The aim of this doctoral thesis was to study the influence of memory, pain, age and education on the regional cerebral blood flow (rCBF), i.e. brain function, in early Alzheimer's disease (AD) and in chronic neck pain patients in comparison to healthy controls and in healthy elderly per se. This was done by optimizing single photon emission computed tomography (SPECT) as a method to study rCBF with the tracer Technetium-99m (99mTc) hexamethylpropyleneamine oxime (HMPAO) and by matching all image data to a brain atlas before evaluation. The rCBF-SPECT was evaluated and developed to obtain higher diagnostic accuracy in AD and in chronic neck pain patients it was used to study basic pain related cerebral processes in chronic pain of different origin. A new semimanual registration method, based on fiducial marker, suitable for investigations with low spatial resolution was developed. The method was used to reconstruct images with an improved attenuation and scatter correction by using an attenuation-map calculated from the patients' previously acquired CT images. The influence of age and education on rCBF was evaluated with statistical parametric mapping, SPM in healthy elderly. The main findings were age related changes in rCBF in regions close to interlobar and interhemispheric space but not in regions typically affected in early AD, except for the medial temporal lobe. The theory of a 'cognitive reserve' in individuals with a longer education was supported with findings in the lateral temporal lobe, a region related to semantic memory, and in the frontal lobe. A cross-sectional study of chronic neck pain patients showed extensive rCBF changes in coping related regions in a non-traumatic pain patients compared to both healthy and a pain group with a traumatic origin, i.e. whiplash syndrome. The whiplash group displayed no significant differences in rCBF in comparison with the healthy controls. This suggests different pain mechanisms in these groups. The AD-patients showed a significantly lower rCBF in temporoparietal regions including left hippocampus. These changes were associated to episodic memory performance, and especially to face recognition. The diagnostic sensitivity for AD was high. The face recognition test (episodic memory) was used in AD patients to improve the sensitivity of method, i.e. memory-provoked rCBF-SPECT (MP-SPECT). The results were compared to healthy controls and the reductions of rCBF in temporoparietal regions were more pronounced in mild AD during provocation. Memory provocation increased the sensitivity of AD-related rCBF changes at group level. If a higher sensitivity for AD at the individual level is verified in future studies, a single MP-SPECT study might then be of help to set diagnosis earlier. In conclusion rCBF in temporoparietal regions are associated to an impaired episodic memory in early AD. Changes in these regions do not have a strong connection to chronological age. The diagnostic sensitivity of rCBF-SPECT in AD is high and there is a potentially higher sensitivity if memory provoked investigations are used. The findings in this thesis have given an increased knowledge of underlying cerebral pain processing in non-traumatic and traumatic (whiplash) neck pain. Preliminary results supporting the theory of 'cognitive reserve' by showing a correlation between long education and preserved rCBF was found in healthy elderly.

Chronic pain is usually defined as pain of more than three months duration. The prevalence of chronic pain among the general population in Sweden is 18%. Compared with the general population, these patients report lower life satisfaction, decreased activity in daily life and higher levels of depression with decreased work ability, and increased sick leave. Research indicates that multimodal rehabilitation (MMR) programmes, including cognitive behavioural approaches for patients disabled by chronic pain, are effective for return to work. The primary aim of this thesis was to assess outcomes by a long-term follow-up of patients with chronic musculoskeletal pain. Furthermore, the aim was to evaluate two different rehabilitation strategies regarding impact on pain intensity, activity, depression, life satisfactions, and sick leave. Two groups, comprising 255 (between the years 1999-2002) and 296 (between 2007-2008) patients respectively, from the Pain Rehabilitation Clinic at Umeå University Hospital, Sweden, were all assessed by interdisciplinary teams. They completed questionnaires regarding pain intensity, disability, life satisfaction, anxiety and depression, and sick leave, before intervention, immediately after intervention (only the first group; n=255), and at one-year follow-up, after participating in a MMR programme in a specialist clinic, or after receiving a rehabilitation plan (RP) with follow-up in primary care. Allocation to either of the two groups was based on the initial interdisciplinary team assessment. Furthermore, a five-year follow-up of 158 patients with whiplash injury was conducted. Pain intensity decreased and life satisfaction increased significantly regarding somatic health in both groups, at follow-up. In addition, depression improved and disability decreased to a higher extent after participating in the MMR programme as compared to RP and subsequent follow-up in primary care. Patients’ positive beliefs about recovery, and positive expectations about work correlated with favourable rehabilitation outcomes. Sick leave at one year follow-up decreased in both groups. Regarding whiplash injury, patients who reported moderate or severe disability also reported significantly higher pain intensity, depression and post-traumatic stress scores and lower perception of general health compared with patients who reported mild or no disability. In conclusion, MMR programmes seem to be beneficial by decreasing pain intensity, depression, disability and sick leave among patients with chronic musculoskeletal pain. Furthermore, patients’ positive beliefs correlate with more favourable long-term outcomes. An interdisciplinary team assessment based on a biopsychosocial approach may be of value for selection of rehabilitation strategy.

Background Spinal pain is one of humanity’s most frequent complaints with high costs for the individual and society, and is commonly related to spinal disorders. There are many origins behind these disorders e.g., trauma, disc hernia or of other organic origins. However, for many of the disorders, the origin is not known. Thus, more knowledge is needed about how pain affects the neck and neural function in pain affected regions. The purpose of this dissertation was to improve the medical examination of patients suffering from chronic whiplash-associated disorders or other pain related neck-disorders. Methods A new assessment tool for objective movement analysis was developed. In addition, basic aspects of proprioceptive information transmission, which can be of relevance for muscular tension and pain, are investigated by studying the coding of populations of different types of sensory afferents by using a new spike sorting method. Both experiments in animal models and humans were studied to accomplish the goals of this dissertation. Four cats where were studied in acute animal experiments. Mixed ensembles of afferents were recorded from L7-S1 dorsal root filaments when mechanical stimulating the innervated muscle. A real-time spike sorting method was developed to sort units in a multi-unit recording. The quantification of population coding was performed using a method based on principal component analysis. In the human studies, 3D neck movement data were collected from 59 subjects with whiplash-associated disorders (WAD) and 56 control subjects. Neck movement patterns were identified by processing movement data into parameters describing the rotation of the head for each subject. Classification of neck movement patterns was performed using a neural network using processed collected data as input. Finally, the effect of marker position error on the estimated rotation of the head was evaluated by computer simulations. Results Animal experiments showed that mixed ensembles of different types of afferents discriminated better between different muscle stimuli than ensembles of single types of these afferents. All kinds of ensembles showed an increase in discriminative ability with increased ensemble size. It is hypothesized that the main reason for the greater discriminative ability might be the variation in sensitivity tuning among the individual afferents of the mixed ensemble will be larger than that for ensembles of only one type of afferent. In the human studies, the neural networks had a predictivity of 0.89, a sensitivity of 0.90 and a specificity of 0.88 when discriminating between control and WAD subjects. Also, a systematic error along the radial axis of the rigid body added to a single marker had no affect on the estimated rotation of the head. Conclusion The developed spike sorting method, using neural networks, was suitable for sorting a multiunit recording into single units when performing neurophysiological experiments. Also, it was shown that neck movement analysis combined with a neural network could build the basis of a decision support system for classifying suspected WAD or other pain related neck-disorders.

This study presents mathematical surrogate models, derived from finite element kinematic response data, to predict car crash-induced occupant head and neck injury risk for a broad range of impact velocities (10 – 45 mph), impact locations, and angles of impact (-45° to 45°). The development of these models allowed for wide-scale injury prediction while significantly reducing the overall required number of impact test cases. From these, increases in both the impact velocity and the impact’s locational proximity to the occupant were determined to result in the greatest head and neck injury risks. Additionally, strong interactions between the impact orientation variables (location and angle) produced significant changes in the head injury risk, while the neck injury risk was relatively insensitive to these interactions; likely due to the uniaxiality of the current standard neck injury risk metrics. Overall, this methodology showed potential for future applications in wide-scale injury prediction or vehicular design optimization.

Ε1. Ποιότητα της ζωής, άγχος και κατάθλιψη σε ασθενείς με κακώσεις νωτιαίου μυελού: Αυτή η μελέτη έχει σκοπό να αξιολογήσει την ποιότητα ζωής, το άγχος και την κατάθλιψη αλλά και τη νευρολογική θέση, σε ένα σύνολο ασθενών που ζουν με κάκωση του νωτιαίου μυελού (SCI). Μία «διατομική» μελέτη χρησιμοποιήθηκε σε 92 ανθρώπους που ζουν με κάκωση νωτιαίου μυελού SCI. Ολοκλήρωσαν το ερωτηματολόγιο της νοσοκομειακής κλίμακας άγχους και κατάθλιψης HADS (ν=42 ), την κλίμακα ποιότητας ζωής SF-36 (ν=42), καθώς επίσης τυποποιήθηκαν οι νευρολογικές (κλίμακα Frankel, Asia motor score), και οι λειτουργικές κλίμακές τους(FIM, MBI). Οι αναλύσεις μελετήθηκαν για ολόκληρο το δείγμα, κατά φύλο, κατά την κλίμακα Frankel, το Asia motor score, την FIM, και το επίπεδο νευρολογικής βλάβης. Αυτή η μελέτη παρουσιάζει τα προκαταρκτικά συμπεράσματα, τα οποία υποστηρίζουν υψηλά αποτελέσματα άγχους και κατάθλιψης (HADS) σε αυτό τον πληθυσμό των ασθενών με SCI, καθώς επίσης και πολύ χαμηλή ποιότητα ζωής. Ε 2. Σεξουαλική λειτουργία σε γυναίκες με κακώσεις νωτιαίου μυελού: Ο στόχος αυτής της μελέτης ήταν να προσδιοριστεί η σεξουαλικότητα των γυναικών με βαριές κακώσεις νωτιαίου μυελού (SCI) χρησιμοποιώντας την κλίμακα γυναικείας σεξουαλικής λειτουργίας. Το ερωτηματολόγιο με 19 ερωτήματα εκφάνσεις της σεξουαλικότητας του FSFI αφορά τη σεξουαλική λειτουργία και την ικανοποίηση στη σεξουαλική ζωή των γυναικών. Σε αυτή τη μελέτη, χρησιμοποίησαμε ένα δείγμα 39 γυναικών ασθενών με σοβαρή κάκωση νωτιαίου μυελού SCI. Συγκρίναμε δε αυτές τις ασθενείς με ένα υγιές δείγμα γυναικών αντίστοιχο σε οικονομικό –εκπαιδευτικό –επίπεδο ηλικίας - και συζυγική θέση- του γενικού πληθυσμού. Η σεξουαλική δραστηριότητα ήταν χαμηλότερη μεταξύ των γυναικών με SCI, αλλά η επιθυμία, η συναισθηματική ποιότητα της ζωής φύλων και η γενική σεξουαλική ικανοποίηση δεν διέφεραν από τις «υγιείς» γυναίκες του γενικού πληθυσμού. Αυτά τα αποτελέσματα καταδεικνύουν ότι η σεξουαλική ζωή σε γυναίκες με κάκωση νωτιαίου μυελού παραμένει σχεδόν απρόσβλητη. E3. Ίλιγγος μετά από κάκωση ΑΜΣΣ δίκην μαστιγίου. Ο ίλιγγος συνοδεύει περιστασιακά μία κάκωση τύπου «whiplash». Η πιστοποίηση του συνδρόμου είναι ιδιαίτερης αξίας, αν αναλογιστούμε τις πολλές προσφυγές στα δικαστήρια και τις υψηλές δαπάνες που προκύπτουν μετά από τέτοιου τύπου κάκωση. Δώδεκα ασθενείς, που αναφέρθηκαν στα εξωτερικά ιατρεία της κλινικής μας, εξαιτίας μακράς διαρκείας υποκειμενικών ενοχλημάτων με κύριο σύμπτωμα τον ίλιγγο μετά από τον αυχενικό τραυματισμό τύπου “whiplash”, υποβλήθηκαν σε κλινικές, εργαστηριακές και ψυχομετρικές εξετάσεις. Κανένας από τους ασθενείς δεν είχε σημαντικά νευρολογικά συμπτώματα,ούτε ιδιαίτερη επίδραση στη ποιότητα ζωής του, και κανένα σημαντικό τραύμα της αυχενικής σπονδυλικής στήλης δεν προσδιορίστηκε με MRI. Τα στοιχεία μας δείχνουν ότι ο ίλιγγος τύπου “whiplash” είναι σημαντικά δυσκολότερο να το χειριστεί και να το αντιμετωπίσει ένας ιατρός συγκριτικά με τον ιδιοπαθή ίλιγγο. Η επαλήθευση του συνδρόμου αυτού απαιτεί ίσως αντικειμενικότερα κλινικά μέσα. Αυτή η έρευνα προτείνει ότι υπάρχει μια οργανική βάση του συνδρόμου αυτού, αλλά δεν δίνει λύση στην πλήρη κατανόηση των παθοφυσιολογικών μηχανισμών που το προκαλούν, δείχνει ότι το σύνδρομο αυτό δεν έχει ιδιαίτερη βαρύτητα στον ελληνικό πληθυσμό και προτείνει αυτό το σύνδρομο να εξετάζεται ως τμήμα του χρόνιου συνδρόμου κάκωσης τύπου “whiplash”, του γενικού όρου δηλαδή στην διεθνή βιβλιογραφία : Chronic or Late Whiplash. / Ε1. Quality of life, anxiety and depression in adults with spinal cord injuries: This study aimed to evaluate Life Satisfaction, the Anxiety and Depression and neurologic status, in a community sample of adults living with a spinal cord injury (SCI). A cross-sectional design was used with 92 people living in the community with an SCI. They completed the HADS (42 pts) and SF-36 (42 pts), Life Satisfaction Questionnaire. Analyses were conducted for the whole sample, by gender, Frankel Scale, ASIA motor score, FIM, and level of injury. No correlation findings between motor neurologic scales and quality of life assessment. Additionally this study presents preliminary findings, which support the psychometric integrity of HADS and high HADS scores within an outpatient population with SCI. Items that included potential somatic components revealed a more complex factor loading profile. E2. Sexual function in females with severe spinal cord injuries: The objective of this study was to identify the sexual adjustment of females with severe cervical spinal cord injuries (SCI) using the Female Sexual Function Index (FSFI). The 19-item questionnaire of the FSFI concerns sexual function and satisfaction in sex life. This study, conducted by the Orthopaedic and Psychiatry Departments of Patras University, used a sample of a series of 39 consecutive female patients with severe traumatic SCI. We compared these female patients with an age–economic–educational level- and marital status-matched control group of the general population. Sexual activity was lower among females with SCI, but the desire, the emotional quality of sex life and overall sexual satisfaction did not differ from the controls. These results demonstrate that sexual life in females with SCI remains almost unaffected. E3. Whiplash vertigo: Vertigo or dizziness occasionally accompanies a rear –end, neck injury or is provoked by a neck posture no matter what the orientation of the head is to gravity. Whiplash vertigo is matter of considerable concern because of the high litigation related costs of whiplash injuries. When Whiplash cervical vertigo is diagnosed, the usual symptoms are vertigo, dizziness associated with neck movement. Twelve patients, which were referred to our Outpatient Clinic because of long-lasting subjective vertigo complaints after cervical whiplash spine injury, underwent clinical, laboratorial and psychometric examinations. None of the patients had typical neurological symptoms, and no important lesions of the cervical spine were identified with MRI. Our data indicate that Whiplash Vertigo significantly is more difficult to treat than idiopathic Vertigo. The verification of Whiplash Vertigo Syndrome requires more objective clinical means. This investigation proposes that an organic base of the syndrome might be considered, but does not promote the comprehension of pathophysiologic mechanisms that induces it and of course this syndrome considered as part of the general term Chronic Whiplash Syndrome.

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