Background: Chiari-like malformation (CM) is a developmental condition, characterised by a conformational change and overcrowding of the brain and cranial cervical spinal cord. CM-associated pain (CM-P) and syringomyelia are increasingly being diagnosed, due to the rising popularity of predisposed brachycephalic breeds and the availability of MRI in veterinary practices.
Aim of the article: This article aims to update the veterinary profession on these conditions, and provides a guide to diagnosis and treatment of clinically relevant disease.
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Clare Rusbridge qualified from the University of Glasgow in 1991. She became a diplomate of the European College of Veterinary Neurology in 1996, a RCVS-recognised Specialist in 1999 and Fellow of the RCVS in 2016. She is currently chief of neurology at Fitzpatrick Referrals, Surrey, and a professor in veterinary neurology at the University of Surrey.
Key learning outcomes
After reading this article, you should understand:
Clinical signs of Chiari-like malformation-associated pain and differential diagnosis;
Clinical signs of syringomyelia and differential diagnosis;
Diagnosis and MRI appearance of Chiari-like malformation-associated pain and syringomyelia;
Medical and surgical management options for Chiari-like malformation-associated pain and syringomyelia;
Breeding recommendations for dog breeds and crossbreeds predisposed to Chiari-like malformation-associated pain and syringomyelia.
Chiari-like malformation (CM) is a complex developmental condition of the skull and craniocervical vertebrae, and is characterised by a conformational change and overcrowding of the brain and cervical spinal cord, particularly at the craniospinal junction. Obstruction to cerebrospinal fluid (CSF) channels can result in pain and a tendency for fluid cavitation of the spinal cord, called syringomyelia (SM) (Figs 1 to 3). The fluid within the cavities (singular syrinx, plural syringes) is similar to CSF. These fluid pockets can expand and can cause irreversible damage to the spinal cord, resulting in clinical signs of pain and neurological deficits.
The rising popularity of predisposed brachycephalic toy breed dogs and availability of MRI has seen CM-associated pain (CM-P) and SM becoming a more common diagnosis in veterinary medicine. CM-P can be a challenging diagnosis because the signs of pain are non-specific and, unlike SM, MRI diagnosis of CM-P is poorly defined or ambiguous. A degree of CM is ubiquitous in predisposed breeds and CM-P can be late onset, meaning it is challenging to distinguish clinically affected dogs using MRI (Figs 1, 2).
The eponymous term Chiari malformation refers to the first detailed description of the analogous human condition by Hans Chiari in 1891 and classically describes a cerebellar herniation through the foramen magnum. Alternative names for the canine condition include caudal occipital malformation syndrome (COMS) and occipital hypoplasia. None of these names are ideal because the malformation is more complex than a cerebellar herniation, simple occipital bone abnormality or small volume caudal fossa.
An alternative term, brachycephalic obstructive cerebrospinal fluid channel syndrome (BOCCS), was proposed to reflect the connection to brachycephaly and obstruction of CSF pathways. However, as CM was the terminology decided at a round table discussion (Capello and Rusbridge 2007), this is the most commonly accepted moniker.
The nomenclature of SM has morphed over the years since the first description in the early 19th century. Authoritative sources use SM rather than historical terms syringohydromyelia, hydrosyringomyelia or hydromyelia. This is because the anatomical distinction between these terms is theoretical rather than a reality (Rusbridge and Flint 2014). It is conventional in veterinary medicine to refer to a central syrinx, less than 2 mm in transverse diameter, as a central canal dilation (Fig 3), even though the ependymal lining of the central canal is disrupted with only minor dilation (Radojicic and others 2007). Non-inflammatory spinal cord oedema, as distinct from cavities containing free fluid, is referred to as presyrinx (presyringomyelia). Presyrinx most commonly affects the dorsal and ventral columns of the spinal cord and may eventually progress to SM (Fig 3). The oedema can reverse if the cause can be addressed. CNS inflammatory diseases can also cause spinal cord oedema and are alternative differentials for spinal cord oedema (Fig 4).
Signalment and prevalence
Brachycephaly with airorhynchy (ie, retroflexion of the facial skeleton on the cranial base) is the major risk factor for CM-P and SM. Any animal with skull shortening including the muzzle with, in dogs, concurrent whole body miniaturisation could be predisposed. The condition is most common in Cavalier King Charles spaniels (CKCS) and their crosses (eg, cavapoos), especially if the cross is with a smaller dog than a CKCS. Other breeds with high prevalence include King Charles spaniels, griffon bruxellois, affenpinschers, Chihuahuas, Yorkshire terriers, maltese, Pomeranians and brachycephalic cats, especially Persians. Occasionally affected dog breeds include French bulldogs, Boston terriers, pugs, havanese, miniature dachshunds, miniature/toy poodles, bichon frisé, and miniature pinschers. Surprisingly, many toy breeds with extreme facial foreshortening such as the Pekinese, Japanese chin and shi tzu, are not as predisposed, perhaps reflecting a different skull shape, brain size and genetic heritage.
When MRI is performed in predisposed breeds, CM is commonly reported, and SM may be an incidental finding. Care must be taken to not overdiagnose, and MRI results should be related to historical and clinical findings. Cerda-Gonzalez and others (2009) found that 92 per cent of CKCS had at least one craniocervical morphological abnormality detected on MRI, and studies looking at groups of 16 or more clinically unaffected CKCS found a high incidence of SM, ranging from 26.5 per cent (Cerda-Gonzalez and others 2009) to 65.4 per cent (Rusbridge and others 2007). These figures increased to 42 per cent and 74.5 per cent, respectively, when dogs with clinical signs were added to the population.
Dogs may be presented with the disease at any age, although many dogs (approximately 45 per cent) will develop first signs of the disease within the first year of life, and approximately 40 per cent of cases have first signs between one and four years of age. As many as 15 per cent develop signs as mature dogs (aged between six and eight years of age) (Plessas and others 2012, Thofner and others 2015).
CM is a developmental malformation characterised by neuroparenchymal disproportion – the ‘box’ (skull and cranial cervical vertebrae) is too ‘short’ for the contents (brain and cranial cervical spinal cord). The key feature of canine CM is premature suture closure (craniosynostosis) and insufficiency of bones forming the skull base and caudal skull (Figs 1, 2). CM is also characterised by a reduction in craniofacial tissue with a loss of the frontal sinus and a more defined ‘stop’ (Knowler and others 2020). The ‘stop’ is the pronounced angle between the nasal/maxilla bones and the frontal bones, which is a defining feature of domesticated mesaticephalic and brachycephalic dogs and by contrast is not present in wolves. The skull insufficiency results in rostrotentorial (forebrain) crowding which further reduces the functional caudotentorial space and causes hindbrain herniation. In addition, some predisposed breeds, such as CKCS, have comparatively big brains.
Chiari malformation-associated pain
CM-P is defined as the clinical signs of pain relating to CM. Compared to clinically normal dogs with CM (CM-N), dogs with CM-P have more extreme brachycephaly; that is, shorter cranial base, more craniofacial hypoplasia with greater neuroparenchymal disproportion and overcrowding (Knowler and others 2017) (Figs 1, 2).
There is yet to be an entirely satisfactory explanation of how fluid cavities develop in the spinal cord following CSF pathway obstruction. Whether syrinx fluid is derived from extracellular fluid or CSF is also controversial. The most accepted theory of the pathogenesis of SM is that obstruction to CSF flow in the subarachnoid space results in a mismatch in timing between the spinal arterial pulse peak pressure and CSF pulse peak pressure. Earlier arrival of peak CSF pressure encourages flow of CSF into the perivascular space. The perivascular space changes in size during the cardiac cycle and is widest when spinal arteriole pressure is low. If at that time peak CSF pressure is high, then the perivascular space could act as a ‘leaky’ one-way valve. From the perivascular space, fluid flows into the central canal ultimately resulting in a syrinx (Stoodley 2014).
SM can occur due to any obstruction to CSF pathways and has been reported in a variety of disorders, including acquired cerebellar herniation secondary to intracranial masses, spinal arachnoid diverticulum, spinal cord tethering and inflammatory conditions, such as feline infectious peritonitis. However, in canine medicine by far the most common cause is CM. The pathogenesis of SM associated with CM is predisposed by two morphological phenotypes: more extreme brachycephaly, as for CM-P, and craniocervical junction deformation, including changes in angulation of the dens and increased proximity of the atlas to the skull and loss of the cisterna magna (Figs 1, 2). Loss of the cisterna magna or other alterations in the CSF volume will affect the compliance of the CNS. This may be influenced by poor venous drainage, intracranial hypertension, and conformational features of the spinal canal.
CM-P is thought to relate to a failure to equilibrate intracranial pressure due to obstruction of CSF pathways. Intracranial pressure is affected by the systolic pulse, venous drainage, the balance between CSF production and absorption and microgravitational effects (eg, when being lifted rapidly or when the head position moves rapidly).
In people, pain in CM is exacerbated by the Valsalva manoeuvre, a brief increase in intrathoracic pressure, for example when coughing or with abdominal straining. Signs of canine CM-P (Table 1) include:
Vocalisation (described as without obvious trigger, when shifting position when recumbent and when being lifted under the sternum to a height);
Head and ear rubbing or scratching;
Aversion to touch;
Refusal or difficulty jumping or climbing stairs;
Exercise intolerance/reduced activity;
Behavioural change described as becoming more anxious, timid, aggressive or withdrawn.
SM-specific signs (SM-S) are associated with large syringes (in CKCS a maximum transverse width of equal to or greater than 4 mm) and include phantom scratching, scoliosis and sensory and motor signs. The neurolocalisation is consistent with the syrinx location (Table 2).
The signs of CM-P and SM (except phantom scratching) are non-specific. Therefore, other possible explanations should be eliminated. Neurological deficits associated with SM will have the same neurolocalisation as the syringe; however, gait disturbances and paresis may be surprisingly mild even with wide SM involving the entire cervical to lumbar spinal cord. Typically, the thoracic limbs are weaker than the pelvic limbs, reflecting the central spinal cord damage. Other differentials should be considered if there is a non-ambulatory tetraparesis or severe paraparesis (Table 3). Likewise, SM is a spinal cord disease and so would not result in epilepsy, facial nerve paralysis or fly catching disorder. CKCS are predisposed to several neurological conditions and comorbidities (Table 3).
CM-P is a diagnosis of exclusion in a predisposed breed or in a dog presenting with the signs mentioned earlier. MRI remains the only diagnostic test to support suspicion of CM-P. Although the bony changes can be demonstrated by CT, MRI is required to detect any associated SM. When undertaking brain and cervical MRI of a predisposed breed, it is recommended that the dog’s microchip or tattoo number (confirmed by the vet) is included on the DICOM (digital imaging and communications in medicine) images in addition to the Kennel Club registration number, if relevant, even if CM-P or SM is not a differential. This is to permit submission to the BVA/Kennel Club’s Chiari malformation/syringomyelia (CM/SM) scheme should the owner request this following the imaging (BVA 2013). For details of MRI protocols to investigate CM and SM see Rusbridge and others (2018).
MRI changes (Box 1) (Figs 1, 2) can support but not confirm the diagnosis of CM-P. Research techniques such as MRI-based morphological measurements or machine learning have yet to be adapted to the clinic (Spiteri and others 2019).
MRI features of Chiari-like Malformation-associated Pain
Craniofacial hypoplasia with absent or minuscule frontal sinuses and reduction in maxillary height. Junction between nasal and maxilla forming an angle rather than a slope.
Simple explanation: facial features of a ‘forehead’ formed by the frontal bone overlying the brain with no or minuscule frontal sinus, together with well-defined or indented stop and a muzzle which is short in height and length (see Fig 1).
Rostrotentorial overcrowding resulting in rostral flattening of the forebrain, reduction and ventral displacement of the olfactory bulbs and increased height of the cranium, especially in the occipital region (see Fig 1).
Simple explanation: the forebrain changes from a rugby to a football shape (see Fig 2). The olfactory bulbs are small and are directed ventrally rather than rostrally.
Obstruction of cerebrospinal fluid (CSF) channels: reduction in the cranial and spinal subarachnoid space in addition to ventriculomegaly of all ventricles and cisterns, except the cisterna magna which is often reduced.
Simple explanation: on T2-weighted (T2W) imaging there is less ‘white’ hyperintense fluid signal in the CSF space around the brain and spinal cord. By contrast, the CSF spaces within the brain are enlarged.
Shortening of the basicranium especially the presphenoid bone.
Simple explanation: a short skull base.
Small caudal cranial fossa, the supraoccipital bone is flatter and the opisthion (dorsal foramen magnum) is rostral with respect to the occipital crest (see Fig 1).
Simple explanation: the back of the skull containing the hindbrain is small.
Rostrotentorial neuroparenchyma is displaced dorsocaudally reducing the functional caudotentorial space contributing to a hindbrain herniation.
Simple explanation: the forebrain is displaced caudally. The space for the hindbrain is compromised rostrally by the forebrain and caudally by the small caudal skull. The cerebellum loses its rounded shape and is pushed out of the foramen magnum.
MRI is required for diagnosis of SM (Box 2). The finding of SM implies a fluid-filled cavity related to disturbance of CSF flow, spinal cord tethering or intramedullary tumour. The cause of SM should be determined (Rusbridge and others 2018). SM is not an appropriate description for myelomalacia or cystic lesions. SM can be an incidental finding, and when interpreting MRI an assessment should be made as to whether the location and severity of the syrinx would account for the signs. It would be exceptional for SM associated with CM to result in a myelopathy localising to T3-L3 with pelvic limb paresis and proprioceptive deficits and normal thoracic limb function. If this is the neurological localisation then other differentials should be investigated (Table 3).
MRI features of Syringomyelia-specific signs associated with Chiari-like Malformation
More extreme brachycephaly than seen with Chiari-like malformation-associated pain (CM-P) (see Box 1).
Change in the conformation of the craniospinal junction (transitional zone between the brain and the spine) because of craniovertebral junction (occiput, atlas and axis) malformation. The atlas is closer to the skull with cervical flexure and acute angulation of the odontoid peg resulting in kinking/elevation of the neuroparenchyma (see Fig 2).
Simple explanation: there is a concertina-like flexure of the bones and nervous tissue at the junction between the skull and spine because of rostrocaudal shortening.
Syringomyelia (SM) is a central cavitation of the spinal cord with fluid that has similar characteristics to cerebrospinal fluid (CSF).
For assessment of syrinx severity, transverse images of the widest part of the syrinx are obtained. Myelopathic signs in Cavalier King Charles spaniels are associated with a syrinx transverse width of 4 mm or more (SM-S) (Fig a).
Phantom scratching and cervicotorticollis/scoliosis are associated with extension of the syrinx into the superficial dorsal horn of the cervical spinal cord ipsilateral to the phantom scratching side and/or contralateral to the head tilt.
Simple explanation: extension of the syrinx to the edges of cervical spinal cord in the two or 10 o’clock position is associated with phantom scratching and scoliosis. Phantom scratching occurs on the same side as the syrinx. In scoliosis, the head twists down on the opposite side to the syrinx (Fig a)
Fluid signal-void sign within the syrinx cavity indicates pulsatile or turbulent flow and is a sign of an ‘active’ and filling syrinx more likely to expand (Fig a).
Simple explanation: on T2-weighted imaging ‘dark’ hypointense regions within the ‘white’ hyperintense syringe indicates moving fluid. Surging fluid in the syrinx expands the cavity
Not all syringes are clinically significant. A quiescent syrinx is centrally located, elliptical on sagittal images and symmetrical, usually circular, on transverse images and results in little or no change to the outline of the spinal cord.
An active and filling syrinx is expansive within the spinal cord and generally has an asymmetrical shape on transverse images.
Simple explanation: if the spinal cord outline is expanded by the syrinx then it is actively filling and more likely significant. A central located symmetrical ‘hole’ is less likely to be significant (Fig a).
Progression and prognosis
There is paucity of large studies on the progression and long-term outcome of dogs affected by CM-P and SM. Studies in breeding CKCS suggest that the proportion of affected CKCS increase from 25 per cent at one year of age to 60 per cent at three years of age. By five years of age, 70 per cent of the population have MRI evidence of SM (Parker and others 2011).
Although syrinx width increases over time, the rate of increase is not constant and it is my unproven impression, supported by computer modelling, that for many dogs the syrinx develops relatively rapidly but then remains remarkably unchanged over years having achieved a dynamic equilibrium. Clinical signs will progress in approximately 75 per cent of dogs and approximately 15 per cent will be euthanased because of CM-P and SM-S.
However, despite progressive signs, many dogs with signs of pain and phantom scratching respond to medical management and are considered by their owners to have an acceptable quality of life (Plessas and others 2012). Cervicotorticollis may slowly improve despite persistence of the syrinx. Dogs that are presented with SM-S before three years of age seem to have a poorer prognosis and are more likely to develop severe weakness which is more difficult to treat.
Medical management of SM is based mostly on anecdotal reports and typically relies on adjuvant analgesics and other unlicensed medication (Fig 5) (Table 4). There have been three short-term (14 to 25 day) clinical trials assessing carprofen, gabapentin and topiramate (Plessas and others 2015) and pregabalin (Sanchis-Mora and others 2019, Thoefner and others 2020), in addition to one long-term (39 [±14.3] months) outcome study (Plessas and others 2012). For the short-term studies, quality of life was improved following prescription of topiramate and gabapentin, but not after prescription of carprofen alone (Plessas and others 2015). Prescription of pregabalin improved owner-reported pain scores, mechanical hyperalgesia, cold hyperalgesia, cold allodynia and was efficacious for treatment of neuropathic pain (Sanchis-Mora and others 2019) and SM-associated phantom scratching (Thoefner and others 2020). For the long-term outcome study, 75 per cent of medically managed dogs had an acceptable quality of life at the end of the follow-up period; the most common medication prescribed was gabapentin or pregabalin (Plessas and others 2012). From this, one can conclude there is poor evidence that clinical signs of pain will improve with prescription of carprofen alone, there is some evidence of improvement with combination of carprofen and gabapentin or carprofen and topiramate, and reasonable evidence of improvement with pregabalin.
Anecdotally, a positive response to antacids, such as cimetidine or omeprazole, is reported. The principle is that these drugs reduce CSF production thus reducing the driving force contributing to CM-P and SM. However, studies assessing the effect of omeprazole on CSF production by evaluating the albumen quotient (QAlb; ratio between CSF and serum albumin concentration) did not support a CSF-reducing effect (Girod and others 2016), although the validity of QAlb as a surrogate marker for CSF production was later disputed (Girod and others 2019). More importantly, omeprazole may not achieve a therapeutic choroid plexus concentration, so the effect, if any, of antacids on CSF production remains unsubstantiated.
There are three recognised surgical options for management of CM-P and SM-S, but none are entirely satisfactory. To date, no published surgical series has provided MRI evidence of sustained collapse of the syringe postoperatively. Documenting that syrinx does not increase in size is not proof of surgical efficacy. If the postoperative MRI reveals a syrinx which is expanding the spinal cord outline then there is active filling. Likewise, surgical efficacy is not proved by stabilisation of clinical signs, as many dogs can be managed successfully on medical management.
Craniocervical decompression surgery
Craniocervical decompression surgery (foramen magnum decompression) aims to decompress the craniospinal junction by removing the supraoccipital bone with a C1 rostral dorsal laminectomy. Tissue is removed until the cerebellum vermis is well exposed. In my experience, successful decompression also requires removal of the tough atlanto-occipital ligament and a durotomy. Closure varies between surgeons; I favour marsupialisation of the dura and covering the defect with biocompatible collagen matrix (Rusbridge 2007). Others advocate covering the bony defect with an implant typically of titanium mesh. Surgery is successful in reducing pain in approximately 80 per cent of cases; approximately 45 per cent of cases may still have a satisfactory quality of life two years after surgery, although many still receive long-term medication (Rusbridge 2007). Contrary to the analogous human condition, craniocervical decompression does not appear to address the factors leading to SM; the syrinx is generally persistent. Much of the clinical improvement is likely attributable to decompression of CSF pathways; that is, surgery is most useful for CM-P rather than SM-S. For some cases, recurrence of signs occurs, often attributed to fibrous tissue adhesions over the foramen magnum; 25 per cent to as many as 50 per cent of cases can eventually deteriorate (Rusbridge 2007). This can occur as early as two months following surgery. There is no convincing evidence that this is less likely with implanted surgery. Fibrous adhesions develop following blood contamination which is common with all surgery.
Ventricular to peritoneal shunting
Ventricular to peritoneal shunting may be an option if the ventricles are significantly expanded, or if there is clinical hydrocephalus. This procedure appears to be more successful in facilitating syrinx collapse. However, shunting procedures have a high complication rate, especially subdural haematoma, infection and shunt blockage.
Syringo to pleural or subarachnoid shunting
Syringo to pleural or subarachnoid shunting involves placement of a shunting device directly into the syrinx, allowing fluid to drain into the pleural cavity/subarachnoid space, respectively. Because of the risk of shunt blockage, subarachnoid adhesions and complications relating to the myelotomy, I only use this technique when other surgeries are inappropriate; for example, in the instance of SM secondary to arachnoid webs (Tauro and Rusbridge 2020).
Which dogs are surgical candidates?
Surgery is more clearly indicated and most likely to be considered successful in dogs with CM-P (with or without SM) that have responded incompletely or not at all to medical management. In this instance, a craniocervical decompression is probably the surgery of choice. However, if clinical signs reflect SM (eg, phantom scratching or weakness) then this procedure is less likely to be successful because the syrinx persists. Many cases with phantom scratching can be managed medically. Management of weakness is more challenging, especially as there are no surgical reports that provide MRI evidence of long-term postoperative syrinx collapse.
Failure to control clinical signs and perceived or actual drug adverse effects drive many owners to seek alternative therapy. Anecdotally, acupuncture has been reported to be a useful adjunctive therapy for some cases. In others, massage may help alleviate signs. Care should be taken as the response to these treatments varies with each animal and some dogs may be more painful afterwards. Spinal manipulation is not recommended because it may cause pain. Exercise should be encouraged, and excessive weight gain discouraged. Hydrotherapy can be useful for some patients, especially those with weakness or proprioceptive deficits.
Genetic factors and breeding advice
The high prevalence, within closely related populations, suggests that SM is inherited in dogs and studies have shown it to be a complex trait, which can be late onset with a moderately high heritability that likely involves genes involved in embryonically active pro-osteogenic signalling pathways. Since the early 2000s, it has been recommended that dogs of breeds predisposed to CM and SM be MRI screened at least twice in their lifetime.
Breeding recommendations based on SM status and ages were formulated in 2006 (Knowler and others 2011). These guidelines concentrated on removing dogs with early onset SM from the breeding pool while maintaining genetic diversity. Early results from this breeding programme indicated that offspring without SM were more common when the parents were both clear of SM. Conversely, offspring with SM were more likely when both parents had SM. In the UK, MRI screens of potential breeding stock can be undertaken through the BVA/Kennel Club’s canine health scheme. However, this does not assess the whole skull or cranial cervical vertebrae nor does it provide an objective measure of risk of developing CM-P or SM. A machine learning approach is being developed with the ultimate aim of creating a simple artificial intelligence tool which will provide an objective measure of risk of developing CM-P or SM in the future (Spiteri and others 2019).
CM and SM is an inherited disorder with a high morbidity in many brachycephalic toy breeds and crosses. It is a pathology affecting the entire skull and craniocervical junction and is characterised by:
increased cranial height;
rostral displacement of atlas and dens;
overcrowding of the craniocervical junction;
obstruction of CSF flow through the foramen magnum;
and development of fluid filled cavities in the central spinal cord.
Although some dogs have no clinical signs, others can present with pain (CM-P) and signs relating to spinal cord damage by the syrinx (SM-S). Surgical and medical treatment options are available, but these have limited success, and from a welfare point of view it would be better to implement a screening and breeding programme that limits the occurrence of this disabling disease.
Open Access publication of this article was funded by the Cavalier Health Fund, with the aim of disseminating knowledge enabling diagnosis, management and prevention of canine Chiari malformation and syringomyelia. I would like to thank Penny Knowler for assistance in figure production.
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