[Subacute ataxia associated with cerebellar ataxia, neuropathy and vestibular areflexia (CANVAS)]. / Ataxia subaguda asociada a ataxia cerebelosa, neuropatía y arreflexia vestibular (CANVAS).

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is a late onset neurodegenerative disorder. Its genetic basis has recently been identified in the gene encoding a subunit of the Replication Factor C (RFC1). We present the case of a 62-year-old woman who experienced a history of a biphasic presentation of imbalance and gait disorders, with rapid onset of symptoms followed by slow and progressive neurological deterioration. The diagnostic process was challenging, and numerous tests were conducted to rule out acquired and genetic causes of ataxia, leading to a diagnosis of late-onset idiopathic cerebellar ataxia. Subsequently, vestibular function tests identified severe bilateral vestibulopathy. This led to considering CANVAS among the diagnoses, which was ultimately confirmed through genetic testing (biallelic expansion of the pentanucleotide AAGGG in the RFC1 gene). This case highlights the importance of this new described genetic disease and its subacute presentation variant, emphasizing the relevance of objective vestibular function tests in idiopathic ataxias to achieve proper diagnosis and eventual genetic counseling for offspring.

El síndrome de ataxia cerebelosa, neuropatía y arreflexia vestibular (CANVAS) es un trastorno neurodegenerativo progresivo que se manifiesta en etapas tardías de la vida. Su base genética ha sido recientemente identificada en el gen que codifica la subunidad 1 del factor C de replicación (RFC1). Presentamos el caso de una mujer de 62 años con una historial de desequilibrio y deterioro de la marcha de presentación bifásica, con un inicio rápido de los síntomas seguido de un deterioro neurológico lento y progresivo. El proceso diagnóstico fue complejo y se realizaron numerosas pruebas para descartar causas adquiridas y genéticas de la ataxia, arribando al diagnóstico de ataxia cerebelosa de inicio tardío idiopática. Ulteriormente, las pruebas de función vestibular identificaron una grave vestibulopatía bilateral. Esto llevó a considerar el CANVAS entre los diagnósticos, que finalmente fue confirmado mediante pruebas genéticas (expansión bialélica del penta-nucleótido AAGGG en el gen RFC1). Este caso subraya la importancia de esta nueva enfermedad genética y su variante de presentación subaguda y enfatiza la relevancia de las pruebas objetivas de función vestibular en las ataxias consideradas idiopáticas para lograr un diagnóstico adecuado y un eventual asesoramiento genético a la descendencia.

Video head impulse test in bilateral vestibulopathy.

INTRODUCTION: Bilateral vestibulopathy is a rare chronic condition with multiple etiologies. Bilateral vestibulopathy is characterized mainly by unsteadiness when walking or standing, which worsens in darkness, as well as oscillopsia. The degree of handicap caused by bilateral vestibulopathy is variable and remains controversial. OBJECTIVES: To determine the value of the video Head Impulse Test in quantifying vestibular deficit and to establish its impact on the quality of life. METHODS: Twenty patients (mean age, 41.9 years; range 14-80 years) fulfilling the recent Barany criteria of bilateral vestibulopathy, responded to the Situational Vertigo Questionnaire and underwent vestibular examination including fixation, positional tests, oculomotor test battery and video head impulse test. RESULTS: The relation between each of the video head impulse test parameters and the scores from the questionnaire were statistically analyzed. We observed that patients with covert saccades on the video head impulse test were more likely to have a better quality of life than those with both covert and overt saccades, regardless of the vestibulo-ocular reflex gain in each semicircular canal. The presence of covert saccades was found to be associated with an improved quality of life regardless of the severity of vestibule ocular reflex-deficit. Our conclusion was that vestibule ocular reflex gain, measured by video head impulse test, does not quantify the severity of affection of quality of life in patients with bilateral vestibulopathy. CONCLUSION: Covert saccades are strategies aiming at minimizing the blurring of vision during head movement, that is an adaptive mechanism that improves quality of life. Therefore, we recommend that video head impulse test should be a part of the routine diagnostic workup of bilateral vestibulopathy.

Brain Structural Signature of RFC1-Related Disorder.

BACKGROUND: The cerebellar ataxia, neuropathy, and vestibular areflexia syndrome was initially described in the early 1990s as a late-onset slowly progressive condition. Its underlying genetic cause was recently mapped to the RFC1 gene, and additional reports have expanded on the phenotypic manifestations related to RFC1, although little is known about the pattern and extent of structural brain abnormalities in this condition. OBJECTIVE: The aim is to characterize the structural signature of brain damage in RFC1-related disorder, correlating the findings with clinical symptoms and normal brain RFC1 expression. METHODS: We recruited 22 individuals with molecular confirmation of RFC1 expansions and submitted them to high-resolution 3T magnetic resonance imaging scans. We performed multimodal analyses to assess separately cerebral and cerebellar abnormalities within gray and white matter (WM). The results were compared with a group of 22 age- and sex-matched controls. RESULTS: The mean age and disease duration of patients were 62.8 and 10.9 years, respectively. Ataxia, sensory neuronopathy, and vestibular areflexia were the most frequent manifestations, but parkinsonism and pyramidal signs were also noticed. We found that RFC1-related disorder is characterized by widespread and relatively symmetric cerebellar and basal ganglia atrophy. There is brainstem volumetric reduction along all its segments. Cerebral WM is also involved-mostly the corpus callosum and deep tracts, but cerebral cortical damage is rather restricted. CONCLUSION: This study adds new relevant insights into the pathophysiological mechanisms of RFC1-related disorder. It should no longer be considered a purely cerebellar and sensory pathway disorder. Basal ganglia and deep cerebral WM are additional targets of damage. © 2021 International Parkinson and Movement Disorder Society.

Is Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome (CANVAS) a Vestibular Ganglionopathy?

OBJECTIVES: CANVAS is an acronym for cerebellar ataxia, neuropathy and vestibular areflexia syndrome. Limited autopsy data has suggested that CANVAS is caused by a focal dorsal root ganglionopathy that damages Scarpa's (vestibular) ganglion, but spares the Spiral (hearing) ganglion. If the vestibular areflexia of CANVAS is in fact due to ganglionopathy, then there should be global reduction of all vestibular responses. MATERIALS AND METHODS: With this hypothesis in mind, a retrospective review of 5 subjects who met the clinical criteria for CANVAS was performed. Recent advances in vestibular testing have made it possible to quantify responses from all 5 vestibular end organs in the inner ear. Results of the Video head impulse test (VHIT), video oculography, caloric test and vestibular evoked myogenic potential (VEMP) were examined to determine if all 5 end organs are nonfunctional in CANVAS. RESULTS: Severe reduction of function of the six semicircular canals and ocular VEMPs were observed. Only the cervical VEMPs were present and reproducible, consistent with either partial sparing of the inferior vestibular ganglia, specific embryologic resistance of the saccule to the degeneration or a mechanism for cervical VEMPs that does not require an intact vestibular ganglion. CONCLUSION: Our results suggest that Scarpa´s ganglia dysfunction could be the mechanism for loss of semicircular canal and utricular function in CANVAS patients, but the preservation of the cervical VEMP response is unexplained.