Prolonged injury symptoms and later visits to psychiatric care after mild traumatic brain injury in school-age.

OBJECTIVE: To investigate demographic and pre-injury factors in Finnish school-aged children admitted to pediatric neurology services after mild traumatic brain injury (mTBI). The relation of these factors to prolonged injury symptoms and later visits into psychiatric care was assessed. METHODS: Demographic information, pre-injury learning status, and neuropsychological test results of 120 patients aged 7-16 years were retrospectively collected from the hospital medical records. Data were compared with self- or parent-reported injury symptoms at 1-3 months post-injury and later visits to psychiatric care. RESULTS: According to medical records, 14.2% of the children with mTBI had a diagnosed neurobehavioral or psychiatric condition pre-injury. Additionally, 53.3% of the children had some neurobehavioral or psychiatric concerns or traits prior to the injury. Over half (56.7%) of the children studied were symptomatic at 1-3 months following the injury. Female gender and presence of prolonged symptoms were predictive for later visit into psychiatric care. CONCLUSIONS: Pre-injury neurobehavioral or psychiatric problems may predict prolonged injury symptoms following pediatric mTBI. In this retrospective patient series, prolonged symptoms and female gender seem to predict the need for later psychiatric care. Monitoring the recovery of children with mTBI and pre-injury risk factors is important for timely interventions.

Head trauma in sports - clinical characteristics, epidemiology and biomarkers.

Traumatic brain injury (TBI) is clinically divided into a spectrum of severities, with mild TBI being the least severe form and a frequent occurrence in contact sports, such as ice hockey, American football, rugby, horse riding and boxing. Mild TBI is caused by blunt nonpenetrating head trauma that causes movement of the brain and stretching and tearing of axons, with diffuse axonal injury being a central pathogenic mechanism. Mild TBI is in principle synonymous with concussion; both have similar criteria in which the most important elements are acute alteration or loss of consciousness and/or post-traumatic amnesia following head trauma and no apparent brain changes on standard neuroimaging. Symptoms in mild TBI are highly variable and there are no validated imaging or fluid biomarkers to determine whether or not a patient with a normal computerized tomography scan of the brain has neuronal damage. Mild TBI typically resolves within a few weeks but 10-15% of concussion patients develop postconcussive syndrome. Repetitive mild TBI, which is frequent in contact sports, is a risk factor for a complicated recovery process. This overview paper discusses the relationships between repetitive head impacts in contact sports, mild TBI and chronic neurological symptoms. What are these conditions, how common are they, how are they linked and can they be objectified using imaging or fluid-based biomarkers? It gives an update on the current state of research on these questions with a specific focus on clinical characteristics, epidemiology and biomarkers.

Peripheral nervous system involvement in primary burning mouth syndrome--results of a pilot study.

OBJECTIVE: The pathophysiology of primary burning mouth syndrome (BMS) has remained enigmatic, but recent studies suggest pathology within the nervous system at multiple levels. This study aimed to investigate in detail the contribution of either focal or generalized alterations within the peripheral nervous system (PNS) in the etiopathogenesis of BMS. SUBJECTS AND METHODS: Intraepithelial nerve fiber density (IENFD) of tongue mucosa was assessed in 10 carefully characterized BMS, and the results were compared to 19 age- and gender-matched cadaver controls, 6 with lifetime diabetes. Extensive neurophysiologic and psychophysical examinations of the trigeminal system and distal extremities were performed to profile PNS function in BMS. RESULTS: Patients with BMS had significantly fewer intraepithelial nerve fibers (0,27, s.e. 0,18 mm(-1); P = 0.0253) than non-diabetic controls (0,92, s.e. 0,15 mm(-1)). In the subepithelial space, the amount of nerve fibers did not differ between the groups. The majority (9/10) of patients with BMS showed neurophysiologic or psychophysical signs of a more generalized PNS dysfunction. CONCLUSIONS: Our results in neurophysiologically optimally characterized BMS patients confirm that pure focal small fiber neuropathy of the oral mucosa has a role in the pathophysiology of primary BMS. Furthermore, BMS may be related to a more generalized, yet subclinical peripheral neuropathy.

Reproducibility of Tract-based and Region-of-Interest DTI Analysis of Long Association Tracts.

PURPOSE: Reproducibility of two different methods for quantifying fiber tracts by using a diffusion tensor imaging (DTI) sequence suitable for clinical magnetic resonance imaging (MRI) protocols was evaluated. METHODS: DTI of 15 subjects was used to analyze intra-rater and inter-rater reproducibility. Another 10 subjects underwent MRI twice for assessment of between-scan reliability. Ten long association tracts were defined by fiber tracking using inclusion and exclusion regions of interest (ROIs). Whole-tract analysis and tractography-based core analysis were performed, and the effect of fractional anisotropy (FA 0.15/0.30) and turning angle threshold (27°/60°) on reproducibility was evaluated. Additionally, ROI measurements were performed in the core of the tracts. RESULTS: For the tract-based methods, intra-rater and inter-rater reliabilities of FA and mean diffusivity (MD) measurements were excellent. Between-scan reproducibility was good or excellent in 127 of 130 of the measurements. There was no systematic difference in the reproducibility of the FA, MD, and volume measurements depending on the FA or turning angle threshold. For the cross-sectional ROI measurements, reliability showed large variation from poor to excellent depending on the tract. CONCLUSIONS: Compared with the commonly used cross-sectional core ROI method, the tract-based analyses seem to be a more robust way to identify and measure white matter tracts of interest, and provide a novel reproducible tool to perform core analysis.

Long-lasting TMS motor threshold elevation in mild traumatic brain injury.

OBJECTIVES: Mild traumatic brain injury (mTBI) is very common, and part of the patients experience persistent symptoms. These may be caused by diffuse neuronal damage and could therefore affect cortical excitability. The motor threshold (MT), measured by transcranial magnetic stimulation (TMS), is a measure of cortical excitability and cortico-spinal tract integrity. MATERIALS AND METHODS: We used navigated TMS (nTMS) and electromyography to determine subjects' left hemisphere MTs. Nineteen subjects with mTBI (11 with persistent symptoms and eight fully recovered) and nine healthy controls were tested. The injuries had occurred on average 5 years earlier. All participants had normal brain MRIs, that is, no signs of injury. None used centrally acting medication. RESULTS: The mean MT in controls was 43.0% (SD 2.5) of maximum stimulator output. The mTBI subjects mean MT was 53.4% (SD 9.7), being higher than the controls' threshold. Subjective recovery did not correlate with MT. CONCLUSIONS: The results show chronic MT elevation in a sample of subjects with symptomatic or recovered mTBI. This suggests that mTBI may be compensated, although not fully recovered, years after the injury. While the cause for MT elevation cannot be concluded from these preliminary observations, possible explanations include decreased cortical excitability and impaired subcortical conduction.

Diffusivity of normal-appearing tissue in acute traumatic brain injury.

BACKGROUND: Apparent diffusion coefficient (ADC) values derived from diffusion-weighted magnetic resonance imaging (MRI) can provide information about traumatic changes not visible in conventional MRI. The ADC values in acute traumatic brain injury (TBI) were measured and correlated with initial severity and outcome scores. METHODS: In this study 22 unselected patients were studied 1 week (mean 7 ± 2 days) after TBI of variable severity. In conventional MRI 7 patients were without visible findings, 15 showed cortical contusions or traumatic axonal injury and 14 healthy subjects served as controls. The ADC values were measured from 46 brain regions away from the visible traumatic changes and compared between the groups. Regional ADC values and the number of abnormal regions were correlated with the Glasgow coma scale (GCS) on arrival in hospital and the Glasgow outcome scale (extended version, GOS-E) at 1 year after injury. RESULTS: The ADC values of TBI patients with and without visible lesions did not show any differences but both groups differed significantly from the controls in several cortical and deep brain regions. Increased ADC values were common in TBI groups but decreased ADC values were relatively uncommon. The regional ADC values and the number of abnormal regions did not correlate with either GCS or GOS-E scores. CONCLUSIONS: Increased diffusion in normal appearing brain tissue is a common finding 1 week after TBI in patients with and without visible lesions in conventional MRI. More investigations are needed to evaluate how these findings could be used for clinical applications.

Cholinergic dysfunction after traumatic brain injury: preliminary findings from a PET study.

OBJECTIVE: There is evidence that the cholinergic system is frequently involved in the cognitive consequences of traumatic brain injury (TBI). We studied whether the brain cholinergic function is altered after TBI in vivo using PET. METHODS: Cholinergic function was assessed with [methyl-(11)C]N-methylpiperidyl-4-acetate, which reflects the acetylcholinesterase (AChE) activity, in 17 subjects more than 1 year after a TBI and in 12 healthy controls. All subjects had been without any centrally acting drugs for at least 4 weeks. RESULTS: The AChE activity was significantly lower in subjects with TBI compared to controls in several areas of the neocortex (-5.9% to -10.8%, p=0.053 to 0.004). CONCLUSIONS: Patients with chronic cognitive symptoms after TBI show widely lowered AChE activity across the neocortex.

Hippocampal volume, brain atrophy, and APOE genotype after traumatic brain injury.

OBJECTIVE: To examine the association between hippocampal volumes, general brain atrophy, and apolipoprotein E (APOE) polymorphism in patients with a remote traumatic brain injury (TBI). METHODS: MRI-based volumetric analyses of the hippocampus and lateral ventricles were performed in 58 patients with TBI of varying severity on average 31.3 years after the trauma. The APOE genotype was determined using standard methods and correlated with the MRI volumetric measurements. RESULTS: Hippocampal or lateral ventricle volumes did not differ significantly in those patients with the APOE-epsilon4 allele (APOE4) vs those without this allele. CONCLUSIONS: The APOE-epsilon4 allele was not associated with the development of hippocampal or ventricular atrophy after traumatic brain injury. If the APOE-epsilon4 allele is associated with an unfavorable outcome after traumatic brain injury as proposed, this association may involve mechanisms other than those responsible for the development of brain atrophy.

Longitudinal cognitive changes in traumatic brain injury: a 30-year follow-up study.

OBJECTIVE: To evaluate longitudinal cognitive changes in patients over three decades following traumatic brain injury (TBI). METHOD: Two hundred ten patients with substantial TBI of variable severity were initially assessed between 1966 and 1972 at Turku University Hospital (Finland). Of these, 61 patients could be studied using the same assessments in the follow-up examination, on average 30 years after the TBI. The results of the follow-up assessment were also compared with an age- and education-matched control group. During each examination, patients were assessed with five subtests of the Wechsler Adult Intelligence Scale, three tests for episodic memory, and the general cognitive decline was determined. RESULTS: The general pattern of slight cognitive decline during a 30-year follow-up contrasted with improvement in semantic memory. Women maintained their cognitive level, but men showed a decline during the follow-up, especially in visuospatial ability and visual memory. Younger patients were likely to maintain or even improve their cognitive functioning. CONCLUSIONS: Most of the patients had mild cognitive decline during the follow-up, but this decline was influenced by gender and age at injury. Unlike the long-term course in the other domains of cognition, semantic memory showed good recovery potential after traumatic brain injury (TBI). The profile of long-term cognitive decline after TBI seems to be qualitatively different from the early signs of dementia of the Alzheimer type.

Recovery of somatosensory deficits in acute stroke.

OBJECTIVES: To study the recovery of somatosensory deficits after acute stroke. MATERIAL AND METHODS: A detailed clinical examination of sensation, median nerve somatosensory evoked potentials (SEP), quantitative sensory tests (QST), and subjective evaluation were performed in five acute stroke patients at three control time points up to 12 months after the stroke. RESULTS: The deficit recovered at least partially in all patients, mostly within 3 months after stroke. The improvement in warm and vibration detection thresholds occurred between 3 and 12 months. The SEP improved both by 3 and 12 months. CONCLUSION: The recovery of subjective sensory disturbance occurred in line with the improvement of the clinical sensory tests and QST. The most sensitive measure for somatosensory dysfunction at the early phase was graphesthesia. In our patients, initially normal SEP with a sensory deficit resulted in excellent clinical recovery, whereas initially absent SEP did not necessarily predict poor outcome.

APOE-epsilon4 predicts dementia but not other psychiatric disorders after traumatic brain injury.

The authors studied the association between APOE-epsilon4 genotype and axis I and II psychiatric disorders an average of 30 years after traumatic brain injury. Sixty patients were dichotomized into subjects with and without APOE-epsilon4 allele. Dementia and subclinical dementia were significantly more common with the presence of APOE-epsilon4. The occurrence of other psychiatric disorders did not differ between patients with and without APOE-epsilon4 allele.

Sensory regeneration following intraoperatively verified trigeminal nerve injury.

OBJECTIVE: To follow recovery of sensory function mediated by both myelinated and unmyelinated axons in relation to the type of inferior alveolar nerve (IAN) injury. METHODS: The authors assessed the function of afferent Abeta-, Adelta-, and C-fibers of the IAN using neurophysiologic (mental nerve blink reflex, sensory nerve conduction [NCS] of the IAN) and quantitative sensory tests (QST; cold, warm, heat pain, and tactile modalities). The tests were done 2 weeks, 1, 3, 6, and 12 months postoperatively and compared to the preoperative baseline in 20 patients undergoing mandibular bilateral sagittal split osteotomy. Nineteen patients underwent intraoperative monitoring. RESULTS: In primarily demyelinating injuries (21/40 nerves), the sensory alteration and all tests normalized on the group level within the first 3 months. After partial axonal lesions (15/40 nerves), neurophysiologic and thermal QST results remained abnormal at 1-year control in a high proportion of the IAN distributions (up to 67%). At 1 year, the tactile QST was abnormal in 40%, but the NCS in 87% of the symptomatic IAN distributions. Neuropathic pain occurred in 5% of the patients, only after severe axonal damage. CONCLUSIONS: Sensory nerve conduction and thermal quantitative sensory testing showed incomplete sensory regeneration at 1 year after axonal trigeminal nerve damage. Clinical examination with tactile quantitative sensory testing was less reliable in the follow-up of sensory recovery. Sensory Abeta-, Adelta-, and C-fibers recovered function at similar rates. The trigeminal nerve does not differ from other peripheral nerves as regards susceptibility to neuropathic pain.

Electrophysiological testing of the trigeminofacial system: aid in the diagnosis of atypical facial pain.

The aim of this study was to evaluate the yield of objective electrophysiological testing of the trigeminofacial system in atypical facial pain (AFP). In addition to the clinical neurological examination, two brainstem reflexes covering both the peripheral parts and the central connections of the trigeminal and the facial nerves, the blink and jaw reflexes (BR and JR), were recorded in 17 AFP patients. The control group consisted of 18 healthy volunteers with no history of facial pain or chronic headache. The AFP patients could be divided into three distinct groups on the basis of the clinical and electrophysiological findings. (1) Major trigeminal neuropathy. Four patients had clinical and electrophysiological signs of trigeminal neuropathy (three patients with an afferent pattern of abnormal BR, and one with absent JR on the clinically affected side) despite normal findings in the MRI-scans of the brain. Thus, electrophysiological testing may be more sensitive than MRI in demonstrating pathology in some of the AFP patients. (2) Minor trigeminal neuropathy. Seven patients had signs of increased excitability of the BR in the form of uni- or bilaterally abnormal (diminished or absent) habituation of the R2 component of the BR; two of these patients also showed clinical signs of trigeminal dysfunction, but the MRI-scans were all normal. This deficient habituation of the BR indicates increased excitability of the BR at brainstem level in nearly 50% of our AFP patients. (3) 'Idiopathic', no signs of trigeminal neuropathy. Five patients had normal findings both in the brainstem reflex recordings and in the clinical examinations. Additionally, one patient had abnormal BAEP and EEG recordings. On the group level, the AFP patients had significantly higher thresholds of the tactile R1 component of the BR than the control subjects. Electrophysiological testing may offer a valuable tool for both the clinical evaluation, and the scientific study of AFP.

Brain substance P receptors in Parkinson's disease.

The distribution of SP receptors was studied both in the normal human brain and in the parkinsonian brain by means of tritiated SP. The highest levels of binding were found in the striatal areas and in the NbM. The distribution was similar to that found in laboratory animals in earlier studies. In PD the binding was significantly reduced in the NbM and parietal cortex as compared with controls. The level of SPLI was reduced in both parts of the SN, in the NbM, and in the GPi.

Substance P immunoreactivity in the post-mortem parkinsonian brain.

The amount of substance P immunoreactivity (SPI) was measured by radioimmunoassay from the cerebral cortex, caudate nucleus, putamen, pallidum, substantia nigra, hypothalamus, nucleus accumbens, amygdala and hippocampus from autopsy brains. The whole material consisted of 42 parkinsonian patients and 31 controls. The amount of SPI was significantly decreased in the substantia nigra of the parkinsonian brain. There was also a significant decrease of SPI in the putamen of those parkinsonian patients, who had not received levoDOPA treatment. The levels of SPI in the other brain regions studied did not show any difference between parkinsonian patients and controls. The results obtained suggest that substance P (SP) may have a role in the pathophysiology of Parkinson's disease.

Brain enkephalin receptors in Parkinson's disease.

Brain enkephalin receptors were studied in post-mortem brain samples of 27 patients with Parkinson's disease and of 26 control subjects without extrapyramidal disorders by the radioligand-binding technique using 3H-leu-enkephalin, 3H-met-enkephalin and 3H-naloxone. The specific binding of both 3H-leu- and 3H-met-enkephalins was significantly increased in the caudate nucleus, putamen, nucleus accumbens, limbic cortex and hippocampus. Scatchard analysis showed that there was an increase in the receptor number, but no significant changes in the mean dissociation constant. Levodopa treatment did not have any significant effect on the enkephalin bindings. A significantly decreased binding of 3H-naloxone was found in the parkinsonian caudate nucleus. Thus there is a supersensitivity of a population of enkephalin receptors in the striatum and limbic system, as well as a loss of other opiate receptors in the striatum, suggesting the involvement of certain brain enkephalin neurons in the pathophysiological process of Parkinson's disease.