Last edited on November 16, 2016 by Timothy C. Hain, MD, Chicago IL.
CANVAS is an easy to remember acronym for cerebellar ataxia, neuropathy, and vestibular areflexia, popularized in several recent articles by Szmulewicz et al. There are only a very few patients reported who have the requisite combination of two rare clinical findings (CA and VA), and the very common peripheral neuropathy. However, due to the power of internet assisted collaboration, it is now possible to find rare situations like this. The acronym presupposes that this is a distinct condition. However, it is also possible that this is just a chance combination, or perhaps a mixture of chance combination in some patients and a distinct condition in others.
At this writing, 2016, it is just too early to be sure whether CANVAS is a syndrome (i.e. a collection of symptoms), or a disease (i.e. an entity with a distinct cause and mechanism). Then, this is the case for many common medical conditions, defined by committees.
Our guess is not very many. In our practice files of 20,000 patients, we have 5 that are "diagnosed" as "CANVAS". Bilateral vestibular loss, which is a portion of CANVAS, has a prevalence of only 26/100,000. There must be less CANVAS patients than BVL. We have 329 BVL patients in our practice database. As we have only 5 CANVAS among the 300 or so BVL patients, it would seem that CANVAS must be about 60 times less comon than BVL. Somewhere around 5/million. So it would not seem that CANVAS can be a common condition. That is probably why it is so obscure.
Patients with CANVAS combine cerebellar ataxia (i.e. coordination problems -- the CA), peripheral nerve damage (neuropathy - N), and loss of vestibular function (vestibular areflexia -- the VA). This combination causes major disturbances to balance as each of these systems alone contributes to balance. Of course, when all are out at the same time, balance is much worse than when only one or two happens to be malfunctioning.
There are also conditions that might be viewed as "partial" CANVAS -- or maybe, "CANVAS minus".
- In Machado-Joseph disease, one the SCA disorders, there may be CANVAS -N: in other words, cerebellar and vestibular loss but no neuropathy (Gordon et al, 2003). A similar group of patients, without the genetic cause of Machado Joseph were described in 2004 by Migliaccio et al.
- In Friedreichs Ataxia, there may be CA and N: but no vestibular areflexia. CANVAS-N.
- Downbeat nystagmus was associated with bilateral vestibular failure in 36% of cases (Wagner et al, 2008). If one accepts downbeat nystagmus as a sign of cerebellar damage, then 36% of bilateral cases are "CANVAS-N". However, this is a dubious statistic -- This group's findings seems likely to be idiosyncratic to the referral patterns of their institution as this is not the case with other series of downbeating nystagmus or for that matter with the author's large experience. We see no reason why the majority of patients with bilateral vestibualar loss, most of which have either aminoglycoside ototoxicity or bilateral vestibular neuritis, should have downbeating nystagmus. Wagner's cases, we suspect, had a selection bias due to being accumulated in a neurology setting.
Similarly now, there are patients who could be reasonably called "CANVAS+". Wu and 17 other authors from New Zealand (2014), reported that autonomic dysfunction is found in 83% of 23 patients that they thought had CANVAS. The latter authors also reported that their CANVAS patients had more downbeating nystagmus (65%) than previously reported CANVAS patients.
As the CANVAS "syndrome" is actually just a combination of three somewhat rare findings, one might question whether or not the term "diagnosis" is appropriate at all. One would not even call people who had three unrelated conditions - -for example -- blue eyes, diabetes, and gastric reflux a "syndrome". One would just say - - well, you found some unusual patients. In other words, "Found patients". Ditto for patients with more or less symptoms.
Probably the truth lies somewhere between the two logical extremes (i.e. a "syndrome" on the one side, and "found" patients). If, for example, CANVAS was determined to be inherited, and the gene isolated - -then we would clearly have a disease.
Szmulewicz et al (2016) proposed "diagnostic criteria" for CANVAS, in a neurology throw-away journal, Neurol Clin Pract. This jumps to the conclusion that CANVAS is a disease rather than a collection of patients found through internet collaboration. We think that larger collections of patients and reports by a larger group of investigators will be needed to approach this in a organized way. We would like to see, for example, results of 100 autopsies on which to base this conjecture.
Other authors have reported other "add-ons" to CANVAS. CANVAS+ perhaps. Two groups -- Krismer and Wenning (2014) and Wu et al (2014) reported autonomic dysfunction as a 4th piece of "CANVAS" -- CANVAS+AD ?. One would think that this may be due to the sensory neuropathy, as the autonomic nervous system uses small nerve fibers to conduct its business.
One would think that there would be many additional CANVAS+ syndromes. Perhaps CANVAS with cardiac findings, with diabetes, with vestibular migraine. Miglaiaccio and Watson (2016) in fact, described a patient with CANVAS lacking bilateral loss, but with migraine. This would be, using our nomenclature, CANVAS-VA+VM.
There are so many possibilities. Is this is getting a little silly ? (:
Szmulewicz reported that in the 3 patients autopsied to date, there was a disorder of the dorsal root ganglia (Szmulewicz, 2014). This is a similar pathology to Friedreich's ataxia. It is too soon to know whether CANVAS is just a grouping of unusual patients thoughout the world, whose collection was made possible by internet communication, or a distinct entity.
Only symptomatic treatment is currently available. Generally these patients require assistive devices early on, as they have three impediments to balance.
A woman in her mid 60's diagnosed with "spinocerebellar ataxia", was evaluated because her physical therapist felt that she had bilateral vestibular loss. She also has a sensory neuropathy and very poor appreciation of vibration in her feet. On exam there are very clear findings of both cerebellar disturbance (strong gaze-evoked nystagmus, downbeating nystagmus, ataxia), and bilateral vestibular loss (very poor vestibular responses).
Rotatory chair shows profound vestibular loss. This was also seen on VHIT test. The VVOR test, however, was normal.
There was downbeating nystagmus in primary position, greatly increased by lateral gaze.
Smooth pursuit was poor (as is common at this age anyway).
Comment: This patient has the core findings for CANVAS as she has cerebellar ataxia, sensory neuropathy, and vestibular areflexia. She does not have the "pivotal sign" of CANVAS - -poor VVOR (Peterson et al, 2013). To our thinking, this is reasonable given that CANVAS, in the few autopsied cases, was associated with deafferentation of the cerebellum from dorsal root ganglion disease.