Enhancing T1 signal of normal-appearing white matter with divided subtracted inversion recovery: A pilot study in mild traumatic brain injury.

Magnetic resonance imaging (MRI) and cognitive profiles in patients with mild traumatic brain injury (mTBI) are often discordant. Conventional MRI seldom captures the full extent of pathological changes in the normal-appearing white matter (NAWM). The divided subtracted inversion recovery (dSIR) technique may enhance T1 differences in NAWM, making them easily visible. We aimed to implement dSIR on a clinical scanner and tested results in mTBI patients. To produce dSIR images, Inversion Recovery-Turbo Spin Echo sequences were modified using six different inversion times (TI) on a 3-T scanner in healthy participants and patients with mTBI. The multiple TIs determined normal white (TIshort) and gray matter (TIlong) nulling points in healthy subjects, which were used to create dSIR images. In one patient, the protocol was repeated at 3 months to identify changes after rehabilitation. Diffusion tensor imaging (DTI)-derived mean diffusivity (MD) and fractional anisotropy (FA) maps were aligned to dSIR images to ensure that signal was not artefactual. Ten healthy participants (five females; age 24 ± 3 [95% CI: 21, 26] years) were included. TIshort and TIlong were set at 450 and 750 ms, respectively. In both patients (one male, age 17 years; one female, age 14 years), dSIR images revealed areas with increased T1 in the NAWM not visible on conventional MRI. dSIR-based hyperintensities corresponded to elevated MD and reduced FA. Substantial changes were found at follow-up with improvement in DTI-based parameters. dSIR images enhance subtle changes in the NAWM of patients with mTBI by amplifying their intrinsic T1 signal.

Hormonal Dysfunction in Paediatric Patients Admitted to Rehabilitation for Severe Traumatic Brain Injury: Analysis of the Associations with Rehabilitation Outcomes.

Traumatic brain injury is often accompanied by defects in hormone levels, caused by either peripheral gland dysfunctions or by an insufficient central stimulation of hormone production. The epidemiology of endocrinological defects after traumatic brain injury is quite well described, but the consequences of hormone defects are largely unknown, especially in paediatric patients undergoing neurological rehabilitation. Only one previous study reported on a cohort of 20 children with traumatic brain injury and found a low incidence of hormone defects and a correlation between some hormone levels and neurological recovery. In this study, we performed a retrospective chart review on patients affected by severe subacute traumatic brain injury. Their levels of cortisol, ACTH, IGF-1, TSH, free T4, free T3, and prolactin were collected and compared with reference ranges; we then used regression models to highlight any correlation among them and with clinical variables; last, we probed with regression models whether hormone levels could have any correlation with clinical and rehabilitation outcomes. We found eligible data from the records of 52 paediatric patients with markedly severe traumatic brain injury, as shown by an average GCS of 4.7; their age was 10.3 years, on average. The key results of our study are that 32% patients had low IGF-1 levels and in multiple regression models, IGF-1 levels were correlated with neurological recovery, indicating a possible role as a biomarker. Moreover, 69% of patients had high prolactin levels, possibly due to physical pain and high stress levels. This study is limited by the variable timing of the IGF-1 sampling, between 1 and 2 months after injury. Further studies are required to confirm our exploratory findings.

Long-Term Vocational Outcome at 15 Years from Severe Traumatic and Non-Traumatic Brain Injury in Pediatric Age.

BACKGROUND: Recent studies suggest that acquired brain injury with impaired consciousness in infancy is related to more severe and persistent effects and may have a cumulative effect on ongoing development. In this work, we aim to describe vocational outcome in a group of patients at 15 years from a severe brain lesion they suffered in developmental age. METHODS: This study included a total of 147 patients aged 1.5 to 14 years with acquired brain lesion. Clinical and functional details ("Glasgow Outcome Scale", "Functional Independent Measure" and Intelligence Quotient) were collected at the time of their first hospitalization and vocational outcome was determined after 15 years. RESULTS: 94 patients (63.9%) presented with traumatic brain injury, while 53 patients (36.1%) presented with a brain lesion of other origin. Traumatic patients had a higher probability of being partly or fully productive than non-traumatic ones: 75.5% of traumatic subjects were working-taking into account limitations due to the traumatic event-versus 62.3% of non-traumatic ones. A relationship between some clinical variables and the vocational outcome was found. CONCLUSIONS: Rehabilitation should adequately emphasize "vocational rehabilitation" because a significant proportion of people experiencing a disorder of consciousness in childhood may show good social integration in adult age.

Spinal cord ischemia rates and prophylactic spinal drainage in patients treated with fenestrated/branched endovascular repair for thoracoabdominal aneurysms.

OBJECTIVE: Spinal cord ischemia (SCI) is a devastating complication after thoracoabdominal aortic aneurysm (TAAA) repair. The benefit of prophylactic cerebrospinal fluid drainage (pCSFD) to prevent SCI is still under investigation. The aim of this study was to evaluate the SCI rate and the impact of pCSFD following complex endovascular repair (fenestrated or branched endovascular repair [F/BEVAR]) for type I to IV TAAA. METHODS: The STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement was followed. A single-center retrospective study was conducted, including all consecutive patients, managed for TAAA type I to IV using F/BEVAR, between January 1, 2018, and November 1, 2022, for degenerative and post-dissection aneurysms. Patients with juxta- or pararenal aneurysms were excluded, as well as cases managed urgently for aortic rupture or acute dissection. After 2020, pCSFD in type I to III TAAAs was abandoned and replaced by therapeutic CSFD (tCSFD), performed only in patients presenting SCI. The primary outcome was the perioperative SCI rate for the entire cohort and the role of pCSFD for type I to III TAAAs. RESULTS: In total, 198 patients were included (mean age, 71.1±3.4 years; 81.8% males), including 50.5% with type I to III TAAA. The primary technical success was 94.9%. The perioperative mortality was 2.5%. and the major adverse cardiovascular event (MACE) rate was 10.6%; 4.5% presented SCI of any type (2.5% paraplegia). When comparing the SCI group with the remaining cohort, patients with SCI presented higher MACE (66.7% vs 7.9%; P < .001) rate and longer intensive care unit stay (3.5 vs 1 day; P = .002). Following type I to III repair, similar SCI, paraplegia, and paraplegia with no recovery rates were reported in the pCSFD and tCSFD groups (7.3% vs 5.1%; P = .66; 4.8% vs 3.3%; P = .72; and 2% vs 0%; P = .37). CONCLUSIONS: The incidence of SCI after TAAA I to IV endovascular repair was low. SCI was associated with significantly increased MACE and intensive care unit stay. The prophylactic use of CSFD in type I to III TAAAs was not associated with lower SCI rates and may not be justified routinely.

Feasibility and Acceptability of a Real-Time Telerehabilitation Intervention for Children and Young Adults with Acquired Brain Injury During the COVID-19 Pandemic: An Experience Report.

This study examined the feasibility and acceptability of a telerehabilitation intervention during the COVID-19 pandemic in a sample of children and young adults with Acquired Brain Injury (ABI). Thirteen patients and/or their families agreed to participate in the speech and neuropsychological telerehabilitation sessions. The treatment was synchronous, patient centered and aimed at improving specific abilities. Sessions were held twice a week over a 10-week period. Two questionnaires were completed both by parents and therapists to assess feasibility and acceptability. Neither technical issues nor clinical obstacles were found. The quality of the therapeutic relationship played a key role in the intervention. Synchronous telerehabilitation provided several advantages both for patients and therapists. Moreover, the patient centered intervention eased the burden of the caregivers at a time of high stress. The real-time telerehabilitation treatments were deemed suitable for children and young adults with ABI. Further studies are needed to support the use of telerehabilitation as an integral part of their standard care.

Drug Use in Pediatric Patients Admitted to Rehabilitation For Severe Acquired Brain Injury: Analysis of the Associations With Rehabilitation Outcomes.

INTRODUCTION: Patients with severe acquired brain injuries require drug therapies in intensive care for life support and injury treatment. Patients who then access rehabilitation usually maintain their drug treatments long term, with a potential influence on the rehabilitation course. Whereas drug effects have been reported for specific drugs and clinical issues in adults, comprehensive data on pediatric patients with traumatic and non-traumatic injuries are scant. OBJECTIVES: The aims of this study were to describe the therapeutic classes and groups of drugs prescribed to pediatric inpatients recovering from severe acquired brain injury when they enter rehabilitation; to assess whether clinical variables may determine the use of drug classes; and to assess whether the use of drug classes may be associated with differences in rehabilitation outcomes. METHODS: We carried out a retrospective chart review, following a previous study on the clinical-epidemiological characteristics of our patients. We collected information on drug therapies present at admittance to rehabilitation and analyzed their distribution according to therapeutic classes and groups. We verified the associations of drug groups with clinical variables (putatively antecedents to drug use) and with rehabilitation outcomes (putatively resultant of drug use and of clinical variables) in regression models. The clinical variables considered were injury etiology, Glasgow Outcome Score (GOS) at admittance to rehabilitation, sex, age at injury, plus two aggregate factors resulting from the previous work, 'neurological dysfunction' regarding the use of devices and 'injury severity' regarding the neurological status. The rehabilitation outcomes used were death after rehabilitation, persistence of a vegetative/minimally conscious state, coma duration, duration of the rehabilitation stay, rehabilitation efficiency (GOS at discharge minus GOS at admittance, divided by the length of rehabilitation stay). RESULTS: We described the distribution of drug classes and groups among pediatric patients with severe acquired brain injuries. Regarding the associations between drug classes and clinical variables, we found greater use of cardiovascular agents with higher patient age, 'neurological dysfunction' score, and with an etiology of hypoxic brain injury. The use of antithrombotic agents was greater with higher patient age and 'neurological dysfunction' score. Glucocorticoid use was greater with higher GOS at admittance and with several etiologies: brain tumor, infective encephalitis, and autoimmune encephalitis. Regarding drug classes and rehabilitation outcomes, we found that the use of cardiovascular drugs was associated with increased occurrence of death after rehabilitation. The use of antispastic drugs was associated with a more frequent permanence in vegetative/minimally conscious states. The use of antispastic drugs and melatonin was associated with longer coma duration. The use of glucocorticoid drugs was associated with decreased rehabilitation efficiency. CONCLUSIONS: We provided a description of drug use in pediatric rehabilitation after severe acquired brain injuries, which was lacking in the literature. Prospective studies should verify our associative observations regarding clinical variables, drugs use, and outcomes, to assess causality.

Joint Neuropsychological Assessment through Coma/Near Coma and Level of Cognitive Functioning Assessment Scales Reduces Negative Findings in Pediatric Disorders of Consciousness.

The present study aimed to: (a) characterize the emergence to a conscious state (CS) in a sample of children and adolescents with severe brain injury during the post-acute rehabilitation and through two different neuropsychological assessment tools: the Rappaport Coma/Near Coma Scale (CNCS) and Level of Cognitive Functioning Assessment Scale (LOCFAS); (b) compare the evolution in patients with brain lesions due to traumatic and non-traumatic etiologies; and (c) describe the relationship between the emergence to a CS and some relevant clinical variables. In this observational prospective longitudinal study, 92 consecutive patients were recruited. Inclusion criteria were severe disorders of consciousness (DOC), Glasgow Coma Scale (GCS) score ≤8 at insult, age 0 to 18 years, and direct admission to inpatient rehabilitation from acute care. The main outcome measures were CNCS and LOCFAS, both administered three and six months after injury. The cohort globally shifted towards milder DOC over time, moving from overall 'moderate/near coma' at three months to 'near/no coma' at six months post-injury. The shift was captured by both CNCS and LOCFAS. CNCS differentiated levels of coma at best, while LOCFAS was superior in characterizing the emergence from coma. Agreement between scales was fair, and reduced negative findings at less than 10%. Patients with traumatic brain injury (TBI) vs. non-traumatic brain injury (NTBI) were older and had neurosurgical intervention more frequently. No relation between age and the level of consciousness was found overall. Concurrent administration of CNCS and LOCFAS reduced the rate of false negatives and better detected signs of arousal and awareness. This provides indication to administer both tools to increase measurement precision.

Severe acquired brain injury aetiologies, early clinical factors, and rehabilitation outcomes: a retrospective study on pediatric patients in rehabilitation.

Objective: Studies on pediatric severe acquired brain injury (sABI) outcomes focused mostly on single etiologies, not clarifying the independent role of clinical factors, and scantly explored inter-dependence between variables. We assessed associations of clinical factors at admission with essential outcomes, controlling for inter-dependence and sABI etiology. Methods: We reviewed the clinical records of 280 patients with traumatic and 292 with non-traumatic sABI, discharged from intensive care to pediatric neurological rehabilitation. We analyzed the distribution of clinical factors based on sABI etiology; conducted a factor analysis of variables; built multivariate models evaluating the associations of variables with death, persistent vegetative states, duration of coma, GOS outcome, length of stay. Results: We described the study sample. Factor analysis of inter-dependence between GCS, time before rehabilitation, dysautonomia, device use, produced the indicators "injury severity" and "neurological dysfunction", independent from sABI etiology, age, sex, and admittance GOS. Multivariate analyzes showed that: coma duration, GOS outcome, and length of stay, which may depend on rehabilitation courses, were directly associated with injury severity, neurological dysfunction, and patients' age; death and persistent vegetative states were also associated with etiology. Conclusion: Future studies should analyze larger cohorts and investigate mechanisms linking specific etiologies and patients' age with outcomes.

Polysomnographic Analysis of a Pediatric Case of Baclofen-Induced Central Sleep Apnea.

ABSTRACT: Respiratory disorders may follow brain injury and may also occur because of comorbidities and drug use, especially central depressants or muscle relaxants. Sleep can precipitate respiratory disorders, thus polysomnography can be a powerful diagnostic tool. By revealing breathing patterns that identify specific sleep disorders, polysomnography may unmask adverse pharmacological effects, for instance connecting central depressant drugs with central sleep apneas. We describe the case of a pediatric patient in rehabilitation from brain injury who developed a central sleep apnea following a baclofen dose increase within the therapeutic range, while assuming an under-dosed benzodiazepine. Polysomnography identified a typical respiration pattern, previously observed in adults treated with baclofen and other central depressants. Baclofen tapering resolved the central sleep apnea. Polysomnography, and this specific pattern, may be proposed as diagnostic tools in patients with high dose baclofen that can be used to prevent potential respiratory disorders in children.

Relationships between enteral nutrition facts and urinary stones in a cohort of pediatric patients in rehabilitation from severe acquired brain injury.

BACKGROUND & AIMS: Urolithiasis affects pediatric patients with severe acquired brain injury, in whom the role of several clinical variables and of the presence and composition of enteral nutrition has not been investigated. METHODS: Retrospective chart review on 371 pediatric patients with severe acquired brain injury. We used an essential electronic database to check the association between stones and enteral feeding. We then picked at random paper clinical records until we collected 20 and 20 complete records for patients with/without stones, not matched. With that information, we tested the association of stones with: nutrition facts of enteral formulae (sodium, potassium, calcium, magnesium, phosphorus, proteins, vitamin C); bladder dysfunction, urinary infections, catheterisms, tracheostomy, gallstones, way of feeding; blood and urine exams before stones diagnosis; age, type and severity of injury; prior physical activity, relevant drugs. RESULTS: All patients with stones were fed enterally. At univariate statistics they were older, weighed more, received bigger volumes of hydration and nutrition; they had worse GCS, more UTIs and they alone received catheterisms; their nutrition mixes were richer in sodium. In multivariate logistic regression for stone development, UTIs (OR 11.4, 95% C.I. 1.6-83.4) and higher sodium nutrition content (OR 7.5, 95% C.I. 1.6-34.3) were risk factors; higher GCS (OR 0.66, 95% C.I. 0.43-0.99) and higher calcium nutrition content (OR 0.14, 95% C.I. 0.03-0.73) were protective factors. CONCLUSIONS: Besides known risk factors for urolithiasis, including UTIs, catheterisms, worse neurological states, also enteral nutrition was a risk factor, particularly with higher sodium and lower calcium contents. Future studies should test the effect of different sodium/calcium nutrition contents on lithogenesis.

Performance of a tracheostomy removal protocol for pediatric patients in rehabilitation after acquired brain injury: Factors associated with timing and possibility of decannulation.

OBJECTIVES: We assessed the performance of a tracheostomy decannulation protocol privileging safety over quickness, in pediatric patients undergoing rehabilitation from severe acquired brain injury. We analyzed factors associated with decannulation timing and possibility and examined cases of failure. HYPOTHESIS: A safe decannulation protocol should minimize failures. STUDY DESIGN: Retrospective observational study. PATIENT SELECTION: Patients aged 0-17 admitted to rehabilitation with tracheostomy in the last 15 years (n = 123). METHODOLOGY: We collected data on clinical and respiratory conditions at admittance, during the first rehabilitation stay and following follow-up controls. We described the sample and tested associations of several factors with the possibility to decannulate patients during either the first stay or follow-up. We described failures, defined as the cases in which tracheostomy tube had to be placed back immediately or after less than 1 month from removal. RESULTS: At admittance, 93.5% patients were dysphagic and 37.9% had respiratory complications (mainly accumulation of supraglottic secretions). At first discharge, dysphagia was reduced (62.1%) and respiratory complications increased (41.1%). Tracheostomy was removed during the first stay in 55.3% patients, during follow-up in 13%, without failures among the 80 patients who followed the protocol. Four decannulations performed against protocol recommendations resulted in three failures. Decannulation was mainly prevented by the persistence of respiratory complications and dysphagia that constituted a relevant risk of aspiration and suffocation; decannulation was mainly postponed because of respiratory complications and breath-holding spells in very young children. CONCLUSIONS: By applying a decannulation protocol that privileges safety over quickness, we encountered no failure. Respiratory complications and dysphagia that lead to supraglottic stagnation, and breath-holding spells, are key elements to consider before performing decannulation in pediatric patients.

Paroxysmal Sympathetic Hyperactivity in Pediatric Rehabilitation: Pathological Features and Scheduled Pharmacological Therapies.

OBJECTIVE: Information on course and treatment of paroxysmal sympathetic hyperactivity (PSH) during rehabilitation and in pediatric patients is lacking. To increase knowledge on the course and treatment of PSH in pediatric patients during rehabilitation, we retrospectively analyzed 23 pediatric patients with PSH, describing the course of PSH and administered drugs, and explored the association of PSH remission with drug doses. SETTING: Neurorehabilitation unit of IRCCS Eugenio Medea, Bosisio Parini (LC), Italy. PARTICIPANTS: Twenty-three pediatric patients with postacute acquired brain injury, who remitted from PSH. DESIGN: Retrospective cohort study. MAIN MEASURES: Description of features and course of PSH, description of drug therapies, and analysis of covariance of their doses. Correlations between remission and drug doses/clinical variables. Estimation of the odds ratios of remission. RESULTS: At admittance patients displayed at least 3 features of PSH with an overall score of 9, which diminished progressively during remission. Therapies with propranolol, baclofen, niaprazine, and diazepam were progressively uptitrated, indicating potential usefulness. When testing possible predictors of remission, we found positive effects of propranolol and diazepam and of traumatic etiology and a negative effect of maximum PSH severity. CONCLUSIONS: Results should be interpreted carefully regarding causal relationships and drug doses and combinations, but they encourage further studies on the use of propranolol and diazepam to favor PSH remission.

Late Post-traumatic Epilepsy in Children and Young Adults: Impropriety of Long-Term Antiepileptic Prophylaxis and Risks in Tapering.

BACKGROUND: After traumatic brain injury, epilepsy affects up to 20 % of children. It is a risk factor, for both clinical recovery and cognitive performance; therefore pharmacological therapy is advisable. Current guidelines recommend prophylaxis to be initiated as soon as possible and tapered 1 week after trauma. However, no guideline exists for paediatric patients and the clinical practice is heterogeneous. OBJECTIVE: In our institute, prophylaxis was routinely tapered 6 months after trauma. Therefore we investigated whether this prophylaxis or its tapering influenced the development of post-traumatic epilepsy, together with several clinical-demographic factors. METHODS: The study population comprised all patients with post-traumatic brain injury referred to this institute between 2002 and 2009 who consented to participate. Clinical, epileptological and pharmacological data were collected. The role of prophylaxis and several other predictors on occurrence of post-traumatic epilepsy was analysed through logistic regressions. RESULTS: Two hundred and three patients (145 paediatric) were followed for 57 months on average. Risk factors for epilepsy were past neurosurgery [odds ratio (OR) = 2.61, 95 % confidence interval (CI) 1.15-5.96], presence of epileptiform anomalies (OR = 6.92, 95 % CI 3.02-15.86) and the presence of prophylaxis (OR = 2.49, 95 % CI 1.12-5.52), while higher intelligence quotient (IQ) was protective (OR = 0.96, 95 % CI 0.95-0.98). While evaluating possible different effects within and after 6 months (tapering, for those under prophylaxis), we found that epileptiform anomalies (OR = 7.61, 95 % CI 2.33-24.93, and OR = 8.21, 95 % CI 3.00-22.44) and IQ (OR = 0.96, 95 % CI 0.94-0.98, and OR = 0.97, 95 % CI 0.95-0.98) were always significant predictors of epilepsy, while neurosurgery (OR = 4.38, 95 % CI 1.10-17.45) was significant only within 6 months from trauma, and prophylaxis (OR = 3.98, 95 % CI 1.62-9.75) only afterwards. CONCLUSIONS: These results suggest that prophylaxis was irrelevant when present; furthermore its tapering increased the risk of epilepsy. Since the presence of epileptiform anomalies was the main predictor of post-traumatic epilepsy, such anomalies may be useful to better direct the choice of prophylaxis.

Psychological problems, self-esteem and body dissatisfaction in a sample of adolescents with brain lesions: A comparison with a control group.

PRIMARY OBJECTIVES: This study aims to describe psychological problems, self-esteem difficulties and body dissatisfaction in a sample of adolescents with acquired brain lesions and to compare them with an age- and gender-matched control group. RESEARCH DESIGN: In an experimental design, the psychological profile of 26 adolescents with brain lesions of traumatic or vascular aetiology, aged 12-18 years, was compared with that of 18 typically-developing subjects. Moreover, within the clinical group, patients with TBI were compared with patients with vascular lesions. METHODS AND PROCEDURES: The psychological and adaptive profile of the adolescents was assessed by a specific protocol, including CBCL, VABS, RSES, EDI-2 and BES. MAIN OUTCOME AND RESULTS: Adolescents with brain lesions showed more marked psychological problems than their healthy peers; they also presented with a greater impairment of adaptive skills and a lower self-esteem. No significant differences were found between patients with traumatic lesions and patients with vascular lesions. CONCLUSIONS: Adolescents with acquired brain lesions were at higher risk to develop psychological and behavioural difficulties. Furthermore, in the clinical sample, some variables such as the long hospitalization and isolation from family and peers were associated to a greater psychological burden than the aetiology of the brain damage.

Polysomnographic Sleep Patterns in Children and Adolescents in Unresponsive Wakefulness Syndrome.

OBJECTIVES: We aimed (i) to search for qualitative sleep patterns for pediatric unresponsive wakefulness syndrome (SPPUWS) in prolonged polysomnographic (PSG) recordings in children and adolescents with subacute severe disorders of consciousness due to an acquired brain damage; (ii) to investigate the clinical relevance of SPPUWS and of possible neurophysiological markers (rapid eye movement sleep and sleep spindles) in PSG recordings of pediatric patients with unresponsive wakefulness syndrome (UWS). METHODS: We performed a PSG study in 27 children with UWS due to acquired brain damage in the subacute phase. Patients received a full neurological examination and a clinical assessment with standardized scales. In addition, outcome was assessed after 36 months. RESULTS: We identified 6 PSG patterns (SPPUWS) corresponding to increasing neuroelectrical complexity. The presence of an organized sleep pattern, as well as rapid eye movement sleep and sleep spindles, in the subacute stage appeared highly predictive of a more favorable outcome. Correlation was found between SPPUWS and recovery, as assessed by several clinical and rehabilitation scales. CONCLUSIONS: Polysomnography can be used as a prognostic tool, as it can help determine the capability to recover from a pediatric UWS and predict outcome well before the confirmation provided by suitable clinical scales.