PAIN AND VERTEBROGENIC SYNDROMES IN PATIENTS WITH MULTIPLE SCLEROSIS (REVIEW OF LITERATURE)

Резюме Розсіяний склероз (РС) – найпоширеніше захворювання центральної нервової системи (ЦНС), що є причиною стійкої інвалідизації осіб молодого працездатного віку. Серед основних синдромів РС, які найчастіше трапляються, – координаційні розлади, порушення зору, центральні парези, розлади діяльності тазових органів, розлади почуттів, але не біль. З’ясовано, що половина хворих на РС страждають від хронічного болю. Дуже часто біль є першим проявом РС, частота якого може сягати 11% випадків.

Patients with pain syndrome mostly suffer from headaches, pain in the cervical-thoracic and lumbar-sacral spine, and neuropathic pain in lower limbs. Considering the urgency of the problem of pain and vertebrogenic syndromes, demyelinating diseases require close observation and further study.
Vertebrogenic syndromes in MS develop due to the infl uence of several factors, mostly, centers of demyelination, dystrophic changes in the spine and osteoporosis. In MS, vertebrogenic syndromes have their own peculiarities: early onset, a long-term pain without clear periods of deterioration or improvement, moderately evident muscular and tonic disorders that are observed in all parts of the spine.
Neurological disorders in MS accelerate the development of diverse functional and organic (dystrophic) processes in the spine. Often, vertebrogenic and pain syndromes precede the widespread clinical picture of the disease, when patients have been treated by vertebrologists, and sometimes by neurosurgeons for months and years. Only timely observation by neurologists and MRI of the brain and spinal cord allow making the correct diagnosis.

Multiple sclerosis and pain syndromes
Multiple sclerosis (MS) is one of the most prevalent common diseases of the central nervous system (CNS), which is the cause of persistent disability of young people in working age [1]. Among the main syndromes of this disorder, coordinative disorders, visual disturbances, central pareses, pelvic disorders, senses of discomfort, but not pain, are observed. It has been established that half of patients with MS suffered from chronic pain. Pain is the fi rst manifestation of MS in 11% of cases.
The clinical picture of these patients shows that pain syndromes occur quite often and are currently characterized by a majority of researchers as a common disorder due to multi-centric demyelinating damage to the nervous system [2,3,4,5]. According to modern studies, from 29 to 90% of patients reported pain at different stages of the disease. Although pain syndromes are not related to typical clinical manifestations of this disease, presence of pain in case of MS can signifi cantly impair the quality of life [6,7] and contribute to worsening of neurological defi cit syndrome [3,8]. At the same time, data on the extent of pain syndromes' effect on the daily life of MS patients and on acceleration of disability development, are ambiguous and need to be clarifi ed [2,3,5,9].
The multicenter study dedicated to prevalence of pain in case of MS [5] determines that major factors associated with the development of pain were longer duration of disease, older age, and non-remitting course of the disease, decreased physical activity, and signifi cant disability. According to other data, pain in case of MS directly correlates with the level of anxiety, depression, and fatigue and increases if sleep disorders and increase of muscular spasticity occur [3,7,10,11].
In some cases, pain syndromes in case of MS are directly related to the demyelinating process in the CNS and its consequences, whereas in other case they result from comorbid diseases with a high probability of mutual aggravated exposure [3,4,5]. However, the degree and direction of this infl uence need to be studied further.
neurogenic pain (usually, directly related to the destruction of the myelin sheath of neural formations) and nociceptive pain (NCP), less commonly mixed pain (MP) and other pain types are observed.
When it comes to the group of neuropathic pain (NPP), the most prevalent in patients with MS are deafferentative pain in extremities (10-29%) caused by multiple demyelinating lesions along the spinal-thalamic-cortical pathways at the level of the sensory cortex and thalamus; trigeminal neuralgia (3-7%), resulting from the compression of the descending root of trigeminal nerve by plaque at the level of medulla oblongata and the lower pontine part; Lhermitte's sign (7-13%) that is associated with lesions of the spinal posterior columns at the cervical level.
The mechanism of NCP in case of MS is primarily related to secondary postural anomalies arising from motor disorders formed as a result of the dominant symptoms of the pyramidal pathways and cerebellum involvement, such as central pareses, spasticity, ataxia, ambulation disorders [3,8].
It is also necessary to consider pathological changes of the musculoskeletal system associated with a signifi cant acceleration of osteoporosis, that leads to rapid progression of the spinal osteochondrosis (mainly located in lumbosacral area) and to that of lower extremities' arthrosis [3,4,8,13,22].
Mixed pain in MS includes painful tonic muscle spasm (5-12%) and pain due to spasticity (27-35%) associated with demyelinating lesions in the pyramidal pathway and increase of stretching tonic refl ex, which, in turn, leads to excessive muscle activity and development of mechanical muscular pain.
Finally, some of pain syndromes in MS (most often, headaches) may be associated with pathogenic treatment for prevention of exacerbations, especially at the beginning of treatment with interferon drugs IFN-beta1b and less often with IFN-beta1a.
In the studied population, they were more prevalent and more severe based on the indicators of McGill pain questionnaire and WAS (Visual Analog Scale) in the group of patients with comorbid pathology. The most evident pain syndromes, according to McGill's pain questionnaire and VAS indicators, were found among MS patients with polymodal pain and in case of poly-comorbidity.
The relation between MS and headache (in particular, the primary one) has been known for a long time. According to one study [16], over 50% of people with confirmed diagnosis of MS noted the presence of cephalgia (mostly, tension headache and migraine). The clearest correlation existed between migraine and relapsing-remitting course of the underlying disease. Another study [17] has shown that primary cephalgia in case of MS has incidence of 73.5% in the remission phase and 38.9% in the exacerbation phase. Primary thunderclap headache was the most common primary cephalgia during exacerbations, and migraine and tension headache -during remissions. It is interesting that according to ремісіях. Цікаво, що згідно з дещо іншими даними, при РС біль голови напруги асоціювався зі старшим віком, чоловічою статтю та вторинно-прогресуючим перебігом [18].
In another study [19], authors compared MS patients with migraine and purely MS patients. It was found that the fi rst group displayed more signifi cant involvement of black matter and red nucleus. These fi ndings highlight the important fact that demyelinating foci in some cerebral parts are more likely to be associated with the onset of cephalgic syndromes than in others. Another area of brain associated with the development of migraine-like episodes in demyelination is periaqueductal gray matter. In fact, in MS patients with plaques in this area, as well as in the midbrain, the risk of migraine-like states is 4-fold higher as compared to patients with no involvement of the abovementioned site [20]. Several cases were described in the medical literature where the onset or deterioration of the already existing migraine were MS manifesting symptoms [21,22]. The same may be said of cluster headache [23]. Although the cases mentioned above underline possible causal link between the centers of demyelination and subsequent development of headache, there exists a notion of bidirectional relationship between RS and migraine / tension headache. Cephalgia is said to possibly infl uence just the course of underlying disease, but also its radiological characteristics [24].
There are many potential therapeutic options available for treatment of cephalic syndromes in these patients, although this pain may be refractory. Patients with MS often suffer from various comorbidities (depression, neuropathic pain, and asthenia), therefore, adequate control of headache is important because it can exacerbate depression in this population group.

Multiple sclerosis and spinal pathology
Dystrophic spinal processes develop during MS as often as they do among general population. Under conditions of spastic paresis and ataxia, fi rst, the load on paravertebral muscles increases, and second, the dystrophic processes accelerate in the intervertebral discs and facet joints.
P. Korovessis et al. [26] report about a patient, who was operated three times on intervertebral disks' hernias at the cervical, thoracic and lumbar levels before the diagnosis of MS was made. Using MRI, C. Poser [27] found cervical lesions typical for MS at the level of spinal cord compression with altered intervertebral discs. Similar results are reported by D.
Thomas et al. [28]. These facts confi rm the hypothesis of R. Brain, M. Wilkinson [29], and D. Oppenheimer [30] about the relation between cervical osteochondrosis and foci at the cervical spinal cord level. However, available radiological literature describes such changes as "foci of myelomalacia" that appear at the level of intervertebral hernia. at lumbar level) in a separate chapter of the book authored by Gusev E., Zavalishin I., Boyko A. and named "Multiple sclerosis and other demyelinating diseases" [31].
Some pathological changes in intervertebral discs and adjacent vertebral bodies (narrowing of the intervertebral fi ssures, Shmorl's hernias, disk calcifi cation, subchondral sclerosis, and osteophytes) were detected in 93% of patients. This is a very high percentage of dystrophic changes' detection, considering that the average age of patients is relatively young (34.7 ± 11.0 years), and 50% of individuals in this group are under the age of 35.
The preconditions for development of scoliosis in case of MS may include coordinative and proprioreceptive disturbances (such mild disorders are detected in patients with scoliosis using special instrumental studies).
In addition, spinal static is infl uenced by changes of pelvic position, which is formed through impaired functioning of the muscles attached to pelvic bones.
The muscular-tonic syndrome was also signifi cantly more pronounced in MS patients, than in healthy individuals, meaningful differences from the group of patients with osteochondrosis were not detected. The peculiarity of these changes in MS include a more "uniform" distribution of musculoskeletal disorders along the spinal column, as well as their moderate severity, whereas in case of osteochondrosis, only one spinal part is involved and severe muscle-tonic syndrome is developed.
Osteoporosis in MS is common, due to limited motor activity, long-term treatment with glucocorticoids, low blood vitamin D levels, and predominance of women among patients. The pain caused by osteoporosis is local and, largely, provoked by a change of body position. According to Cosman F, Nieves J, Komar L et al. [32], spontaneous fractures occur in 22% of MS patients (2% among healthy people). During 2 years of followup, bone mass loss in the vertebral bodies of MS patients with MS was 1.6-3.5%, while the control group had no such changes. The bone mass of vertebral bodies among women with MS was 10% below the age-matched standard. Such disorders increase the risk of fractures by 2-6 times.

Conclusions
Neurological disorders in MS accelerate the development of diverse functional and organic (dystrophic) spinal processes.

Література
Often, vertebrogenic and pain syndromes precede the widespread clinical picture of the disease, when the patient has been treated by manual therapists, and sometimes -by neurosurgeons for months or even years. Only a timely neurological examination and MRI of the brain and the spinal cord may help make a correct diagnosis. MS patients with pain syndrome mostly have headache, pain in the cervical-thoracic and lumbar-sacral spine and neuropathic pain in lower limbs. Given the urgency of the problem of pain and vertebrogenic syndromes in demyelinating diseases, it requires close attention and further study.