The Ann Conroy Memorial Lecture

Syringomyelia-Chiari 2018 International Symposium Organised by the Ann Conroy Trust, in association with Aesculap Academia.

 

Syringomyelia-Chiari 2018

 

The Ann Conroy Memorial Lecture

 

One Health; learning from our best friends

 

Clare Rusbridge

 

Syringomyelia is an increasingly common diagnosis in veterinary medicine and most frequently associated with Chiari-like malformation (CM). Eponymous terms are discouraged in veterinary medicine, although not without precedent (for example Horner’s syndrome and Wallerian degeneration). However this label, chosen in a round table discussion was considered less restrictive than an anatomical description such as hindbrain herniation because the latter could prove to be too simplistic or inaccurate in the future. This was a wise decision because, in the 20 years since the first description in the dog, our understanding of CM has morphed from a description of cerebellar herniation (dogs do not have cerebellar tonsils) to a complex developmental malformation of the skull and craniocervical vertebrae characterized by a conformational change and overcrowding of the brain and cervical spinal cord, particularly at the craniospinal junction. CM is associated with miniaturisation and brachycephalism and is prevalent in several toy dog breeds particularly Cavalier King Charles Spaniel and Chihuahua to a lesser extent, the fashionably popular French Bulldog and Pug dog. Perhaps surprising, many toy breeds with extreme facial foreshortening such as the Pekinese, Japanese chin and Shi Tzu, are not predisposed perhaps reflecting a different skull shape, brain size and genetic heritage. Since the bony and parenchymal changes between and within individuals in each breed are different, CM might be considered an umbrella term with a common tendency towards pain associated with CM and the development of syringomyelia. As in humans, obstruction of the foramen magnum and cerebrospinal fluid channels is pivotal in the pathogenesis of syringomyelia and the variation in phenotype makes this condition similar to brachycephalic obstructive airway syndrome (BOAS) - the most common cause of respiratory distress in companion dogs. Many dogs are affected by both conditions. Although there is a phenotypic variation, this is not as marked as in humans and consequently our canine companions represent a huge resource for understanding the pathogenesis of syringomyelia, diagnosis, natural history of the disease, treatment options, and genetics. Machine learning techniques, (as illustrated in one of the free papers at the symposium), could revolutionise diagnosis providing an objective measure of CM. The principle can be readily applied to humans. Another of the veterinary papers describes computer modelling of syringomyelia from canine MRI. This technique provides insights into the pathogenesis and, in theory, might be developed to model surgical outcome. The hypothesis being that different surgeries can be modelled on a patient in vivo in order to select the most appropriate procedure. As a naturally occurring and long-lived model of syringomyelia and central neuropathic pain that are subject to similar co-morbidities such as obesity and cardiovascular disease, clinical trials in dogs could provide insights into pain management in humans. Studies into the genetics of the condition have shown CM/SM 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. To date, three candidate genes have been identified: SALL-1 (in humans Mutations in the SALL1 gene cause Townes-Brocks Syndrome which can be associated with CM); PCDH17, a CNS cell adhesion molecule; and ZWINT of which expression is associated with neuropathic pain. Thus Chiari malformation and syringomyelia are an excellent examples of One Health since “solutions require everyone working together on all the different levels” (quotation from William Karesh credited with coining the modern usage of the term via journalist Rick Weiss Washington Post). And this certainly applies in this case to ‘Man and his Dog’.

 

 

 

 

 

 

The symposium is co-organised by The Ann Conroy Trust, in association with Aesculap Academia.

 

The Ann Conroy Trust is Registered Charity No: 1165808.

We provide Support, Education and Research for patients living with Chiari Malformation, Syringomyelia and associated conditions.