WHIPLASH INJURYA clinical, radiographic and psychological investigation

AKADEMISK AVHANDLING

som med vederbörligt tillstånd av Rektorsämbetet vid Umeå Universitet för avläggande av doktorsexamen i medicinsk vetenskap kommer att offentligen

försvaras i sal B, byggnad ID, 9 tr (Tandläkarhögskolan), Norrlands

Universitetssjukhus, fredagen den 8 november 1996, kl 09.00

av

Kurt Pettersson

Fakultetsopponent: Professor Seppo Santavirta, Helsingfors, Finland.

UMEÅ UNIVERSITY MEDICAL DISSERTATIONS New series No 484 - ISSN 0346-6612 - ISBN 91-7191-233-9

W HIPLASH INJURYA clinical radiographic and psychological investigation

Kurt Pettersson

From the Department of Orthopaedics, Umeå University, S-901 85, Umeå, SwedenA bstract

Whiplash injury is a common and troublesome disorder and approximately 10-40 per cent of its victims develop chronic symptoms. The annual incidence is estimated at 1/1000 inhabitants and the prevalence at 1%. The cause of chronic symptoms after whiplash injury is still unknown and no effective treatment has been presented so far.

The present study is divided into two parts; the first part includes clinical, radiographic and psychological investigations, and the second part the effect of surgical intervention as well as intervention with medication.

MRI studies (n=39) showed a larger proportion of pathologic findings compared to normal subjects, but no correlation with initial neurologic deficits was found. At the 2-year follow-up all patients with disc herniations with medullary impingement had persistent symptoms. Three patients had disc herniations that deteriorated from slight and moderate initial changes on the MRI to severe changes with medullary cord impingement. This deterioration might be a first sign of disc degeneration. Thus our results indicate that disc pathology is a contributing factor in the development of chronic symptoms.

Measurements from standard lateral radiographs taken in neutral position were evaluated (n=48). A graphic digitizer connected to a microcomputer was used and the sagittal diameters were determined. Multivariate analysis of variance showed that the spinal canal was significantly smaller in patients with persistent symptoms indicating that a narrow spinal canal is unfavourable in patients subjected to whiplash injury.

A psychological investigation (n=70) revealed no relationship between pre-existing personality traits and persistent symptoms. In our study, whiplash patients showed no differences in personality traits compared to normal controls.

Our results after discectomy and anterior cervical fusion (n=20) because of chronic symptoms after whiplash injury were not satisfactory. We noticed that about half of the cases had less headache and neck pain but no beneficial effects on radicular pain, vertigo, visual and auditory symptoms were observed. Based on the criteria of a surgical evaluation, two patients were classified as good, nine as fair and nine as poor.

A prospective randomised double-blind study of high-dose methyl-prednisolone compared to placebo was conducted (n=40). A clinical follow-up with repeated neurological examinations and a standardised questionnaire including VAS-scales and a pain sketch form were used for the evaluation of initial symptoms, before drug administration and at the follow-ups at 2 weeks, 6 weeks, and 6 months after the injury. At the 6-month follow-up there was a significant difference between the actively treated patients and placebo concerning disabling symptoms defined as inability to return to previous work, number of sick-days and sick-leave profile. All the actively treated patients had returned to work and none had multiple symptoms though three of them complained of intermittent neck pain. Our conclusion is therefore that acute treatment with high-dose corticosteroids might be beneficial to the prevention of disabling symptoms after whiplash injury.

Key words: Cervical spine, whiplash injury, MRI, personality traits, steroid therapy, sagittal canal diameter, chronic symptoms.

UMEÅ UNIVERSITY MEDICAL DISSERTATIONS

New series No 484 - ISSN 0346-6612

From the Department of Orthopaedics, Umeå University, S-901 85 Umeå, Sweden

WHIPLASH INJURY

A clinical, radiographic and psychological investigation

Kurt Pettersson

Umeå 1996

Copyright © 1996 by Kurt Pettersson

ISBN 91-7191-233-9

Printed in Sweden by the Printing Office of Umeå University

Umeå 1996

Kunskapens träd ger inte bara kunskap om gott och ont. Det är också på gott och ont.

Georg Henrik von Wright

Tomy beloved wife, Annica,

for her endless love and support and to

my dear parents for all they have done

for their children

6

UMEÅ UNIVERSITY MEDICAL DISSERTATIONS New series No 484 - ISSN 0346-6612 - ISBN 91-7191-233-9

WHIPLASH INJURYA clinical, radiographic and psychological investigation

Kurt PetterssonFrom the Department of Orthopaedics, Umeå University, S-901 85, Umeå, Sweden

AbstractWhiplash injury is a common and troublesome disorder and approximately 10-40

per cent of its victims develop chronic symptoms. The annual incidence is estimated at 1/1000 inhabitants and the prevalence at 1%. The cause of chronic symptoms after whiplash injury is still unknown and no effective treatment has been presented so far.

The present study is divided into two parts; the first part includes clinical, radiographic and psychological investigations, and the second part the effect of surgical intervention as well as intervention with medication.

MRI studies (n=39) showed a larger proportion of pathologic findings compared to normal subjects, but no correlation with initial neurologic deficits was found. At the 2- year follow-up all patients with disc herniations with medullary impingement had persistent symptoms. Three patients had disc herniations that deteriorated from slight and moderate initial changes on the MRI to severe changes with medullary cord impingement. This deterioration might be a first sign of disc degeneration. Thus our results indicate that disc pathology is a contributing factor in the development of chronic symptoms.

Measurements from standard lateral radiographs taken in neutral position were evaluated (n=48). A graphic digitizer connected to a microcomputer was used and the sagittal diameters were determined. Multivariate analysis of variance showed that the spinal canal was significantly smaller in patients with persistent symptoms indicating that a narrow spinal canal is unfavourable in patients subjected to whiplash injury.

A psychological investigation (n=70) revealed no relationship between pre-existing personality traits and persistent symptoms. In our study, whiplash patients showed no differences in personality traits compared to normal controls.

Our results after discectomy and anterior cervical fusion (n=20) because of chronic symptoms after whiplash injury were not satisfactory. We noticed that about half of the cases had less headache and neck pain but no beneficial effects on radicular pain, vertigo, visual and auditory symptoms were observed. Based on the criteria of a surgical evaluation, two patients were classified as good, nine as fair and nine as poor.

A prospective randomised double-blind study of high-dose methyl-prednisolone compared to placebo was conducted (n=40). A clinical follow-up with repeated neurological examinations and a standardised questionnaire including VAS-scales and a pain sketch form were used for the evaluation of initial symptoms, before drug administration and at the follow-ups at 2 weeks, 6 weeks, and 6 months after the injury. At the 6-month follow-up there was a significant difference between the actively treated patients and placebo concerning disabling symptoms defined as inability to return to previous work, number of sick-days and sick-leave profile. All the actively treated patients had returned to work and none had multiple symptoms though three of them complained of intermittent neck pain. Our conclusion is therefore that acute treatment with high-dose corticosteroids might be beneficial to the prevention of disabling symptoms after whiplash injury.

Key words: Cervical spine, whiplash injury, MRI, personality traits, steroid therapy, sagittal canal diameter, chronic symptoms.

7

TABLE OF CONTENTS

A b s t r a c t .................... 6O riginal p ap ers................................................................. 8I n tr o d u c t io n ........................................................................ 9

Background .................................................................... 9Aetiology and pathogenesis..................................... 11Symptoms........................................................................ 19Pathology ........................................................................ 23Psychological aspects ................................................ 26Treatment and prognosis .......................................... 27

A im s .......................................................................................... 29M aterial and m ethods..................................................... 30R e s u l t s ..................................................................................... 33G eneral d iscu ss io n ........................................................... 35C o n c lu s io n s .......................................................................... 43A c k n o w le d g e m e n ts .......................................................... 44R e f e r e n c e s ............................................................................. 45Paper I ....................................................................................Paper I I ...................................................................................Paper I II .................................................................................Paper IV .................................................................................Paper V ...................................................................................Paper V I...................................................................... ..........

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O R IG IN A L PAPERS

This thesis is based on the following papers, which will be referred to by their Romannumerals.

I Pettersson K, Hildingsson C, Toolanen G, Fagerlund M, Björnebrink J. MRI and neurology in acute whiplash trauma. No correlation in prospective examination of 39 cases. Acta Orthop Scand 1994 ; 65(5): 525-28.

II Pettersson K, Hildingsson C, Toolanen G, Fagerlund M, Björnebrink J. Disc pathology after whiplash injury. A prospective MRI and clinical investigation. Spine, in press.

III Algers G, Pettersson K, Hildingsson C, Toolanen G. Surgery for chronic symptoms after whiplash injury. Follow-up of 20 cases. Acta Orthop Scand 1993; 64(6): 654-6.

IV Pettersson K, Schiette P, Brändström S, Toolanen G, Adolfsson R, Hildingsson C, Nyländer P-O. Can personality deviations explain the persistence of symptoms after whiplash injury ? Submitted.

V Pettersson K, Kärrholm J, Toolanen G, Hildingsson C. Decreased width of the

spinal canal in patients with chronic symptoms after whiplash injury. Spine 1995; 20(15): 1664-67.

VI Pettersson K, Toolanen G. High-dose methyl-prednisolone prevents extensive sick-leave after whiplash injury. A prospective randomised double-blind study. Submitted.

9

INTRODUCTION

BACKGROUND

Hyperextension hyperflexion injuries to the neck were first described when travelling by train became popular and train accidents thus started to occur during the latter half of the 19th century (Evans 1992a). In 1928 Crowe introduced the term whiplash injury to describe a syndrome resulting from rear-end motor vehicle accidents. The term whiplash is descriptive, and is defined as an acceleration- deceleration mechanism of energy transfer to the neck (Spitzer et al 1995). Whiplash injury has classically been described in association with movements in the sagittal plane following a rear-end impact (Gay and Abbott 1953), but it is clear that other movements can also result in whiplash injury (Barnsley et al 1994a). The majority of these injuries take place in motor vehicle accidents ( Gotten 1956, Hohl 1974, Norris and Watt 1983, Dvorak et al 1989) although other injury mechanisms including athletic activities or falls have been described ( Hohl 1989, Spitzer et al 1995).

The clinical syndrome of whiplash injuries has proved to be a very common and troublesome disorder, and is becoming increasingly worrisome in the Western world (Spitzer et al 1995). The annual incidence is estimated at 1/1000 inhabitants and the prevalence at 1% (Hildingsson and Toolanen 1990, Barnsley et al 1994a).

Not all patients who suffer a whiplash injury develop chronic symptoms. Several studies indicate that approximately 12 to 44% develop chronic neck pain (Deans et al 1987, Hildingsson and Toolanen 1990, Gargan and Bannister 1990, Pennie and Agambar 1991). Spitzer et al (1995) stated that patients who are still symptomatic or who suffer from residual disability 6 months or more after injury are designated as chronic. Long-term retrospective studies show that symptoms do not alter significantly after 2 years (Robinson et al 1993) and some (Gargan and Bannister 1990, Maimaris et al 1988) suggest that the chronic state may be reached as soon as 2 or 3 months after the injury. This suggestion has been further emphasised by Gargan and Bannister (1994) in a prospective study.

Whiplash injury is still controversial and some (Bovim et al 1994, Schrader et al 1996) even doubt that the late whiplash syndrome really exists. However, these reports are retrospective with a low response frequency (Bovim et al 1994, Schrader et al 1996). The age distribution was higher than in whiplash material in general, 44 years, and gender was unevenly distributed with a predominance of men , 78 per cent (Schrader et al 1996).

10

In a Finnish population study (Mäkelä et al 1991), chronic neck syndrome was

diagnosed in 9.5% of the men and 13.5% of the women in general but in the 30-44 years age cohort only 3.3% of the men and 7.1% of the women had chronic neck pain. They also found that when age and sex had been adjusted for, the prevalence of the neck syndrome was associated with a history of injury. Furthermore, no detailed information on the severity and character of the neck pain was provided (Bovim et al 1994, Schrader et al 1996), although several authors have shown that initial status could in fact influence the outcome of whiplash injury (Spitzer et al 1995).

The cause of chronic symptoms after whiplash injury is still unknown, although various theories ranging from psychological disturbances to different organic lesions have been put forward. From these circumstances the thesis presented has developed.

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AETIOLOGY AND PATHOGENESIS

Anatomy and Biomechanics

Whiplash trauma includes several trauma mechanisms.Hyperextension of the cervical spine results in compressive forces to the posterior

structures and tensile forces to the anterior structures. As for the posterior structures especially the zygapophyseal joints are at risk, and as for the anterior structures it is especially the anterior longitudinal ligament, the anterior cervical muscles and the intervertebral discs which are at risk.

In contrast to extension, hyperflexion applies compressive forces to the anterior and tensile forces to the posterior structures as mentioned above. The anterior structures at risk are the intervertebral discs and vertebral bodies, whereas the posterior structures stretched by flexion are mainly the zygapophyseal joint capsules, articular pillars and posterior neck muscles.

In lateral flexion the zygapophyseal joint capsules on both sides and the intervertebral discs will be at most risk.

Hypertranslation, described by Penning (1992b), will produce horizontal shear between the cervical vertebrae, resulting in compression of the zygapophyseal joints and stretching of the annular fibres at the anterior part of the disc (Barnsley et al 1994a).

In the classical experiments by Severy et al (1955), the most important discovery was that in low-impact rear-end collisions the head and neck were exposed to acceleration forces up to 2.5 times those of the vehicle itself and at higher-speed collisions up to 4-10 times the acceleration forces of the car. These findings have been further validated by recent research where modern car models were used (Svensson 1993, McConnell et al 1993). This may explain why motorists can sustain a soft tissue injury at relatively low-impact speeds. Later research has also pointed out that a head restraint provides only minimal protection and, in some cases, it will intensify the injury due to a very complicated transference of energy from the seat back and the head restraint to the head and neck. The seat back stores elastic energy and serves as a catapult at the same time as the head has not begun to accelerate and is instead moving rearwards into extension (Svensson 1993, Croft 1995). In a recent study no significant beneficial effect of the use of seat belts, and the presence of head restraints could be found (Sturzenegger et al 1994). There are also suggestions in the literature that seat belts may even increase the incidence of neck injuries, especially when they are not accurately used (Spitzer et al 1995).

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In general, the lower segments are believed to receive a maximum of the damage. Jackson (1977) stated that C4-5 is under the severest strain and stress in hyperextension and C5-6 in hyperflexion. These findings are in agreement with an earlier statement by McKensie and Williams (1971) who concluded that C5-6 is the most stressed segment. However, Penning (1992a) also observed that normal translation of the head produces a remarkable degree of motion at the cranio-vertebral junction CO-2. The hypothesis is that acceleration injuries will lead to hypertranslation of the head, and subsequently result in damaging hyperflexion or hyperextension of the cranio-vertebral junction.

The spinal cord is enclosed within the relatively hard spinal canal. The spinal canal varies in length and cross sectional area as a result of physiologic flexion, extension, lateral bending and axial rotation (White and Panjabi 1990). Anatomical studies by Yoo et al (1992) showed that extension and ipsilateral rotation significantly reduce the foraminal area. The spinal cord itself is supported and protected by surrounding soft tissue. Three membranes cover the spinal cord; the dura mater, the pia mater and the arachnoid. In the cervical and thoracic region dentate ligaments are formed by the pia mater on each side of the anterior and posterior roots. These ligaments transverse the subarachnoid and subdural spaces are fixed to the inner side of the dura (White and Panjabi 1990). The spinal cord, thanks to its structural design, is very flexible up to a certain limit and under very small pressure but changes suddenly and offers stiff resistance when an attempt is made to produce any further deformation (White and Panjabi 1990).

The intervertebral discs provide height and spacing for the vertebral column, offering spinal nerves a safe exit preventing injury and pressure from the mobile bony structures of the vertebral column. The discs are composed of a tough outer zone of collagenous fibers (annulus fibrosus) and an inner zone of dense white fibrocartilagious bundles arranged in concentric lamellae (nucleus pulposus). This pattern provides both mobility, strength and compressibility. The discs are adherent to the hyaline cartilage end plates which cover the vertebral body inferiorly and superiorly. The discs are also strongly adherent to the anterior and posterior longitudinal ligaments. The intervertebral discs are avascular and obtain their nutrition by diffusion from spongy bone through the end plates. In patients younger than 30 years the nucleus pulposus contains approximately 90% water and when they are in their eighties this percentage decreases to less than 70%. From the fourth through the fifth decade the nucleus pulposus in particular undergoes desiccation (Connell and Wiesel 1992).

13

The ligamentum flavum and the internal venous plexus are the only structures known not to be innervated; all other structures of the spine can be considered a potential source of pain (Stolker et al 1994). Free nerve endings have been demonstrated in capsules of facet joint (Jackson 1966), in the anterior and posterior longitudinal ligaments, and the annulus fibrosus (Jackson 1966, Yoshizawa et al 1980, Groen et al 1990) and nerve fibers as well as mechanoreceptors have been found in human cervical intervertebral discs (Mendel et al 1990) and facet joints (Yamashita et al 1990) fig 1. Nerve fibers containing Substance P have been found in the dura (Edvinsson et al 1983), facet joints (Grönblad et al 1991a, Ashton et al 1992), posterior longitudal ligament (Korkala et al 1985, Konttinen et al 1990) and in the intervertebral disc (Weinstein et al 1988, Coppes et al 1990, Palmgren et al 1996). Parke and Watanabe (1990) suggest that other neural structures, e.g. branches of the sinu-vertebral nerve may also be involved and even be ruptured by a herniated disc. Degenerative changes may stimulate or compress the sinu-vertebral nerve and since each nerve supplies several spinal segments, irritation at one location can cause symptoms in multiple areas (Xiuqing et al 1988).

The vertebral column is multisegmentally innervated except for the dorsal dura, which receives more or less monosegmental innervation (Groen et al 1988). This circumstance may also have therapeutic consequences and imply that pain projection and patterns are not specific and therefore insufficient in themselves for accurate diagnosis (Groen et al 1988, 1990, Gillette et al 1993).(fig 2)

14

NP = Nucleus pulposus, AF = Annulus fibrosus,VR = Ventral rami, SC = Spinal Cord, SVN =Sinu-vertebral nerve, ST = Sympathetic trunk

Fig 1 Innervation of the intervertebral disc (schematic drawing compiled from the literature)

15

ZJ

ALL = Anterior longitudinal ligament, PLL= Posterior longitudinal ligament,IVD = Intervertebral disc, ST = Sympathetic trunc, SG = Spinal ganglion, DR =Dorsal ramus (Spinal nerve), VR = Ventral ramus, MB = Medial branch of the dorsal ramus, SVN = Sinu-vertebral nerve, ZJ = Zygapophyseal joint

Fig 2 Innervation of the vertebral column (schematic drawing compiled from the literature)

16

Biochemical and cellular events

A number of articles have been published on the relationship between an increased production of eicosanoids and the pathogenesis of spinal cord injury since the mid­seventies (Jonsson and Danieli 1976, Mitsuhashi et al 1994). Animal experiments have shown that lesions as a result of whiplash injuries reveal similarities with those resulting from spinal cord injuries (Unterharnscheidt 1982, Jane et al 1985, Svensson1993). The mechanism of injury causes disturbances in cell membranes which, in turn, raise the Ca++ levels. The increased Ca++ levels rapidly depress cellular metabolism which leads to an accumulation of lactic acid, and, secondly, oxygen free radicals due to incomplete reduction of residual oxygen. Ca++ also activates the release of free arachidonic acid by the membrane lipase (phospholipases). Arachidonic acid is enzymatically converted to prostaglandins and leukotrienes, producing additional free radicals. Increase in prostaglandins and leukotrienes also directly causes secondary inflammatory reactions, oedema, ischemia and, eventually, cell death (Young 1992, Hall 1992, Ellis 1993). (fig 3). As a result of free radical-induced lipid peroxidation, which occurs within minutes after the injury, posttraumatic autodestruction of the spinal cord tissue may occur (Anderson et al 1985).

Recent observation by Saal et al (1990) of extremely high levels of phospholipase A2 ( the rate limiting enzyme in the production of prostaglandins and leukotrienes) enzyme activity within herniated disc tissue is quite interesting. It has earlier been suggested that nerves within the outer layer of the discs may become sensitised by some unknown stimuli, for example, locally produced inflammatory mediators, such as Substance P and Vasoactive-Intestinal Peptide (Weinstein et al 1988). Later research has proposed that prostaglandin release from sequestered discs and facet joints causes inflammatory reactions (Willburger and Wittenberg 1994, OT)onnell and OT)onnell 1996). Animal experiments have shown that injury to the intervertebral annulus causes secondary cellular reactions, similar to the process observed in human disc degeneration (Kääpä et al 1995).

Neuropeptides are known to affect the inflammatory process (Payan et al 1987) and stimulate the release of degradative enzymes (Lotz et al 1987). Measurable amounts of neurochemicals in the dorsal root ganglion, where neuropeptides are produced, can be altered by external manipulation of the disc by means of discography (Weinstein et al 1988). Neuro-chemical changes in the intervertebral discs could therefore be caused by injured annular nociceptors, and could to some extent be modulated by the dorsal root ganglion (Grönblad et al 1991b). Rydevik et al (1988, 1989) suggest that due to the vascular supply and tight capsule, mechanical compression of the ganglion may result in the release of neuropeptides from the dorsal root ganglion, which has been further

17

validated in later experimental models (Chatani et al 1995). This could cause progressive degeneration due to the stimulation of the synthesis of inflammatory agents and degradati ve enzymes (Grönblad et al 1991b), and subsequently intraneural oedema and pain (Rydevik et al 1989). All these results are based on studies on the lumbar spine.

In recent years it has become apparent that the nervous system and the immune system are not entirely independent of each other (Savino and Dardenne 1995, Wehling et al 1996). Various cytokines capable of inducing inflammation and the degrading of connective tissue are released in the vicinity of the nerve roots by macrophages and the antigen-presenting cells of the immune system. Those inflammatory cells can also produce chemotactic cytokines (monocyte chemotactic protein 1-alpha, macrophage inflammatory protein 1-alpha), which can recruit further inflammatory cells ( Haro et al 1996). The interleukins 1, 6, and 8 are also known to cause hyperalgesia in animals. Moreover, interleukin 1 is a causal factor in experimental radiculitis (Wehling et al 1996) and interleukin 6 has been demonstrated in herniated intervertebral discs (Kang et al 1996). Neuropeptides are related to the production of interleukin which complicates the interaction between the immune system and inflammatory mediators even further. Normally the CNS astrocytes do not only protect neuronal cells directly by inducing endothelial cell tight junction formation within the blood-brain barrier, but it also maintains the internal milieu by regulating the extracellular electrolyte balance. It may also regulate both the chemotaxis of infiltrating inflammatory cells such as leukocytes and macrophages, and the synthesis of leukotrienes, prostaglandins, numerous growth factors and cytokines (O'Brien et al1994).

18

TRAUMA^ f f f c | j l ^ f (

J§3 I Ö ^

Ca++

Phosholipase activation - • • ' ■ t .* - .*.v • ' / v v.* *. > v* * .. / Ö Corticosteroids

Depressed cellular metabolism

II Lactatic acidosis

tz^2> # o fI Lipid peroxidationlArachidomc Acid

Endoperoxide

NSAID*=fe

White blood cells

Hydroperoxide

Leukotriene

\Prostaglandins Thromboxane Prostacyclin

Platelet aggregation Vasoconstriction

*Chemical mediators m̂uauiiiiaiiun^ Oedema ^ Ischemia Cell death

* Cytokines, chemikines, histamine, bradykinin

Fig 3 Biochemical and cellular events subsequent to trauma, (schematic drawing compiled from the literature)

19

SYMPTOMS

Neck pain

Neck pain is the most common symptom after whiplash injury. Its incidence after whiplash injury has been reported to be as high as 98-100% (Hohl 1974, Norris and Watt 1983). The pain may be immediate, but it is generally delayed up to 24 hours (MacNab 1982) and it is often protracted (Croft 1995). In a study by Hildingsson and Toolanen (1990), 77 patients out of 93 complained of neck pain within 5 hours after the injury and 85 patients (91%) within 15 hours.

The pain is perceived over the back of the neck and is either dull and aching exacerbated as a result of movements, or sharp related to arm movements, especially above shoulder height.

There may be numerous factors contributing to this phenomenon. Tears in muscles and ligaments are a possible cause of pain, but if this was the case they would heal within weeks and result in loss of pain (Barnsley et al 1994a). Injuries to the zygapophyseal joints may disrupt the congruity of the joint surfaces, producing painful posttraumatic osteoarthritis. Haemarthrosis may also lead to inflammation and chronic post-traumatic synovitis with ongoing pain and joint damage. The intervertebral discs are avascular but innervated. Tears in annulus fibrosus are therefore unlikely to heal or might at best heal very slowly, and the process would be accompanied by an inflammatory reaction and pain. Whiplash patients with chronic head and neck pain could therefore well suffer from persistent disc injury or annular tear (Senter 1995).

Pain from epidural adhesions has been observed after spinal surgery but may also develop without previous surgery (Stolker et al 1994). A possible mechanism of injury might be tensile pressure on the dentate ligaments during flexion - extension as described by White and Panjabi (1990).

Headache

Headache is the second most frequently reported symptom after whiplash injury. Hohl (1974) observed complaints of headache in 72% of the patients, whereas Norris and Watt (1983) registered 66% in their study. The pain is usually sub-occipital or occipital, radiating into temporal or orbital regions.

A theory for the genesis of headache was put forward by Cailliet (1984) who suggested that spasm, injury, or inflammation of the muscles of the cervical spine or myofascial connections to the cranial periosteum occur subsequent to trauma. The greater and lesser occipital nerves may then be trapped and irritated within these structures. This may result in pain along the distribution of the nerve paths. Keith

20

(1986) described a small number of patients with a headache due to injury to the C2 ganglion and nerve. By contrast, Weinberger (1978) stated that the C2 root has not been injured in whiplash patients. Tamura (1989) reported that 40 patients suffered from Barré-Lieou syndrome (headache, vertigo, tinnitus and ocular problems) after whiplash injury. The underlying theory was that lateral disc herniation at C3/4 causes irritation of the nerve root which, in turn, communicates with the superior cervical ganglion of the sympathetic chain, resulting in symptoms related to the sympathetic nervous system. Headache could then be seen as a result of a spasm of the internal and external carotid vessels.

Injuries to the cervical sympathetic nerves in patients with post-traumatic headache following whiplash injuries have been documented ( Khurana 1995). The author advocated that the cephalic pain was mediated through the trigeminovascular system.

Trigeminal sensory impairment in patients with chronic disabling symptoms after whiplash injury has been reported, suggesting lesions of the brain-stem (Knibestöl et

al 1990).Bogduk (1986) concluded that afférents of the upper three cervical nerves terminate

in the cervical portion of the trigeminal nucleus, so that pain originating from this region could be referred pain to the distribution of the trigeminal nerve, due to injury to the upper cervical structures. In later studies Lord et al (1994) concluded that referred pain from the C2-3 zygapophyseal joint was the cause of headache in 53% of the cases with chronic pain after whiplash injury.

Another theory is that headache after whiplash injury are in some cases, a trauma induced vascular headache of the migraine type. The migraneous features appeared soon after the injury and the patients responded to treatment with propanolol, which supported this theory (Winston 1987).

Temporomandibular joint injury is still controversial and the problem of overdiagnosis is an acknowledged problem (Clark et al 1993). However, several authors regard temporomandibular disorders as the major cause of nondental pain in the orofacial region (Sharav and Benoliel 1993, Croft 1995).

Paraesthesia

A sensation of numbness and radiating pain in whiplash patients has been reported by several authors (Gay and Abbott 1953, Hohl 1974, Norris and Watt 1983, Pennie and Agambar 1991) but no convincing theory of its origin has yet been put forward. Hohl (1989) stated without any explanatory theory, that in whiplash patients arm pain and numbness are rarely caused by nerve root compression. Contrary to this Jónsson et al (1994) found in their study that protrusion of the disc was a major cause of radiating pain. In some cases the thoracic outlet syndrome has been proposed to be one

21

possible explanation resulting from compression of the lower cords of the brachial plexus (Capistrant 1986). Referred pain and paresthesia from the zygapophyseal joints is another possible cause proposed by Bogduk and Marsland (1988) and Dwyer et al (1990).

Dizziness, vertigo and visual disturbances

Vertigo and dizziness are often used synonomously and describe sensations such as spinning, swaying and sometimes severe vertigo on rotation of the head and loss of consciousness. These findings have been reported in many series of whiplash injuries (Pearce 1989, Dvorak et al 1989, Olsson et al 1990, Teasell and Shapiro 1993).

Pathophysiological explanations vary from vertebral artery injury resulting in vestibular dysfunction or vertebral nerve irritation producing a neurally mediated spasm due to the close relation between the sympathetic trunk and the vertebral artery (Bogduk 1986). More subtle disturbance of balance and equilibrium may result from the interference with proprioceptive information and postural reflexes from cervical afferents (Bogduk 1981, Hinoki 1985, de Jong and Bles 1986). Tamura (1989) suggested that vertigo might be caused by ischemia of the brain produced by sympathetic vasoconstriction of the internal carotid artery.

Chester (1991) reported a high percentage of patients with inner ear dysfunction following whiplash injury and leading to unsatisfactory control of balance. More recent research has shown similar findings (Rubin et al 1995). Oosterveld et al (1991) found abnormal ENG findings in whiplash patients as compared to normal controls, and further studies by Ettlin et al (1992) reported abnormalities in 10 out of 18 patients after otoneurological examination. This might be another piece of evidence of vestibular dysfunction, suggesting either a central or peripheral injury.

Visual disturbances mostly take the form of blurred vision and may be associated with retrobulbar pain. Other visual impairments may include photophobia and nystagmus. Hildingsson et al (1989a, 1993) demonstrated objective abnormalities of the oculomotor function in patients with chronic symptoms as well as in patients in the subacute phase following whiplash injury. In some cases with pronounced oculomotor dysfunction, lesions of the brain-stern might be a possible explanation, while in other patients with moderate oculomotor dysfunction it might be caused by an afferent proprioceptive dysfunction of the cervical spine (Hildingsson et al 1989a, 1993).

22

Cognitive symptoms

There are a number of retrospective studies indicating cognitive impairment. The impairment found in these studies involved attentional deficits mainly (Schwartz et al 1987, Olsnes 1989, Kiscka et al 1991, Radanov et al 1992). In one study memory dysfunction (Yarnell and Rossie 1988) was reported. Bohnen et al (1993) reported unsatisfactory information processing and memory function in two whiplash patients with central otoneurological abnormalities.

In a controlled follow-up study Radanov et al (1993) showed that all neuropsychological functions improved and became normal within 6 months. Somatic symptoms, i.e. pain, may also interfere with cognitive performance (Radanov et al 1992, Schwartz et al 1987). In studies by Yarnell and Rossie (1988) a CT and MRI investigation disclosed non-specific brain abnormalities in a few cases and later studies by Ettlin et al (1992) showed no abnormalities on the MRI in the acute phase. EEG examination has not proved any relationship between whiplash injury and impaired cognitive function (Shapiro et al 1993).

Radanov et al (1996) stated that impaired cognitive function relates to somatic or psychologic symptoms, and current research does not indicate that the higher cognitive functions are impaired after whiplash injury. However it is possible that our clinical, neurophysiological and radiological tests are still too crude. One study with single­photon emission tomography has been performed (Otte et al 1996). This study showed a bilateral parieto-occipital hypoperfusion in whiplash patients with cognitive impairment. Maybe future examinations with positron emission tomography (PET) or single photon emission computed tomography (SPECT) could contribute to an understanding of cognitive dysfunction and its possible relation to whiplash injuries.

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PATHOLOGY

Muscles

Muscle damage has been seen in animal experiments (MacNab 1966, Wickstrom et al 1967) but those findings could not be further validated in recent animal experiments by Svensson (1993). Muscle tears have also been visualised on ultrasound examination (Martino et al 1992). MRI investigations have not been able to verify any muscular damage (Borchgrevink et al 1995) so far, however.

Bogduk and Simons (1993) proposed that the trigger point of the neck overlies the cervical zygapophyseal joints and that the reported pain patterns of the cervical trigger points are identical with those of the referred pain from the zygapophyseal joints. However, no studies have shown any reliable data regarding the occurrence of trigger points and myofascial pain after whiplash injury (Barnsley et al 1994a).

Ligaments

Ligamentous injuries have been reported in animal experiments (MacNab 1966, Wickstrom et al 1967) in post-mortem studies (McMillan and Silver 1987) and peroperatively (Jónsson 1992). MRI has confirmed those findings within 4 months of the injury in a small group of mixed patients with hyperextension injuries and direct frontal head trauma (Davis et al 1991). Contrary to this, recent experimental (Svensson 1993) and clinical studies with scintigraphy (Hildingsson et al 1989b) and MRI (Jónsson et al 1994, Borschgrevink et al 1995) have not verified these findings. Thus it seems possible that lesions of the ligaments do exist, but that they are rather uncommon. One explanation to the divergent findings in earlier animal experiments might be that the animals were exposed to a more severe trauma, severe enough to result in the lesions described.

Discs

Injuries to the intervertebral discs have been reported in a number of studies. Animal experiments (Wickstrom et al 1967, LaRocca 1978) and peroperative findings (MacNab 1966, Jónsson 1992) all indicate lesions of the intervertebral discs. Separation of the disc from the vertebral endplate and tears in the annulus fibrosus have been visualised on the MRI (Davis et al 1991) and in a recent study disc abnormalities were found in 23% of the cases (Borschgrevink et al 1995). However, Boden et al (1990) concluded that disc pathology is a relatively frequent finding in asymptomatic patients (8 per cent herniated nucleus pulposus) and that such lesions are

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part of the normal ageing process of the spine. Watkinson et al (1991) studied a group of patients with significant symptoms 10 years after the injury. In that study all patients had developed degenerative changes on their X-rays, which might be an indication of the development of post-traumatic disc degeneration.

Zvgapophvseal hints

Several authors have claimed that the cervical zygapophyseal joints may be a source of neck pain (Okada 1981, Dory 1983, Wedel and Wilson 1985, Bogduk and Marsland 1988). Experimental data (Clemens and Burow 1972), animal experiments (Wickstrom et al 1967, LaRocca 1978), post-mortem (McMillan and Silver 1987) and peroperative findings (Jónsson 1992) have found lesions of the cervical zygapophy seal joints. Experiments in healthy volunteers have also shown that the cervical zygapophy seal joints can be a source of local neck pain and/or referred pain of the neck and shoulder (Aprili et al 1990, Dwyer et al 1990).

Spinai cord and neural tissue

In animal experiments Svensson (1993) showed that cervical spine trauma during whiplash injury causes damage to the neural structures through intraspinal pressure effects, and histopathological examination revealed membrane dysfunction in the nerve cells of the spinal ganglia. These lesions resemble those seen after spinal cord injury

(Ellis 1993).In animals sustaining a brief loss of consciousness but no sequel after acceleration-

deceleration non-impact injury. Histological examinations revealed degenerated axons in the inferior colliculus, pons and dorsolateral medulla (Jane et al 1985). According to the authors, this indicates a primary brain-stem locus for the concussion and concomitant damage to neural structures without direct head trauma. Experimental, clinical and histological examinations have verified lesions of the brain-stem (Unterharnscheidt 1982, Ettlin et al 1992, Serra et al 1994) as well as changes in the permeability of the blood-brain barrier (Domer et al 1979) after whiplash injury. Furthermore, oculomotor dysfunction similar to that observed in patients with brain­stem lesions has been described in acute as well as in chronic whiplash patients (Hildingsson et al 1989a, 1993, Oosterveld et al 1991) and seems to be accompanied by a less favourable outcome (Hildingsson et al 1993).

In animal experiments, acceleration injuries without direct head trauma have caused haemorrhage in and around the brain, brainstem and spinal cord (Wickstrom et al 1967, Ommaya et al 1968, LaRocca 1978). In humans, sub-dural hematomas (Ommaya and Yarnell 1969) and a raised total protein content and erythrocytes in

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cerebrovascular fluids (Ellertsson et al 1978) have been observed as a result of whiplash injury. EEG studies have revealed conflicting results. Torres and Shapiro (1961) and Gibbs (1971) reported EEG abnormalities in whiplash patients while Jacome (1987) failed to replicate these results.

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PSYCHOLOGICAL ASPECTS

Psychiatric illness produces pain, especially headache, sometimes (Merskey and Spear 1967, Sternbach 1968). Pain might be related to serotonin deficiency (Russel 1993) which is common also to depression and could be enhanced by affective disorders or other psychological disturbances (Walters 1961). Persistent pain, on the other hand may produce psychiatric symptoms as a phenomenon secondary to the injury itself (Merskey 1984, 1993).

Previous studies (Hodge 1971, Gorman 1974a,b, Blinder 1978) suggested that pre­existing personality traits or psychiatric problems might create or contribute to somatic symptoms after whiplash injury. Mayou et al (1993) found that whiplash patients scored significantly higher on the neurotic scale of the Eysneck personality inventory. Contrary to this, Radanov et al (1994) found no correlation between personality traits and the course of recovery from whiplash injury. Furthermore, Radanov et al (1991) concluded that psychosocial factors can hardly explain the recovery from whiplash injury. They also suggested that psychological and cognitive problems are rather a secondary phenomenon connected with the disease, and that whiplash injury can initiate a vicious circle, which may explain the secondary neurotic reaction in whiplash patients.

”Litigation neurosis”, a concept made popular by Miller (1961) in the 1960s has been refuted by several authors who say that it is not a significant factor of the outcome of persisting symptoms (Maimaris et al 1988, Watkinson et al 1991, Evans 1992b, Bohnen and Jolies 1992, Croft 1993). In a newly published report Swartzman et al (1996) found that litigation status did not predict post-injury employment status. According to the authors, this suggests that secondary gain does not influence the functionality of whiplash patients. Nor did litigation status affect pain-related disability

or psychological distress. Barnsley et al (1994a) stated that there is no real evidence that malingering for financial gain contributes in any significant way to the natural history of whiplash injury.

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TREATMENT AND PROGNOSIS

Increasing age, injury related cognitive impairment and the severity of initial neck pain have been found to predict persistent symptoms (Radanov et al 1991). However, it is possible that age is a confounding factor due to pre-existing degenerative changes (Barnsley et al 1994a). Norris and Watt (1983) concluded that the factors affecting the prognosis were the presence of objective neurological signs, stiffness of the neck and pre-existing degenerative spondylosis. The presence of objective neurologic deficits has also been associated with poor prognosis by other authors (Hohl 1974, Maimaris et al 1988, Hirsch et al 1988, Evans 1992b) and Radanov et al (1991) found that finger paresthesia was a predictive sign of the development of persistent symptoms.A relationship between the number of symptoms and signs and poor prognosis has also been reported by several authors (Gargan and Bannister 1990, Watkinsson et al 1991, Evans 1992b).

Contrary to these findings, Hildingsson and Toolanen (1990) found no early symptoms or signs of prognostic significance.

Symptoms persisting for more than two months indicated prolonged disability (Maimaris et al 1988) and Gargan and Bannister (1994) stated that the chronic state may be reached as soon as 3 months after the injury. Prolonged symptoms persisting for more than 6 months are to be considered chronic (Spitzer et al 1995)

Spitzer et al (1995) presented an extensive literature research and according to their findings few treatments have been evaluated from a scientifically rigorous point of view, and the treatments that have been scientifically evaluated bear little or no evidence of efficiency.

No studies on the effect of psychosocial intervention have been published (Spitzer et al 1995).

A controlled double-blind study demonstrated that patients mobilised early without cervical collar managed better; their pain decreased and their cervical motion improved (Mealy et al 1986). However, another prospective study (Pennie and Agambar 1991) demonstrated no difference between early active treatment with physiotherapy and rest in a collar and unsupervised mobilisation. Immobilisation with cervical collar may promote inactivity, which can delay recovery (Spitzer et al 1995). Teasell et al (1993) stated that continuous use for more than 2 weeks should be discouraged.

Randomised and controlled, attempts at treatment in the acute phase of injury addressing different physiotherapy modalities have shown no convincing advantages so far (Barnsley et al 1994a).

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Pharmacological intervention with analgesics and non-steroidal anti-inflammatory drugs combined with early mobilisation are effective for a limited period of time (Spitzer et al 1995).

Pulsed electromagnetic treatment has proved to have anti-inflammatory effects (Goldin et al 1981, Binder et al 1984) and in two clinical double-blind studies it was reported to have beneficial effects on acute whiplash injury (Foley-Nolan et al 1990, 1992).

Surgery for chronic neck pain has been of some benefit (DePalma and Subin 1965, Whitecloud and Seago 1987, Metzger et al 1989). Although there are few reports on the results of surgical treatment of patients with persisting symptoms after whiplash injury, there is general agreement that surgical treatment should not be recommended primarily. (Gotten 1956, DePalma and Subin 1965, MacNab 1971, Marshall 1976, Wickström and LaRocca 1977, Balia 1980, Spitzer et al 1995, Saal et al 1996). However, Jónsson et al (1994) reported good results after early surgical intervention.

Subcutaneous sterile water injections given to patients with chronic neck pain after whiplash injury have been reported to improve the cervical range of motion and to reduce reported pain (Byrn et al 1993). Although, a major limitation was that no control group was used.

Intra-articular steroid injections in the cervical zygapophyseal joints proved not to be effective as compared to local anaesthetics alone in a recent study on chronic pain after whiplash injury (Barnsley et al 1994b).

Localised occipital tenderness and pain in the area innervated by the greater occipital nerve may be indicative of occipital neuralgia and, in suspected cases, local injections of anaesthetics (Occipital nerve blocks) may produce temporary pain relief (Teasell et al 1993)

Cervical epidural steroid injections for chronic neck pain have given no better results than would be expected from placebo alone (Shulman 1986). Barnsley et al (1994a) stated that the use of cervical epidural steroid injections in whiplash patients is not very rational.

Percutaneous radiofrequency neurotomy of painful cervical zygapophyseal joints has been advocated but the data are limited and controversial (Lord et al 1995b).

To sum up, the treatment of chronic symptoms after whiplash injury seems rather unsatisfactory, and to date the real value of early treatment is also questionable.

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AIMS

The overall aim of the present study was to obtain more knowledge about whiplash injury and the pathophysiology of its genesis and to find a possible way of preventing disabling symptoms.

SPECIFIC AIMS WERE;

I To identify soft-tissue damage after whiplash injury and to evaluate the relationship between MRI findings and clinical symptoms and signs.

I I To evaluate the possible development of disc pathology and its relationship with chronic symptoms.

*> I I I To study the effects of discectomy and anterior cervical fusion in whiplashpatients with chronic symptoms.

IV To evaluate the relationship between persistent symptoms and personality traits and the predictive value of pre-existing personality traits during recovery from whiplash injury.

** V To evaluate the relationship between the width of the spinal canal measuredon radiographs and chronic symptoms after whiplash injury.

V I To evaluate the possible effectiveness of high-dose methyl-prednisolone in acute whiplash trauma.

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MATERIAL AND METHODS

DEFINITION

All patients included in this thesis were admitted to the Department of Orthopaedics, University Hospital of Northern Sweden, because of whiplash trauma caused by car accidents. Contacts were taken with the primary health care, ambulance personnel and staff at the emergency unit and the they were all informed about the aim of our study before each study began in order to minimise drop-outs. All types of car impact directions were included.

The inclusion criteria for acute whiplash trauma were initial neck pain and musculoskeletal signs and/or neurological sign(s) which have later been classified as grades II and III WAD (Spitzer et al 1995).

Patients with head injuries, unconsciousness, fracture or dislocation of the cervical spine, and a previous history of neck injury or neck pain were excluded.

All patients were treated indentically; a soft collar (Philadephia) for 1 to 2 weeks, physiotherapy and analgesics were prescribed in the same way for every patient. Return to regular activities was encouraged and recommended as soon as possible.

In patients considered as chronic the main symptoms were daily neck pain, headache and intermittent arm pain and numbness for six months or more.

All studies except for no III are prospective controlled studies. Studies no I, III, V and VI are based on a separate patient material. Study no II is a follow-up based on the same patient material as no I, and study no IV is based on study no VI and the latter part of no II.

SUMMARY OF MATERIAL AND METHODS

(I) M RI and neurology in acute whiplash traum a.

A prospective series of 39 cases was performed. The patients were initially examined at the emergency ward by an orthopaedic surgeon on duty and acute radiographs were taken of each patient. A neurological examination was performed the same day as the MRI investigation and without any knowledge of the MRI findings. An MRI was performed at a mean of 11 days after the injury and the results were evaluated by two radiologists who knew nothing about the patients' clinical status.

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(II) Disc pathology after whiplash injury.

A prospective two-year follow-up (n=39) was performed with repeated neurological examinations and a standardised questionnaire including VAS-scales and a pain sketch form for evaluation of the symptoms. An MRI investigation was performed at baseline and two years after the injury.

(III) Surgery for chronic symptoms after whiplash injury.

Twenty patients with a history of disabling neck pain for a mean of seven years were examined by an independent observer four years after the discectomy and anterior cervical fusion. An indication of surgery was persistent headache, neck and radicular pain where symptoms and clinical findings were in agreement with the radiographic findings.

(IV) Can personality deviations explain the persistence of symptoms after whiplash injury ?

The prospective cohort study included 70 patients divided into two groups. The first group comprised 40 patients who all completed the Temperament and Character Inventory (TCI) within 8 hours after the injury. In the second group (n=30) the TCI was filled in at the two-year follow-up.

Controls were recruited from a random population survey, where all participants were subjected to an extensive medical, psychiatric and neuropsychological examination.

(V) Decreased width of the spinal canal in patients with chronic symptoms after whiplash injury.

We evaluated 48 consecutive patients from a series of 132 patients. Twenty-four patients had persistent symptoms after 12 months, while 24 patients had recovered completely. All measurements were made from standard lateral radiographs with a graphic digitizer connected to a microcomputer. Multivariate analysis of variance was used to evaluate any association between gender, remaining symptoms at the follow- up and the recorded values of the width of the spinal canal.

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(VI) High-dose methyl-prednisolone prevents extensive sick-leave after whiplash injury.

A prospective randomised double-blind study of high-dose methyl-prednisolone as compared to placebo was performed (n=40).

A clinical follow-up with repeated neurological examinations and a standardised questionnaire including VAS-scales and a pain sketch form was used for the evaluation of symptoms initially before drug administration and at the follow-ups at 2 weeks, 6

weeks, and 6 months after the injury.Psychological examinations were performed the same day as the injury occurred.

The TCI personality inventory was used for this.Disabling symptoms, severe enough to make the patients unable to return to work,

number of sick-days before and after the injury, and sick-leave profile after the injury were used as parameters for the evaluation of the effects of the treatment. Baseline demographic data were controlled as for when the statistical analysis had been performed.

The sealed document containing the numbered sets of active/placebo substance which had been filed by the hospital pharmacist, was opened when the last patient in the study had attended the 6-month follow-up.

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RESULTS

(I) MRI and neurology in acute whiplash trauma.

We found a larger proportion of pathologic intervertebral discs in whiplash patients than earlier findings have reported regarding asymptomatic subjects without neck injury. Twenty-five per cent had disc herniations in our series. No ligament ruptures or bleedings were found. However, in one patient a muscle damage was seen initially but at a later control classified as muscle oedema.

We found no general correlation between pathologic findings on the MRI and the neurological deficits in the acute phase. Three patients with disc herniations suffered from segmental radicular pain and impaired sensitivity to an extent that corresponded to the affected level.

(II) Disc pathology after whiplash injury.

We found 13 patients (33 %) with disc herniations with medullary (six cases) or dura (seven cases) impingement during the two-year follow-up. The majority of the disc herniations were at the C4-6 levels. At the follow-up all the patients with medullary impingement had persistent or increased symptoms, while three (eleven %) out of 27 patients with no or slight changes on the MRI had persistent symptoms. One patient showed a spontaneously reduced disc herniation and had no symptoms at the 6- week follow-up nor at the 2-year follow-up. Two patients had deteriorated and demonstrated moderate to severe changes and one patient had gone from slight changes to severe changes. They all had persistent and increased symptoms as compared to one patient out of 14 without disc pathology.

No ligament injuries were detected.No correlation was found between patients" age, gender, or car impact directions

and MRI abnormalities.

(III) Surgery for chronic symptoms after whiplash injury.

At the follow-up eleven patients had reduced headache and neck pain while nine remained the same. Paresthesia had improved in six and radicular pain in three patients. No improvement regarding vertigo, visual and auditory symptoms was seen. Based on the criteria presented by Robinsson et al (1962), and White et al (1973) concerning the evaluation of surgical results, two patients showed good, nine fair and nine poor results.

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(IV) Can personality deviations explain the persistence of symptoms

after whiplash injury ?

We found that the whole whiplash patient group (n=70) showed no psychological abnormalities when compared to normal controls. Furthermore, we found no major differences between the two whiplash groups examined in their acute phase and at the 2-year follow-up. Complete recovery after whiplash injury correlated to a personality profile consisting of a temperament profile of low HA (Harm Avoidance), high RD (SReward Dependence), and high NS (Novelty Seeking). Moreover, we found that patients with moderate symptoms after injury scored lower on HA (Harm-Avoidance) and higher on RD (Reward Dependence) than the controls.

(V) Decreased width of the spinal canal in patients with chronic symptoms after whiplash injury.

The multivariate test including all measured cervical levels (C2-C6) showed a significantly smaller sagittal diameter in symptomatic patients (p=0.032), also when the diameter was related to the size of the vertebral body (Torg ratio). A significant difference was found between men and women at most levels (p=0.001), with larger values in men.

In a separate multivariate test, based on the measurements of each segment, significant differences between symptomatic and non-symptomatic patients were found as for the second cervical level (p=0.003), the fourth cervical level (p=0.029), the fifth (p=0.015) and the sixth cervical level (p=0.02). On the third cervical level no difference was found.

(VI) High-dose methyl-prednisolone prevents extensive sick-leave after whiplash injury.

At the 6-month follow-up there was a significant difference between the actively treated patients and placebo concerning disabling symptoms (p=0.047), defined as inability to return to previous work, number of sick-days (p=0.0097) and sick-leave profile (p=0.003). Four of the 19 patients in the placebo group were still on sick-leave and all four complained of multiple symptoms including continuous neck pain. One patient had multiple symptoms and chronic neck pain but was able to work part time. One patient did not attend the follow-up. All the actively treated patients had returned

to work and none had multiple symptoms but three complained of intermittent neck pain.

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GENERAL DISCUSSION

The following discussion is based on the separate papers presented in numerical order I-VI, but angled at the connecting thoughts of this thesis and therefore not traditionally strictly by its titles.

This part focuses first on the possible role of soft-tissues, especially intervertebral discs and their part in the whiplash syndrome. Then follows a discussion about whether or not there is evidence of developmental deterioration in disc pathology and its possible correlation with chronic symptoms. If so, is surgery a practicable way of treating whiplash patients? Further discussion focuses on personality traits: do they play a major part in the recovery after whiplash injury, or could there be different anatomical conditions which can explain why some patients recover while others do not? Finally, is it possible that the whiplash syndrome is a result of lesions in neural structures and of post-traumatic degenerative changes and can it then be treated?

Are soft-tissue lesions detected with the MRI correlated to symptoms and signs ? ( I )

In patients with whiplash injury neurologic deficits have been taken to indicate prolonged disability by several authors (Hohl 1974, Maimaris et al 1988, Radanov et al 1991, Evans 1992b). However there are few prospective studies which present objective neurologic deficits in the acute phase (Norris and Watt 1983). Contrary to earlier reports, but in accordance with a recent report by Ettlin et al (1992) we found in our study that the majority of our patients had discrete neurological deficits at the clinical examination in the acute phase. The difference may be explained by our early examination as well as by the discrete neurological findings which could be overlooked at a routine examination in the emergency ward. It is also well known that clinical examinations could be biased even though strictly matched protocols and inclusion criteria are followed as was the case in our study. In order to prevent interobserver variability one of the authors examined all the patients. This may be another source of bias, due to the risk of repeated misinterpretation.

Injuries to intervertebral discs and other soft-tissue injuries have been suggested to explain the symptoms and physical findings after whiplash injury. In our study disc herniations were seen in 25% of the patients. No ligament rupture or other significant soft-tissue injuries were seen, which is in agreement with earlier experimental and clinical studies (Hildingsson et al 1989b, Svensson 1993, Jónsson et al 1994, Borchgrevink et al 1995), but contrary to earlier classic animal experiments (MacNab 1966, Wickström et al 1967). One explanation is that the animals in the earlier experiments were exposed to a more severe trauma. However, although two

36

radiologists did a first reading separately and then a second reading together to obtain consensus in all cases, there is a risk of misinterpretations and thus of which could affect the results of our study. Furthermore, it is possible that a mean period of eleven days (4-15), from injury to examination, is too long a time to detect some soft-tissue lesion on the MRI.

No correlation between the pathologic MRI findings and the neurologic deficits was found except in three patients with disc herniations that had segmental radicular pain and impaired sensitivity corresponding to the affected level. These results support earlier findings, i.e. arm pain and numbness are caused by mechanic compression of neural structures caused by disc herniation in only a few cases (Hohl 1989). Another point to be noted is the relatively large proportion of disc herniation in asymtomatic subjects without neck injury (eight %), (Boden et al 1990), which could complicate the clinical picture. Recently it has also been suggested that significant disc tear often escapes MRI detection (Schellhas et al 1996). The substantial overlap in the innervation of the spine implies that pain projection and patterns are not specific which could cause diagnostic problems. Hirabayashi et al (1991) also pointed out the discrepancy between clinical symptoms and the affected level of the cervical spine. Another confusing factor is referred pain and rhizopathy which could emanate from the zygapophyseal joints (Bogduk and Marsland 1988) and which are not possible to detect on the MRI (Fletcher et al 1990). However, we found that if no neurologic deficits and pathologic MRI findings were presented initially, the risk of developing chronic symptoms seems limited. This finding indicates that it is, to some extent, possible to estimate the severity of the injury in the acute phase.

Post-traumatic disc pathology - relating to chronic symptoms ? ( I I )

Although some studies have reported pathological MRI findings after whiplash injury, no prospective follow-up study has, to our knowledge, been published. To identify initial soft-tissue damage after whiplash injury and development of disc pathology and its relationship with clinical findings, a prospective MRI study was designed. Our findings of a total of 13 patients (33 %) with disc herniations graded moderate to severe (grades 2 to 3, with dura and medullary impingement, respectively) pointed to a frequency higher than the frequencies recently reported after MRI examinations of patients with a history of whiplash injury (Jónsson et al 1994, Borchgrevink et al 1995). The majority of disc herniations were at the C4-6, which is in agreement with an earlier statement that these are the most stressed segments (Jackson 1977, McKensie and Williams 1971).

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Among the patients demonstrating severe changes (grade 3) on the MRI initially and at the 2-year follow-up, all but one had persistent or increased symptoms which correlated with the deteriorated intervertebral discs detected on the MRI. The patient who showed a spontaneously reduced disc herniation had no symptoms at the 6-week follow-up, nor at the 2-year follow-up. Our findings suggest that disc herniations can deteriorate with time from slight and moderate to severe changes with medullary cord impingement. This deterioration might be a first sign of post-traumatic disc degeneration. Our findings as well as recent suggestions by Hamer et al (1993) indicate that there seems to be a connection between whiplash injury and of the cervical disc disease. Earlier studies indicating post-traumatic changes were based on plain X- ray evaluation and can therefore not be compared to our results (Watkinson et al 1991). However, it is possible that a 2-year follow-up time is too short for detection, though

The normal age-related degeneration of the intervertebral disc described by Buckwalter et al (1995) may be accelerated by a trauma to the cervical spine. Experimental studies on sheep revealed annulus rim lesions in which only the outer third part of the annulus showed a capacity to heal and a partial separation of the disc caused early degeneration (Osti et al 1990). Tear in annulus fibrosus has been detected on the MRI in a series of mixed cases of direct frontal head trauma and hyperextension injuries (Davis et al 1991). Recent experimental studies suggest that injury to the annulus causes secondary cellular reactions in the nucleus pulposus, similar to the process observed in human disc degeneration (Kääpä et al 1995). Further studies have shown that biochemical mediators of inflammation that be involved in the biochemistry of disc degeneration and the patophysiology of radiculopathy (Kang et al 1996, Virri et al 1996, Habtemariam et al 1996). In conclusion it can be said that it seems that biomechanic forces give rise to structural changes within the intervertebral discs, which may subsequently lead to degenerative changes and chronic pain.

Our theory is that trauma to the cervical spine results in degenerative disc disease and this is one contributing factor in the development of chronic symptoms after whiplash injury, even though the aetiology of the different symptoms seems multifactorial.

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Can patients with chronic symptoms after whiplash be cured with surgery ? ( I I I )

Patients with chronic neck pain have been subjected to surgery with varying results. Surgical treatment of whiplash injuries has not been recommended due to the relatively poor outcome as compared to surgery to cure patients with chronic neck pain and cervical radiculopathi (Bohlman et al 1993). Contrary to this, Jónsson (1992) reported very good results in a series of 10 patients who underwent early surgical treatment.

Anterior cervical fusion in patients with chronic pain after whiplash injury produced unsatisfactory results. However, it is important to point out that our study was retrospective and uncontrolled. Subjective headache and neck pain had diminished in about half of the cases, while radicular pain, vertigo, and visual and auditory symptoms remained more or less unchanged. With regard to the good results reported by Jónsson et al (1994) our results may be taken to indicate that the time interval between injury and treatment is important to the outcome. Early surgical intervention may interfere with the repair and remodelling stage described by Croft (1995) and prevent patients from entering the chronic phase accompanied by degenerative changes. It is also possible that disc herniations in asymptomatic patients (Boden et al 1990) may account for some cases with an excellent outcome after early surgical intervention. In spite of extensive diagnostic evaluation it is difficult to identify the

painful segment (Study no I). Since the vertebral column is multisegmentally innervated, this may also have therapeutic consequences. Other structures such as the zygapophyseal joints have by several authors (Barnsley et al 1994a) been assumed to be a major cause of neck pain, and referred pain and paresthesia may emanate from the zygapophy seal joints (Dwyer et al 1990) or the plexus brachialis (Capistrant 1986). This could clearly interfere with our results after surgery as well as with the results of others. To date, cervical zygapophyseal joint pain has been evaluated by means of diagnostic blocks. However, falsely positive diagnostic blocks as well as placebo response are a source of error (Silvers 1990, Wall 1992, Lord et al 1995a), and, as mentioned earlier, the vertebral column is multisegmentally innervated. This may necessitate multilevel blockades and consequently produce additional diagnostic problems (Stolker et al 1994). All these results could interfere with the diagnostic evaluation of patients with neck pain and paresthesia and consequently also with the reported results after surgery. In the light of these facts it is important to stress that pathological MRI findings, for example, must be strictly matched with clinical signs and symptoms before any decision regarding surgical treatment is considered.

In study no II, two patients underwent early surgery (discectomy and anterior fusion) due to clinical and radiographic signs of nerve root compression. A solid anterior fusion was achieved in both patients. They improved as for arm pain and neck pain but cognitive impairment, vertigo and headache remained the same. This

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experience of surgical intervention in the acute phase after whiplash injury may imply a more complex relationship between the variety of symptoms and the pathophysiology of whiplash injury.

Personality traits - an explanation to persistent symptoms ? ( I V )

The importance of psychosocial factors to behaviour during illness is widely recognised. Especially two factors are thought to be related; negative affectivity (e.g. anger, guilt, fearfulness, depression) and neuroticism (Costa and McCrae 1987).

We found that the whole whiplash patient group revealed no psychological abnormalities compared to normal controls. However, the patients who recovered completely and the patients with remaining moderate symptoms at the follow-up scored significantly lower on both the higher and the lower order dimensions of HA (Harm avoidance) than normal controls, which indicates that they are less neurotic. These findings contradict earlier studies on selected cases after whiplash trauma (Berstad et al 1975, Mayou et al 1993). The divergent findings might simply be due to the fact that our work was based on a prospective series of non-selected cases. No correlation between persisting symptoms in general and personality traits was found. In a recent study Wallis et al (1996) stated that the psychological profiles and pain intensity ratings in patients with chronic symptoms after whiplash injury did not differ from those of patients suffering from rheumatoid arthritis and low back pain of organic origin. Our results indicate that patients with moderate symptoms after whiplash injury are more sensitive to rejection, afraid of being ignored and more eager to discuss their emotional status and symptomatology with others. It is possible that our findings regarding minor personality deviations in patients with moderate symptoms may, to some extent, be explained by their pain profiles (Wallis et al 1996). No major differences were found between the two whiplash groups examined acutely and at the 2-year follow-up. Thus no time aspect or development of personality deviations seems to be involved, which may explain the persistence of symptoms as a secondary phenomenon related to whiplash injury as has earlier been proposed (Merskey 1984, 1993, Radanov et al 1994).

The conclusion we drew was that there is no relationship between specific personality traits and persistent symptoms after whiplash injury, even though a temperament profile of low HA (Harm Avoidance), high RD (Reward Dependence) and high NS (Novelty Seeking) seems to correlate with complete recovery. This profile correlates with the development of a more mature personality (Cloninger and Svrakic 1994). It is possible that this could affect recovery in a positive direction and help the patient to cope with his situation after whiplash injury.

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Different anatomical conditions - another conceivable cause ? ( V )

A narrow sagittal diameter of the cervical spinal canal has correlated with neurologic deficits in degenerative conditions and after fractures (Edwards and LaRocca 1983,

1985, Eismont et al 1984, Matsuura et al 1989, Kang et al 1994).The sagittal diameter measured on lateral radiographs correlates accurately with

measurements on the CT (Herzog et al 1991). This technique is also easily applicable in the cervical spine. Matsuura et al (1989) concluded that it is not the total volume of the spinal canal that is the critical factor; it is the shape. They also found that either the sagittal or the transverse diameter of the spinal canal could be used even though the ratio between the two measurements produces a more reliable discriminator, although this requires computerised tomography.

In our study, we found a significantly narrower spinal canal in patients with persistent symptoms after whiplash trauma. In combination with a further reduction of the foraminal area where the cervical spine is subjected to ipsilateral rotation and/or hyperextension during whiplash trauma this may result in abnormal strain in the spinal cord and nerve roots. In an anatomical study, cervical extension and ipsilateral rotation were found to generate nerve compression and even neural injury because of a reduced foraminal area (Yoo et al 1992). Neck extension also increased the intraspinal pressure and correlated with a reduced foraminal size after cervical spine motion as noted by Yoo et al (1992) (Farmer and Wisneski 1994). Later experimental studies have verified that the volume of the spinal canal decreases with an increasing extension angle (Holmes et al 1996). Furthermore, Sturzenegger et al (1994) reported that rotated head position at the moment of the impact was a feature of accident mechanism associated with more severe symptoms after whiplash injury. Several animal and clinical studies have shown that trauma to the cervical spine might cause injuries to the spinal ganglia, brain-stem and other neural tissues (Unterharnscheidt 1982, Jane et al 1985, Hildingsson et al 1989a, Oosterveld et al 1991, Ettlin et al 1992, Serra et al 1994, Otte et al 1996). Trauma to the cervical spine during whiplash injury increases the flow velocity of the spinal fluid above the physiological levels and causes injuries to the spinal structures through transient pressure effects. Histological examination revealed membrane dysfunction in the spinal ganglia (Svensson 1993) which may lead to degenerative processes and autodestruction and subsequently to persistent symptoms. A narrow spinal canal could theoretically enhance these pressure effects.

In a separate multivariate test of each cervical segment we found a significant difference on the second, fourth, fifth and sixth cervical levels but not on the third level, findings similar to those presented by Matsuura et al (1989) in patients with an injured spinal cord. Biomechanical studies indicate that there seem to be two cervical

41

areas at risk; the cranio-vertebral junction (CO-2) due to hypertranslation (Penning 1992b) and the C4-6 due to hyperextension/flexion (McKenzie and Williams 1971, Jackson 1977). A combination of biomechanical forces applied to these cervical areas at risk during whiplash trauma and a narrow spinal canal, may be unfavourable and result in soft tissue lesions.

Whiplash injury - a result o f minor lesions o f the central nervous system and post- traumatic degenerative changes ? ( V I )

Whiplash injury may result in lesions of the intervertebral discs, the zygapophyseal joints or the central nervous system as has earlier been mentioned. These lesions, secondary to the mechanism of trauma, are believed to cause disturbances in the cell membranes and induce activation of membrane lipases, which causes an increase in arachidonic acid, prostaglandins and leukotrienes. These cellular and biochemical events, subsequent to trauma, may, in turn, lead to secondary inflammation, oedema, and ischemia.

Lesions of the intervertebral discs have been detected on the MR! after whiplash injury (Davis et al 1991, Jónsson et al 1994). These damaged discs could release inflammatory mediators (Willburger and Wittenberg 1994). Biochemical mediators of inflammation which may be involved in the process of disc degeneration, facet joint osteoartritis and the patophysiology of radiculopathy, could also be mediated by means of neuropeptides released from the dorsal root ganglion due to mechanical factors, e.g. disc herniations. Impaired nerve function, axonal injury and primary Schwann cell damage have been observed after epidural application of the autologous nucleus pulposus. These observations show the complexity of the biochemically induced nerve fiber lesions in connection with disc herniation (Olmarker et al 1996).

The cervical zygapophyseal joints have been considered a common source of neck pain after whiplash injury (Barnsley et al 1995). Underlying causes are believed to be degenerative changes initiated by the trauma. Based on these hypotheses, treatment with intraarticular injections of corticoids has been investigated but this offered no other therapeutic benefit than did local anaesthetics alone (Barnsley et al 1994b). However, the study consisted of only chronic cases and can thus not be compared to intervention in the acute phase.

Since whiplash injury in many ways differs from spinal cord trauma it is not possible to compare results because of differences regarding outcome, severity of trauma, concomitant head injury etc. On the other hand, our theory is that there are similarities regarding pathophysiology and biochemical events, which makes a comparison interesting. Clinical and animal studies have verified lesions of the neural structures, especially in the brain-stem region, after whiplash trauma (Domer et al

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1979, Unterharnscheidt 1982, Oosterveld 1991, Ettlin et al 1992, Svensson 1993, Hildingsson et al 1993, Serra et al 1994, Örtengren et al 1996).

Our hypothesis is that chronic symptoms after whiplash injury are not only of musculoskeletal origin but could also emanate from the central nervous system. Thus, patients with multiple symptoms including persistent neck pain, dizziness, paraesthesia and cognitive impairment may have a lesion of the central nervous system contrary to monosymptomatic patients with intermittent neck pain.

Experimental studies have shown the neuroprotective effect of methyl-prednisolone (Olmarker et al 1994) in addition to its potent anti-inflammatory effect. Other studies reported that glucocorticoid steroids given soon after spinal cord injury improved recovery (Hall 1992, Ellis 1993). A clinical multicentre trial showed significant neurologic improvement after treatment with high-dose methyl-prednisolone within 8 hours after spinal cord injury (Bracken et al 1992, Ducker and Zeidman 1994).

High-dose methyl-prednisolone treatment interferes with many biochemical mechanisms. The pharmacology of methyl-prednisolone is complex and not fully understood (Hall 1992). In high doses it is believed to be antioxidative and to block the activation of phospholipases, and it may also restore the calcium balance over the cell membrane (Olmarker et al 1994, Ducker and Zeidman 1994). Furthermore, methyl-prednisolone may also decrease inflammation by stabilising the leucocyte- lysosomal membranes, preventing the release of destructive hydrolases, inhibiting macrophage accumulation in inflamed areas and oedema formation (Braughler and Hall 1982, Ellis 1993).

It is tempting to conclude that trauma to the cervical spine during whiplash injury causes lesions of the central nervous system as well as adjacent structures such as the intervertebral discs and zygapophyseal joints with concomitant inflammatory reactions, which may subsequently lead to a plethora of persisting symptoms. Therefore it should be susceptible to treatment in the acute phase with a highly effective anti­inflammatory drug. In agreement with earlier experimental and clinical studies as well as with our reported results it seems probable that whiplash injury causes lesions of and initiates a degenerative process in several structures, which gives rise to multiple symptoms that cannot be cured with conventional therapies.

From the results of our study we conclude that acute treatment with high-dose methyl-prednisolone was beneficial to the prevention of disabling symptoms after whiplash injury. However, the number of patients in our study is small, so further controlled prospective studies are needed. In the light of these circumstances and as things stand we cannot recommend this treatment until further studies have verified our results. Then there is the problem involved in the selection of patients who could benefit from this treatment that must be weighed against the cost of providing intensive treatment for a large number of patients who sustain an acute whiplash injury.

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CONCLUSIONS

I In 25 per cent of the patients disc herniations were detected on the MRI, but no ruptures of ligaments, muscles or bleedings could be visualised. No correlation between the pathologic MRI findings and the initial neurologic deficits was found.

II Disc pathology detected on the MRI seems to be one contributing factor inthe development of chronic symptoms after whiplash injury.

III Our results after discectomy and anterior cervical fusion in patients with chronic symptoms after whiplash injury were not very satisfying.

IV We found no relationship between pre-existing personality traits and persistent symptoms after whiplash injury. In our study, whiplash patients showed no psychological abnormalities when compared to normal controls.

V The spinal canal was significantly smaller in patients with persistent symptoms, which indicates that a narrow spinal canal is unfavourable in victims of whiplash injury.

** VI In our prospective randomised double blind study, acute treatment with high-dose methy 1-prednisolone, was beneficial to the prevention of disabling symptoms after whiplash injury.

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ACKNOWLEDGEMENTS

I would like to express my sincere gratitude to:

Christer Hildingsson and Göran Toolanen, my tutors for guidance through the academic world.Lars-Ake Broström, Professor, for constructive criticism during the revision of my

thesis and for providing working facilities.Sven Friberg, Associate Professor, Head of the Department of Orthopaedics, for encouragement, personal support, and valuable views and for providing working facilities.Johan Kärrholm, Associate Professor, my co-author and colleague, for pleasant co-operation and constructive criticism during the preparation of my thesis.Håkan Dahlström for personal support and encouragement and for introducing me to orthopaedic surgery.Göran Algers, Markku Fagerlund, Jan Björnebrink, P-O Nylander, Paul Schiette, Rolf Adolfsson, and Sven Brändström, my co-authors for fruitful co-operation.Olle Carlsson, Associate Professor, for statistical advice and calculations, and for taking a lot of personal interest in my project.Clas Backman for personal support and encouragement.Ulla-Stina Frohm for a very good job, and for her wonderful temper.Margareta Nilsson, for keeping the patient lists in order.All staff at the Orthopaedic policlinic, nursing ward II and the emergency unit, for all their help throughout my study.All the patients, who have patiently tolerated all the examinations, without which I would never have been able to carry out my project.

Financial support was provided by the Faculty of Medicine, Umeå University, the National Societies for Aiding Traffic Accident Victims and Polio Victims, Trygg- Hansa Insurance Company, the Swedish Association for Persons Disabled by Traffic Accidents or Cancer, and Samverkansnämnden.

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