analysis of neuropathic pain after spinal cord injury

Thesis for doctoral degree (Ph.D.)
2008
Thesis for doctoral degree (Ph.D.) 2008
ANALYSIS OF
NEUROPATHIC PAIN AFTER
SPINAL CORD INJURY
ANALYSIS OF NEUROPATHIC PAIN AFTER SPINAL CORD INJURY
Illustrations by Franco Costa
Lars Werhagen
Lars Werhagen
From the Department of Clinical Sciences, Danderyd Hospital,
Karolinska Institutet, Stockholm, Sweden
ANALYSIS OF
NEUROPATHIC PAIN AFTER
SPINAL CORD INJURY
Lars Werhagen
Stockholm 2008
All previously published papers were reproduced with permission from the publisher.
Published by Karolinska Institutet.
© Lars Werhagen, 2008
ISBN 978-91-7357-497-6
Printed by
2008
Gårdsvägen 4, 169 70 Solna
VISSI D’ARTE VISSI D’AMORE
TOSCA SECONDO ATTO
G.PUCCINI
1 ABSTRACT
Longstanding neuropathic pain is a challenge in spinal cord injury (SCI) rehabilitation.
Once established it is difficult to treat successfully. Neuropathic pain has a negative
influence on quality of life and on the outcome of rehabilitation. The prevalence of
neuropathic pain after SCI varies in different studies. However, pain in adults with spina
bifida (SB) seems to be a minor problem.
The aim of this thesis was to study the prevalence of neuropathic pain in patients with
traumatic and non-traumatic SCI and in adults with SB and to relate neuropathic pain to
completeness and level of injury, gender, age at time of lesion and to study the impact of
neuropathic pain on daily life. Another aim was to study the neurological and functional
outcome as well as prevalence of neuropathic pain in patients with central cord syndrome
(CCS). Patients with SCI who had their yearly check-up at the Spinalis outpatient clinic
between 1995 and 2000 were included in the study. Data were gathered from the checkup and include ASIA impairment scale, the neurological level, and the impact of
neuropathic pain on daily life.
Patients with CCS rehabilitated at the spinal unit of Florence, Italy during the years 19962002 were included. A follow-up visit was performed at least 18 months after discharge.
Data were gathered from the examination at admission and discharge from hospital and at
follow up. Studied data included ASIA impairment scale, neurological level, WISCI
(walking ability), FIM (Functional Independence Measure), spasticity and neuropathic
pain. The patients were divided in age groups according to age at the time of injury.
Longstanding neuropathic pain was present in 40% and in 38% of the patients with
traumatic and non-traumatic SCI, respectively, and in 11% of adults with SB. In the
traumatic group neuropathic pain was more common in adults injured late in life. Females
in the non-traumatic group had more often below level pain than males. In both traumatic
and non-traumatic SCI neurological level and completeness of injury had no relation to
the development of neuropathic pain. When pain was present it influenced daily life in the
majority of cases.
Patients with CCS over 65 years of age at the time of injury had impaired neurological
and functional recovery and more often experienced neuropathic pain (60%) than
individuals injured earlier in life (20%). Spasticity was equally common in individuals
injured late and early in life.
It is concluded that neuropathic pain is common in traumatic and non-traumatic SCI, and
in patients with CCS but is less frequent in adults with SB. Patients with traumatic CCS
injured at a young age had better neurological and functional outcome than patients
injured later in life.
Keywords: Spinal cord injury, spina bifida, central cord syndrome, neuropathic pain,
neuralgia
ISBN 978-91-7357-497-6
2 LIST OF PUBLICATIONS
The thesis is based on the following papers, which are referred to in the text by the
corresponding Roman numerals.
I
Werhagen L, Budh CN, Hultling C, Molander C.
Neuropathic pain after traumatic spinal cord injury-relations to
gender, spinal level, completeness, and age at the time of injury.
Spinal Cord 2004 Dec; 42(12):665-73.
II
Werhagen L, Hultling C, Molander C.
The prevalence of neuropathic pain after non-traumatic spinal cord
lesion.
Spinal Cord 2007 Sep; 45(9):609-15.
III
Werhagen L.
Neuropathic and nociceptive pain in adults with spina bifida,
relations to gender, completeness of injury, the neurological level and
hydrocephalus.
Submitted.
IV
Aito S, D’Andrea M, Werhagen L, Farsetti L, Cappelli S, Bandini B,
Di Donna V.
Neurological and functional outcome in traumatic central cord
syndrome.
Spinal Cord 2007 Apr; 45(4):292-7.
1
CONTENTS
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Abstract....................................................................................................... 1
List of Publications..................................................................................... 2
List of abbreviations ................................................................................... 4
Introduction ................................................................................................ 5
4.1 Spinal cord ........................................................................................ 5
4.2 Classification of SCI ......................................................................... 6
4.3 Spinal cord injuries (SCI) ................................................................. 9
4.4 Traumatic SCI..................................................................................10
4.5 Central cord syndrome (CCS)......................................................... 11
4.6 Non-traumatic SCI.......................................................................... 11
4.7 Congenital SCI spina bifida (SB) ................................................... 12
4.8 Prognosis after SCI ......................................................................... 13
4.9 Pain after SCI.................................................................................. 14
4.10
Other medical complications after SCI ....................................... 16
4.11
Incomplete spinal cord syndromes .............................................. 18
4.12
Rehabilitation after SCI............................................................... 19
Aim of the thesis....................................................................................... 20
Material and Methods............................................................................... 21
6.1 Paper I-III........................................................................................ 21
6.2 Paper IV .......................................................................................... 22
Statistical analysis..................................................................................... 23
7.1 Paper I-III........................................................................................ 23
7.2 Paper IV .......................................................................................... 23
Results ...................................................................................................... 24
8.1 Traumatic SCI (I)............................................................................ 24
8.2 Non-traumatic SCI.(II).................................................................... 25
8.3 Spina bifida (SB) (III)..................................................................... 26
8.4 Traumatic central cord syndrome (CCS) IV................................... 27
Discussion................................................................................................. 29
9.1 Methodological issues..................................................................... 29
9.2 Neuropathic pain aetiology and age................................................ 29
9.3 Neuropathic pain and gender .......................................................... 30
9.4 Neuropathic pain and completeness of injury and level of SCI...... 30
9.5 Effect of pain on daily life .............................................................. 31
9.6 SB compared with the other diagnostic groups .............................. 31
9.7 Complications during in hospital rehabilitation/associated injuries31
General Conclusions................................................................................. 32
Future studies............................................................................................ 33
Sammanfattning på svenska ..................................................................... 34
Analisi del dolore neuropatico in pazienti affetti da lesione midollare .... 35
Acknowledgements .................................................................................. 38
References ................................................................................................ 40
2
3 LIST OF ABBREVIATIONS
ASIA
American Spinal cord Injury Association
C
Cervical
Central Cord Syndrome
CCS
DVT
Deep venous thrombosis
FIM
Functional independence measurement
HC
Hydrocephalus
IASP
the International Association for the Study of Pain
ISCOS
International Spinal Cord Society
L
Lumbar
LOS
Length of Stay in hospital
MC
Meningocele
MMC
Myelomeningocele
NSCI
Non-traumatic Spinal Cord Injury
NT
Non Testable
QoL
Quality of Life
R0M
Range Of Movements
S
Sacral
SB
Spina Bifida
SCI
Spinal Cord Injury
SCL
Spinal Cord Lesion
SCIM
Spinal Cord Injury independence measure
Th
Thoracic
UTI
Urinary tract infection
VAS
Visual Analogue Scale
WISCI
Walking Index for Spinal Cord Injured Individuals
ZPP
Zone of Partial Perseveration
3
4 INTRODUCTION
4.1
Spinal cord
The spinal cord is a part of the central nervous system (CNS) and is a continuation of the
neuronal tissue of the brain. It occupies the upper two thirds of the spinal canal and ends below
the first lumbar vertebra. At that level the cord broadens to form the conus medullaris. Neural
tissue identified as nerve roots constitutes the cauda equina and occupies the remainder of the
lumbar canal. The average length of the spinal cord is 43-45 cm. The cord, conus and cauda
equine are surrounded by the meninges. The spinal cord consists of 8 cervical nerves C (1-8), 12
thoracic nerves Th (1-12), 5 lumbar nerves L (1-5) and five sacral nerves S (1-5). The cervical
nerves control signals to the back of the head, the neck and shoulders, the arms and hands, and
the diaphragm. The thoracic nerves Th (1-12) control signals to the chest muscles, some muscles
of the back, and parts of the abdomen and the lumbar spinal nerves. L (1-5) control signals to the
lower parts of the abdomen and the back, the buttocks, some parts of the external genital organs,
and parts of the leg. Finally the sacral spinal nerves S(1-5) control signals to the thighs and
lower parts of the legs, the feet, most of the external genital organs, and the area around the anus.
The vertebral column is composed of 33 vertebrae: 7 cervical, 12 thoracic, 5 lumbar, 5 sacral
which are fused and 3 to 5 fused coccygeal vertebrae. The typical vertebra consists of body and
arch and the spinal cord lying within the arch (Gerald Fletcher et al 1992).
The blood supply of the spinal cord derives mainly from the anterior spinal artery. The grey
matter of the spinal cord is surrounded by white matter consisting of ascending and descending
fibres. Fibres carrying similar sensory information or motor functions travel together in tracts.
The major spinal pathways are as shown in table 1.
4
Table 1. Motor and Sensory tracts (according to Martha Freeman Somers et al 1992)
NAME
Travels in the
cord ipsilateral
or contra
lateral to
muscle it
innervates
Type of control
MOTOR
Lateral corticospinal
Ipsilateral
TRACTS
Voluntary motions
(limbs)
Ventral
corticospinal
Contra lateral
Voluntary motions
(axial)
Vestibuspinal
Both
Postural reflexes
Rubrospinal
Ipsilateral
Voluntary motions
(limbs)
Pontine
reticulospinal
Both
Modulation of spinal
reflexes
Medullar
reticulopsinal
Both
Modulation of spinal
reflexes
Lateral
spinothalamic
Contra lateral
Sharp pain temperature
light touch
Dorsal columns
Ipsilateral
Proprioception 2-point
discrimination, vibration,
fine touch.
Spinoreticular
Ipsilateral
Deep pain
SENSORY
TRACTS
4.2 Classification of SCI
Traumatic SCI is classified into five types by the American Spinal Cord Injury Association
(ASIA) and the International Spinal Cord Injury Classification System
The American Spinal Cord Injury Association or ASIA has defined an international
classification as shown in table 2 based on neurological levels, touch and pinprick sensations
tested in each dermatome (table 3), and strength of ten key muscles on each side of the body
(table 4), i.e. shoulder shrug (C4), elbow flexion (C5), wrist extension (C6), elbow extension
(C7), hip flexion (L2), knee extension (L3), ankle dorsiflexion (L4), long toe extension (L5), and
ankle plantar flexion (S1) (Ditunno et al 1994).
5
Table 2. ASIA classification A-E, type of SCI and description
ASIA
grade
SCI
Description
A
Complete
No motor and sensory functions preserved in the sacral
segments S 3-4
B
Incomplete
Sensory but not motor functions preserved below injury
C
Incomplete
Motor function is preserved below the neurological
level and more than half of key muscles below the
neurological level have a muscle grade less than 3.
D
Incomplete
Motor function is preserved below the neurological
level
and at least half of key muscles below the neurological
level have a muscle grade of 3 or more.
E
Normal
Table 3. Motor index 0-5*
Grade
Description
0
Total paralysis
1
1 palpable or visible contraction
2
Active movement, full range of motion, gravity eliminated
3
Active movement, full range of motion, against gravity
4
Active movement, full range of motion, against gravity and provides some
resistance
5
Active movement, full range of motion, against gravity and provides normal
resistance
5*
Muscle able to exert, in examiner’s judgement, sufficiently, pain on effort or
contracture
NT
6
Table 4. Sensory functions 0-2
Grade
Description
0
Absent
1
Impaired
2
Normal
The following definitions are important in order to understand SCI.
Complete SCI
Absence of sensory and voluntary motor functions in S3/4 segments.
Incomplete SCI
Some voluntary motor or sensory functions present in S3/4 segments
Neurological level
The lowest segment where motor and sensory function is preserved on both sides.
Paraplegia
Refers to damage in thoracic, lumbar and sacral, including conus medullaris and cauda equine,
but excluding lumbosacral plexus and peripheral nerve lesions. The result of the injury is an
impaired function of the lower extremities and /or pelvic organs, depending on the level of
lesion.
Tetraplegia
Refers to damage in cervical segments of the spinal cord resulting in impaired function in all
four extremities as well as the trunk and the pelvic organs
Vertebral (skeletal) level
The vertebral level is defined as the level of the vertebral / skeletal injury
Zone of partial perseveration
Only in complete SCI and includes dermatomes and myotomes caudal to the neurological level
that remains partially innervated.
Spasticity classification
For the classification of spasticity the most important and internationally used scale is the
modified Ashworth scale (Table 5).
7
Table 5. Modified Ashworth Scale
Score
Description
0
No increase in muscle tone
1
Slight increase in tone- a catch and release at the end of the range of motion.
1+
Slight increase in tone- catch followed by minimal resistance in remainder of
range of motion.
2
More marked increase in muscle tone through most of range
3
Considerable increase in tone, passive movement difficult
4
Affected parts rigid in flexion or extension
WISCI (Walking Index for Spinal Cord Injuries)
Walking index for SCIs is an international walking scale that has established reliability and
validity. The scale ranges from 0-20. 0 means no walking capability and 20 means that the
patient can walk without assistance or devices. With this scale it is possible to evaluate walking
capacity and the need for devices or assistance (Ditunno et al 2000, Kim et al 2007, Morganti et
al 2005).
FIM (Functional Independence Measure)
The Functional Independence Measure (FIM) is an 18-item, 7-level scale developed to
uniformly assess the severity of patients’ disability and medical rehabilitation functional
outcome. It measures different functional aspects of daily life. The FIM emerged from a
thorough developmental process overseen by the National Task force of Rehabilitation Research
(Hamilton et al 1994, Ottenbacher et al 1996).
SCIM (Spinal Cord Injury Independence Measure)
SCIM is a newly developed disability scale for patients with SCI. Its sensitivity to functional
changes in all subgroups of SCI (incomplete and complete injuries, paraplegia and tetraplegia)
was found to be better than that of the FIM (Catz el al 2001, Itzikovich et al 2007, Catz et al
2007).
4.3 Spinal cord injuries (SCI)
SCI is a serious lesion in the CNS that may cause lifelong disability.
There are mainly three types of SCI
1. Traumatic SCI
2. Non-Traumatic SCI
3. Congenital SCI spina bifida (SB)
8
4.4
Traumatic SCI
The annual incidence of traumatic SCI, not including those who die at the scene of the accident
is estimated to be approximately 40 cases per million population in the U.S. or approximately
11,000 new cases each year (Price et al 1994). In Sweden the incidence is about 16 cases per
million and the incidence in Europe is about 17,5/million (ISCOS meeting report Aito 2004).
The incidence of traumatic SCI is highest among young persons. Most patients have their injury
when they are between 20 and 40 years of age. About 80% of the SCI patients are males
(Pagliazzi et al 2003). Complete SCI is most common early in life and after violent accidents.
Patients injured after the age of 40 more often have an incomplete spinal cord injury. These days
few patients die during their in-hospital treatment (O’Connor 2005). Traffic accidents are the
most common cause of SCIs. Both drivers and passengers are at risk of SCIs from car,
motorcycle and bicycle accidents (table 1) ( Acton et al 1994, Zargar 2007). The second most
common cause is falling accidents which can be both from high heights and minor falls at home.
Spinal stenosis (a narrowing of the spinal canal) is common in older patients with SCI after falls
at home. Sports accidents are the cause of about 7% of the traumatic SCIs (De Vivo 1997).
Diving accidents are the most common sporting accidents and usually give rise to a complete
motor tetraplegia. Gun shot injuries are uncommon in Europe but occur more frequently in the
United States and in South America (Carroll 1997). The traumatic SCI patient has often suffered
from multitrauma. The most common associated injury is light head trauma (Davidoff et al
1992). Other common associated injuries are fractures, pneumothorax, wounds, severe head
injuries and injuries to the lungs and abdomen (Table 6). In traumatic SCI patients with
remaining SCI about 40% are tetraplegics and 60% are paraplegics. Complete SCI occurs in
about 40% of the cases and incomplete injuries in 60%.
Table 6. Causes of traumatic SCI, n=1016.
Causes
in
percent
Associated
injuries in
percent
Road traffic
accidents
52
56
Falling accidents
32
50
Sports accidents
7
19
Gun shots
2
50
Injuries at work
2
50
Other traumas
5
50
10
9
4.5
Central cord syndrome (CCS)
CCS is an incomplete syndrome that involves a greater motor weakness in the upper extremities
than in the lower extremities. The pattern of motor weakness shows greater distal involvement in
the affected extremity than proximal muscle weakness. Sensory loss is variable, and the patient
is more likely to lose pain and/or temperature sensation than proprioception and/or vibration.
Dysesthesias, in the upper extremities (e.g., sensation of burning in the hands or arms), is
common as well as sacral sensory sparing. Patients with traumatic CCS are older at the time of
injury than other traumatic SCI patients. This is probably due to the fact that many patients with
CCS have cervical spinal stenosis and get their SCI after a minor fall at home. Pickett et al 2003
and McKinley et al 2007 stated that CCS is the most common incomplete spinal cord syndrome
representing 44% of all cases, followed by cauda equine representing 26% of the incomplete
spinal cord syndromes. The prognosis after CCS is usually good (Harrop et al 2006, Pollard and
Apple 2003).
4.6
Non-traumatic SCI
Non-traumatic SCI is a growing problem as we currently live longer. The non-traumatic SCI
patients are in most cases older at the time of injury than patients with traumatic SCI. Most
patients are over 40 years of age at the onset of the disorder (Pagliacci et al 2003). About 40% of
the patients are females (Nair et al 2005). Patients with non-traumatic SCI more often have an
incomplete SCI than the traumatic SCI patients. The patients with non-traumatic SCI frequently
have other medical problems like hypertension, cardiac diseases, degenerative disorders, arthritis
and diabetes mellitus (McKinley et al 1999). Their rehabilitation is therefore complicated and
they have more medical needs than the traumatic SCI patients (Yokoyama et al 2006).
The major causes of non-traumatic SCI are infections, vascular myelopathies (Frisbie 2002) and
spinal stenosis both at lumbar and cervical level. In the last group the patients in many cases get
their SCI during or after surgical treatment. Tumours within the nervous system, both benign
e.g. meningeomas, lipomas and malignant e.g. astrocytomas, ependymomas and glioblastomas
are a cause of non-traumatic SCI. Myelitis can be the first sign of multiple sclerosis ( Fadil et al
2007).
Metastasis can giver rise to SCI but cancer patients are not included in the non-traumatic SCI
population due to the fact that they have a progressive malignant disease and therefore have
other medical needs. Furthermore they are not treated in a spinal cord unit.
11
10
4.7
Congenital SCI spina bifida (SB)
SB is a developmental defect which occurs within the first six weeks of pregnancy, possibly
caused by a combination of genetic and environmental factors (Padmanabhan 2006, Northrup
and Volcik 2000).
The rate of SB among newborns in Sweden gradually diminished from 0.55 per 1000 to 0.29 per
1000 between 1973 and 1993 (Nikkilä et al 2006).
SB is an incomplete closure of the vertebral column which usually is associated with a similar
anomaly of the spinal cord. In early embryo the nervous system is represented by the neural
groove, the lateral folds which unite dorsally to form the neural tube. An arrest in this process of
development leads to defective closure of the bony vertebral canal. In severe cases a sac
protrudes through the vertebral opening which may contain meninges only or also the flattered
open spinal cord meningomyelocele (MMC). In the least severe cases there is no protrusion but
a defect in the laminar arches may be palpable as a depression sometimes is covered by a dimple
or a tuft of hair (spina bifida occulta).
The causes of SB are largely unknown. Some evidence suggests that genes may be involved,
though in most cases there is no familial connection. Women with diabetes mellitus are more
likely to give birth to a child with SB. Apparently folic acid can decrease the occurrence of
neural tube defects, especially MMC even when it is given once a week.
The lumbosacral region is the most common site of SB, although it is sometimes also found in
the neck. SB may also be associated with other congenital abnormalities such as hydrocephalus
(HC). Approximately 90% of newborns with MMC also have HC, an accumulation of fluid in
and around the brain caused by the Arnold Chiari malformation. This must be managed early
with a shunt, or brain damage will occur when the baby’s head may no longer enlarge, after the
skull bones have fused. In Sweden about 80% of children with SB develop HC.
In a study on young adults with SB in Holland 67% suffered from HC (Barf el al 2007).
Children who have MMC have a varying degree of paresis in the lower extremities and higher
than usual occurrence of learning disabilities and attention deficits. Children with SB also tend
to be less adaptable, are more easily distracted, less attentive and persistent, and less predictable.
Neurogenic bladder is a major problem for children with SB and they also have problems with
bowel function (Verhoef et al 2005). Most children with MMC, and a small number with
meningocele (MC) or spina bifida occulta, have a tethered spinal cord.
12
11
4.8
Prognosis after SCI
Neurological recovery and functional improvement occur after traumatic and non-traumatic SCI
during standard treatment and rehabilitation, as a part of the natural recovery process. The
degree of recovery depends on the type, level and the severity of injury (Celani et al 2001).
Studies show that ASIA classification on admission to hospital after the injury is of utmost
importance for the prognosis (Burns and Ditunno 2001). If the SCI is complete the prognosis is
poor and a majority of the patients will remain complete on discharge from hospital (Alander et
al 1994, Coleman et al 2004, Fisher et al 2006, Kirshblum et al 2004, Schönherr et al 1999).
However, if the injury is incomplete the prognosis is much better (Catz 2002, Citterio et al 2004)
About half of the patients who are ASIA B (motor complete) on admission will improve at least
one ASIA grade on discharge. For patients that are ASIA C and D the prognosis is even better as
shown in table 7 ( Scivoletto et al 2004).
In summary, predicting the final neurological and functional outcome is of great importance in
planning the treatment, rehabilitation and discharge of patients with SCI.
Table 7. ASIA on Admission and discharge for traumatic SCI, percent, n=816
DISCHARGE
ADMISS
ION
A
A
92
4
4
0
0
B
2
48
49
1
0
C
D
0
2
30
60
8
0
0
0
2
68
30
E
B
C
13
D
E
12
4.9
Pain after SCI
Longstanding pain is a common problem after spinal cord injury in both traumatic and nontraumatic SCI ( Ragnarsson 1997, Turner et al 1999, Finnerup et al 2001, Norrbrink Budh et al
2003). The pain may be nociceptive or neuropathic (for definition see table 8). The incidence of
chronic pain was found in earlier studies to vary between 18% and 94%. A study carried out in
1962 which attempted to classify chronic pain in SCI subjects found that 37% of 52 suffered
from chronic pain (Kaplan et al 1962). Some years later another study reported an incidence of
suffering in 77% (Richards et al 1980). More recent studies have found that nearly all patients
with SCI during the in-hospital rehabilitation experience pain and that neuropathic pain is one of
the most common types of pain (New et al 1997). Furthermore that 61% of patients with SCI
suffered from pain with severe to moderate intensity (Demirel et al 1998).
Nevertheless neuropathic pain is one of the most challenging problems after SCI and
neuropathic pain affects quality of life.
A taxonomy of pain was developed and proposed by the SCI pain task force of the International
Association for the Study of Pain (IASP). In this classification which is mechanism based, the
pain is classified in three tiers (Siddall et al 2000 and 2001) (Table 9). The pain types are firstly
divided into nociceptive and neuropathic pain and secondly into musculoskeletal and visceral,
and thirdly into above-, at- or below- level neuropathic pain types. The third tier aims to identify
pain based on specific structures and pathology when it is possible.
In this thesis the IASP classification of pain was used
Several studies show that neuropathic pain currently affects quality of life and has a negative
impact on several domains of life (Nepomuceno et al 1979, Widerstrom-Noga 2001). In
Wollaar’s (2007) study chronic SCI pain and quality of life were both largely associated with
several psychological factors of which pain catastrophifing and SCI helplessness were the most
important (Wollaars 2007).
Usually neuropathic pain starts soon after the SCI. However in the acute phase after injury
patients, and especially those with traumatic SCI, may have other pain due to associated injuries
like fractures. Nowadays a high percentage of patients with traumatic SCI undergo surgical
treatment in order to stabilize the vertebrae and thus avoid further damage to the spinal cord
(Aito et al 2005).
One of the most important tasks in the rehabilitation after SCI is to treat neuropathic pain.
Neuropathic pain is difficult to treat successfully and there is currently no existing curative
therapy.
Treatment options may include pharmacotherapy, physiotherapy and psychological intervention.
Table 8. Definition neuropathic and nociceptive pain
Neuropathic pain
Nociceptive pain
A pain is diagnosed neuropathic when
burning or shooting in an area with
sensory disturbances to pinprick and
touch and without relation to movements
or signs of inflammation.
A pain is diagnosed nociceptive when
aching in an area with signs of
inflammation or / and with painful joint
movements.
14
13
Table 9. Proposed classification of pain related to an SCI (Siddall et al 2000 and 2001)
Broad type
Broad system
Bone joint, muscle trauma or inflammation
Specific structures and pathology
tier 1
tier 2
tier 3
Nocicpetive
Musculoskeletal
Bone joint, muscle trauma or inflammation
Mechanical instability
Muscle spasm
Visceral
Secondary overuse syndrome
Renal calcanus, bowel and /or sphincter
Dysfunction etc
Dysreflexic headache
Neuropathic
pain
Above–level
Compressive mononeuropathies
Complex regional pain syndrome
At level
Nerve root compression (incl. cauda
syndrome)
Syringomyelia
Spinal cord trauma/ischemia (transitional zone
etc)
Dual-level cord and root trauma (double lesion
syndrome)
Below level
Spinal cord trauma ischemia (central
dysesthesia syndrome)
15
14
4.10 Other medical complications after SCI
4.10.1 AUTONOMIC DYSREFLEXIA
SCI and especially cervical SCI imply serious disturbances in autonomic nervous system
function (Weaver et al 2006).The symptoms are episodes of high blood pressure, headache,
sweating and bradycardia. The rise in blood pressure can cause sudden death due to brain
haemorrhage. Common causes of autonomic dysreflexia are an over extended bladder, severe
constipation, sexual activity or urinary tract infections (UTI) (Chua et al 1996, Karlsson 2006,
Bravo et al 1998).
4.10.2 BOWEL DYSFUNCTION
Bowel dysfunction constitutes a problem in both the acute and chronic phase. Neurogenic bowel
dysfunction can cause both faecal incontinence and constipation. Bowel dysfunction has a
marked impact on quality of life (Lynch et al 2000). Hemorrhoids are common in the SCI
population. SCI patients more often than normal persons are on laxatives. Tetraplegic patients
had the highest prevalence of constipation, while patients with low paraplegia were less prone to
constipation (de Looze et al 1998, Han et al 1998).
4.10.3 DECUBITE/PRESSURE ULCERS
Pressure sores are more common in complete SCI patients (McKinley et al 1999) and occur over
bony prominences. Decubiti can lead to osteomyelitis, sepsis and even death. Several factors
make SCI patients vulnerable to the formation of decubiti:
1. SCI patients lack the sensation that stimulates protective weight shifts.
2. Skin collagen degradation
3. Compromised peripheral blood flow resulting in decreased blood flow and nutrient
supply to the tissue,
4. The skin and subcutaneous tissue are more vulnerable to normal trauma. Wherever
external pressure on soft tissue is greater than capillary pressure the result will be
ischemia.
When pressure ulcers occur, healing takes long time, and treatment is costly and may include
hospitalization and surgery (Walter et al 2002).
4.10.4 DEEP VEIN THROMBOSIS (DVT)
DVT occurs frequently following SCI, particularly in the acute phase. Peripheral vasodilatation,
absent or reduced lower extremity muscular function and immobility leads to venous stasis and
are important factors for the DVT development. Thrombi in the deep veins are potentially life
threatening and can lead to pulmonary embolism (Jones et al 2005).
4.10.5 DEPRESSION
SCI both traumatic and non-traumatic causes lifelong disability and may lead to depression both
in the acute and in the chronic phase. Depression is a significant problem associated with poorer
outcome of rehabilitation and lower quality of life (Anderson et al 2007). The suicide rate
among individuals with SCI is higher than in the general population especially in females (de
Vivo et al 1991). Hence, there is a need for increased awareness among rehabilitation staff and
general practitioners regarding depression and psychological adjustment difficulties after SCI
(Hartkopp et al 1998).
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4.10.6 HETEROTROPHIC OSSIFICATION
Ectopic bone formation is the formation of new bone within muscular and other connective
tissue below the level of lesion. It normally appears from 1 month to 4 months after injury and
leads to impaired functional status and contractures (Banovac et al 2004).
4.10.7 OEDEMAS, SWELLING OF LEGS AND FEET
Blood and lymph are not evacuated normally after a spinal cord injury and this will cause
swelling of legs and feet especially soon after the injury.
4.10.8 OSTEOPOROSIS
Following spinal cord injury both calcium and collagen are lost from the bones. The resulting
osteoporosis increases the likelihood of fractures. Osteoporosis progresses gradually for five
years after injury, at which time it reaches a plateau. Osteoporosis can cause fractures after light
traumas (Jiang et al 2006, Giangregorio et al 2006).
4.10.9 PNEUMONIA/ RESPIRATORY INSUFFICIENCY
Respiratory complications are the most common cause of death following spinal cord injury
(Frankel et al 1998). These complications occur as a result of a reduction in inspiratory and
expiratory ability. Inadequate inspiration results in reduced ventilation of the lungs leading to
atelectasis. Ineffective coughing allows secretions to build up in the lungs with subsequent
atelectasis, pneumonia, and respiratory insuffiency resulting (Soden et al 2000).
4.10.10 SPASTICITY
Spasticity is a disorder of the motor system that occurs after injury to the CNS, which may
increase the disability of individuals with SCI. In SCI patients symptoms of spasticity are often
present after a period of spinal shock and in many cases, the quality of life (QoL) is negatively
affected. Spasticity is more prevalent in higher lesions and in incomplete lesions and the
presence of problematic spasticity has been significantly correlated with cervical incomplete
(ASIA B-D) injury (Sköld et al 1999). There is a significant association between spasticity and
contractures (reduced ROM). Quick stretching of muscles excite exaggerated reflex responses,
cutaneous stimuli also evoke abnormal reflex responses. The Ashworth scale is used to measure
spasticity. There was a poor correlation between clinically rated (Ashworth Scale) spasticity and
self-rated general spasticity and a modest correlation between Ashworth Scale and self-rated
present spasticity (Lechner 2006).
Treatment includes rehabilitation techniques and modalities, physiotherapy pharmacological
options, injection techniques, intrathecal baclofen, and surgery (Adams et al 2005, Sköld 2000).
A SCI patient can benefit from spasticity in daily living, when dressing, walking and transfers.
To measure spasticity a combination of electrophysiological and biomechanical techniques gives
hope of a full characterization of the spastic syndrome (Biering-Sörensen et al 2006).
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4.10.11SEXUAL PROBLEMS
Sexual function and its impact on QoL is a major issue to a majority of people living with SCI.
Most SCI women remain fertile and can conceive and bear children.
Depending on the level of injury, men may have problems with erection and ejaculation, and
most will have compromised fertility due to decreased motility of their sperm (Linsenmeyer and
Pekash 1991, Slot et al 1989). Treatments for men include vibratory or electrical stimulation and
drugs such as sildenafil.Many couples may also need assisted fertility treatments to aid spinal
cord injured men to father children. As SCI victims often are young at the time of injury
sexuality and fertility are of utmost importance for living a full-worthy life (Westgren et al 1997,
Monga et al 1999).
4.10.12UROLOGICAL PROBLEMS
Most spinal cord injuries affect bladder functions because the nerves that control the functions of
those organs originate in the segments near the lower termination of the spinal cord and are cut
off from brain input. Without coordination from the brain, the muscles of the bladder and urethra
cannot work together effectively, and urination becomes impaired. The bladder can empty
suddenly without warning, or become over-full without releasing. In some cases the bladder
releases, but urine backs up into the kidneys because it is not able to get past the urethral
sphincter. The great risk that urologic dysfunction poses is possible damage to the kidney
function. It is therefore essential that the bladder is emptied completely to avoid urinary tract
infections (UTI), which is a common complication after SCI. (Stover et al 1989 Biering
Sörensen et al 1999 Esclarin de Ruz et al 2000).
Most people with spinal cord injuries use intermittent catheterization to empty their bladders
(Cardenas et al 1995 Moore et al 2006).
4.11 Incomplete spinal cord syndromes
1. Anterior cord syndrome involves loss of motorfunction /movement and sensation of
pain and temperature, but with preserved deep sensation and vibration.
2. Brown-Séquard syndrome involves a relatively greater ipsilateral loss of
proprioception and motor function, with contra lateral loss of pain and temperature
sensation.
3. Central cord syndrome is described above.
4. Conus medullaris syndrome is a sacral cord injury with or without involvement of the
lumbar nerve roots. This syndrome is characterized by areflexia in the bladder, bowel,
and to a lesser degree, lower limbs. Motor and sensory loss in the lower limbs is
variable.
5. Cauda equina syndrome involves injury to the lumbosacral nerve roots and is
characterized by an areflexic bowel and/or bladder, with variable motor and sensory loss
in the lower limbs. Because this syndrome is a nerve root injury rather than a true SCI,
the affected limbs are areflexic. This injury is often caused by a central lumbar disk
herniation.
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4.12 Rehabilitation after SCI
The rehabilitation after SCI starts immediately after the accident. The rehabilitation of SCI can
be divided in three parts.
1. The first part is acute rehabilitation which takes place during the first months after the
SCI. This period can also be called in-hospital rehabilitation period. The immediate
course of action may be a neurosurgical intervention to stabilize the spinal canal in order
to avoid further damage to the spinal cord. Following that the patient begins learning to
live with the SCI, learning to empty the bladder and bowel and learning to use adequate
aids. When this period is over the patient is usually discharged from hospital and the
second part starts. Usually the in-hospital period is three months for a paraplegic patient
and 6 months for a tetraplegic patient. The in hospital period can be much longer due to
medical and social complications.
2. During the second part the patient learns to live in his normal environment, to get in
contact with his work, in order to gain optimal quality of life
3. During the third phase of the rehabilitation the patient is back to “normal” but has to do
physiotherapy and yearly check-ups to avoid complications. The rehabilitation after SCI
is a life long process.
Spinalis SCI unit
The Spinalis unit is an outpatient clinic for patients with traumatic and non-traumatic SCI and
for adults, over the age of 18 with SB in the greater Stockholm area. The greater Stockholm
area comprises a population of about 2, 0 million. The Spinalis SCI unit provides a life-time
care for these patients. The primary activity is a yearly check-up which started in 1991 as a
project; Solberga projektet. In 1995 the unit became a part of the Local Muncipal Health.
Today the Spinalis SCI unit is a part of the Karolinska University hospital.
Spinal Unit of Florence
The initial activity started in 1978 under the leadership of Professor Massimo Missau. During
the years the activity has increased and the spinal unit currently has 50 beds. The director is Dr
Sergio Aito. The spinal unit is a part of the Careggi hospital which is the university hospital of
Florence. The unit has a urological department and an outpatient clinic for follow-up and
visits. The professional staff of the unit includes specialists in neurology, anaesthesiology,
rehabilitation medicine, orthopaedic surgery and urology.
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5 AIMS OF THE THESIS
The general aim of this thesis was to analyse the prevalence of neuropathic pain in different
types of SCI and its relation to different neurological and functional parameters. Furthermore,
the neurological and functional outcome after traumatic CCS was analyzed.
The specific aims of the four papers included in the thesis were as follows:
I and II. To analyse the prevalence of neuropathic pain in (I) traumatic and (II) non-traumatic
SCI and to asses the predictive values of age at time of injury, gender, level of injury, and
completeness of injury for the development of at level and below level neuropathic pain.
Furthermore, the impact of neuropathic pain on daily life was evaluated.
III. To analyse the prevalence of neuropathic and nociceptive pain in adults with SB and relate
the pain to the level of injury, completeness of injury and to the presence of hydrocephalus.
IV. To analyse the functional and neurological outcome, the prevalence of neuropathic pain and
spasticity in patients with traumatic CCS and relate these factors to age at the time of injury.
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6 MATERIAL AND METHODS
6.1
Paper I-III
All patients consulting the Spinalis SCI unit, outpatient clinic during the period 1995-2000 with
SCI were included in the retrospective register study. The Spinalis post-acute unit provides
yearly check-ups for patients with traumatic and non-traumatic SCI and for adults (over the age
of 18) with SB living in the greater Stockholm County. Data were gathered at the patients’ first
examination at the unit. For the traumatic injured patients the median time point from injury to
examination was 6 years (range 0-48 years). A classification according to ASIA (A-E) was
performed. Patients with incomplete SCI were due to small numbers of patients with ASIA B
and C analysed together. Patients classified as ASIA E were re-classified according to their
initial classification usually ASIA E to ASIA D.
Neurological level of injury was defined and the level of injury was classified as tetraplegia or
paraplegia. Included in the studies were 402 patients with traumatic SCI, 95 with non-traumatic
SCI and 110 adults with SB.
The traumatic (n=402) and non-traumatic SCI (n=95) patients were divided into five age groups
according to age at the time of injury/disorder (0-19, 20-29, 30-39, 40-40 and over 50 years of
age) Furthermore, the patients with non-traumatic SCI were divided in 5 groups according to the
diagnosis of the spinal cord disorder (vascular myelopathy, spinal stenosis both lumbar and
cervical, infections, benign tumours, malignant tumours).
Adults with SB (n=110) were divided in two groups; patients with and without HC.
The pain was diagnosed by the experienced examining neurologist as neuropathic when it met
the criteria presented by the IASP task force.
When neuropathic pain was diagnosed it was classified as above level pain, at level pain and
below level pain. Injuries at level of L3 and below were considered by the examining
neurologist as difficult to divide in at level and below level pain. In our study only one included
patient with neuropathic pain had a neurological level below L3. This patient’s pain was
classified as at-level neuropathic pain. In the SB group, pain was not divided in above-, at- or
below neuropathic pain due to the fact that most patients with SB have a lumbar level and
therefore it is difficult to divide the pain according to the neurological level.
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6.2
Paper IV
All patients with traumatic CCS undergoing acute rehabilitation at the Spinal Unit of Florence,
Italy during January 1996 to June 2002 underwent a follow up visit at the outpatient clinic 2004.
The follow up was performed at least 18 months after the injury.
In total 87 patients with CCS were admitted to acute rehabilitation at the Spinal unit of Florence
during this period. Subjects were excluded if they 1) had died before the follow-up visit; 2) if
data were missing 3) they were unable to be assessed by FIM/WISCI due to mental illness or
orthopaedic extremity impairment. In total five patients were excluded and thus 82 patients were
included in the study.
The collected data were; year of injury, gender, age at time of injury, cause of injury, vertebral
lesion (level and type) treatment of vertebral lesion (conservative or surgical) length of inpatient
rehabilitation, and complications during the acute rehabilitation, ASIA A-E on admission,
discharge and at follow-up, FIM and WSCI on discharge and at follow-up and the presence of
spasticity and neuropathic pain at follow-up.
The causes of injury were divided into three groups 1) falls 2) road traffic incidents 3) sport
injuries.
The types of vertebral lesions were divided into four groups 1) SCIWORET (SCI without
evidence of trauma) 2) fracture 3) fracture/dislocation and 4) pure dislocation.
The treatment of the vertebral lesions was classified as conservative or surgical. Neurological
evaluation was performed according to ASIA including motor and sensory scores. The activity
of daily living was evaluated by means of the FIM scale (0-126), and the ability to walk was
measured by the WISCI scale 0-20. The patients were divided in three groups, group 1 (score
range) 0-2: almost impossible to walk, group 2 (score range 3-17) ability to walk with different
degrees of help and group 3 (score range 18-20) ability to walk independently.
The pain was classified as neuropathic according to the IASP (Siddall et al 2001) when
experienced as burning or shooting in an area with sensory disturbances to pin prick and touch
and with no relationship to movements and inflammatory signs. The pain could be spontaneous
or provoked by touch or cold, continuous and /or with paroxysmal components. Spasticity was
measured by the modified Ashworth scale (0-5)
Finally the patients were divided into four age groups according to the age at the time of injury
1) 0-30 years 2) 31-50 years 3) 51-65 years 4) over 65 years of age.
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7 STATISTICAL ANALYSIS
7.1
Paper I-III
Groups and subgroups are presented as absolute numbers and percentages.
Fisher’s exact test was used to compare groups when the numbers were too small to allow for
chi2 test.
Logistic regression was used to quantify the association between some possible risk factors
P<0, 05 was considered significant.
Categorical variables were compared using chi2 test.
7.2
Paper IV
Groups and subgroups are presented as absolute numbers and percentages.
The differences in FIM and WISCI scores across the clinical demographic explanatory variables
were assessed using the one way analysis of variance and the corresponding F statistic.
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8 RESULTS
8.1
Traumatic SCI (I)
Overall presence of neuropathic pain
40% of the patients included in the study met the criteria of neuropathic pain. 34 % of the
patients with neuropathic pain described at level neuropathic pain and 66 % described below
level neuropathic pain.
Age
The prevalence of neuropathic pain increased with age up to 30-39 years of age. There was a
slight relative decrease in the group aged 40-49 years. The patients above 50 years of age at the
time of injury showed the highest prevalence. The prevalence of either an at level pain and
below level pain or both in different age groups were significantly different (chi2= 12.37 df=4)
and the contribution of the increasing trend with age groups was significantly different
(chi2=12.37, df=4).
ASIA impairment scale
42% of the patients with complete SCI (ASIA A) and 39% of the patients with incomplete SCI
reported neuropathic pain. Neuropathic pain at the neurological level was present in 9% of the
patients with complete SCI and in 15 % of the patients with incomplete injury. Below level pain
was present in 33% of the patients with complete SCI and in 24% of the patients with
incomplete injury.
Gender
There was a predominance of males in all age-groups. However, in total 46% of the females and
38% of all males described neuropathic pain.
Tetraplegia/paraplegia
In total, 41% of the patients with tetraplegia and 40% of the patients with paraplegia experienced
neuropathic pain. Of the patients with tetraplegia 16% had at level neuropathic pain and of the
paraplegic patients 11% had at level pain. 29% of the patients with paraplegia and 26% of the
patients with tetraplegia described below level neuropathic pain.
Furthermore patients with low complete paraplegia (Th10-S4) more often experienced
neuropathic pain than patients with high complete paraplegia (Th1-9) This difference reached
statistical significance (chi2= 44,57 df=1).
Patient rating of the pain as a problem in daily life
In total 72% of the patients with neuropathic pain reported that their pain was a problem in their
daily life. The remaining 28% reported that pain was not a problem in their daily life.
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8.2
Non-traumatic SCI.(II)
Prevalence of neuropathic pain
In total 38% of the patients experienced neuropathic pain. 39% reported at level neuropathic
pain 61% reported below level neuropathic pain.
Age
No statistically significant difference was found in the prevalence of neuropathic pain between
those diagnosed at ages up to 39 years of age and those aged 40 years of age or more (chi 2
=1,30, df=1).
ASIA impairment scale
The frequency of neuropathic pain was similar in patients with complete lesion (ASIA A) and
those with incomplete lesion (ASIA B-D).
Gender
Half of the women reported neuropathic pain compared with 30% of the males. However the
difference was not statistically significant (chi2=1.88, df=1). Females had more often below
level pain than males and this difference was statistically significant (chi2=5, 27, df=1).
Paraplegia/tetraplegia
44% of the patients with tetraplegia and 35% of the patients with paraplegia reported
neuropathic pain.
Patient rating of the pain as a problem in daily life
67% of the patients with neuropathic pain rated their pain as a severe problem or a problem to
some extent in their daily life. Patients diagnosed with neuropathic pain in older age reported
pain as a problem in daily life more often than younger patients. The difference reached
significance statistically (p= 0,01). Women reported that pain was a problem in daily life more
than males. Also this difference reached significance statistically ( p=0,05).
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8.3
Spina bifida (SB) (III)
Prevalence of neuropathic pain
In total 11% experienced neuropathic pain. Eight of 67 patients with lumbar level and 3 of 29
patients with thoracic level experienced neuropathic pain. Five of 54 patients with complete SCI
and 6 of 43 patients with incomplete SCI suffered from neuropathic pain. In patients with HC 3
of 57 and 10 out of 53 of the patients without HC experienced neuropathic pain.
Prevalence of nociceptive pain
Nociceptive pain was present in 24% of the patients included in the study. Back pain was the
most common type of pain which affected 14 patients. 11 of these patients were walking with or
without aids and/or devices. Shoulder pain was present in five patients and four patients were
not able to localize their pain.
Age
Most of the patients included in the study were young; 59% were between 18 and 29
years of age and only 19% were over the age of 40. The mean age at the time of
examination was 28,7 years (range 18-55 years of age).
Gender
In the material there was a slight female predominance. There was no statistical difference
between males and females regarding the prevalence of neuropathic pain.
ASIA impairment scale
49% were classified as ASIA A, 38% patients had an incomplete
SCI (ASIA B-D), 9% were ASIA E and 4% were not testable due to cognitive or
other intellectual dysfunctions.
Neurological level
In total 26% had a thoracic level and 61% had a lumbar level. L3 was
the most common neurological level followed by L1.
HC
HC was present in 52% and was most common in younger patients. In the age group 18-29
years, 63% had HC and 19% had HC in the age groups over of 40 years. This difference reached
statistical significance (p=0.011).
In the study 63 % of the males and 43% of the females had HC. This difference was statistically
significant (p=0.0186).HC was most common in individuals with complete SCI and in patients
with a thoracic level of injury. 43% of the individuals with a lumbar level had HC. This
difference is statistically significant (p= 0, 0036). 83% of patients with a complete SCI and 17%
with an incomplete SCI (ASIA B-D) had HC. This difference was also statistically
significant (p=0,001).
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8.4
Traumatic central cord syndrome (CCS) IV
Prevalence of neuropathic pain
Neuropathic pain was present in 47% of patients at follow-up and was more common in older
patients.
Age
Patients aged over 65 years of age at the time of injury had poorer neurological and functional
outcome and more often experienced neuropathic pain than patients injured before 65 years of
age.
ASIA impairment scale and the neurological level
On admission, two patients were classified as ASIA A, 12 as ASIA B, 37 as ASIA C and 31 as
ASIA D. On discharge no patient was classified as ASIA A or B, while eleven scored ASIA C,
70 ASIA D, and one was ASIA E. At follow-up eight patients, who were discharged as ASIA D,
became ASIA E. The C6 level was found to be the most common neurological level on
admission, discharge and at follow-up.
Gender
12% of the included patients were females and 88% were males.
Causes of injury
Road traffic accidents (57%) were the most common cause of injury followed by falls (36%).
Diving was the most common sport accident.
The mean age for falls was 58 years of age, for road traffic accidents 50 years of age and for
sport related injuries 23 years of age.
Vertebral lesion
58% sustained hyperextension injury without evidence of fracture/dislocation (SCIWORET) by
imaging/X-ray, but showed evidence of spinal canal stenosis. Fractures in the spine were found
in 26% of patients, fracture/dislocation in 13% and pure dislocation in 3%. Patients without
radiological evidence of fracture/dislocation were older than patients with fracture dislocation.
Surgical treatment
45% of the patients underwent surgical treatment with anterior decompression and fusion and
55% of the patients were treated conservatively.
Associated injuries
More than half of the patients had associated injuries. Light brain injury was the most common
associated injury and was present in 34% followed by fractures in 14% of the patients.
Complications during the acute rehabilitation
Complications occurred in 28% of the cases. The most common complications were respiratory
problems (in 30%) and DVT (in 26%). Other complications were cardiac arrhythmia in 13% and
pyelonnephritis, gastric ulcer and pressure sores in 22%
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Length of stay (LOS) in hospital
The mean LOS was 120 days (range 24-390) and was longer for patients who underwent
surgical treatment. The explanation was that patients who underwent surgery had a more severe
vertebral injury (see discussion). Patients aged between 31 and 50 at the time of injury had the
longest hospitalisation while patients aged 66 years or more at the time of injury had a shorter
stay in hospital. The older patients were often referred to other hospitals for rehabilitation.
Spasticity
Spasticity at follow-up was present in 66% of the patients. 72% of patients with spasticity
claimed that their spasticity was a serious problem in their everyday living. Regarding spasticity,
there was no statistically significant difference found between patients aged less than 50 years of
age and those aged over 50 years of age at the time of injury.
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9 DISCUSSION
9.1
Methodological issues
In all four studies neuropathic pain was studied regardless of its intensity. This method is likely
to give a higher frequency of pain reports than studies which include only patients spontaneously
complaining of pain, as described in earlier studies. However, in many studies chronic pain and
not only neuropathic pain has been included (Richards et al 1980, Turner et al 2001).
The standard criteria presented by the IASP task force (Siddall et al 1997, Siddall et al 2000)
were used to identify neuropathic pain. In general the reliability is high but the response might
be influenced by environmental and psychological factors. Especially in adults with SB the pain
diagnosis might be influenced by the cognitive dysfunction that may be present in many adults
with SB (Fletcher at al 2002, Dennis et al 2007, Barf et al 2003).
Data were gathered at different times after the onset of the SCI. For patients with traumatic SCI
data were gathered in several cases many years after the injury. For the non-traumatic group the
data were in most cases gathered within a year after the SCI diagnosis. Adults with SB were in
all cases examined after the age of eighteen. The CCS data were gathered at minimum 18
months after trauma and maximum eight years after trauma. Patients with traumatic CCS injured
between 1996 and 2002 were examined at follow-up in the year 2004.The pain at various ages
was studied rather than pain related to age regardless of the age when the accident happened.
Some patients had their injury many years ago and at that time the quality of care was not as it is
today. This might be an explanation as to why they had a higher risk of developing neuropathic
pain. For example treatments of UTI and pressure sores were not as advanced 20 years ago as
they are today. Insufficiently treated pain may give rise to central sensitisation that may induce
neuropathic pain or increase the magnitude of a present neuropathic pain. For instance intense
and insuffiently treated nociceptive pain may give rise to central sensitisation processes that
increase the magnitude of already present neuropathic pain.
All patients in study I-III were examined at their first visit and were classified according to
ASIA and the neurological level. In all four studies the ASIA impairment scale was used. This
scale was initially created for traumatic SCI and is therefore an excellent measure for the
patients with traumatic SCI and for those with traumatic CCS. For patients in study II and III we
used the ASIA classification although it is not created for these types of injuries and thus not
validated. The ASIA classification was used as there is currently no better existing scale.
However, in future methodological studies, a validation of ASIA scales needs to be carried out
in these patient groups.
9.2
Neuropathic pain aetiology and age
In the traumatic group the cause of the SCI was not analysed. This means that the patients were
not divided in groups according to the cause of the traumatic SCI. Dividing the patients into
different groups on the basis of the cause of the SCI may give additional information. Patients
with non-traumatic SCI were divided into five diagnostic groups. 95 patients in total were
included which means that in, for example, the group diagnosed with malignant tumours only 11
patients were included. As astrocytoma mostly affects children, the mean age in this group was
16, 3 years at the time when the spinal cord symptoms appeared (Yule 2001).
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The patients in the subgroup vascular myelopathies had the highest mean age which was
expected since the diagnoses in this subgroup (aortaaneyrysm, infarction and other vascular
myelopathies) mainly affect persons above the age of 50 (Ohsawa et al 2007).
In CCS, neuropathic pain was analysed at follow-up, performed at least 18 months after injury.
Neuropathic pain was most common in the oldest group of patients. Like in the traumatic SCI
group neuropathic pain increased with age at the time of injury. Patients with traumatic CCS are
usually older at the time of injury than other traumatic SCI. In the present study on patients with
traumatic CCS the mean age was 56 years which is more than 10 years older at the time of
injury than other traumatic SCI. The result shows that the prevalence of below level neuropathic
pain had its peak in patients aged up to 40 years at the time of injury whereas the prevalence of
at level neuropathic pain was predominant in those injured after 40 years of age. On the other
hand in adults with SB neuropathic pain was found to be rare and was not considered to be a
major problem in daily life as was the case among the other studied groups of patients.
9.3
Neuropathic pain and gender
In traumatic SCI there was a strong male predominance (79, 5%). The same predominance was
not found in the non-traumatic group but in the group of traumatic CCS patients.
In adult SB patients there was in contrast to the other patient groups a slight female
predominance.
A male dominance in the traumatic SCI is likely due to a higher exposure to violent accidents. In
the traumatic group it is well-known that the most common cause of accidents is road traffic
accidents (Connor 2002). The cause of injury was studied in traumatic CCS and 57 % of the
cases in this study were due to traffic accidents.
The analysis of pain showed that a statistically significant difference was found between men
and women regarding below level neuropathic pain in non-traumatic SCI. This was however not
unexpected. A number of clinical studies have shown that men and women experience pain
differently (for a review see Berkley 1997). Females have lower thresholds, greater ability to
discriminate, higher pain rating and less tolerance of stimuli. This is valid for all types of pain
except Horton’s headache. SCI women also had a higher use of analgesics than males
(Norrbrink Budh et al 2003).
9.4
Neuropathic pain, completeness of injury and level of SCI
There were no differences in neuropathic pain between paraplegia/tetraplegia and incomplete
/complete SCI. When the patients with complete paraplegia were analysed in detail, those with
low paraplegia (Th10-S4) more often had neuropathic pain than those with a higher neurological
level (Th1-9). This difference however, is not an effect of age as they had almost the same mean
age. Thus, this might be due to the level of injury.
In the non-traumatic SCI group 38% of the patients suffer from neuropathic pain. As in the
traumatic group no relation was found between level of lesion and completeness of lesion. It
must be emphasized that in the non-traumatic group only 12% had a complete SCI.
In adults with SB no differences in the prevalence of neuropathic pain were found between
patients with complete/incomplete lesion or with paraplegia/ tetraplegia.
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9.5
Effect of pain on daily life
Pain is one of the factors that influences daily life (Felix 2007).
Patients with traumatic and non-traumatic SCI were interviewed about the impact of pain on
daily life. 70% of both traumatic and non-traumatic SCI patients experienced a great impact
from pain on their daily life. One third of the patients with pain reported that pain was a big
problem in their daily life. This is in accordance with a study done by Anke et al 1995 showing
that pain caused a significant psychosocial stress in half of the patients. In the studies on patients
with traumatic CCS and adults with SB the patients were not interviewed if the pain influenced
their daily life. It is reasonable to believe that patients with traumatic CCS also are highly
affected by pain on their daily life. Adults with SB seldom complain about pain. This might be
due to the fact that SB is an early developmental disease and that they have experienced their
pain for many years. Another explanation might be that their cognitive dysfunction makes it
difficult for them to express their pain when interviewed. The latter seen to be the most plausible
explanation.
9.6
SB and compared with the other diagnostic groups
SB is an early developmental defect. One of the major problems in this diagnostic group is HC,
present in about half of the patients included in the study. The prevalence of HC in the study is
low compared to other studies. This may be explained by the fact that some patients with HC die
during childhood due to shunt-complications (Alatise et al 2006). Another main problem for
patients with SB is a cognitive dysfunction causing severities with learning, attention, memory
and in social life (Fletcher et al 2002, Iddon et al 2003, Barf et al 2003) thus, it can be difficult to
rehabilitate adults with SB.
In study III nociceptive pain was also studied in adults with SB and not only neuropathic pain.
The prevalence of nociceptive pain was 26% and it was concluded that it was due to overuse of
muscle. Patients with walking capability had back pain. This implies that it is essential to teach
the adults with SB to use adequate aids/devices when walking.
9.7
Complications during in hospital rehabilitation/associated injuries
In study IV (traumatic CCS) studied data included different types of vertebral injury, treatment
of vertebral lesion, associated injuries complications during the in-hospital rehabilitation.
Furthermore, walking capability, FIM, bowel and bladder function, spasticity and LOS were
studied. The data give a good understanding of the functional and neurological outcome after
traumatic CCS. They showed that half of the patients had associated injuries and that
complications occurred in 28% of the cases. Interestingly 58% of the patients with traumatic
CCS sustained hyperextension injury without fracture or luxation (Pickett et al 1996). 45%
underwent surgical treatment, a low figure when compared with other types of SCI. Nowadays
the majority of patients with traumatic SCI are surgically treated (Aito et al 2005). In summary
the prognosis is usually good after traumatic CCS but older patients have poorer outcome than
younger patients. The length of stay in hospital is long for CCS patients as it is for most of the
traumatic SCI patients.
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10 GENERAL CONCLUSIONS
-Neuropathic pain is a major problem in patients after traumatic and non-traumatic SCI. It
affects the quality of life.
-In traumatic SCI the prevalence of neuropathic pain increases with age at the time of injury.
-No correlation was found between the development of neuropathic pain and level of injury and
completeness of injury in both traumatic and non traumatic SCI.
-Age at the time of injury had no impact on spasticity in patients with traumatic CCS.
-No subgroup of SCI with a greater risk of developing neuropathic pain could be identified.
-Patients with CCS are mostly older at time of injury than other traumatic SCI syndromes.
-Adults with SB rarely experience neuropathic and nociceptive pain. Nociceptive pain in
patients with SB was mostly back pain in patients with walking capability.
-The most common cause of traumatic CCS was traffic accidents followed by falls.
.
-The prognosis for patients with CCS is normally good but individuals injured at an older age
have a poorer outcome than individuals injured early in life.
-About half of the patients with traumatic CCS underwent surgery after their SCI. This figure is
low compared to other traumatic SCI.
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11 FUTURE STUDIES
There are several areas in SCI research that need to be further high-lighted.
1) There is a need for a standardized international classification for the taxonomy of pain In a
recently published paper (Treede et al 2007) a definition and a grading system was presented
developed by a group of experts from the neurological and pain community. This has to be
further evaluated in order to be included in the clinical routine.
2) Concerning pharmacological treatment the important questions are a) when to start
pharmacological treatment and which substances to use. Age at the time of injury and pain
intensity are factors that play a major role in the choice of pharmacological treatment and have
to be further analyzed.
3) Factors associated with neuropathic pain must be identified. Is there a difference between
patients stating that their pain has no impact on daily life and patients who classify their pain to
be a big problem that affects their quality of life (Hanley et al 2006)? Is neuropathic pain more
common in patients with psychiatric diseases or in those who got their SCI after a suicide
attempt?
4) Aging with SCI is a very important topic as patients with SCI today can have a normal
lifespan. What will happen with pain over time? Will it be more intense due to aging or to other
medical complications such as for example arthrosis?
5) In the SB group cognitive impairments and socioeconomic factors need more attention. How
can we help young individuals with SB to live a full-worthy life? To find an adequate
occupation for these patients is an important task. Today many SB patients live a life apart from
the society in general.
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12 SAMMANFATTNING PÅ SVENSKA
Neuropatisk smärta är ett vanligt och svårbehandlat symptom efter både traumatisk och icketraumatisk ryggmärgsskada. Prevalensen varierar från tidigare studier. Hos vuxna med
ryggmärgsbråck är neuropatisk smärta ovanlig.
Mål med avhandlingen var att analysera prevalensen av neuropatisk smärta hos patienter med
traumatisk och icke-traumatisk ryggmärgsskada samt hos vuxna med ryggmärgsbråck. Vidare
studerades hur mycket smärtan påverkade livskvaliten. Finns skadetyp med ökad risk att
utveckla neuropatisk smärta? Slutligen studerades prognosen efter central cord syndrome.
Patienter med traumatisk (n=402) och icke-traumatisk ryggmärgsskada (n=95) samt vuxna med
ryggmärgsbråck (n=110) som kontrollerades på Spinalismottagningen under åren 1995-2000
ingick. Data insamlades från årskontrollen då patienterna undersöktes och klassificerades enligt
ASIA (A-E), neurologisk skadenivå samt intervjuades avseende förekomst av smärta och hur
mycket smärtan påverkade livskvaliten. Smärta klassificerades som neuropatisk om kriterier
uppsatta av IASP (Internationell Association for the Study of Pain) uppfylldes. Traumatiska och
icke-traumatiska ryggmärgsskador indelades i 5 åldersgrupper avseende ålder vid skadetillfället.
Icke-traumatiska ryggmärgsskador indelades i fem diagnosgrupper. Vuxna med ryggmärgsbråck
indelades efter huruvida hydrocephalus förelåg eller ej.
Patienter med central cord syndrom som vårdades på Spinalenheten i Florens, Italien under
perioden 1996-2004 ingick. Follow-up besök skedde minst 18 månader efter skade-tillfället.
Data studerades från inkomst till sjukhus, vid utskrivning samt vid follow-up. Data som
studerades var skadeorsak, associerade skador, behandling (konservativ eller kirurgisk), ASIA,
typ av skelettskada, ålder, kön, neurologisk skadenivå, komplikationer under vårdtiden, FIM och
WISCI (gångskala). Patienterna indelades i åldersgrupper avseende på ålder vid skadetillfället.
Neuropatisk smärta förekom hos 40% respektive 38% procent av patienterna med traumatisk
och icke traumatisk ryggmärgsskada samt hos 11% av vuxna med ryggmärgsbråck. Neuropatisk
smärta hos traumatiska men ej hos icke-trauamtiska ryggmärgsskador ökade med ålder vid
skadetillfället. Det förelåg ej någon skillnad i neuropatisk smärta mellan patienter med tetraplegi
/paraplegi eller mellan inkompletta /kompletta skador. När neuropatisk smärta förelåg påverkade
den livskvaliten. Det framkom ingen skillnad mellan patienter med hydrocephalus eller ej
avseende smärta. Hälften av patienterna med ryggmärgsbråck hade hydrocephalus . Vanligaste
skadeorsaken vid central cord syndrom var trafikolyckor följt av fallolyckor. Lindrig hjärnskada
var vanligaste associerade skadan. Patienter med hög ålder vid skadetillfälle hade sämre prognos
och ofta mer neuropatisk smärta än de som skadats i yngre år. Spasticitet var lika vanlig hos
äldre som hos yngre patienter.
Sammanfattningsvis är neuropatisk smärta vanligt hos patienter med traumatisk, icke-traumatisk
ryggmärgskada samt hos patienter med central cord syndrom men är mindre vanlig hos vuxna
med ryggmärgsbråck. När smärta förekommer påverkar den livskvaliten. Ingen skadetyp med
ökad risk att utveckla neuropatisk smärta framkom. Hos icke-traumatiska ryggmärgsskador var
smärta under skadenivån vanligare hos kvinnor än hos män. Patienter med CCS som skadats i
unga år har bättre prognos än de som skadats senare i livet.
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13 ANALISI DEL DOLORE NEUROPATICO IN PAZIENTI AFFETTI DA
LESIONE MIDOLLARE
Lavori inclusi nella ricerca
1. Il dolore neuropatico dovuto ad una lesione midollare traumatica è in relazione al sesso,
all’entità della lesione ed all’età del paziente nel momento in cui è insorta la lesione.
2. La prevalenza del dolore neuropatico in seguito a lesione midollare non traumatica.
3. Il dolore neuropatico e muscolosceletrico in adulti con spina bifida in rapporto all’entità della
lesione, al livello neurologico, al sesso e alla presenza di idrocefalo.
4. L’outcome neurologico e funzionale nei pazienti affetti da sindrome centromidollare posttraumatica.
Introduzione
Secondo studi fatti in precedenza, la prevalenza del dolore neuropatico, dovuto a lesioni
midollari traumatiche e non traumatiche, è variabile.
Il dolore neuropatico in pazienti con diagnosi di spina bifida è meno frequente ed a questo
proposito mancano dati.
La sindrome centromidollare è una lesione incompleta che si differenzia dalle altre lesioni
midollari e si manifesta soprattutto negli arti superiori.
Obiettivo della tesi
Analizzare la prevalenza del dolore neuropatico in pazienti con lesioni midollari traumatiche e
non traumatiche
Individuare gruppi di pazienti affetti da lesione midollare che corrono un rischio maggiore di
sviluppare il dolore neuropatico.
Analizzare in che misura il dolore neuropatico influenzi la loro vita quotidiana.
Definire gli outcome neurologici e funzionali nei pazienti affetti da sindrome centromidollare
post-traumatica, diagnosticata clinicamente alla dimissione dall’Unità Spinale di Firenze.
Materiali e metodo
Studi I-III
Nella nostra ricerca sono stati reclutati 402 pazienti affetti da lesione midollare traumatica, 96 da
lesione midollare non traumatica e 110 adulti con spina bifida. Tutti questi pazienti sono stati
visitati presso l’ambulatorio “Spinalis” dal 1995 al 2000.
L’attività principale dello Spinalis è il controllo annuale, durante il quale i pazienti sono
esaminati e classificati secondo la scala ASIA, American spinal cord injury association* (vedi
nota).
Durante il controllo annuale il paziente deve riferire circa l’eventuale presenza di dolore. Ogni
qualvolta ci si trovi di fronte ad un dolore di ordine generale, questo viene classificato come
dolore neuropatico, secondo i criteri dettati dal IASP (International Association for the Study of
Pain).
In presenza dell’accertamento di un dolore neuropatico, questo viene classificato secondo il
livello neurologico. Infine viene chiesto ai pazienti di definire l’intensità del dolore e la misura
in cui questo influenza la loro vita quotidiana.
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Nella nostra ricerca abbiamo suddiviso i pazienti con lesione midollare traumatica in cinque
gruppi, secondo l’età in cui è insorta la lesione.
I pazienti con lesioni midollari non traumatiche sono stati suddivisi a loro volta in cinque gruppi
diagnostici ed ulteriormente in altri cinque gruppi a seconda dell’età in cui è insorta la lesione.
Gli adulti di età superiore ai 18 anni affetti da spina bifida sono stati suddivisi in due gruppi: a
seconda della presenza o meno di idrocefalo.
Studio IV
In questa ricerca abbiamo incluso tutti i pazienti che, ricoverati dal 1996 al 2002 con diagnosi
di sindrome centromidollare, avevano ricevuto una cura omni-comprensiva presso l’Unità
Spinalis di Firenze. I pazienti venivano successivamente chiamati ad una visita di controllo
almeno 18 mesi dopo la dimissione.
I dati raccolti all`ammissione erano, oltre a sesso, causa della lesione, lesioni associate, tipo e
livello della lesione vertebrale, trattamento conservativo o chirurgico, anche il livello
neurologico e l`esame neurologico secondo sia la scala ASIA (A-E) che quella FIM (functional
indipendence measurement).
I dati raccolti al momento della dimissione erano: le eventuali complicazioni durante il ricovero,
la gestione vescicale ed intestinale, la scala WISCI (walking index for spinal cord injured
individuals) ed il livello neurologico secondo sia la scala FIM che quella ASIA.
Infine i dati raccolti al follow-up erano il livello neurologico, l’esame neurologico, la scala
ASIA, WISCI e quella FIM, la gestione vescicale ed intestinale ed inoltre la presenza o meno di
dolore e spasticità.
Risultati
Il dolore neuropatico era presente nel 40% dei pazienti con lesioni midollari traumatiche. Il 28 %
accusava dolore inferiormente rispetto al livello neurologico. Il dolore neuropatico era più
frequente nei pazienti al di sopra dei quarant’anni al momento della lesione. Durante la ricerca
non è stata rilevata nessuna differenza statistica fra uomini e donne e neppure nel dolore
neuropatico tra pazienti tetraplegici e paraplegici. Risultati non statisticamente significativi sono
stati riscontrati anche quando venivano analizzati pazienti portatori di lesioni complete od
incomplete. Circa il 70% di coloro che accusavano dolore dichiaravano che quest’ultimo
influenzasse la loro vita quotidiana in modo accentuato.
Il dolore neuropatico era presente nel 38% dei pazienti con una lesione midollare non traumatica
ed il 15% accusava dolore neuropatico nel punto della lesione. Le donne accusavano con
maggiore frequenza il dolore neuropatico inferiormente rispetto al livello neurologico. L’età non
influenzava la prevalenza del dolore neuropatico. Rispetto agli altri gruppi diagnostici, i pazienti
con un tumore maligno accusavano più spesso dolore neuropatico. Nel 70% dei pazienti con
dolore neuropatico questo veniva considerato un problema più o meno grave nella loro vita
quotidiana.
Soltanto l’11 % dei pazienti con spina bifida accusava dolore neuropatico. L’idrocefalo era
presente nel 52% dei pazienti ed era più frequente in quelli con un livello neurologico toracale e
in quelli che avevano una lesione completa (ASIA A).
Per quanto riguarda il dolore, nessuna differenza èstata rilevata tra pazienti con e senza
idrocefalo. Lo stesso dicasi per quanto concerne il sesso e l`entità della lesione. Il dolore
muscoloschelettrico compariva nel 25% dei pazienti con spina bifida ed era maggiore in quelli
che potevano camminare con o senza assistenza, infine il dolore era localizzato soprattutto nella
schiena.
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L’outcome neurologico nei pazienti con sindrome centromidollare era peggiore nei pazienti che
avevano già un’ età avanzata al momento dell’incidente, rispetto a quelli più giovani. Il dolore
neuropatico era più frequente nei pazienti più anziani. La spasticità era uguale nei due gruppi.
La causa più comune della lesione era l’incidente stradale seguito dalle cadute. La lesione
associata più frequente era un leggero trauma cranico.
Conclusioni
Questa ricerca vuole dimostrare come il dolore neuropatico sia un sintomo rilevante nei
pazienti con lesioni midollari traumatiche e non traumatiche. La maggior parte di loro infatti
accusa dolore neuropatico sotto il livello neurologico. In presenza di dolore neuropatico il
70% di essi dichiara che questo influenza in modo determinante la loro vita quotidiana. Nei
pazienti con lesioni midollari non traumatiche il dolore neuropatico, sotto il livello
neurologico, è più frequente nelle donne che negli uomini. Non è stato rilevato nessun tipo di
lesione che comporti un maggior rischio di sviluppare dolore neuropatico. La presenza del
dolore neuropatico è significativamente più bassa nei pazienti con diagnosi di spina bifida.
Non è stata rilevata nessuna differenza per quello che riguarda il dolore neuropatico tra i
pazienti con o senza idrocefalo. Il dolore muscoloscheletrico compare nel 24% dei casi ed è
più frequente nei pazienti che possono camminare con o senza assistenza ed è localizzato nella
schiena.
Gli anziani con diagnosi di sindrome centromidollare hanno un outcome neurologico e
funzionale peggiore ed accusano più spesso dolore a carattere neuropatico rispetto a quelli
lesionati in età giovanile. La spasticità compare con la stessa frequenza nei pazienti lesionati in
età giovanile che in quelli lesionati in età avanzata. Un’attenta analisi del dolore neuropatico è la
premessa per curare i pazienti in modo adeguato e può migliorare notevolmente il risultato della
loro riabilitazione in seguito ad una lesione midollare.
*La scala d’ASIA (American Spinal Cord Injury Association) A-E
ASIA A: lesione midollare completa. Questo termine viene utilizzato per descrivere una lesione
totale del midollo spinale. In questa situazione si ha una perdita totale della capacità di inviare
impulsi nervosi sensoriali e motori.
ASIA B-D: lesione midollare incompleta. Questo termine si riferisce invece ad un danno
parziale del midollo spinale. In questa situazione alcune funzioni motorie e sensoriali continuano
ad essere attive
ASIA E: funzioni motorie e sensoriali normali
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14 ACKNOWLEDGEMENTS
I would like to express my sincere gratitude to
Professor Kristian Borg my main supervisor for all his support and for helping med with the
scientific work, with all applications and for sharing his professional knowledge with me.
Dr Claes Hultling, co supervisor, for all his help, inspiration and support during many years, for
never giving up and also for his continuous work with the spinal cord injured population.
Associate professor Carl Molander for introducing me to the scientific world and for all support
he has given me during the scientific work.
Dr Sergio Aito, director of the Spinal Unit of Florence, for giving me the possibility to work at
the Spinal Unit of Florence.I always enjoy being in Italy.
Dr Maurizio D’Andrea, maestro, his wife Lia and to Fabio Fortini and his wife Dania for all
their support and friendship during my stays in Florence. The years in Florence have been the
best time in my life.
Dr Sergio Baglioni and his wife Laura for renting a flat to me when I am in Florence and for
sharing many good moments in Florence
Ninni Westgren, head of the Spinalis SCI unit for supporting my clinical and scientific work.
Associate professor Richard Levi for his important work in establishing a database for spinal
cord injured population in the greater Stockholm region. Without the database this thesis would
not have been made.
Lisbet Broman, for excellent help with the lay-out.
Franco Costa for excellent artwork
The Spinalis Team for valuable collaboration and for making Spinalis a wonderful place to
work at.
My colleagues in Sweden, and Italy for friendship and for sharing their professional knowledge
with me.
My coauthors Cecilia Norrbrink, Lucia Farsetti, S. Cappelli, B. Bandini and V di Donna for
skilful collaboration.
Linda Ekman, Gionni Benacchio,Ebba Werme and Lorenzo Pasquali for excellent
language help
My mother Gunborg and my late father Erik for love and support during the years.
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My sister Karin for support and friendship. Our summers in Falsterbo have always been the best
part of the year.
My friend since childhood Helen Ljungberg for friendship, help and support.
Last but not least I would like to thank all the patients who have participated in my work and
have shared their situation to help others.
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