Long-term outcome in patients with mild traumatic brain injury: a prospective observational study.

BACKGROUND: Mild traumatic brain injury (MTBI) is common; up to 37% of adult men have a history of MTBI. Complaints after MTBI are persistent headaches, memory impairment, depressive mood disorders, and disability. The reported short- and long-term outcomes of patients with MTBI have been inconsistent. We have now investigated long-term clinical and neurocognitive outcomes in patients with MTBI (at admission, and after 1 and 10 years). METHODS: Patients of a previous study investigating MTBI short-term outcome were prospectively reassessed after ±10 year using the same standardized data entry form and validated questionnaire (Beltztest with Beltz Score [BeSc]) for evaluation of Quality of life (QoL) and neurocognitive outcome (higher scores indicate lower QoL). RESULTS: Eighty-six of 176 patients (49%) could be reassessed (n = 75 lost to follow-up; n = 8 second brain trauma; n = 7 death), 10.4 ± 2 years after initial evaluation. Over time, overall BeSc was significantly increased (5.92 ± 10.3 [admission] vs. 10.7 ± 12.8 [1 year] vs. 20.86 ± 17.1 [10 year]; p < 0.0001); only 54 of 86 patients (62.8%) presented with a normal BeSc. Long-term complaints were fatigue, insomnia, and exhaustion. Ten of eighty-six patients (11.6%) had intracranial injury (ICI) and initial BeSc was almost twofold higher in patients with ICI than in patients without ICI (10.0 ± 8.4 vs. 5.3 ± 9.6; p = 0.007). This difference was not seen after 1 year or after 10 years (10.3 ± 11.6 vs. 10.3 ± 10.1 and 21.4 ± 17.3 vs. 16.1 ± 16.4, respectively). Eight of eighty-six patients (9.3%) lost their jobs because of persistent complaints after MTBI. CONCLUSION: BeSc deteriorates over time; our data suggest a decline in general health and QoL in a substantial proportion of patients (37.2%) 10 years after MTBI. Patients without ICI appear to have a better long-term outcome with regard to subjective complaints and QoL.

Course of psychological variables in whiplash injury--a 2-year follow-up with age, gender and education pair-matched patients.

This study evaluated the course of psychological variables during a 2-year follow-up in patients after common whiplash of the cervical spine. From a sample of 117 non-selected patients with common whiplash (investigated on average 7.2 +/- 4.2 days after trauma) a total of 21 suffered trauma-related symptoms over 2 years following initial injury. These patients (symptomatic group) were compared with 21 age, gender and education pair-matched patients, who showed complete recovery from trauma-related symptoms during the 2-year follow-up (asymptomatic group). Both groups underwent standardised testing procedures (i.e., Freiburg Personality Inventory and Well-Being Scale) at referral, and at 3, 6 and 24 months. In the symptomatic group during follow-up no significant changes in rating of neck pain or headache were found. Significant differences between the groups and significant deviation of scores over time were found on the Well-Being and Nervousness Scales. There was a lack of significant difference between the groups on the Depression Scale, indicating a possible somatic basis for changes in psychological functioning in the investigated sample. With regard to scales of Extraversion or Neuroticism, there were neither significant differences between the groups nor significant deviation over time. These results highlight that patients' psychological problems are rather a consequence than a cause of somatic symptoms in whiplash.

Evidence for spinal cord hypersensitivity in chronic pain after whiplash injury and in fibromyalgia.

Patients with chronic pain after whiplash injury and fibromyalgia patients display exaggerated pain after sensory stimulation. Because evident tissue damage is usually lacking, this exaggerated pain perception could be explained by hyperexcitability of the central nervous system. The nociceptive withdrawal reflex (a spinal reflex) may be used to study the excitability state of spinal cord neurons. We tested the hypothesis that patients with chronic whiplash pain and fibromyalgia display facilitated withdrawal reflex and therefore spinal cord hypersensitivity. Three groups were studied: whiplash (n=27), fibromyalgia (n=22) and healthy controls (n=29). Two types of transcutaneous electrical stimulation of the sural nerve were applied: single stimulus and five repeated stimuli at 2 Hz. Electromyography was recorded from the biceps femoris muscle. The main outcome measurement was the minimum current intensity eliciting a spinal reflex (reflex threshold). Reflex thresholds were significantly lower in the whiplash compared with the control group, after both single (P=0.024) and repeated (P=0.035) stimulation. The same was observed for the fibromyalgia group, after both stimulation modalities (P=0.001 and 0.046, respectively). We provide evidence for spinal cord hyperexcitability in patients with chronic pain after whiplash injury and in fibromyalgia patients. This can cause exaggerated pain following low intensity nociceptive or innocuous peripheral stimulation. Spinal hypersensitivity may explain, at least in part, pain in the absence of detectable tissue damage.

The narcoleptic borderland: a multimodal diagnostic approach including cerebrospinal fluid levels of hypocretin-1 (orexin A).

OBJECTIVES: Biological markers of narcolepsy with cataplexy (classical narcolepsy) include sleep-onset REM periods (SOREM) on multiple sleep latency tests (MSLT), HLA-DQB1*0602 positivity, low levels of cerebrospinal fluid (CSF) hypocretin-1 (orexin A), increased body mass index (BMI), and high levels of CSF leptin. The clinical borderland of narcolepsy and the diagnostic value of different markers of narcolepsy remain controversial and were assessed in a consecutive series of 27 patients with hypersomnia of (mainly) neurological origin. METHODS: Diagnoses included classical narcolepsy (n=3), symptomatic narcolepsy (n=1), narcolepsy without cataplexy (n=4), idiopathic hypersomnia (n=5), hypersomnia associated with psychiatric disorders (n=5), and hypersomnia secondary to neurological disorders or of undetermined origin (n=9). Clinical assessment included BMI, Epworth Sleepiness Scale (ESS), Ullanlinna Narcolepsy Scale (UNS), and history of REM-symptoms (sleep paralysis, hallucinations). HLA-typing, electrophysiological studies (conventional polysomnography, MSLT, 1-week actigraphy), and measurements of CSF levels of hypocretin and leptin were also performed. RESULTS: Hypocretin-1 was undetectable in three patients with classic narcolepsy and detectable in the remaining 24 patients. Other narcoleptic markers also frequently found in patients without narcolepsy included ESS>14 (78% of 27 patients), UNS>14 (75%), REM symptoms (30%), sleep latencies on MSLT<5 min (41%), >/=2 SOREM (30%), DQB1*0602 positivity (52%), BMI>25 (52%), and increased CSF leptin (48%). Hypersomnia was documented by an increased time 'asleep' in 41% of patients. Overlapping clinical and electrophysiological findings were seen mostly in patients with narcolepsy without cataplexy, idiopathic hypersomnia, and psychiatric hypersomnia. CONCLUSIONS: (1) Hypocretin dysfunction is not the 'final common pathway' in the pathophysiology of most hypersomnolent syndromes that fall on the borderline for a diagnosis of narcolepsy. (2) The observed overlap among these hypersomnolent syndromes implies that current diagnostic categories are not entirely unambiguous. (3) A common hypothalamic, hypocretin-independent dysfunction may be present in some of these syndromes.

Ranking of tests for pain hypersensitivity according to their discriminative ability in chronic neck pain.

BACKGROUND AND OBJECTIVES: Quantitative sensory testing (QST) is widely used to investigate peripheral and central sensitization. However, the comparative performance of different QST for diagnostic or prognostic purposes is unclear. We explored the discriminative ability of different quantitative sensory tests in distinguishing between patients with chronic neck pain and pain-free control subjects and ranked these tests according to the extent of their association with pain hypersensitivity. METHODS: We performed a case-control study in 40 patients and 300 control subjects. Twenty-six tests, including different modalities of pressure, heat, cold, and electrical stimulation, were used. As measures of discrimination, we estimated receiver operating characteristic curves and likelihood ratios. RESULTS: The following quantitative sensory tests displayed the best discriminative value: (1) pressure pain threshold at the site of the most severe neck pain (fitted area under the receiver operating characteristic curve, 0.92), (2) reflex threshold to single electrical stimulation (0.90), (3) pain threshold to single electrical stimulation (0.89), (4) pain threshold to repeated electrical stimulation (0.87), and (5) pressure pain tolerance threshold at the site of the most severe neck pain (0.86). Only the first 3 could be used for both ruling in and out pain hypersensitivity. CONCLUSIONS: Pressure stimulation at the site of the most severe pain and parameters of electrical stimulation were the most appropriate QST to distinguish between patients with chronic neck pain and asymptomatic control subjects. These findings may be used to select the tests in future diagnostic and longitudinal prognostic studies on patients with neck pain and to optimize the assessment of localized and spreading sensitization in chronic pain patients.

Ranking of parameters of pain hypersensitivity according to their discriminative ability in chronic low back pain.

Low back pain is associated with plasticity changes and central hypersensitivity in a subset of patients. We performed a case-control study to explore the discriminative ability of different quantitative sensory tests in distinguishing between 40 cases with chronic low back pain and 300 pain-free controls, and to rank these tests according to the extent of their association with chronic pain. Gender, age, height, weight, body mass index, and psychological measures were recorded as potential confounders. We used 26 quantitative sensory tests, including different modalities of pressure, heat, cold, and electrical stimulation. As measures of discrimination, we estimated receiver operating characteristics (ROC) and likelihood ratios. Six tests seemed useful (in order of their discriminative ability): (1) pressure pain detection threshold at the site of most severe pain (fitted area under the ROC, 0.87), (2) single electrical stimulation pain detection threshold (0.87), (3) single electrical stimulation reflex threshold (0.83), (4) pressure pain tolerance threshold at the site of most severe pain (0.81), (5) pressure pain detection threshold at suprascapular region (0.80), and (6) temporal summation pain threshold (0.80). Pressure and electrical pain modalities seemed most promising and may be used for diagnosis of pain hypersensitivity and potentially for identifying individuals at risk of developing chronic low back pain over time.

Are symptoms of late whiplash specific? A comparison of SCL-90-R symptom profiles of patients with late whiplash and patients with chronic pain due to other types of trauma.

OBJECTIVE: Focusing on symptoms referred to as specific for late whiplash may contribute to misconceptions in assessment, treatment, and settlements. We compared Symptom Checklist 90-Revised (SCL-90-R) symptom profiles of patients with late whiplash and patients with chronic pain due to other types of trauma. METHODS: We compared 156 late whiplash patients (WP group) with 54 chronic pain patients who had suffered different bodily trauma (non-WP group) with regard to the following aspects of the SCL-90-R: the Positive Symptom Total (PST); the nine SCL-90-R dimensions and additional global indices, i.e., Global Severity Index (GSI) and Positive Symptom Distress (PSD); and complaints referred to as specific for late whiplash syndrome. RESULTS: The mean adjusted T score for PST was in the normal range for the WP group (T = 56.1, 95% CI 54.1-58.1) and in the pathological range for the non-WP group (T = 61.1, 95% CI 57.3-64.9). Both the WP and non-WP groups showed mean T scores in the pathological range for the dimensions "Somatization," "Obsessive-Compulsive," and PSD. Only the non-WP group had an average score in the pathological range for the dimensions "Depression," "Anxiety," and "Phobic Anxiety" and for the global indices GSI and PST. Multivariable regression controlling for gender and education level was used to identify complaints "specific for late whiplash" that were significantly associated with being in the WP group rather than the non-WP group: greater headache (OR 1.54; 95% CI 1.16, 2.03; p = 0.003) and lower emotional lability (OR 0.96; 95% CI 0.93, 0.98; p = 0.003) were the only significant variables. CONCLUSION: Late whiplash is not a chronic pain condition characterized by specific symptoms, other than greater headache.

The nociceptive withdrawal reflex: normative values of thresholds and reflex receptive fields.

Assessments of spinal nociceptive withdrawal reflexes can be used in human research both to evaluate the effect of analgesics and explore pain mechanisms related to sensitization. Before the reflex can be used as a clinical tool, normative values need to be determined in large scale studies. The aim of this study was to determine the reference values of spinal nociceptive reflexes and subjective pain thresholds (to single and repeated stimulation), and of the area of the reflex receptive fields (RRF) in 300 pain-free volunteers. The influences of gender, age, height, weight, body-mass index (BMI), body side of testing, depression, anxiety, catastrophizing and parameters of Short-Form 36 (SF-36) were analyzed by multiple regressions. The 95% confidence intervals were determined for all the tests as normative values. Age had a statistically and quantitatively significant impact on the subjective pain threshold to single stimuli. The reflex threshold to single stimulus was lower on the dominant compared to the non-dominant side. Depression had a negative impact on the subjective pain threshold to single stimuli. All the other analyses either did not reveal statistical significance or displayed quantitatively insignificant correlations. In conclusion, normative values of parameters related to the spinal nociceptive reflex were determined. This allows their clinical application for assessing central hyperexcitability in individual patients. The parameters investigated explore different aspects of sensitization processes that are largely independent of demographic characteristics, cognitive and affective factors.

Patients with mild traumatic brain injury: immediate and long-term outcome compared to intra-cranial injuries on CT scan.

BACKGROUND: Mild traumatic brain injury (MTBI) defined as Glasgow Coma Scale (GCS) 14 or 15 has shown contradictory short- and long-term outcomes. The objective of this study was to correlate intra-cranial injuries (ICI) on CT scan to neurocognitive tests at admission and to complaints after 1 year. METHODS: Two hundred and five patients with MTBI underwent a CT scan and were examined with neurocognitive tests. After 1 year complaints were assessed by phone interviews. RESULTS: The neurocognitive tests in 51% of the patients showed significant deficits; there was no difference for patients with GCS 14-15, nor was there a difference between patients with ICI to patients without. After 1 year patients with ICI had significantly more complaints than patients without ICI, the most frequent complaint was headache and memory deficits. CONCLUSIONS: No correlation was found between GCS or ICI and the neurocognitive tests upon admission. After 1 year, patients with ICI have significantly more complaints than patients without ICI. No cost savings resulted by doing immediate CT scan on all.

Modulation of central hypersensitivity by nociceptive input in chronic pain after whiplash injury.

OBJECTIVE: Chronic pain after whiplash injury is associated with hypersensitivity of the central nervous system to peripheral stimulation. It is unclear whether central hypersensitivity is modulated by peripheral nociceptive input. We hypothesized that changes in nociceptive input would correlate with changes in magnitude of central hypersensitivity. DESIGN: Fifteen patients with chronic pain after whiplash injury were investigated. Changes in nociceptive input were induced by infiltration of painful and tender muscles with bupivacaine (0.25%). Such infiltrations produce either pain reduction or pain enhancement, the latter effect probably resulting from transient injection-induced trauma. We used this individual variability in correlation analyses. Changes in intensity of neck pain, as assessed by a visual analog scale (VAS), after infiltration were assumed to reflect changes in nociceptive input. Changes in pressure pain thresholds recorded at healthy tissues (nonpainful point of the neck and the second toe) were used to measure changes in central hypersensitivity. The correlations between the change in VAS score and changes in pressure pain thresholds 15 minutes after infiltration were analyzed. RESULTS: Statistically significant negative correlations were found between change in VAS score and changes in threshold measurements performed at the neck, but not at the toe. CONCLUSIONS: Different mechanisms underlie hyperalgesia localized at areas surrounding the site of pain and hyperalgesia generalized to distant body areas. Central hypersensitivity as a determinant of neck pain is probably a dynamic condition that is influenced by the presence and activity of a nociceptive focus.