"Whiplash, a controversial posttraumatic disorder", lezing gegeven door Leo Geeraedts oktober 2015...

Whiplash, a controversial posttraumatic disorder

Mrs Dr Liliana SugihartoFounder of the Atma Jaya

Anatomy MuseumJune 5, 1995

Presentation by

Leo MG Geeraedts srMD, PhD, anatomist and neuroscientist (ret.)Radboud University Medical Center,Nijmegen, The Netherlands.Board member of the Dutch Whiplash Foundation

Presentation for

Atma Jaya Medical Faculty,On the occasion of the 20th anniversary of the Atma Jaya Anatomy Museum,Jakarta, Indonesia

October 28, 2015


Chronic whiplash is not only a neck disorder but often

also a brain disorder 2011

I. What is whiplash?A. ImpactB. Whiplash mechanismC. Whiplash injuriesD. Whiplash-associated disorders

II. Why is whiplash so controversial?A. Problems in diagnosisB. Persistent prejudicesC. Causes for controversy

III. New evidence for the diagnosis whiplashA. Chiari type I malformationB. Cervical facet mediated painC. Elevated inflammatory biomarkers and focal

tissue inflammation D. Trigger pointsE. Fatty infiltratesF. Cervico-ocular reflexG. Cerebrospinal fluid leakH. Sleep disturbancesI. MRI of alar ligaments

IV. Recent knowledge about whiplash painA. Definitions of painB. Pain perceptionC. Nociceptive versus neuropathic painD. Central sensitization

V. Conclusions

Contents of presentation2/44


The definition of whiplash according to the Quebec Task Force on Whiplash-Associated Disorders (Spitzer et al, 1995) is frequently used:

“Whiplash is an acceleration-deceleration mechanism of energy transfer to the neck. It may result from rear-end or side-impact motor vehicle collisions, but can also occur during diving or other mishaps. The impact may result in bony or soft-tissue injuries (whiplash injury), which in turn may lead to a variety of clinical manifestations (Whiplash-Associated Disorders).”

So, there is:A.An impact or motor vehicle collision, that causes:B.A whiplash mechanism, ie. a ‘lash of a whip’-like movement of head and neck that causes:C.One or more whiplash injuries, ie. lesions in the head and neck region, that causes:D.Several Whiplash-Associated Disorders, =WAD; =postwhiplash syndrome, ie. the patient’s complaints

A – D = ‘sequence of whiplash events’

I. What is whiplash?3/44

Rear-end collisions are the most significant cause of whiplash (Caillet 2006)

Car collision is often (85%) a low velocity rear-end car collision (∆v < 15 km/h):Acceleration of the struck vehicle (target vehicle) and occupant(s): often whiplashDeceleration of the striking vehicle (bullet vehicle) and occupant(s): often no whiplash (Croft 2009)

Other impacts are: blow to the head, fall on the head, explosion blast, head penetrating bullet, shaking of baby

Note 1: There is lack of relationship between target vehicle damage and occupant injury (Chiro-Trust.org 2014; Croft et al., 2005)

Note 2: The often cited fact that a ∆v < 10-15 km/h is unlikely (Castro et al., 1997) to result in a significant whiplash injury, is only a myth (Davies, 1998; Freeman 2015)

Whiplash, a controversial posttraumatic disorderI. What is whiplash?

A. Impact

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B. Whiplash mechanism

What happens to the occupant in the target vehicle during rear-end impact?

Note 1: Impact causes forward acceleration of target car and its seat back. Seat back forces occupant’s thorax forwards, inducing an acceleration of the head and neck complex via inertial loading mechanism. The cervical spine compensates for the differential motion between the head and thorax by developing a transient non-physiological S-shape (Siegmund, 2002; Stemper et al., 2011)

Note 2: Occupant’s head is exposed to acceleration forces that are about 2,5 times greater than the acceleration of the target vehicle

Acceleration curves recorded during a rear-end impact trial (∆v = 7,5 km/h) together with the EMG signal. Car: acceleration of passengers compartment; Chest: peak thorax acceleration; head: peak head acceleration (Meyer et al., 1998)

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Movements of a fresh cadaveric cervical spine mounted on a acceleration (2,5, 4,5, 6,5, 8,5 g) producing whiplash apparatus; high speed cinematography (Grauer et al., 1997; Panjabi et al., 1998)

NP: neutral position; crash duration is 175 milliseconds50-75 ms: transient, non-physiological S-shaped curvature of cervical spine with hyperflexion in upper cervical spine and hyperextension in lower cervical spine; potential injury

phase100-125 ms: C-shaped curvature of entire cervical spine with extension within the physiological

range; lesions less likelyCervical muscles: minimal reaction time for an unwarned victim to develop sufficient muscle force to

brace (stabilize) the cervical spine is approximately 200 ms; so, a protecting muscular brace will be too late


B. Whiplash mechanism

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C. Whiplash injuries

Anatomical sites within the neck showing macroscopical and microscopical lesions; they have been described and photographed in:

Post-mortem studies after fatal car accidentsCrash studies on cadaveric C-spinesAcceleration studies with intact human cadaversExperimental neck injury studies in primates, goats and rats

Most of these experimental whiplash lesions are undetected (!) by conventional imaging (plain radiographs, CT, MRI) (Yoganandan et al., 2001; Taylor, 2002; Siegmund et al., 2009; Curatolo et al., 2011; Uhrenholt et al., 2011; Elliott, 2011; Yoganandan et al., 2013)

Biomechanical evaluation of a cadaveric cervical spine

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Question: are there similar lesions in whiplash patients?Answer: there is few objective MRI evidence for soft tissue lesions in whiplash patients

Anatomical sites of whiplash lesions

Macroscopical and microscopical pathoanatomical lesions

1. Facet joints Synovial fold contusion, capsular avulsion, subchondral fractures, bleeding

2. C-spine ligaments Tears or complete rupture

3. Intervertebral discs Tears in anterior anulus, avulsion of disc, disc bulging

4. Vertebral arteries Spasm and/or narrowing by stretching; tearing of intimal layer

5. Dorsal root ganglia Compression by narrowing of intervertebral foramen; interstitial bleeding

6. Cervical bones Bone contusion and occult fractures of vertebral bodies

7. Neck muscles Direct injury to muscle remains inconclusive; bleeding into muscle; tears

8. Oesophagus Laceration, rupture

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Recent study (Anderson et al., 2012):to compare the MRI findings in 100 acute WAD I and II patients with those in 100 matched healthy control subjects. MRI examinations of the C-spine within 48 hours after a motor vehicle accident. Interpretation of MRI’s by four blinded independent readers.

Results:Interreader reliability and diagnostic accuracy of MRI were poorSeveral of the socalled whiplash injuries were also found in healthy control subjectsIt is difficult to distinguish MRI findings of whiplash associated injuries from age related degenerative changesOnly abnormalities of vertebral bodies and muscle abnormalities are associated with acute whiplash injury

Conclusion:MRI reveals only limited evidence of specific changes in patients with acute symptomatic whiplash injury compared with healthy controls Sagittal MRI of C-spine:

fracture and bone marrow oedema Th1 (and Th2)

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Conclusions made by doctors:

‘if we don’t see lesions in the neck, then there are no lesions’. This is a kind of naive arrogance, for normal imaging does not exclude organic pathology.

If we cannot find an organic basis of whiplash, then whiplash must have an entire psychosocial genesis (Evans, 2010)

Cadaver and animal investigations make it very plausible that whiplash has an organic basis, but our present-day diagnostic tools are rather limited. So, further research is needed.

“But doctor, where is your brain?”

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D. Whiplash-Associated Disorders, = WAD; = postwhiplash syndrome, ie. the patient’s complaints

The ‘Quebec Classification of Whiplash-Associated Disorders’ of 1995 is primarily based on the severity of signs and symptoms following whiplash injury (Spitzer et al., 1995). Today this classification is still in use. The classification regards primarily acute whiplash complaints.

Note: a group of symptoms and disorders that may be manifest in all grades includes deafness, dizziness, tinnitus, headache, memory loss, dysphagia and temporomandibular joint pain (Spitzer et al., 1995).

Grade Clinical presentation

0 No complaint about the neck; no physical sign(s)

I Neck complaint of pain, stiffness, or tenderness only; no physical sign(s)

II Neck complaint AND musculoskeletal sign(s): decreased range of motion and point tenderness

III Neck complaint AND neurological sign(s): decreased or absent deep tendon reflexes, weakness, and sensory deficits

IV Neck complaint AND fracture or dislocation

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Grades:Grade 0: only for legal, not for medical purposeGrade IV: regards chronic orthopedic or neurosurgical patientsGrades I, II, (III): refer to WAD-patients

WAD patients: the vast majority of all WAD-patients can be classified as WAD grade II patients (Sterling, 2004; Kivioja et al., 2008)

Comments on the ‘Quebec Classification of Whiplash-Associated Disorders (WAD)’ of 1995

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Complaints: two sets of complains can be found in acute WAD patient (1995):neck related complaints (see clinical presentation in slide 11)Other complaints (see slide 11) including cognition deficits

neck related complaints:

Neck painNeck stiffnessHeadacheParaesthesiaShoulder painArm painRadicular painMuscle weakness

Remarks: 1.These complaints are also found in chronic whiplash2.As neck lesions will cause both focal pain and referred pain it is difficult to attribute the neck pain to a specific lesion in one of the various structures of the neck (localization of pain generators in the neck is difficult)


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Other complaints

Sleep disordereIrritabilityFatiqueBack painConcentration deficitsBurn-out feelingsDizzinessMemory deficitVisus problemsAuditory problemsDysphagia, swallowing problems

Remarks:1.These complaints are also found in chronic whiplash, plus depression2.These complaints are nonspecific complaints; they are also found in disorders as: chronic LBP, fibromyalgia, irritable bowel syndrome, chronic fatigue syndrome, postconcussion syndrome, RA, OA, and other chronic pain syndromes 3.These complaints can not directly be attributed to a lesion in the neck

Complaints: two sets of complains can be found in acute WAD patient (1995):neck related complaints (see clinical presentation in slide 11)Other complaints (see slide 11) including cognition deficits


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The key messages of the Quebec Task Force (1995) to WAD patients are:Whiplash-associated disorders are usually self-limitedWhiplash pain is not harmful, is usually short-lived, and is controllable

Now, in 2015, we know better:WAD’s are usually not self-limited; about 50% of the acute WAD’s become chronic (complaints exist > 3 months) (Carroll et al., 2009; Elliott et al., 2009). Chronic whiplash patients can be viewed as being chronic pain patients.Chronic whiplash pain can be nociceptive pain or neuropathic pain; both can modify the way the CNS (brain and spinal cord) works, so that a patient becomes more sensitive for pain and gets more pain with less provocation. This phenomenon is called central sensitization. It is difficult to treat (Woolf C, 2011; Ossipov et al., 2010).


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Whiplash, a controversial posttraumatic disorderII. Why is whiplash so controversial?

A. Problems in diagnosis:

Normally: clinical diagnosis is the proces of determining which disease explains the signs and symptoms of the patient; this proces is based on history taking, physical examination and laboratory tests.

However in whiplash:The diagnosis whiplash is difficult to make because it encompasses many different pathophysiological mechanisms

Conventional imaging hardly reveals whiplash injuries; there is a lack of diagnostic tools (laboratory tests) to objectify whiplash injuries; we need new diagnostic tools in whiplash.

In the medical world there are some persistent prejudices concerning whiplash:In the ‘sequence of whiplash events’: when whiplash injuries cannot be localized, then there cannot exist a causal relationship between injuries and acute complaints; therefore, the complaints must have an ‘other’ (unknown) origin…There are several complaints that refer to brain dysfunctions in whiplash, so, whiplash must have at least partly a psychological origin…Sprain and strain of the neck are supposed to heal within 6 weeks, just as in an ankle sprain. Why do the complaints become chronic? Chronic inflammatory sources in the neck have never been demonstrated, so chronicity of whiplash complaints must have to do with faking whiplash injuries for profit…

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B. Persistent prejudices concerning whiplash and consequences:

For whiplash patients: no proper diagnosis means no proper treatment; this often results in medical shopping, loss of work and income, family problems, frustration, depression

For doctors: several of them don’t take the whiplash patient seriously; they may disregard the patient’s whiplash complaints and may believe that the patient is exaggerating or malingering his complaints to pretend illness so as to avoid duty. He may also believe that chronic whiplash pain has nothing to do with the car-crash, but with ‘something between the ears’.

For the general public: a growing belief that whiplash injuries are simply expressions of greed or fraud, so there is little tolerance for complaints of whiplash patients in daily life.

For insurance companies: they often deny liability; the biggest insurance company in The Netherlands states that most of the whiplash patients must be able to recover from the injury within a period of two or three months. By that, the existence of chronic whiplash is totally denied by this company.

For personal injury lawyers: he/she provides the legal representation for those who claim to have been injured by another person, and knows precisely how to obtain the best compensation for the claimant. Usually he/she is conducting a lawsuit against the insurance company of the opposite party

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C. Causes for controversy

1. The sequence of whiplash events and possible pathophysiological mechanisms are poorly understood

2. There is lack of diagnostic tools to confirm the disorder whiplash.

3. There is a persistent prejudice by doctors, insurance companies and the general public against whiplash

4. Recognition of chronic whiplash as a primarily biological disorder will cost a lot of money

5. Doctors should take their whiplash patients seriously

So, we have discovered that there is something we don’t understand. Therefore, we need to expand our knowledge with new objective evidence for the diagnosis whiplash. What are new findings about whiplash in the literature of the past 10 years?

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Whiplash, a controversial posttraumatic disorderIII. New evidence for the diagnosis whiplash

A. Chiari type I malformation

Is a caudal herniation of cerebellar tonsils through the foramen magnum, also called cerebellar tonsillar ectopia or CTERadiological definition: herniation of ≥ 5 mm below the level of foramen magnus (Sekula et al., 2011)Definition used in a recent study on Chiari type I malformation and whiplash: herniation of ≥ 1mm below the level of foramen magnum (Freeman et al., 2010)Complaints of Chiari type I malformation: occipital headache, neckpain, upper extremity numbness and paresthesias and muscle weakness

Normal Chiari type I malformation

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A. Chiari type I malformation

Recent study (Freeman et al., 2010): cervical MRI scans of 1200 neck patients; 600 chronic whiplash cases, and 600 non-trauma but with neckpain controls.

Results:

Conclusions:Upright MRI is more sensitive than supine MRI in demonstrating CTE in whiplash patients.CTE is found more frequently in whiplash patients, compared with the controls

600 chronic whiplash patients 600 controls non-trauma but with neck pain

300 supine MRI 300 upright MRI 300 supine MRI 300 upright MRI

9,8% CTE 23,3% CTE 5,7% CTE 5,3% CTE

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B. Cervical facet mediated pain

There is circumstantial evidence from post mortem studies and clinical studies that the capsular ligaments of cervical facet joints may be sites of tissue damage and generators of chronic neck pain after whiplash (Bogduk, 2011; Gellhorn, 2011)

In whiplash patients: clinical diagnosis of chronic cervical facet mediated pain is made by a diagnostic nerve block of certain cervical facet joints with a local anesthetic; this is done with fluoroscopy or ultrasound guided; if it gives a temporary but complete relief of pain the diagnosis cervical facet mediated pain is a fact (Barnsley et al., 1995; MacVicar et al., 2012; Steilen et al., 2014)

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B. Cervical facet mediated pain

A therapeutic nerve block can be administered when the diagnostic nerve block is positive (= complete relief of pain). Three types of therapeutic nerve blocks are used to manage chronic facet mediated pain:Intra-articular injection with local anesthetic and/or steroidMedial branch nerve block by a long acting local anestheticNeurotomy by radiofrequency or cryoneurolysis of nerve branches of facet joints

Results:Especially the cervical radiofrequency neurotomy (RFN) can be very effective when performed in a rigorous manner in appropriately selected patientsPatients maintain a complete or partial pain relief for a duration of 9-20 months; thereafter the pain returns and a repeated treatment may be necessary (Boswell et al., 2007; MacVicar et al., 2012)Pain, disability, psychological distress, and pain catastrophization decrease significantly following cervical RFN (Smith et al., 2014)

Conclusion:Cervical facet mediated pain is a cause of chronic neck pain in several whiplash patients

Two medial nerves have to be ablated to denervate one facet joint

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C. Elevated inflammatory biomarkers in serum and focal tissue inflammation:

C-reactive protein (CRP) is measured in acute (< 2-3 weeks) and chronic (at 3 months) WAD grade II patients, and compared to healthy controls:Acute WAD: elevated CRP both in recovered/mild and in moderate/severe disabled patientsChronic WAD: elevated CRP only in moderate/severe disabled patients (Sterling et al., 2013)

Deprenyl (= selegiline) = antiparkinson drug:The radioactive tracer deprenyl (11C-D-deprenyl) is a potential marker for inflammationInjected in the bloodstream, the chronic WAD grade II patients will display significantly elevated tracer uptake in the neck, particularly in regions around the spineous process of the second cervical vertebraIt can be seen on Positron Emission Tomography scans, combined with CTThis suggests that chronic whiplash patients have signs of local peripheral tissue inflammation (Linnman et al., 2011)

Conclusion: Elevated inflammatory biomarkers in chronic whiplash patients may be due to ongoing chronic inflammation from injured soft tissue

Radioactive deprenyl uptake in a person with chronic WAD

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D. Trigger points (TP’s) are peripheral pain generators

Features of TP:Small, palpable hardening (taut band) in a muscle bellyLocal twitch response, severe pressure pain, and characteristic referred pain while manipulating the TPRecognition of the elicited pain as the patient’s known and familiar pain (Dommerholt et al., 2006; Ettlin et al., 2008)

Two triggerpoints in descending trapezius muscle and location of referred pain (red)

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D. Trigger points (TP’s) are peripheral pain generators

TP’s more often in WAD patients than in nontraumatic neckpain and healthy controls (Ettlin et al., 2008; Castaldo et al., 2014)

TP’s often cause central sensitization for pain with allodynia and hyperalgesia (Dommerholt et al., 2006; Fernandez-de-las Penas et al., 2007; Botwin et al., 2008; Ge et al., 2011; Castaldo et al., 2014). Local anesthetic in TP’s of chronic WAD patients, who are centrally sensitizised, leads to an immediate decrease of the central sensitization (Freeman et al., 2009)

Therapeutic possibilities:Massage and stretching; spraying and stretching; dry needlingRecently: ultrasound-guided injection with both local anesthetic and corticosteroidTriggerpoint-ectomy: surgical excision of trigger points in conscious patients (Nystrom et al., 2011)

Conclusion:There are several diagnostic and therapeutic techniques available to deal with TP’s in WAD-patients

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E. Fatty infiltrates in deep extensor and flexor muscles of the neck

T1-weighted axial MRI scans of whiplash patients show fatty infiltrates in:Suboccipital musclesMultifidus musclesSemispinalis cervicis musclesLongus colli/capitis musclesSternocleidomastoid muscles

T1-weighted axial MRI at the C2–C3 vertebral segment illustrating a ROI for the longus capitis/colli muscles in a subject with chronic whiplash (A) and a healthy control (B)

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E. Fatty infiltrates in deep extensor and flexor muscles of the neck

Fatty infiltrates cause increase of muscle cross-sectional area (hypertrophy)

Amount of fatty infiltrates:Largest amount of fatty infiltrates at level C2-C3At 4 weeks after impact: some degree of fatty infiltrates in all whiplash patientsAt 3 and 6 months after impact: moderate and severe WAD patients have larger fatty infiltrates compared with recovered/mild WAD patientsIncrease of fatty infiltrates is proportional to the duration of whiplash symptomsHighest amount of fatty infiltrates is found in chronic WAD patients, low amount in chronic non-traumatic neck pain, and low amount in healthy controls

Cause of fatty infiltrates is unknown, but disuse atrophy is unlikely

A connection between fatty infiltrates and WAD complaints is unknown (Elliott et al., 2009; Elliott et al., 2010; Elliott et al., 2011; Abbott et al., 2015)

Conclusion:Fatty infiltrates in certain neck muscles is quite characteristic for WAD, but an explanation for this fact is not yet found

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F. Cervico-ocular reflex (COR) is increased in acute and chronic WAD

In whiplash patients: several alterations of the oculomotor control have been demonstrated, including disturbed eye follow movement, gaze stabilization, and eye-head coordination

Abnormal eye follow movements can be caused by disorders of the vestibular system, the visual system, and as a result of abnormal afferent input from the neck (abnormal propriocepsis from cervical facet joints and/or muscles)

COR can be tested by way of the smooth pursuit neck torsion test: this test differentiates between smooth pursuit abnormalities of a vestibular or CNS cause from those of a cervical cause

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F. Cervico-ocular reflex (COR) is increased in acute and chronic WAD

Smooth pursuit neck torsion test: Patient is sitting on a swivel chair; his head is fixed

(no vestibular impulses), and the room is darkened (no visual impulses)

Patient follows with his eyes a visual target (point) in the wall, that moves slowly in a sinusoidal pattern from left to right or reversed

Then, the chair is rotated 45 degrees to the right or to the left, activating the neck proprioceptive elements

Visual target movements and smooth pursuit eye follow movements are recorded simultaneously and electronically (ENT department setting) (Montfoort et al., 2008; Yu et al., 2011; Della Casa et al., 2014, Jorgensen et al., 2014)

Conclusion: The smooth pursuit neck torsion test is probably

the most reliable test to verify the diagnosis whiplash

The red line is the target the patient follows with their eyes. This is usually a moving light. The red and blue line should match. Here the patient badly undershoots the target

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G.Cerebrospinal fluid leak should be considered in some cases of chronic WAD

56% of a group of 66 chronic WAD grade II and III patients appeared to have a cerebrospinal fluid (CSF) leakage at thoracolumbar (Ishikawa et al., 2007; Hashizume et al., 2012a; Hashizume et al., 2012b)

leakage can lead to intracranial CSF hypotension with the following complaints: headache (often orthostatic, postural dependent), neckpain, neck stiffness, interscapular pain, dizziness, nausea, visual disturbances, hearing problems, memory problems, brain sagging in computed tomography myelography

diagnosis CSF leakage is usually made by radio-isotope cisternography: injection of radio-isotope in cisterna lumbaliswhole body scans after 1, 2,5 , 5, 12, 24 and 48 hoursabnormal is:too early radioactivity in urinary bladder ( after 1 h in stead of normally after 5 h)retarded ascent of radioactivity to base of the brain (longer than 24 h)one or more aggregations of radioactivity close to the sides of the spine (parathecal accumulation of radioactivity) indicating places of leakage by way of small tears in dura around nerve roots

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G.Cerebrospinal fluid leak should be considered in some cases of chronic WAD

treatment: epidural blood patching with 10 – 30 ml of the patient’s own blood; this causes a quick and considerable improvement of the patients complaints, but the neck pain remains (Mokri, 2013) Conclusion: CSF leaks can be caused by a whiplash, and epidural blood patching is here the therapy of choice

Cisternographic findings in two WAD patients (A1 and B1) 2,5 h after radio-isotope injection; CSF leaks in lower thoracic and lumbar region (black arrows) and early accumulation into the urinary bladder (arrow heads). A2 and B2 after epidural blood patching

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H. Sleep disturbances are frequently diagnosed in chronic WAD patients

sleep disorders in the general population: 30,7%; in chronic whiplash 74,1- 77% (Ihlebaek et al., 2006; Valenza et al., 2013)

sleep disorders result in insomnia and fatigue during daytime, and are a major cause of motor vehicle accidents (de Mello et al., 2013) one of the sleep disorders found in whiplash patients , is the Delayed Sleep Phase Disorder (DSPD) (Wieringen van et al., 2001):DSPD: a person’s sleep is delayed by approximately 3 or more hours beyond the socially or conventionally bedtime. This delay in falling asleep causes difficulty in waking up at the desired time. This may result often in extreme fatigue and insomnia during daytimeDSPD is classified in the International Classification of Sleep Disorders 2014 as a Circadian Rhythm Sleep-Wake Disorder the normal sleep-wake timing is regulated by the biological clock in a circadian rhythm: a rhythm consisting of approximately 24 hours

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H. Sleep disturbances are frequently diagnosed in chronic WAD patients

diagnosis DSPD: clinical interview, sleep diary, actigraphic monitoring, measurement of the onset of endogenous melatonin production by sampling endogenous melatonin in saliva

normally in adults: the onset of endogenous melatonin starts to rise between 19.30 and 21.30 h; in DSPD: the onset is retarded bij approximately 3 h (Micic et al., 2015) therapy: during 4 weeks, daily 5 mg exogenous melatonin, 5 hours before endogenous melatonin onset in patient (van Geilswijk et al., 2010; Keijzer et al., 2013); other therapies (i.e. light therapy, chronotherapy)

Conclusion: sleep disorders in whiplash are very common; one of them, i.e. the Delayed Sleep Phase Disorder, can be recognized rather easily, and treated

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I.High resolution MRI of upper cervical spine ligaments in chronic WAD patients shows high signal intensity areas in alar ligaments and transverse ligament: true or not true ?

areas of high signal intensities are identified in alar and transverse ligaments of chronic WAD patients

these gray to white areas in alar and transverse ligaments are read as whiplash lesions

there would be a causal relation between severity of these lesions and the intensity of the whiplash complaints (Kaale et al., 2005a: Kaale et al., 2005b; Krakenes et al. 2006)

Axial MRI of the transverse ligament (C1)A: low signal intensity (black) in normal patient. B: high signal intensity (grey/white) in acute WAD patient

A

B

III. New evidence for the diagnosis whiplash34/44


However:high signal intensities in the alar and transverse ligaments are identified in chronic whiplash patients as frequently as in chronic non-traumatic neck patients as in healthy controls (Myran et al., 2008)high signal intensities in the alar and transverse ligaments are also observed in acute whiplash patients. These signal intensities are not caused bij the whiplash mechanism, but are nothing more than artefacts (Vetti et al., 2010; Vetti et al., 2011)signal alterations on MRI scans of alar and transverse ligaments are naturally in healthy symptom- free individuals (Wenz et al., 2015)

Conclusion: whether MRI signal changes of the alar and transverse ligaments are responsable for complaints of WAD patients is at least controversial and probably not true

I.High resolution MRI of upper cervical spine ligaments in chronic WAD patients shows high signal intensity areas in alar ligaments and transverse ligament: true or not true ?

III. New evidence for the diagnosis whiplash35/44

Whiplash, a controversial posttraumatic disorderIV. Recent knowledge about whiplash pain

A. Definitions of pain according to the International Association for the Study of Pain, 2012

pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.

another pain definition comes from the pain nurse Margo McCaffery, 1968: pain is whatever the experiencing person says it is, and exists whenever he says it does

pain can be acute (during < 3 months) or chronic (> 3 months)

there are two types of pain; sometimes they are mixed up:nociceptive pain: pain arising from actual or threathening damage to non-neural tissue and is due to activation of nociceptors, e.g. infections, inflammation, traumaneuropathic pain: pain caused by a lesion or disease of the central and/or peripheral somatosensory nervous system, e.g. transsection or impingement of a peripheral nerve, postherpetic pain, trigeminal pain, multiple sclerosis, phantom pain

chronic pain is a major problem in mankind:prevalence of chronic pain in Europe is 25-30% (Leadley et al., 2012)approximately 15-25% of the people with chronic pain have neuropathic pain (Cohen et al., 2014)about 50% of the acute WAD patients become chronic pain patients (Carroll et al., 2009; Elliott et al., 2009)

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B. Pain perception is a function of a number of brain areas that can be visualized by fMRI

the visualized pain-related brain areas form a network, often referred to as the pain matrix

example of a pain matrix activated by an acute nociceptive stimulus (painful experience):brain areas are bilaterally active, but with more dominant activation on the contralateral hemisphere

most common areas found to be active during acute pain are: thalamus, S1 and S2, insula, anterior cingulate cortex, prefrontal cortex. Also active in this example are: amygdala, hippocampus, posterior parietal cortex,basal ganglia, crebellum and brainstem (Tracey, 2008)

pain perception comprises three dimensions: sensory-discriminative, affective-emotional, and cognitive-evaluative. Question: which area(s) mediate(s) which dimension ?

nociceptive and neuropathic pain matrices have a distinct although overlapping brain activation pattern (Moisset et al., 2007)

Nociceptive pain matrix

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C. Scheme nociceptive versus neuropathic pain

acute nociceptive pain acute neuropathic pain

tissue damage: burns, fracture, bruises, inflammation, infections

damage to somatosensory system:often not early recognized; becomes easely chronic; usually accompanied by non-nervous tissue damage

medication:NSAID’s, acetaminophen, opioids

medication:antidepressants, anticonvulsants

chronic nociceptive pain chronic neuropathic pain

severe and prolonged tissue damage:pain is well localized, constant, aching, throbbing

severe and prolonged damage to nervous tissue:pain is burning or coldness, lancinating, electrical shock-like, tingling, deep stinging, shooting, dull, ’pins and needless sensations’, constant or intermittent

transport of pain by way of Aδ and C fibers to spinal cord and brain

transport of pain by way of Aδ, C fibers and other somatosensory fibers to spinal cord and brain

activation of nociceptive pain matrix in the brain(Garcia-Larrea et al., 2013)

activation of neuropathic pain matrix in the brain(Garcia-Larrea et al., 2013)

Central sensitization

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D. Facts about central sensitization (CS):

There is compelling evidence for the existence of central sensitization in patients with chronic WAD as underlying mechanism of their complaints (van Oosterwijck et al., 2013; Stone et al., 2013; Coppieter et al., 2015); CS is not a characteristic feature of chronic non-traumatic neck pain (Malfliet et al., 2015)

The pain matrix in CS is altered: increased activity in brain areas known to be involved in acute pain sensations, and brain activity in regions that are generally not involved in acute pain sensations (Nijs et al., 2011; Apkarian et al., 2011).

Central sensitization causes an abnormal and intense enhancement of pain by mechanisms in the CNS

The enhancement of pain is probably caused by chronic peripheral pain that induces hyperexcitability of pain-related neurons in the brain (‘pain hurts the brain’); moreover, there is a decrease of the function of the endogenous pain inhibiting system (Ossipov et al., 2010)

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hyperexcitability and impaired endogenous pain inhibiting system means an impaired central pain modulation with widespread pain; it cause, moreover, an exagerated responsiviness of the CNS not only for pain, but also for a variety of other stimuli (electrical, pressure, cold, heat, light, medication)

Features of central sensitization:allodynia: painful sensation to a normally non-painful stimulushyperalgesia: excessive sensitivity to a normally painful stimulus, such as pressureunusually prolonged pain after the stimulus has been removed (usually burning, throbbing, tingling, or numbness)referred pain across multiple spinal segments, leading to chronic widespread painfailure of endogenous pain inhibitory system

Central sensitization is a central hyperexcitability pain condition that very probably is sustained by peripheral pain generators sending nociceptive input to the brain (Gerdle et al., 2014)

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Central sensitization is found in many chronic pain disorders: fibromyalgia, whiplash, some headaches, irritable bowel syndrome; chronic fatigue syndrome, temporomandibular disorders, chronic pelvic pain syndrome, OA, RA, chronic low back pain, epicondylitis, shoulder pain, cancer pain, multiple sclerosis ( Woolf, 2010; Nijs et al., 2015)

These chronic pain disorders have many features (so-called non-organic symptoms) in common, including pain, fatigue, poor sleep, cognitive deficits, headaches, anxiety, depression, suggesting that they may share a common etiology (Meeus et al., 2015)

These so-called non-organic symptoms for which no specific organic cause can be found, are very probably induced by the central sensitization.

If a clinician considers the possibility of central sensitization, he may use the Central Sensitization Inventory Part A and B. It is a validated questionnaire, designed to assess key somatic and emotional complaints often associated with central sensitization (Mayer et al., 2012)

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Whiplash, a controversial posttraumatic disorderV. Conclusions

1. Whiplash is a pain syndrome caused by trauma to the neck and head. The trauma is usually caused by a rear-end motor vehicle collision. The complaints of these patients are always neck-related but can also include non-specific, often more cognitive, complaints. This pain syndrome can become chronic.

2. Unfortunately, damage to the target vehicle or change in velocity during impact does not predict if this pain syndrome will arise. And though the ‘whiplash mechanism’ causes a large variety of lesions in various anatomical locations of the C-spine in cadaveric studies, these lesions cannot be found in vivo with modern day imaging.

3. Thus sofar a clearcut explanation (through a pathophysiological mechanism = evidence based medicine) for this pain syndrome has not been found by researchers for many years. This has led to a widespread prejudice among doctors, insurance companies and the general public, making the diagnosis ‘whiplash’ at best a controversial one.

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Whiplash, a controversial posttraumatic disorderV. Conclusions

4. However, over the past 10 years new insights have been gathered, and several different pathophysiological mechanism have been described and objectified: Chiari type I malformation, cervical facet joint mediated pain, elevated inflammatory biomarkers, painful trigger points, abnormal cervico-ocular reflex, cerebrospinal fluid leakage, sleep disturbances, and possible lesions of the high cervical ligaments.

5. These mechanisms may (in part) explain the neck-related complaints of whiplash patients and suggest that this pain syndrome can result through different pathways. Analogous to other chronic pain syndromes the non-specific (cognitive) complaints may be explained through a hyperexcitability of the brain known as central sensitization.

6. Despite these new insights the diagnosis whiplash remains difficult in a clinical setting. The mounting evidence however suggests that whiplash is ‘real’ and these patients should therefore be taken seriously.

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Is there a whiplash problem in

Jakarta?

Many thanks for your attention

Whiplash, a controversial posttraumatic disorderLiterature

Literature slide 2:1.Sterling M, Kenardy J. 2011Whiplash. Evidence base for clinical practice. Churchill Livingstone, Chatswood, NSW, Australia Literature slide 3:1.Spitzer WO, Skovron ML, Salmi LR, Cassidy JD, Duranceau J, Suissa S, Zeiss E. 1995Scientific monograph of the Quebec Task Force on Whiplash-Associated Disorders: refining ‘whiplash’and its management. Spine 20: 8S-58S Literature slide 4:1.Cailliet R. 2006

Whiplash Associated Diseases. American Medical Association. ISBN 1-57947-77472.Croft AC. 2009

Whiplash and mild traumatic brain injuries. Spine Research Institute of San Diego Press. ISBN 978-0-578-01880-53.https://chiro-trust.org/whiplash/low-impact-motor-vehicle-collisions-whiplash-injury/ Febr.7, 20144.Croft AC, Freeman MD. 2005

Correlating crash severity with injury risk, injury severity, and long- term symptoms in low velocity motor vehicle collisions. Med Sci Monit 11 (10): RA316-3215.Castro WH, Schilgen M, Meyer S, Weber M, Peuker C, Wortler K. 1997

Do ‘whiplash injuries’ occur in low-speed rear impacts ? Eur Spine J 6 (6): 366-3756.Davies CG.1998

Rear-end impacts: vehicle and occupant response. J Manipulative Physiol Ther 21 (9): 629-639


Literature slide 4 (continued):7.Freeman MD. 2015Medicolegal causation analysis of a lumbar spine fracture following a low speed rear impact traffic crash. Journal of Case Reports in Practice 3 (2): 23-29 Literature slide 5:1.Meyer S, Weber M, Castro W, Schilgen M, Peuter C. 1998

The minimal collision velocity for whiplash. In: Gunzburg R, Szpalski M. Whiplash injuries. Lippincott Williams and Wilkins, Philadelphia, pages 95-1152.Siegmund GP.2002

The biomechanics of whiplash injury. BCMJ 44 (5): 243-2473.Stemper BD, Yoganandan N, Pintar FA, Maiman DL. 2011

Mechanism of injury. In: Sterling M, Kenardy J. Whiplash: evidence base for clinical practice. Churchill Livingstone, Chatwood, NSW, Australia, pages 16-28 Literature slide 6:1.Grauer JN, Panjabi MM, Cholewicki J, Nibu K, Dvorak J. 1997

Whiplash produces an S-shaped curvature of the neck with hyperextension at lower levels. Spine 22 (21):2489-24942.Panjabi MM, Cholewicki J, Nibu K, Grauer JN, Babat LB, Dvorak J. 1998

Mechanism of whiplash injury. Clin Biomech (Bristol, Avon) 13 (4-5): 239-249


Literature slide 7:1.Yoganandan N, Cusick JF, Pintar FA, Rao RD. 2001

Whiplash injury determination with conventional spine imaging and cryomicrotomy. Spine 26 (22): 2443-24482.Taylor JR. 2002

The pathology of whiplash: neck sprain. BCMC 44 (5): 252-2563.Siegmund GP, Winkelstein BA, Ivanic PC, Svensson MY, Vasavada. 2009

The anatomy and biomechanics of acute and chronic whiplash injury. Traffic Inj Prev 10 (2): 101-112 4.Curatolo M, Bogduk N, Ivancic PC, McLean SA, Siegmund GP, Winkelstein B. 2011

The role of tissue damage in whiplash associated disorders: discussion paper 1. Spine 36 (25 Suppl): S309-S3155.Uhrenholt L, Freeman MD, Jurik AG, Jensen LL, Gregersen M, Boel LW, Kohless SS, Thomsen AH. 2011

Esophageal injury in fatal rear-impact collisions. Forensic Sci Int 206 (1-3): e52-e576.Elliott J. 2011

The evidence for pathoanatomical lesions, In : Sterling M, Kenardy J. Whiplash: evidence base for clinical practice. Churchill Livingstone, Chatswood, NSW, Australia, pages 29-397.Yoganandan N, Stemper B, Rao RD. 2013

Patient mechanisms of injury in whiplash-associated disorders. Seminars in Spinal Surgery 25 (1): 67-74


Literature slide 9:1.Anderson SE, Boesch C, Zimmermann H, Busato A, Hodler J, Bingisser R, Ulbrich EJ, Nidecker A, Buitrago-Tellez CH, Bonel HM, Heini P, Schaeren S, Sturzenegger M. 2012Are there cervical spine findings at MR imaging that are specific to acute symptomatic whiplash injury? A prospective controlled study with four experienced blinded readers. Radiology 262 (2): 567-575 Literature slide10:1.Evans RW. 2010Persistent post-traumatic headache, postconcussion syndrome, and whiplash injuries: evidence for a non-traumatic basis with a historical review. Headache 50 (4):716-724 Literature slide 11:1.Spitzer WO, Skovron ML, Salmi LR, Cassidy JD, Duranceau J, Suissa S, Zeiss E. 1995Scientific monograph of the Quebec Task Force on Whiplash-Associated Disorders: refining ‘whiplash’and its management. Spine 20: 8S-58S

Literature slide 12:1.Sterling M. 2004

A proposed new classification system for whiplash associated disorders – implications for assessment and management. Manual Therapy 9: 60-702.Kivioja J, Jensen I, Lindgren U. 2008

Neither the WAD-classification nor the Quebec Task Force follow up regimen seems to be important for the outcome after whiplash injury. A prospective study on 186 consecutive patients. Eur Spine J 17: 930-935


Literature slide 15:1.Carroll LJ, Holm LW, Hogg-Johnson S, Cote P, Cassidy JD, Haldeman S, Nordin M, Hurwitz EL, Carragee EJ, van der Velde G, Peloso PM, Guzman J. 2009

Course and prognostic factors for neck pain in whiplash-associated disorders (WAD): results of the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and its Associated Disorders. J Manipulative Physiol Ther 32 (2 Suppl): S97-S1052.Elliott JM, Noteboom JT, Flynn TW, Sterling M. 2009

Characterization of acute and chronic whiplash associated disorders. J Orthop Sports Phys Ther 39: 312-3233.Woolf CJ. 2011

Central sensitization: implications for the diagnosis and treatment of pain. Pain 152 (3 Suppl): S2-S154.Ossipov MH, Dussor GO, Porreca F. 2010

Central modulation of pain. J Clin Invest 120 (11): 3779-3787 Literature slide 19:1.Sekula RF, Arnone GD, Crocker C, Aziz KM, Alperin N. 2011

The pathogenesis of Chiari I malformation and syringomyelia. Neurol Res 33 (3): 232-2392.Freeman MD, Rosa S, Harshfield D, Smith F, Bennett R, Centeno CJ, Komel E, Nystrom A, Heffez D, Kohles SS. 2010

A case control study of cerebellar tonsillar ectopia ( Chiari) and head/neck trauma (whiplash). Brain Inj 24 (7-8): 988-994


Literature slide 20:1.Freeman MD, Rosa S, Harshfield D, Smith F, Bennett R, Centeno CJ, Komel E, Nystrom A, Heffez D, Kohles SS. 2010

A case control study of cerebellar tonsillar ectopia ( Chiari) and head/neck trauma (whiplash). Brain Inj 24 (7-8): 988-994 Literature at slide 21:1.Bogduk N. 2011

On cervical zygapophysial joint pain after whiplash. Spine 36 (25 Suppl): S194-S1992.Gellhorn AC. 2011

Cervical facet-mediated pain. Phys Med Rehabil Clin N Am 22 (3): 445-4583.Barnsley L, Lord SM, Wallis BJ, Bogduk N. 1995

The prevalence of chronic cervical zygapophysial joint pain after whiplash. Spine 20 (1): 20-254.MacVicar J, Borowczyk JM, MacVicar AM, Loughnan BM, Bogduk N, 2012

Cervical medial branch radiofrequency neurotomy in New Zealand. Pain Med 13 (5): 647-6545.Steilen D, Hauser R, Woldin B, Sawyer S. 2004

Chronic neck pain: making the connection between capsular ligament laxity and cervical instability. The Open Orthopaedics Journal 8: 326-345


Literature slide 22:1.Boswell MV, Colson JD, Sehgal N, Dunbar EE, Epter R. 2007

A systematic review of therapeutic facet joint interventions in chronic spinal pain. Pain Physician 10 (1): 229-2532.MacVicar J, Borowczyk JM, MacVicar AM, Loughnan BM, Bogduk N, 2012

Cervical medial branch radiofrequency neurotomy in New Zealand. Pain Med 13 (5): 647-6543.Smith AD, Jull G, Schneider G, Frizzell B, Hooper RA, Dunne-Proctor R, Sterling M. 2014

Cervical radiofrequency neurotomy reduces psychological features in individuals with chronic whiplash symptoms. Pain Physician 17 (3): 265-274 Literature slide 23:1.Sterling M, Elliott JM, Cabot PJ. 2013

The course of serum inflammatory biomarkers following whiplash injury and their relationship to sensory and muscle measures: a longitudinal cohort study. PLOS ONE 8 (10): e 77903 (pages 1-8)2.Linnman C, Appel L, Fredrikson M, Gordh T, Soderland A, Langstrom B, Engler H. 2011

Elevated [11C]-D-Deprenyl uptake in chronic whiplash associated disorder suggests persistent musculoskeletal inflammation. PLOS ONE 6 (4): 219182 (pages 1-6) Literature slide 24:1.Dommerholt J, Bron C, Franssen J. 2006

Myofascial trigger points: an evidence-informed review. J Manual Manipulative Therapy 14 (4): 203-2212.Ettlin T, Schuster C, Stoffel R, Bruderlin A, Kischka U. 2008

A distinct pattern of myofascial findings in patients after whiplash injury. Archives of Physical Medicine and Rehab 89 (7): 1290-1293


Literature slide 25:1.Castaldo M, Ge HY, Chiarotto A, Villafane HJ, Arendt-Nielsen L. 2014

Myofascial trigger points in patients with whiplash-associated disorders and mechanical neck pain. Pain Med 15 (5): 842-8492.Fernandez-de-las-Penas C, Simons D, Cuadrado ML, Pareja JA. 2007

The role of myofascial trigger points in musculoskeletal pain syndromes of the head and neck. Current Pain and Headache Reports 11 (5): 365-3723.Botwin KP, Sharma K, Saliba R, Patel BC. 2008

Ultrasound-guided trigger point injections in the cervicothoracic musculature: a new and unreported technique. Pain Physician 11 (6): 885-8894.Ge HY, Fernandez-de-las-Penas C, Yue WW. 2011

Myofascial trigger point: spontaneous electrical activity and its consequencies for pain induction and propagation. Chin Med 6 : 13 ( 9 pages)5.Freeman MD, Nystrom A, Centeno C. 2009

Chronic whiplash and central sensitization; an evaluation of the role of myofascial trigger points in pain modulation. J Brachial Plex Peripher Nerve Inj 4 (1): e13-e206.Nystrom AN, Freeman MD. 2011

‘Trigger Point’ surgery for soft tissue pain in chronic whiplash syndrome. International Whiplash Trauma Congress, Lund, Sweden. Abstract in: J Rehabil Med Suppl 50:27


Literature slide 27:1.Elliott J, Sterling M, Noteboom JT, Treleaven J, Galloway G, Jull G. 2009

The clinical presentation of chronic whiplash and the relationship to findings in the cervical extensor musculature: a preliminary investigation. Eur Spine J 18 (9): 1371-13782.Elliott JM, O’Leary S, Sterling M, Hendrikz J, Pedler A, Jull G. 2010

Magnetic resonance imaging findings of fatty infiltrate in the cervical flexors in chronic whiplash. Spine 35 (9): 948-9543.Elliott J, Pedler A, Kenardy J, Galloway G, Jull 2011

The temporal development of fatty infiltrates in the neck muscles following whiplash injury: an association with pain4.Abbott R, Pedler A, Sterling M, Hides J, Murphy T, Hoggarth M, Elliott L. 2015

The geography of fatty infiltrates within the cervical multifidus and semispinalis cervicis in individuals with chronic whiplash-associated disorders. J Orthop Sports Phys Ther 45 (4): 281-288 Literature slide 29:1.Montfoort I, van der Geest JN, Slijper HP, de Zeeuw CI, Frens MA. 2008

Adaptation of the cervico- and vestibulo-ocular reflex in whiplash injury patients. J Neurotrauma 25 (6): 687-6932.Yu LJ, Stokell R, Treleaven J. 2001

The effect of neck torsion on postural stability in subjects with persistent whiplash. Man Ther 16 (4): 339-3433.Della Casa W, Affolter Helbing J, Meichtry A, Luomajoki H, Kool J. 2014

Head-eye movement control tests in patients with chronic neck pain; Inter-observer reliability and discriminative validity. BMC Musculoskeletal Disord 15: 16 (11 pages)4.Jorgensen R, Ris I, Falla D, Juul-Kristensen B. 2014

Reliability, construct and discriminative validity of clinical testing in subjects with and without chronic neck pain. BMC Musculoskeletal Disord 15: 408 ( 13 pages)


Literature slide 29 (continued):4.Jorgensen R, Ris I, Falla D, Juul-Kristensen B. 2014

Reliability, construct and discriminative validity of clinical testing in subjects with and without chronic neck pain. BMC Musculoskeletal Disord 15: 408 ( 13 pages)

Literature slide 30:1.Ishikawa S, Yokoyama M, Mizobuchi S, Hashimoto H, Moriyama,E, Morita K. 2007

Epidural blood patch therapy for chronic whiplash-associated disorder. Anesthesia Analgesia 105 (3): 809-8142.Hashizume K, Watanabe K, Kawaguchi M, Taoka T, Shinkai T, Furuya H. 2012a

Comparison of computed tomography myelography and radioisotpe cisternography to detect cerebrospinal fluid leakage in spontaneous intracranial hypotension. Spine 37 (4): E237-E2423.Hashizume K, Watanabe K, Kawaguchi M, Fujiwara A, Furuya H. 2012b

Comparison between computed tomography-myelography and radioisotope-cisternography findings in whiplash-associated disorders suspected to be caused by traumatic cerebrospinal fluid leak. Spine 37 (12): E721-E726 Literature slide 31:1.Mokri B. 2013

Spontaneous low pressure, low CSF volume headaches: spontaneous CSF leaks. Headache 53 (7): 1034-1053


Literature slide 32:1.Ihlebaek C, Odegaard A, Vikne J, Eriksen HR, Laerum E. 2006

Subjective health complaints in patients with chronic whiplash associated disorders (WAD). Relationships with physical, psychological, and collision associated factors. Norsk Epidemiologi 16 (2): 119-1262.Valenza MC, Valenza G, Gonzalez-Jimenez E, De-la-Llave-Rincon AI, Aroyo-Morales M, Fernandez de las Penas C. 2012

Alteration in sleep quality in patients with mechanical insiduous neck pain and whiplash-associated neck pain. Am J Phys Med Rehabil 91(7): 584-5913.de Mello MT, Narciso FV, Tufik S, Paiva T, Spence DW, Bahammam AS, Verster JC, Pandi-Perumal SR. 2013

Sleep disorders as a cause of motor vehicle collisions. Int J Prev Med 4 (3): 246-2574.Wieringen van S, Jansen T, Smits MG, Nagtegaal JE, Coenen AML. 2001

Melatonin for chronic whiplash syndrome with delayed melatonin onset. Randomized, placebo-controlled trial. Clin Drug Invest 21 (12): 813-820 Literature slide 33:1.Micic G, Lovato N, Gradisar M, Burgess HJ, Ferguson SA, Kennaway DJ, Lack L. 2015

Nocturnal melatonin profiles in patients with delayed sleep-wake phase disorder and control Sleepers. J Biol Rhythms 30 (5): 437-4482.van Geijlswijk IM, Korzilius HPLM, Smits MG. 2010

The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis. Sleep 33 (12): 1605-1614


Literature slide 33 (continued):3.Keijzer H, Smits MG, Duffy JF, Curfs LMG. 2014

Why the dim light melatonin onset (DLMO) should be measured before treatment of patients with circadian rhythm sleep disorders. Sleep Med Rev 18 (4): 333-339

Literature slide 34:1.Kaale BR, Krakenes J, Albrektsen G, Weter K. 2005a

Whiplash-associated disorders impairment rating: neck disability index score according to severity of MRI findings of ligaments and membranes in the upper cervical spine. J Neurotrauma 22 (4): 466-4752.Kaale BR, Krakenes J, Albrektsen G, Weter K. 2005b

Head position and impact direction in whiplash injuries: associations with MRI-verified lesions of ligaments and membranes in upper cervical spine. J neurotrauma 22 (11): 1294-13023.Krakenes J, Kaale BR. 2006

Magnetic resonance imaging assessment of craniovertebral ligaments and membranes after whiplash trauma. Spine 31 (24): 2820-2826 Literature slide 35:1.Myran R, Kvistad KJ, Nygaard OP, Andresen H, Folnik M, Zwart J-A. 2008

Magnetic resonance imaging assessment of the alar ligaments in whiplash injuries. Spine 33 (18): 2012- 20162.Vetti N, Krakenes J, Eide GE, Rorvik J, Gilhys NE, Espeland A. 2010

Are MRI high-signals changes of alar and tranverse ligaments in acute whiplash injury related to outcome ? BMC Musculoskeletal Disorders 11: 260


Literature slide 35 (continued):3.Vetti N, Krakenes J, Damsgaard E, Rorvik J, Gilhus NE, Espeland S. 2011

Magnetic resonance imaging of the alar and transverse ligaments in acute whiplash-associated disorders 1 and 2. Spine 36 (6): E434-E4404.Wenz H, Kerl HU, Maros ME, Wenz R, Kalvin K, Groden C, Nolte I. 2015

Signal changes of the alar ligament in a healthy population: a dispositional or degenerative consequence ? J Neurosurg Spine Jul 17: 1-7 [Epub ahead of print]

Literature slide 36:1.Leadley RM, Armstrong N, Lee YC, Allen A, Kleijnen J. 2012

Chronic diseases in the European Union: the prevalence and health costs implications of chronic pain. J Pain Palliat Care Pharmacother 26 (4): 310-3252.Cohen SP Mao J. 2014

Neuropathic pain: mechanisms and their clinical implications. BMJ; 348: f76563.Carroll LJ, Holm LW, Hogg-Johnson S, Cote P, Cassidy JD, Haldeman S, Nordin M, Hurwitz EL, Carragee EJ, van der Velde G, Peloso PM, Guzman J. 2009

Course and prognostic factors for neck pain in whiplash-associated disorders (WAD): results of the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and its Associated Disorders. J Manipulative Physiol Ther 32 (2 Suppl): S97-S1054.Elliott JM, Noteboom JT, Flynn TW, Sterling M. 2009

Characterization of acute and chronic whiplash associated disorders. J Orthop Sports Phys Ther 39: 312-323


Literature slide 37:1.Tracey. 2008

Imaging pain. Br J Anesth 1001 (1): 32-392.Moisset X, Bouhassira D. 2007

Brain imaging of neuropathic pain. Neuroimage 37. Suppl 1: S80-S88 Literature slide 38:1.Garcia-Larrea L, Peyron R. 2013

Pain matrices and neuropathic pain matrices: a review. Pain 154 Suppl 1: S29-S43

Literature slide 39:1.van Oosterwijck J, Nijs J, Meeus M, Paul L. 2013

Evidence for central sensitization in chronic whiplash: a systematic literature review. Eur J Pain 17 (3): 299-3122.Stone AM, Vicenzino B, Lim EC, Sterling M. 2013

Measures of central hyperexcitability in chronic whiplash associated disorder – a systematic review and meta-analysis. Manual Therapy 18 (2): 111-1173.Coppieter I, Ickmans K, Cagnie B, Nijs J, de Pauw R, Noten S, Meeus M. 2015

Cognitive performance is related to central sensitization and health-related quality of life in patients with chronic whiplash-associated disorders and fibromyalgia. Pain Physician 18: E389-E4014.Malfliet A, Kregel J, Cagnie B, Kuipers M, Dolphens M, Roussel N, Meeus M, Danneels L, Bramer WM, Nijs J. 2015

Lack of evidence for central sensitization in ideopathic, non-traumatic neck pain: a systematic review. Pain Physician 18: 223-235


Literature slide 39 (continued):5.Nijs J, van Wilgen CP, van Oosterwijck J, van Ittersum M, Meeus M. 2011

How to explain central sensitization to patients with ‘unexplained’ chronic musculoskeletal pain: practice guidelines. Manual Therapy 16: 413-4186.Apkarian AV, Hashmi JA, Baliki MN. 2011

Pain and the brain: specificity and plasticity of the brain in clinical chronic pain. Pain 152 (3 Supp): S49-S647.Ossipov MH, Dussor GO, Porreca F. 2010

Central modulation of pain. J Clin Invest 120 (11): 3779-3787

Literature slide 40:1.Gerdle B, Larsson B, Forsberg F, Ghafouri N, Karlsson L, Stensson N, Ghafouri B. 2014

Chronic widespread pain: increased glutamate and lactate concentrations in the trapezius muscle and plasma. Clin J Pain 39 (5): 409-420 Literature slide 41:1.Woolf CJ. 2010

Central sensitization: implications for the diagnosis and treatment of pain. Pain 152 (3 Suppl): S2-S152.Nijs J, Meeus M, Versypt J, Moens M, Bos I, Knaepen K, Meeusen R. 2015

Brain-derived neurotrophic factor as a driving force behind neuroplasticity in neuropathic and central sensitization pain: a new therapeutic target ? Expert Opin Ther Targets 19 (4): 565-576


Literature slide 41 (continued):3.Meeus M, van Oosterwijck J, Ickmans K, Baert I, Coppieter I, Roussel N, Struyf F, Pattyn N, Nijs J. 2015

Interrelationships between pain processing, cortisol and cognitive performance in chronic whiplash-associated disorders. Clin Rheumatol 34 (3): 545-5534.Mayer TG, Neblett R, Cohen H, Howard KJ, Yun HC, Williams MJ, Perez Y, Gatchel RJ. 2012

The development and psychometric validation of the Central Sensitization Inventory (CSI). Pain Pract 12 (4): 276-285

"Whiplash, a controversial posttraumatic disorder", lezing gegeven door Leo Geeraedts oktober 2015...

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Transcript of "Whiplash, a controversial posttraumatic disorder", lezing gegeven door Leo Geeraedts oktober 2015...