Neural Mechanisms In Idiopathic Scoliosis Aetiology - Current

							Neural Mechanisms In Idiopathic Scoliosis
Aetiology - Current Hypotheses
Mr Michael Edgar 149 Harley Street, London, W1N 2DE, Great Britain
REVIEWED MATERIAL Medline 1986 - 1996 SRS Annual Meeting abstracts
1982 - 1996 BSS abstracts 1980 - 1997 ESDS and ESS abstracts 1986 - 1996
JBJS articles 1980 - 1997 Spine volumes 1 - 22 Relevant editions Clin Qrth 1973
- 1997 Zorab Symposium proceedings 1970 - 1993 Pathogenesis of Idiopathic
Scoliosis Ed Jacobs R R (1984), Scoliosis Research Society NEURAL
MECHANISMS IN IDIOPATHIC AETIOLOGY - CURRENT HYPOTHESES

A Neurological Dysfunction



1. Dorsal Column Dysfunction



i) Vibratory impairment

ii) Proprioceptive impairment



2. Spinal Cord Monitoring
3. Equilibrial Dysfunction
4. Oculo-Vestibular Dysfunction
5. Dysfunction of Higher Centres


B Abnomal Neuroanatomy


1. Spinal nerve root lesions
2. Spinal cord abnormalities
3. Brain stem and mid brain lesions


C Neuro-hormonal Abnormality

NEUROLOGICAL DYSFUNCTION
1 Dorsal Column Dysfunction
i) Vibratory impairment


Abnormal vibratory sensation has been looked for in controlled clinical studies as the most
sensitive test of dorsal column function. 16,62,77. The PVD Bio-Thesiometer has been standard.
Early findings showed a hypersensitivity to vibration compared with controls. The vibratory
hypersensitivity can affect all 4 limbs but is not related to the magnitude of the curve18. No
asymmetry of findings related to the side of the scoliosis was apparent. A more recent study
suggests hyposensitivity confined to the great toe60. The key reference Maclnnes et al, 1991,39
publishes a thorough investigation in which the Bio-thesiometer is shown to be unreliable with
considerable variation between patients without statistically provable vibratory dysfunction.


ii) Proprioceptive impairment


Again the literature on controlled clinical studies is split. Findings vary between no abnormality
23,32 and significant pathology affecting both upper and lower limbs 7,74,85. Tests include finger
and elbow position matching 32,74 and knee angle reproducibility (7). The key reference is
Yekutiel et al, 1981,85. In this study only the Sharpentier test, which involves comparisons of
weights of different shaped objects held in each hand was significantly abnormal in MS patients
compared to controls. Interestingly the blind-folded Sharpentier test revealed no difference.
Impaired proprioception is not a constant feature.


2 Spinal Cord Monitoring


Long tracts in the spinal cord have been monitored with SSEPs, MEPs and EMG studies. Only 2
papers consider aetiology. Machida et al, 1991,40 after experimental work in chickens performed
cortical SSEPs in MS patients which compared with controls showed a right I left latency
difference. Pathology in the thalamocortical pathways was proposed. MacGuire et all 37,38 using
sophisticated EMG techniques has demonstrated long latency reflex activity in MS patients not
present in controls or other scoliosis. The descending tracts from higher centres which control this
were not investigated.


3 Equilibrial Dysfunction


This concept was put forward by Yamada, Iakta and Yamamoto et al, 1969,80. Sahlstrand,
1977,64 describes the technique of stabilometry to assess sway pattern. The concept has been
further developed 29,54,84 with confirmation of abnormal sway patterns using stabilometry
19,61,62, verticality perception and single limb standing 16,79. There is no difference between
progressive and non-progressive curves 62,79. Postural sway reverts to normal at skeletal
maturity 79,81. Lidstrom, 1989,34 considers the effect largely secondary supported by Gregoric
et al, 1989,26. DeMuth et al, 1996,16 found considerable variability and suggests neurological
heterogeneity in MS.


4 Oculo-vestibular Dysfunction


Ocular and vestibular impulses are important equilibrial factors affecting the equilibrium centre in
the brain stem 80. Vestibular dysfunction in MS was reported by Sahlstrand, 1977, 64. Abnormal
nystagmus measured by electronystromography (ENG) using caloric tests or post-rotational state
has been demonstrated 28,50,64,76,79. Abnormal nystagmus can herald the beginning of
scoliosis among siblings of MS patients 51. A recent study found no difference between AIS
patients and controls with post-rotatory nystagmus.
The ocular influence in sway patterns using stabilometry (see section 3 above) has been
investigated by Sahlstrand 65 and Herman 28,29 with opposite results. Sahlstrand found that
lateral sway pattern was worse without visual input suggesting vestibular insufficiency. Herman
found the lateral sway pattern more marked when visual information was available proposing an
abnormal vestibulo-ocular reflex. This was found to be asymmetrical in MS patients and not
present in congenital scoliosis. Further influence of the visual and somatosensory systems in
producing abnormal sway has been recently produced by Byl and Gray 13. Congenital visual and
inner ear defects produce a lower incidence of MS than expected 50,76.


6 Dysfunction of Higher Centres


Herman, 1984,29 hypothesizes that vestibulo-ocular reflex asymmetry results from asymmetric
maturation of higher cortical centres. No further work has been done. EEG studies have
demonstrated some variation in MS patients compared with controls 55,62. Asymmetry was not
related to the curve and there was no difference between progressive and non-progressive
scoliosis. Goldberg and Dowling, 1988, 18 demonstrated that left or right handedness correlated
statistically with the side of the MS convexity. An asymmetry of higher cortical function was
proposed though the place of genetic determination was not considered.


B ABNORMAL NEUROANATOMY
1 Spinal Nerve Root Lesions


Experimental intradural posterior rhizotomy over at least 3 levels causes scoliosis, with the
convexity ipsilateral to the lesion in the immature rabbit36,69,70, dogs35 and in monkeys57.
There is controversy with rabbits that experimental scoliosis only develops when ventral horn
cells are involved1,52,70. The only human anatomy study concerns the innervation of spinal
ligaments in MS patients which although not asymmetrical is deficient in nerve density compared
with controls4. This is probably a secondary feature.


2 Spinal Cord Abnormalities


Pincott and Taffs, 1982, 58 classic work demonstrated unilateral destruction of posterior horn
grey matter in association with the development of scoliosis. The asymmetrical destruction of
Clarke's column and associated spinocerebellar tracks was the most consistent pathology with
the convexity of the curve on that side. Curves are long and have a neuropathic rather than
idiopathic appearance. Similar findings occur in the rabbit10.
Children with juvenile or early adolescent curves have an incidence of cervicothoracic syrinx and
Chiari I malformations occurring from 17.9% to 47% (see refs 3,6,12,14,15,17,22,27,
30,31,33,59,67,71,73,75,86). A controlled study 22 demonstrated that those curves are similar to
'normal' idiopathic deformities except they are more progressive and have a higher proportion of
left-sided curves 22,31,44,67. Controversy exists between those who have found normal
neurology 14,18,22,30,31,33,59,73 and those who state that subtle neurology involving
asymmetrical abdominal reflexes or nystagmus is always present if carefully looked for 15,71,86.
Abdominal reflex abnormality can be present without abnormal neuroanatomy 72. Drainage of the
syrinx or decompression of the forama magnum can lead to improvement of the scoliosis as well
as improvement of any neurology present 21,25,53,56. The debate is whether the syrinx leads to
subclinical neurology and causes a "neuropathic" curve or whether the syrinx and scoliosis are
both associated with a primary cause as yet undetected.


3 Stem and Mid Brain Lesions
Stereotactic minute brain stem lesions in growing rats produced progressive scoliosis in 10% and
this was associated with quite marked ataxia. Further work in rabbits with a unilateral lesion in the
periaqueductal grey matter was carried out 82. Accurate asymmetrical lesions in the gracilis
nucleus, the superior colleculus and the lateral vestibular nucleus was produced in rabbits11 and
25% developed scoliosis. Hypophysectomy with its inevitable damage to the roof of the third
ventricle produces abnormal cortical evoked SSEPs 41,42. The hypothesis given by Machida,
Dubousset, Yamada and colleagues is a destruction of sensory (thalamo-cortical) fibres rostral to
the brain stem.
MRI documentation of the mid and hind brain in MS subjects has demonstrated pathological
asymmetry. Geissele et al, 1991,24 demonstrated asymmetry of the ventral portion of the pons
and medulla oblongata conveying the corticospinal tracts. This occurred in 27% of MS patients
but only 9% of controls. Asymmetry did not relate to the side of curve. Stevens et al, 1992,68
found a more common asymmetry of the cerebral peduncles with the larger side related to the
convexity of the curve. This work has not been substantiated.


C NEURO-HORMONAL ABNORMALITY


Experimental pinealectomy in chickens is associated with abnormal cortical SSEPs 41,42,43. It is
not known whether this impairment of conduction is due to damage of neurological tracts
(thalamo-cortical) or grey matter in the roof of the third ventricle or whether it is due to an upset of
the hormonal neurotransmitters as a result of the pinealectomy. Dubousset et al, 1982,83
demonstrated that pinealectomy does cause some neurological damage in this key area of the
diencephalon. It is suggested that this could be the site for the equilibrium control centre. Re-
implantation of the pineal gland or the administration of melatonin in chickens prevents the
scoliosis 44,45,46,47,48. This would favour a neurotransmitter cause of neurological impairment.
Post-pinealectomy scoliosis does not develop in normal quadriped mammals (rats, hamsters) 5
but young bipedal rats are vulnerable49.


D COMMENT
Impairment of the dorsal columns involving vibrationary and proprioceptive impulses is not a
factor in idiopathic aetiology. Similarly experimental sensory deficiencies in immature animals
produce neuropathic rather than idiopathic curves.
Concept of equilibrial dysfunction related perhaps to vestibulo-ocular reflex asymmetry, as
suggested by Herman and supported by the visual findings of Byl and Gray and consistent with
the visual influence of co-ordination and proprioceptive noted by Yekutiel et al during the
Sharpentier tests, is the most attractive area of neurological dysfunction. Further work is clearly
needed. Asymmetrical maturation of higher cortical control of equilibrium fitting in with Goldberg
and Dowling's work requires further work and confirmation.
If abnormal neuro-anatomy exists it should come to light with better resolution of MR techniques
which could demonstrate asymmetry of spinal tracts and grey matter in the brain stem and mid
brain.
Chiari I malformation and cervicothoracic syrinx in juvenile and early adolescent idiopathic
scoliosis needs further investigation particularly with regard to its neuro-anatomy and neuro-
physiology. This is the nearest syndrome to idiopathic scoliosis without a known neuropathic
cause and may give the clue to the aetiological process.
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