Wobbler syndrome, including updated diagnostics (Proceedings)

The term "wobbler" or "wobbler syndrome" describes a group of developmental anomalies and degenerative conditions involving the cervical vertebrae of ataxic horses (Hahn et al. 1999; Mayhew 2009). Several more or less descriptive abbreviations are used in wobbler terminology. The most important of these are CVM (cervical vertebral malformation, cervical vertebral malformation and malarticulation), CSM (cervical stenotic myelopathy), and CCM (cervical compressive myelopathy). More recently, the remarkably inelegant CVSM (cervical vertebral stenotic myelopathy) seems to have gained currency (Levine et al. 2008). Two overlapping CSM syndromes are recognized, possibly with quite different developmental histories (Mayhew 2009). (1) Type I. There is focal or multifocal stenosis of the vertebral canal between C1 and C5 that is worse on flexion (dynamic stenosis). Affected horses typically are less than 2 years of age. (2) Type II. There is bony and occasionally soft-tissue impingement into the vertebral canal resulting from remodelling of the articular facets of the caudal cervical vertebrae (C6 to T1). Usually this impingement is present in all positions of the neck (static stenosis) but may also have a dynamic component with worsening during hyperextension. Horses with static stenosis are usually young to middle-aged. Both syndromes involve aberrations in cartilage and bone development which may precede clinical ataxia by many months (perhaps even in utero in the case of type I CSM).

Pathogenesis

Type 1 CSM is another manifestation of the group of developmental orthopaedic diseases (DOD) or osteochondroses that include physitis, contracted tendons, osteochoncritis dissecans (OCD), subchondral bone cysts, and malformation of the cuboidal bones of the carpus and tarsus. Study of wobbler matings has indicated a propensity for rapid growth and superior performance among offspring, but no clear evidence that CSM was genetically predetermined (Falco et al. 1976; Wagner et al. 1985). Interestingly, other developmental orthopaedic diseases were overrepresented. Because rapid growth and large size appear to be risk factors for CSM, it is not surprising that studies have tentatively implicated as risk factors high protein and caloric intake. Marginally low levels of trace minerals such as copper may come into play during rapid growth.

As a result of presumed genetic, physical, and dietary factors, there is early osteochondrosis of the articular facets and metaphyseal growth plates of the vertebrae of foals. Genetic predisposition, calcium/phosphorus imbalance, low dietary copper and high dietary zinc all have been associated with DOD in young animals of various species but their roles as risk factors for CSM isn't clear. Osteochondrosis of the vertebral physes results in multiple vertebral abnormalities include flaring and enlargement of the caudal epiphyses and metaphyses of the vertebral body ("ski jumps"), and disparity of longitudinal growth of the vertebral body and dorsal lamina. These deformities cause stenosis (narrowing) of the vertebral canal and susceptibility to dynamic compression, respectively. In severe form, the latter abnormality forces pairs of vertebrae into a permanently flexed malarticulated kyphotic position in which severe vertebral canal stenosis (both static and dynamic) is likely. Flaring of the caudal metaphyseal-epiphyseal unit contributes to the narrow caudal orifice commonly seen in vertebrae of horses with CSM.

Osteochondrosis of the articular facets may result in later joint instability, osteoarthritis and remodelling of the dorsal intervertebral joints. Associated with degenerative joint disease of the these dorsal intervertebral joints are gross enlargements due to osteophyte development. Affected facet pedicles may be relatively brittle and susceptible to trauma. Fractured facets are found quite frequently in diseased intervertebral joints at post-mortem although they cannot often be seen in lateral radiographs. Pedicle fractures caused by trauma likely contribute to the massive asymmetric remodelling seen in some of these joints. There may also be hypertrophy and fibrosis of the synovial membrane and joint capsules of the dorsal intervertebral joints, and fibrovascular proliferation of the ligamentum flavum. These soft tissue structures or fluid-filled cysts associated with them may cause static stenosis and compression of the spinal cord and spinal nerves.

Necropsy findings

Horses with CSM have one or more focal compression-type lesions in the cervical spinal cord (Hahn et al. 1999; Mayhew et al. 1978). Grossly, such lesions may appear as flattening and palpable softening of the cord. Histological, they are characterized by swollen and disrupted axons and phagocytosis of myelin in white matter. Mild haemorrhages sometimes are seen in acute lesions. In the white matter of chronically affected animals, there is continued degeneration of neuronal fibres, proliferation of capillaries with prominent fibrous coats and astrofibrosis. More severely affected horses also have neuronal necrosis, loss of cell bodies and sometimes astrofibrosis in the gray matter. Massive focal lesions also occur with cavitating necrosis of white matter, particularly in lateral funiculi and occasionally in gray matter. Markedly asymmetric lesions are found in horses with prominently asymmetric clinical signs. Cranial to the focal lesions, there is secondary degeneration of neuronal fibres (axons and myelin) in ascending (proprioceptive) tracts for variable distances, depending on the extent and age of the focal lesion. Caudal to the lesion, there is secondary fibre degeneration in descending (motor) tracts. This fibre degeneration is the result of neuronal fibres being severed from their cell bodies by the focal lesion. It is most prominent in dorsolateral funiculi cranial to the lesion, and deep lateral and ventromedial funiculi caudal to the lesion.

Clinical signs

Most animals with type I CSM are 6 to 18 months old, while those developing type II CSM are typically 18 months to 5 years although there are many exceptions to these ranges. A recent study of 1616 horses in the US indicated that Thoroughbreds, warmbloods, and Tennessee Walking Horses were significantly more likely to have CSM than Quarter Horses; Standardbreds and Arabians were significantly less likely to have CSM (Levine et al. 2008). Large warmblood breeds are notably affected by type II CSM (Levine et al. 2007). Males are over-represented among horses with CSM (Levine et al. 2008). Affected horses often are well grown, and some have a history or signs of other developmental orthopaedic diseases, such as OCD or physitis.

Clinical signs of ataxia and paresis may begin insidiously or present suddenly. In the latter case, there is often a history of some minor fall or training incident that confuses the diagnosis (was the fall a precipitating cause or a result of the disease?). After they have been recognised, signs typically progressively worsen for a period of months and then may stabilise or even regress. Spontaneous complete recovery is very rare, though waxing and waning signs are frequent. In general, horses with CSM appear physically normal; however, occasionally, palpable swellings of the cervical vertebrae corresponding to enlarged intervertebral joints are palpable and severe flexion-fixations, particularly at C2-C3, occasionally are externally visible and palpable. Pain in response to pressure over the transverse processes, or reluctance of the horse to flex the neck laterally are common findings in horses with type II CSM. Occasionally, pressure on caudal cervical nerve roots as they traverse the epidural space and intervertebral foramen in type II horses is sufficient to cause apparent thoracic limb lameness (Ricardi and Dyson 1993). The principal neurologic signs are ataxia, weakness and spasticity of the limbs (Hahn et al. 1999; Mayhew 2009). Generally, the pelvic limbs are more affected than the thoracic limbs. Dynamic stenosis usually is associated with symmetric signs while static stenosis may cause asymmetric signs. Occasionally, severe arthrosis of the joints between C6-7 or C7-T1 causes signs more severe in the thoracic limbs. The first sign noticed may be stumbling or clumsiness when the horse is moving into or out of a box stall. During exercise gallops, the rider may comment on a feeling of looseness or "losing the back end" around turns. Reluctance to change or maintain leads, cross-cantering or –galloping, or even falls after stumbling are other early signs in horses being ridden. With progression, affected horses may have an obviously stiff incoordinated gait at the walk; the prominent truncal sway or "wobble" explains the common name for horses with CSM. Because of pelvic limb extensor weakness, some wobblers catch their patellas or have persistent upward patella fixation. Bilateral 2-beat "pacing" movement at walking speed also occasionally is seen in horses with CSM (as it can be in any condition caused by cervical spinal cord disease). In addition to the signs already mentioned, careful neurologic examination usually discloses some to all of the following: (1) Abnormal pelvic movements during walking when observed from behind including excessive swivelling of the line from between the tuber sacrale to the tailhead, excessive rotation of the pelvis around its long axis (seen as exaggerated amplitude of the rise and fall of the tuber coxae) and side-to-side truncal sway. (2) Decreased resistance to pulling the tail laterally while the horse is walking; (3) Apparent stiffness during the swing phase of the stride in the thoracic and/or pelvic limbs. This may be associated with scuffing of the toes. When the horse's head is raised during walking, especially down a gentle slope, the stiff hypometric gait in the thoracic limbs may be exaggerated and is sometimes described colloquially as a "marching" or "tin-soldier" gait. (3) Circumduction of each outside pelvic limb when the horse is walked in small circles. (4) Interference between the thoracic limbs and pivoting around the pelvic limbs when the horse is moved in tight circles. (5) Absence of the thoracolaryngeal ("slap") reflex. In horses with markedly asymmetric compression (usually horses with asymmetric caudal intervertebral arthritis), there also may be marked asymmetry of stride length between the pelvic limbs.

Diagnosis

Radiography is the most important tool Hett et al. 2006; Hudson and Mayhew 2005; Moore et al. 1994; Papageorges et al. 1987; Tomizawa et al.1994). A presumptive diagnosis usually can be obtained with plain cervical radiographs by finding narrowing of the vertebral canal. The diagnosis is buttressed by additional demonstration of malformation, OCD, or enlargement of the facet joints, metaphyseal and epiphyseal flaring of the vertebral body, relative elongation of the dorsal lamina, or flexion-fixation (kyphosis) of pairs of vertebrae. Minimal intravertebral sagittal ratios for vertebrae behind C2 is calculated as the ratio [minimal sagittal diameter] ÷ [maximal sagittal diameter of the cranial half of the vertebral body]. The denominator normalizes for variation in horse size and object-film distance. A value for sagittal ratio of ≤0.51 from C3-C6 inclusive and ≤0.54 at C7 predicts spinal cord compression with >95% sensitivity and specificity according to the original description Moore et al. 1994). In practice, cut-off values of 0.50 for C3-C6 and 0.52 for C7 are typically used. Even horses with static stenosis, which may have predominantly lateral compression from large joints, usually are detected by analysis of sagittal ratios. Several more complex measurement systems have been devised which purport to detect CSM with greater accuracy than is possible with sagittal ratios alone (Hahn et al. 2008; Hett et al. 2006; Tomizawa et al. 1994). One of these introduces the use of intervertebral sagittal diameters to fully capture the effect of kyphotic angles on the vertebral canal. It will be very important to evaluate all of these predictive measurements against the gold standard of post-mortem diagnoses in future studies.

When plain radiographs are abnormal, contrast myelography may be used to further support the diagnosis, establish the number of vertebrae involved, and the severity of lesions in each, and to define the soft tissue contribution to spinal cord compression. These factors are especially important if surgical stabilization is contemplated. Under general anesthesia, 30 to 50 ml iohexol or iopamidol are injected slowly into the atlantooccipital subarachnoid space after a similar volume of CSF has been removed (Mayhew 2009). After injection has been completed, the head is raised for 5 minutes to encourage caudal flow of dye, then the head is lowered and radiographs are taken. Spinal cord impingement due to dynamic compression is clearly defined in lateral views of the flexed cervical spine if the dorsal and ventral dye columns are completely extinguished at diametrically opposed sites. When there is less than complete compression of the dorsal column, several different diagnostic criteria have been used, none of which is completely satisfactory (Van Biervliet et al. 2004). In the author's experience, the criterion of reduction between midbody and intervertbral views of ≥30% has high diagnostic accuracy, especially in neutral views. The traditional standard of complete compression of the ventral dye column and ≥50% compression of the dorsal column at diametrically opposed sites is sensitive but has poor specificity (i.e., there are many false-positives). Sites affected in order of frequency are C3-C4, C4-C5 and C5-C6. Multiple sites may be affected in a single horse. The typical myelographic feature of static stenosis is spinal cord compression throughout the full range of vertebral motion. The C6-C7 articulation most frequently is involved, and C5-C6 to a lesser extent. At these sites, absolute narrowing of the minimal dural diameter is the most accurate diagnostic criterion. In those cases in which the plane of compression is transverse rather than dorsoventral, the dural diameter is usually abnormal; however, less objective criteria may have to be considered when measurements are normal. These include widening of the spinal cord diameter and fading of the dye columns over the area of lateral compression. CSF analysis generally is normal. At most there is xanthochromia and elevated protein (70 to 130 mg/dL)

Treatment

Medical

Horses less than a year of age (and preferably less than 6 months of age at diagnosis can be tried on a restrictive "Paced Diet". This diet reduces intake of energy and protein and increases trace minerals. The essential elements are as follows: (1) immediately wean if still suckling; (2) feed free-choice grass hay (e.g., coastal bermuda hay) plus 3.5 pounds daily of a low energy, nutrient-rich ration balancer (e.g., Buckeye's Grow 'N' Win supplement). At one year of age (based on birth date), the supplement is reduced over 1 week to one pound daily. Foals should be confined in a stall except for limited round-pen or equivalent turnout time, certainly without access to pasture. Good results are claimed for slightly affected foals although breaking, training and racing are set back several months and the foals look poor as yearlings.

Surgical

Vertebral interbody fusion is the principal procedure. In this surgery, pairs of vertebrae are fused in extension by implantation of a cylindrical stainless steel or titanium basket filled with cortical bone fragments. A recent modification of the surgery uses a threaded implant that screws into place without removal of bone. The surgery provides immediate relief from dynamic stenosis and may improve static stenosis over months by causing atrophy of arthritic intervertebral joints. This procedure results in improvement in neurologic status in 44% to 90% of horses with dynamic compression and 12% to 62% of treated horses return to athletic function. Dorsal laminectomy is described but technically is extremely difficult. It can be used after vertebral trauma or to relieve static stenosis.

Intra-articular steroid injection

Intervertebral joints can easily be seen ultrasonographically and corticosteroid (e.g., methylprednisolone acetate) can be injected under ultrasound guidance. This procedure appears to provide symptomatic relief of neck pain but whether or not it significantly affects spinal cord compression has yet to be determined.

References

Falco M, Whitwell K, Palmer A. An investigation into the genetics of 'wobbler disease' in thoroughbred horses in Britain. Equine Veterinary Journal 1976;8:165-169.

Hahn CN, Mayhew IG, MacKay RJ. The nervous system In: Colahan PC, Mayhew IG, Merritt AM, Moore JN. eds. Equine medicine and surgery. 5 ed. St Louis: Mosby, 1999.

Hahn CN, Handel I, Green SL, Bronsvoort MB, Mayhew IG. Assessment of the utility of using intra- and intervertebral minimum sagittal diameter ratios in the diagnosis of cervical vertebral malformation in horses. Veterinary Radiology and Ultrasound 2008;49:1-6.

Hett AR, Busato A, Ueltschi G. Radiographic measurements of the equine cervical spine with arthrotic alterations - a retrospective statistical study. Pferdeheilkunde 2006;22:241-+.

Hudson NPH, Mayhew IG. Radiographic and myelographic assessment of the equine cervical vertebral column and spinal cord. Equine Veterinary Education 2005;17:34-38.

Levine JM, Ngheim PP, Levine GJ, Cohen ND. Associations of sex, breed, and age with cervical vertebral compressive myelopathy in horses: 811 cases (1974-2007). Journal of the American Veterinary Medical Association 2008;233:1453-1458.

Levine JM, Adam E, MacKay RJ, Walker MA, Frederick JD, Cohen ND. Confirmed and presumptive cervical vertebral compressive myelopathy in older horses: A retrospective study (1992-2004). Journal of Veterinary Internal Medicine 2007;21:812-819.

Mayhew IG. Large animal neurology. Oxford, England: Wiley-Blackwell, 2009.

Mayhew I, deLahunta A, Whitlock R, Krook L, Tasker JB. Spinal cord disease in the horse. Cornell Veterinarian 1978;68 (Suppl 6):1-207.

Moore BR, Reed SM, Biller DS, Kohn CW; Weisbrode SE. Assessment of vertebral canal diameter and bony malformations of the cervical part of the spine in horses with cervical stenotic myelopathy. American Journal of Veterinary Research 1994;55:5-13.

Papageorges M, Gavin P, Sande R, Barbee DD, Grant BD. Radiographic and myelographic examination of the cervical vertebral column in 306 ataxic horses. Vetetinary Radiology 1987;28:53-59.

Ricardi G, Dyson SJ. Forelimb lameness associated with radiographic abnormalities of the cervical vertebrae. Equine Veterinary Journal 1993;25:422-426.

Tomizawa N, Nishimura R, Sasaki N, Kadosawa T,Senba H, Hara S, Takeuchi A. Efficacy of the new radiographic measurement method for cervical vertebral instability in wobbling foals. Journal of Veterinary Medical Science 1994;56:1119-1122.

Van Biervliet J, Scrivani PV, Divers TJ, Erb HN, Delahunta A, Nixon A. Evaluation of decision criteria for detection of spinal cord compression based on cervical myelography in horses: 38 cases (1981-2001). Equine Veterinary Journal 2004;36:14-20.

Wagner PC, Grant BD, Watrous BJ, Appell LH, Blythe LL. A study of the heritability of cervical vertebra malformation in horses. 31st Annual Convention of the American Association of Equine Practitioners 43-50, 1985.