Anders Lundin

Symptoms and disability until 3 months after mild TBI

Objective: Examine frequency, character and course of symptoms until 3 months after MTBI and the relation between symptoms and disability. Methods: Prospective cohort study of 122 consecutive patients with MTBI. Symptom assessment after 1, 7 and 14 days and 3 months post-injury by use of Rivermead Post-concussional Questionnaire. Disability assessment by use of Rivermead Head Injury Follow-up Questionnaire. Results: Patients reporting one or more symptoms declined from 86% on day 1 to 49% 3 months post-injury, when 25% also reported change in one or more domains of everyday activities. Poor memory, sleep disturbance and fatigue were most commonly reported. Symptom and disability scores were correlated (τ = 0.60; p < 0.001). Early symptom load correlated with late symptom load (τ = 0.38; p < 0.01). Conclusions: Symptoms gradually decline post-injury. Symptoms correlate with disability at 3 months. Patients with early high symptom load are at risk for developing persisting complaints.

Predictors of nursing home placement in Huntington disease

Objective: To determine whether motor, behavioral, or psychiatric symptoms in Huntington disease (HD) predict skilled nursing facility (SNF) placement. Methods: Subjects were participants in the Huntington Study Group’s Unified Huntington Disease Rating Scale Database (Rochester, NY) between January 1994 and September 1999. Specific motor, psychiatric, and behavioral variables in subjects residing at home and in SNF were analyzed using χ2 and Student’s t-tests. For a subset of subjects for whom longitudinal data existed, a Cox proportional hazards model controlling for age, sex, and disease duration was used. Results: Among 4,809 subjects enrolled, 3,070 had clinically definite HD. Of these, 228 (7.4%) resided in SNF. The SNF residents’ average age was 52 years, average disease duration was 8.6 years, and they were predominantly women (63%). The SNF residents had worse motor function (chorea, bradykinesia, gait abnormality, and imbalance, p < 0.0001); were more likely to have obsessions, compulsions, delusions, and auditory hallucinations; and had more aggressive, disruptive (p < 0.0001), and irritable behaviors (p = 0.0012). For 1,559 subjects, longitudinal data existed (average length of follow-up, 1.9 years), and 87 (5%) moved from home to SNF. In the Cox model, bradykinesia (HR 1.965, 95% CI 1.083 to 3.564), impaired gait (HR 3.004, 95% CI 1.353 to 6.668), and impaired tandem walking (HR 2.546, 95% CI 1.460 to 4.439) were predictive of SNF placement. Conclusions: Institutionalized patients with HD are more motorically, psychiatrically, and behaviorally impaired than their counterparts living at home. However, motor variables alone predicted institutionalization. Treatment strategies that delay the progression of motor dysfunction in HD may postpone the need for institutionalization.

Road tunnel air pollution induces bronchoalveolar inflammation in healthy subjects

Traffic-related air pollution is associated with adverse respiratory effects. The aim of the present study was to investigate whether exposure to air pollution in a road tunnel causes airway inflammatory and blood coagulation responses. A total of 16 healthy subjects underwent bronchoscopy with bronchial mucosal biopsies and bronchoalveolar lavage (BAL) on two occasions, in random order: once at 14 h after a 2-h exposure to air pollution in a busy road tunnel, and once after a control day with subjects exposed to urban air during normal activities. Peripheral blood was sampled prior to bronchoscopy. The road tunnel exposures included particulate matter with a 50% cut-off aerodynamic diameter of 2.5 μm, particulate matter with a 50% cut-off aerodynamic diameter of 10 μm and nitrogen dioxide which had median concentrations of 64, 176 and 230 µg·m−3, respectively. Significantly higher numbers of BAL fluid total cell number, lymphocytes and alveolar macrophages were present after road tunnel exposure versus control. Significantly higher nuclear expression of the transcription factor component c-Jun was found in the bronchial epithelium after exposure. No upregulation of adhesion molecules or cellular infiltration was present and blood coagulation factors were unaffected. In conclusion, exposure of healthy subjects to traffic-related air pollution resulted in a lower airway inflammatory response with cell migration, together with signs of an initiated signal transduction in the bronchial epithelium.

S100 and cognitive impairment after mild traumatic brain injury

OBJECTIVE The aim of this study was to explore the relationship between the proteins S100B and S100A1B and symptoms and signs of cognitive impairment for 3 months after mild traumatic brain injury (MTBI). METHODS Serum concentrations of S100A1B and S100B were examined in a prospective cohort study of patients with MTBI and a Glasgow Coma Scale score of 14 or 15. Cognitive performance was assessed by repeated computerized neuropsychological testing and an extended neuropsychological test. Symptoms were assessed using the Rivermead Post-Concussion Symptoms Questionnaire. RESULTS Concentrations of S100B and S100A1B were above cut-off in 31% and 48% respectively. Eight percent of the patients had signs of cognitive impairment according to the computerized neuropsychological tests and 30% according to the extended test. Symptoms of cognitive impairment were reported by 44% of the patients on the first day post-injury and by 26% at 3 months. No significant associations between S100B or S100A1B concentrations and symptoms or signs of cognitive impairment were found. CONCLUSION Abnormal S100 serum concentrations and symptoms or signs of cognitive impairment were not significantly associated in patients with MTBI and a Glasgow Coma Scale score of 14 or 15.

S100 in mild traumatic brain injury

Primary objectives: To examine the diagnostic value of S100 in mild traumatic brain injury (MTBI). Research design: Prospective cohort study. Methods and procedures: S100B, S100A1B and S100BB concentrations were examined in sera from patients with MTBI with an arrival Glasgow Coma Scale score of 15 or 14, patients with orthopaedic injuries and non-injured subjects. Main outcome and results: Mean values and proportions of subjects above cut-off limits for S100B and S100A1B were significantly higher in each trauma group than in non-injured controls, but only for S100A1B when patients with MTBI were compared with controls with orthopaedic injuries. Using a 97.5 percentile cut-off limit, the sensitivity of S100A1B for MTBI vs orthopaedic injury was 61% (95% confidence interval (CI) 49–73%), specificity 77% (95% CI 62–93%). The area under the ROC curve did not approach 0.9 for any cut off limit. Conclusions: Diagnostic validity of S100 in acute MTBI was not demonstrated. S100A1B has merits for long-term prognostic studies.

Larger CAG expansions in skeletal muscle compared with lymphocytes in Kennedy disease but not in Huntington disease

The size of CAG repeats was compared in lymphocytes and skeletal muscle from nine patients with Huntington disease (HD) and two patients with Kennedy disease (KD). In HD, the number of CAG repeats did not differ between lymphocytes and skeletal muscle. In the two KD patients, however, the CAG expansion was larger in muscle than in lymphocytes. The difference in trinucleotide expansion between lymphocytes and muscle cells is not a universal phenomenon in trinucleotide repeat disorders, but seems to occur in disorders primarily affecting the neuromuscular system.

Cognitive reserve and persistent post-concussion symptoms—A prospective mild traumatic brain injury (mTBI) cohort study

Abstract Primary objective: Having three or more persisting (i.e. > 3 months) post-concussion symptoms (PCS) affects a significant number of patients after a mild traumatic brain injury (mTBI). A common complaint is cognitive deficits. However, several meta-analyses have found no evidence of long-term cognitive impairment in mTBI patients. The study sought to answer two questions: first, is there a difference in cognitive performance between PCS and recovered mTBI patients? Second, is lower cognitive reserve a risk factor for developing PCS? Research design: Prospective inception cohort study. Methods and procedure: One hundred and twenty-two adult patients were recruited from emergency departments within 24 hours of an mTBI. Three months post-injury, participants completed the Rivermead Post Concussion Symptoms Questionnaire and a neuropsychological assessment. A healthy control group (n = 35) were recruited. The estimate of cognitive reserve was based upon sub-test Information from Wechsler Adult Intelligence Scale and international classifications of educational level and occupational skill level. Main outcome and results: mTBI patients showed reduced memory performance. Patients with lower cognitive reserve were 4.14-times more likely to suffer from PCS. Conclusions: mTBI may be linked to subtle executive memory deficits. Lower cognitive reserve appears to be a risk factor for PCS and indicates individual vulnerabilities.

111Indium-labeled ultrafine carbon particles; a novel aerosol for pulmonary deposition and retention studies

Continuous environmental or occupational exposure to airborne particulate pollution is believed to be a major hazard for human health. A technique to characterize their deposition and clearance from the lungs is fundamental to understand the underlying mechanisms behind their negative health effects. In this work, we describe a method for production and follow up of ultrafine carbon particles labeled with radioactive 111Indium (111In). The physicochemical and biological properties of the aerosol are described in terms of particle size and concentration, agglomeration rate, chemical bonding stability, and human lung deposition and retention. Preliminary in vivo data from a healthy human pilot exposure and 1-week follow up of the aerosol is presented. More than 98% of the generated aerosol was labeled with Indium and with particle sizes log normally distributed around 79 nm count median diameter. The aerosol showed good generation reproducibility and chemical stability, about 5% leaching 7 days after generation. During human inhalation, the particles were deposited in the alveolar space, with no central airways involvement. Seven days after exposure, the cumulative activity retention was 95.3%. Activity leaching tests from blood and urine samples confirmed that the observed clearance was explained by unbound activity, suggesting that there was no significant elimination of ultrafine particles. Compared to previously presented methods based on Technegas, 111In-labelled ultrafine carbon particles allow for extended follow-up assessments of particulate pollution retention in healthy and diseased lungs.

The pulmonary deposition and retention of indium-111 labeled ultrafine carbon particles in healthy individuals

Context: Particulate air pollution, for example, from ultrafine (UF) particles, has negative health effects. However, there is still limited knowledge regarding the fate of inhaled particles in the human body. Objectives: To describe the normal lung deposition and 1 week particle retention of indium-111 labeled UF carbon particles in healthy subjects. Additionally, the possibility to extend the follow-up period to 4 weeks was also investigated for one of the subjects. Results: The cumulative pulmonary particle clearance 1 week post-administration, corrected for activity leaching and mucocilliary transport of activity deposited in the central airways, was 4.3 ± 8.5% (average ± standard deviation at group level), with marginal translocation of particles from lungs to blood, 0.3%. There was no observable elimination of particles from the body via urine. Seven days after exposure, the cumulated activity leaching was 3% (group level), which indicates a stable bonding between the particles and Indium-111. The volunteer followed for a total of 4 weeks, showed a cumulative decrease of activity retention in the lungs of 10.5%. After correction for activity leaching and clearance from central airway deposition, the estimated particle clearance was about 2%. Conclusions: No evidence for particle translocation from the lungs could be proven 7 days after exposure. It is possible to follow-up Indium-111 labeled UF carbon particles at least 1 month post-administration without increasing the administered activity.

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.