoscopic gastroscopy (PEG) tube (univariate logistic regression analyses). Multivariate analysis demonstrated that tracheostomy and epilepsy retained significance even after incorporating acute injury severity into the model. 3 months after injury, factors associated with unfavourable outcome were tracheostomy and heterotopic ossification (Fisher's test), infection, hydrocephalus, autonomic instability, PEG feeding and weight loss (univariate logistic regression). PEG feeding and weight loss at 3 months were retained in a multivariate model. CONCLUSIONS: Subacute complications occurred in two-thirds of patients. Presence of a tracheostomy or epilepsy at 3 weeks, and of PEG feeding and weight loss at 3 months, had robust associations with unfavourable outcome that were incompletely explained by acute injury severity.

Associations between care pathways and outcome 1 year after severe traumatic brain injury.

OBJECTIVE: To assess associations between real-world care pathways for working-age patients in the first year after severe traumatic brain injury and outcomes at 1 year. SETTING AND DESIGN: Prospective, observational study with recruitment from 6 neurosurgical centers in Sweden and Iceland. Follow-up to 1 year, independently of care pathways, by rehabilitation physicians and paramedical professionals. PARTICIPANTS: Patients with severe traumatic brain injury, lowest (nonsedated) Glasgow Coma Scale score 3 to 8 during the first 24 hours and requiring neurosurgical intensive care, age 18 to 65 years, and alive 3 weeks after injury. MAIN MEASURES: Length of stay in intensive care, time between intensive care discharge and rehabilitation admission, outcome at 1 year (Glasgow Outcome Scale Extended score), acute markers of injury severity, preexisting medical conditions, and post-acute complications. Logistic regression analyses were performed. RESULTS: A multivariate model found variables significantly associated with outcome (odds ratio for good outcome [confidence interval], P value) to be as follows: length of stay in intensive care (0.92 [0.87-0.98], 0.014), time between intensive care discharge and admission to inpatient rehabilitation (0.97 [0.94-0.99], 0.017), and post-acute complications (0.058 [0.006-0.60], 0.017). CONCLUSIONS: Delays in rehabilitation admission were negatively associated with outcome. Measures to ensure timely rehabilitation admission may improve outcome. Further research is needed to evaluate possible causation.

Disorders of consciousness after severe traumatic brain injury: a Swedish-Icelandic study of incidence, outcomes and implications for optimizing care pathways.

BACKGROUND: Very severe traumatic brain injury may cause disorders of consciousness in the form of coma, unresponsive wakefulness syndrome (also known as vegetative state) or minimally conscious state. Previous studies of outcome for these patients largely pre-date the 2002 definition of minimally conscious state. OBJECTIVES: To establish the numbers of patients with disorder of consciousness at 3 weeks, 3 months and 1 year after severe traumatic brain injury, and to relate conscious state 3 weeks after injury to outcomes at 1 year. DESIGN: Multi-centre, prospective, observational study of severe traumatic brain injury. INCLUSION CRITERIA: lowest (non-sedated) Glasgow Coma Scale 3-8 during the first 24 h; requirement for neurosurgical intensive care; age 18-65 years; alive 3 weeks after injury. Diagnosis of coma, unresponsive wakefulness syndrome, minimally conscious state or emerged from minimally conscious state was based on clinical and Coma Recovery Scale Revised assessments 3 weeks, 3 months and 1 year after injury. One-year outcome was measured with Glasgow Outcome Scale Extended (GOSE). RESULTS: A total of 103 patients was included in the study. Of these, 81% were followed up to 1 year (76% alive, 5% dead). Three weeks after injury 36 were in coma, unresponsive wakefulness syndrome or minimally conscious state and 11 were anaesthetized. Numbers of patients who had emerged from minimally conscious state 1 year after injury, according to status at 3 weeks were: coma (0/6), unresponsive wakefulness syndrome (9/17), minimally conscious state (13/13), anaesthetized (9/11). Outcome at 1 year was good (GOSE > 4) for half of patients in minimally conscious state or anaesthetized at 3 weeks, but for none of the patients in coma or unresponsive wakefulness syndrome. These differences in outcome were not revealed by prognostic predictions based on acute data. CONCLUSION: Patients in minimally conscious state or anaesthetized 3 weeks after injury have a better prognosis than patients in coma or unresponsive wakefulness syndrome, which could not be explained by acute prognostic models.