Syndrome of cerebellar ataxia, neuropathy and vestibular areflexia: Diagnosis by caloric vestibular stimulation

Dear Editor:

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a recently-described progressive degenerative disease whose exact prevalence remains unknown. This syndrome appears mainly sporadically and occasionally affects siblings. This has led researchers to consider the possibility of a recessive inheritance pattern, but the disease has not yet been linked to changes at a specific locus.^1,2 According to published cases, age at onset ranges from 33 to 71 years; after 10 years with the disease, most patients require support when walking.²

We present the case of a 74-year-old man who for 21 years had experienced gait instability exacerbated by darkness, and diminished foot sensation, which progressively increased until he became unable to walk unaided 5 years ago. Neurological examination revealed absent Achilles reflexes, wide-based stance, positive results on the Romberg test, and markedly ataxic gait requiring bilateral support. Vibratory sensation was abolished below the iliac crests, diminished above that level, and normal in the face; algesia was preserved. The patient presented dysmetria, movement decomposition with essential tremor, scanning dysarthria, saccadic movements during eye tracking, horizontal and vertical gaze-evoked nystagmus, and refixation saccade in the horizontal plane during the Halmagyi head thrust manoeuvre.

Among complementary data, videonystagmography (VNG) showed horizontal spontaneous pendulum movements in the primary gaze position and eye tracking consisting of saccadic movements. Bilateral caloric stimulation induced only small erratic eye movements and the audiometry test showed normal hearing.

The brain MRI revealed cerebellar global atrophy, especially in the superior part of the vermis, with crus I impairment; the membranous labyrinths showed no changes. MR imaging showed normal spinal cord morphology, size, and signal.

An electroneurography study revealed absence of sensory nerve action potentials, as well as normal motor conduction velocity and normal motor unit action potential amplitudes in the nerves in all 4 limbs.

Dynamic mutations of spinocerebellar ataxia (SCA) types 1, 2, 3, 6, and 7, Friedreich ataxia (FRDA), and fragile X-associated tremor/ataxia syndrome were all excluded. Antigen and alpha-fetoprotein levels were normal; tests for anti-GAD antibodies, endomysium, peroxidase, anti-Hu, anti-Yo, anti-Ri, and anti-Tr antibodies, as well as tests for Brucella, syphilis, and Borrelia burgdorferi in serum and cerebrospinal fluid yielded negative results.

Before CANVAS was described, researchers were already aware of the association between cerebellar ataxia and bilateral vestibulopathy,³ the presence of peripheral neuropathy in cases of vestibulopathy,^4,5 and the presence of periodic vestibulocerebellar ataxia.⁶

In this case, cerebellar impairment presented with ataxic gait, limb dysmetria, wide-based stance, and scanning dysarthria. Achilles tendon areflexia was useful for detecting sensory neuropathy (confirmed by electroneurography). While topography may have suggested spinal cord disease, that entity was ruled out by MRI.

Vestibular hypofunction was suspected when doctors performed the head thrust test, which resulted in saccadic movements to refixate,⁷ rather than the eyes maintaining fixation during the manoeuvre. In addition, caloric stimulation generated a very anomalous oculomotor response instead of the typical response (consisting of horizontal nystagmus in the direction of the quick component in response to heat or in the opposite direction in response to cold). This finding confirmed the presence of bilateral vestibular hypofunction.^8,9

Vestibular areflexia in CANVAS is caused by neural loss in Scarpa's ganglion, which was described in the only autopsy in the literature.¹⁰ In contrast, vestibular organs remained intact¹⁰ according to the head MRI.

Findings from this study coincide with those described for CANVAS cases; however, subsequent studies are needed in order to better define this syndrome. Meanwhile, we believe that tests of vestibular function in ataxic patients lacking a precise diagnosis may be helpful for detecting cases with vestibulocerebellar impairment.

Acknowledgements

We would like to thank María Jesús Pablo Zaro, Department of Clinical Neurophysiology, Hospital San Jorge, Huesca; Ana Carmen Vela, Department of Radiology, Hospital Universitario Miguel Servet, Zaragoza; and Pilar Larrodé, Department of Neurology, Hospital Clínico Universitario Lozano Blesa, Zaragoza.