Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a relatively poorly understood autosomal recessive neurodegenerative disease. The molecular basis of CANVAS was discovered only in 2019 and it is associated with the biallelic pentanucleotide AAGGG expansion carriage in the RFC1 gene. With the advent of genetic diagnostics, the understanding of the phenotypic spectrum and variety of clinical manifestations of this disease has expanded, including a combination of cerebellar ataxia and sensory neuropathy, as well as isolated sensory polyneuropathy/ganglionopathy. This review details current information on the etiology, pathogenesis, clinical presentation and diagnosis of CANVAS in order to increase the awareness of practitioners and early diagnosis of this disease.
The article presents two clinical cases of 51 and 57-year-old patients living in regions endemic for tick-borne encephalitis in which the differential diagnosis between progressive supranuclear palsy (PSP) and the extremely rare parkinsonian variant of chronic tick-borne encephalitis (CTBE) resulted in a diagnostic challenge. In both cases there was a clinical presentation of progressive symmetric levodopa-resistant parkinsonism with vertical gaze palsy, cognitive impairment of the executive type, frontal lobe signs, focal dystonia and in one case — early onset of postural instability, which corresponds to the diagnosis of probable PSP. The parkinsonian variant of CTBE was supported by the lack of tick-borne encephalitis virus IgG-antibodies negativity in the blood for several years, intrathecal oligoclonal antibody synthesis in one patient, the absence of typical neuroimaging signs of PSP, and delayed disease onset after a tick bite. Difficulties in diagnosis and possible mechanisms of the pathogenesis of primary progressive CTBE, as well as the similarity of the clinical and pathomorphological presentation of PSP, von Economo encephalitis lethargica, and postencephalitic parkinsonism are discussed.
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