Olli Tenovuo

Sensory dysfunction in burning mouth syndrome

&NA; Our preliminary observations on a small group of burning mouth syndrome (BMS) patients indicated a change in the non‐nociceptive, tactile sensory function in BMS and provided evidence for the hypothesis of a neuropathic etiology of BMS. In the present clinical study on a group of 52 BMS patients, we used quantitative sensory tests (QST) in addition to the blink reflex (BR) recordings in order to gain further insight into the neural mechanisms of BMS pain. Based on electrophysiologic findings, the BMS patients could be grouped into four different categories: (1) The results of the BR were suggestive of brainstem pathology or peripheral trigeminal neuropathy in ten (19%) patients. In most of the cases, the abnormalities in the BR seemed to represent subclinical changes of the trigeminal system. (2) Increased excitability of the BR was found in the form of deficient habituation of the R2 component of the BR in 11 (21%) of the patients. Two of these patients also showed signs of warm allodynia in QST. (3) One or more of the sensory thresholds were abnormal indicating thin fiber dysfunction in altogether 35 patients (76%) out of the 46 tested with QST. Thirty‐three of these patients showed signs of hypoesthesia. (4) There were only five patients with normal findings in both tests. The present findings with strong evidence for neuropathic background in BMS will hopefully provide insights for new therapeutic strategies.

Role of the dopaminergic system in chronic pain -- a fluorodopa-PET study.

&NA; Recent data from animal experiments suggest an important role for the basal ganglia in the processing and sensorimotor gating of nociceptive information. However, very little is known about their possible participation in human pain. Because of our previous finding of increased excitability of the blink reflex (a brainstem reflex under dopaminergic inhibitory control) in some burning mouth syndrome (BMS) patients, we have studied the dopaminergic function of the striatum (putamen and caudatus) of BMS patients with positron emission tomography (PET). 6‐[18F]fluorodopa (FDOPA) PET scans were done on ten BMS patients and 14 healthy control subjects. The presynaptic dopaminergic function was significantly decreased in the right putamen (20%, P=0.04) of the BMS patients compared to control subjects. On the left side, the FDOPA uptake was decreased by 17% (P=0.08). The mean FDOPA uptake was not significantly changed in the caudate nucleus of the patients. The finding of decreased striatal FDOPA uptake in the putamen supports our previous neurophysiological observations indicating decreased dopaminergic inhibition in BMS patients. The present result provides direct evidence of the involvement of the nigrostriatal dopaminergic system in pain for the first time in a clinical pain condition.

Abnormalities of the blink reflex in burning mouth syndrome.

&NA; To our knowledge, this is the first report on pain‐related abnormalities of the eye blink reflex (BR) in a clinical pain patient population. The objective of this study was to evaluate the possible neuropathic mechanisms underlying the burning mouth syndrome (BMS), by means of objective electrophysiological examination of the trigemino‐facial system. We studied the BR with stimulation of the supraorbital nerve (SON) with particular emphasis on the occurrence of the pain‐related ultralate R3 components, and the habituation response of the R2 components. The subjects consisted of eleven BMS patients and 10 healthy control subjects. All patients underwent thorough clinical oral and neurological examinations. The motor function of the trigeminal nerve was assessed with a jaw reflex recording, and a needle‐EMG examination of the facial and masticatory muscles was performed in the patients with abnormalities in the BR recordings. The jaw reflexes, the latencies of the BR components, and the needle‐EMG examinations were normal in all patients. As a group, the BMS patients had statistically significantly higher stimulus thresholds for the tactile R1 components of the BR compared with the control subjects. With non‐noxious stimulation, the BMS patients showed more frequently pain‐related R3 components (11/22 SONs) compared with the controls (3/20 SONs). In addition, four BMS patients had abnormal habituation of the R2 components. In two of these patients, the findings were segmental (i.e., unilateral), coinciding with the side of the subjective BM symptoms. The abnormalities of the BR tests appeared to be related to longer disease duration. Our results suggest a possible pathologic involvement of the nervous system in chronic BMS.

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.

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 Aβ-, Aδ-, 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 Aβ-, Aδ-, and C-fibers recovered function at similar rates. The trigeminal nerve does not differ from other peripheral nerves as regards susceptibility to neuropathic pain.

Differences and similarities between atypical facial pain and trigeminal neuropathic pain

Objective: To investigate contribution of neuropathic mechanisms to clinically diagnosed atypical facial pain (AFP) using neurophysiologic and thermal quantitative sensory testing (QST) and comparing findings in AFP with those in definite trigeminal neuropathic pain (TNP). Methods: Twenty patients with AFP and 12 patients with TNP participated after thorough clinical diagnostic workup. All patients underwent blink reflex (BR) recordings, habituation of the BR, and (except one patient with TNP) thermal QST. The results were compared with the reference values of our laboratory for normality. Results: Of the patients with AFP, 75% showed abnormal findings. The BR responses were abnormal in three (15%) AFP patients (in two patients, the findings were compatible with a peripheral neuropathy and in one with a brainstem lesion), and in seven (58%) TNP patients. Seven (35%) patients with AFP and four (33%) with TNP showed increased excitability of the BR in the form of deficient habituation. Thermal QST indicated abnormal small fiber function in 11 (55%) patients with AFP and in all patients with TNP tested. QST showed thermal hypoesthesia in 45% and warm allodynia in 10% of patients with AFP. In TNP, all findings indicated thermal hypoesthesia. Abnormalities in BR and thermal QST were less frequent in AFP than TNP, but when present, type and pattern of findings were similar in both conditions. Conclusions: Clinical diagnosis of atypical facial pain represents a heterogeneous entity and seems to form a continuum regarding the level and extent of neuropathic involvement. Without detailed neurophysiologic and quantitative sensory examinations, neuropathic cause of chronic orofacial pain may be overlooked. GLOSSARY: Aβ = β-amyloid protein; AFP = atypical facial pain; BR = blink reflex; CDT = cold detection threshold; HPT = heat pain threshold; QST = quantitative sensory testing; TN = trigeminal nerve; TNP = trigeminal neuropathic pain; WDT = warm detection threshold.

Return to work after traumatic brain injury: Systematic review

Abstract Objective: To evaluate the evidence on pre- and post-injury predictors of vocational outcome after traumatic brain injury (TBI). Literature selection and critical analysis: The search was conducted on PubMed and Central databases since 1990. A clinical question was formulated according to the PICO framework. Clinical relevance of the selected studies was evaluated following the GRADE framework. Main outcomes and results: The main outcome measures were employment status and return to work after TBI. Methodological quality of most of the relevant 12 controlled and 68 uncontrolled studies included in the review was estimated as very low. There was weak evidence that age, educational level, pre- and post-injury occupational status, severity of TBI, functional status, level of depression and anxiety, gender and race may be predictive for the vocational outcome after TBI. Conclusions and implications for further research: No strong evidence was found that vocational outcomes after TBI could be predicted or improved. There is a need for both experimental and observational well-conducted studies on this important subject. Researchers are strongly encouraged to use unified and standardized terms and scales in further studies. The authors suggest the International Classification of Functioning, Disability and Health (ICF) as the best tool available for this purpose.

Cognitive functions in relation to MRI findings 30 years after traumatic brain injury.

Objective: The aim of the study was to relate cognitive effects of a remote traumatic brain injury (TBI) to MRI findings and severity of injury. Method: Sixty-one patients were assessed on average 30 years after a TBI of variable severity. A comprehensive cognitive test battery was used to evaluate memory, executive functions and cognitive overall impairment. Multiple regression analyses were used to examine the relationships between cognitive variables and MRI volumetric findings (the volumes of the hippocampus and the lateral ventricles) and local contusions on MRI. Also, the effect of injury severity on cognitive outcome was evaluated. Results: Reductions in hippocampal volumes and lateral ventricular enlargement were significantly associated with impaired memory functions, memory complaints and executive functions. Of the MRI parameters used, the best predictor for cognitive outcome was the volume of the lateral ventricle. There was only a modest relationship between severity of injury and cognitive performance. Conclusions: The results show that long-term memory impairments after TBI are associated with MRI volumetric measures. This suggests that the degree of diffuse injury leading to atrophic changes is prognostically more important than the initial severity of TBI.

Clinical assessment of hemispatial neglect: Evaluation of different measures and dimensions

The multidimensional nature of the neglect syndrome constitutes a challenge for clinical assessments. This study evaluates the sensitivity of different clinical measures to detect neglect and explores ways to evaluate the diversity of the syndrome in a clinical sample. An extensive battery of tests was used to examine aspects of visuospatial, representational, and personal neglect. A total of 31 normal control participants and 34 patients with right hemisphere stroke were examined 16.8 days post-stroke, on average. Of the patients, 24 showed neglect in at least one task. The Random shape cancellation test, Star cancellation, and two line bisection tasks appeared to be the most sensitive tests of visuospatial neglect. Personal neglect and neglect in far space occurred only together with extrapersonal neglect. Besides near space, other spatial aspects of neglect are important to consider in clinical assessments, but standardized methods are needed. In this patient group a minimum of 10 tests were needed to cover various aspects of detection, dissociations, and severity of neglect. A multifactorial approach in clinical testing of neglect is recommended.

APOE-∈4 predicts dementia but not other psychiatric disorders after traumatic brain injury

The authors studied the association between APOE-ε4 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-ε4 allele. Dementia and subclinical dementia were significantly more common with the presence of APOE-ε4. The occurrence of other psychiatric disorders did not differ between patients with and without APOE-ε4 allele.