scholarly journals Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS): genetic and clinical aspects

2021 ◽  
pp. practneurol-2020-002822
Author(s):  
Andrea Cortese ◽  
Riccardo Curro' ◽  
Elisa Vegezzi ◽  
Wai Yan Yau ◽  
Henry Houlden ◽  
...  
Keyword(s):  
Cerebellar Ataxia ◽  
Genetic Basis ◽  
Sensory Neuropathy ◽  
Sensory Nerves ◽  
Clinical Aspects ◽  
Sensory Disturbance ◽  
Recessive Ataxia ◽  
Common Cause ◽  
Ocular Reflex ◽  
Vestibulo Ocular Reflex

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) typically presents in middle life with a combination of neuropathy, ataxia and vestibular disease, with patients reporting progressive imbalance, oscillopsia, sensory disturbance and a dry cough. Examination identifies a sensory neuropathy or neuronopathy and bilaterally impaired vestibulo-ocular reflex. The underlying genetic basis is of biallelic AAGGG expansions in the second intron of replication factor complex subunit 1 (RFC1). The frequency and phenotype spectrum of RFC1 disease is expanding, ranging from typical CANVAS to site-restricted variants affecting the sensory nerves, cerebellum and/or the vestibular system. Given the wide phenotype spectrum of RFC1, the differential diagnosis is broad. RFC1 disease due to biallelic AAGGG expansions is probably the most common cause of recessive ataxia. The key to suspecting the disease (and prompt genetic testing) is a thorough clinical examination assessing the three affected systems and noting the presence of chronic cough.

scholarly journals A – C.A.N.V.A.S (CEREBELLAR ATAXIA, NEURONOPATHY AND VESTIBULAR AREFLEXIA WITH AUTONOMIC DYSFUNCTION): A FASCINATING CLINICAL PORTRAIT

2018 ◽  
Vol 4 (3-4) ◽  
pp. 3-8
Author(s):  
Carlo Canepa-Raggio
Keyword(s):  
Cerebellar Ataxia ◽  
Autonomic Dysfunction ◽  
Cerebellar Atrophy ◽  
Sensory Neuropathy ◽  
Nerve Biopsy ◽  
Sural Nerve Biopsy ◽  
Downbeat Nystagmus ◽  
Charcot Marie Tooth Disease ◽  
Ocular Reflex ◽  
Vestibulo Ocular Reflex

57-year-old male patient with a 30-year history chronic cough, balance difficulties (most noticeable in the dark), ataxia and sensory neuropathy. There was also evidence of orthostatic hypotension and hypohydrosis. Examination revealed downbeat nystagmus, an abnormal visually-enhanced vestibulo-ocular reflex, length-dependent sensory neuropathy, high-stepping tandem ataxia and bilateral dysmetria. MRI brain shows marked vermian cerebellar atrophy (more noticeable in lobes VI and VIIa/b) and nerve conduction studies reveal absent sensory conductions (ganglionopathy). Genetic testing for Friedrich’s ataxia, spinocerebellar ataxia and hereditary motor sensory neuropathy (Charcot-Marie-Tooth disease) were all negative. Sural nerve biopsy showed pattern of severe loss of myelinated fibres. This patient was diagnosed with cerebellar ataxia, neuronopathy (ganglionopathy) and vestibular areflexia with autonomic dysfunction. Keywords: ataxia, neuronopathy, vestibular areflexia, autonomic dysfunction.

scholarly journals Update on Cerebellar Ataxia with Neuropathy and Bilateral Vestibular Areflexia Syndrome (CANVAS)

2020 ◽  
Author(s):  
Mathieu Dupré ◽  
Ruben Hermann ◽  
Caroline Froment Tilikete
Keyword(s):  
Cerebellar Ataxia ◽  
Late Onset ◽  
Genetic Disorder ◽  
Axonal Neuropathy ◽  
Sensory Neuropathy ◽  
Bilateral Vestibulopathy ◽  
Familial Form ◽  
Vestibulo Ocular Reflex ◽  
Classical Triad ◽  
Factor C

Abstract The syndrome of cerebellar ataxia with neuropathy and bilateral vestibular areflexia (CANVAS) has emerged progressively during the last 30 years. It was first outlined by the neurootology/neurophysiology community in the vestibular areflexic patients, through the description of patients slowly developing late-onset cerebellar ataxia and bilateral vestibulopathy. The characteristic deficit of visuo-vestibulo-ocular reflex (VVOR) due to the impaired slow stabilizing eye movements was put forward and a specific disease subtending this syndrome was suggested. The association to a peripheral sensory axonal neuropathy was described later on, with neuropathological studies demonstrating that both sensory neuropathy and vestibular areflexia were diffuse ganglionopathy. Clinical and electrophysiological criteria of CANVAS were then proposed in 2016. Besides the classical triad, frequent chronic cough, signs of dysautonomia and neurogenic pains were frequently observed. From the beginning of published cohorts, sporadic as well as familial cases were reported, the last suggestive of an autosomal recessive mode of transmission. The genetic disorder was discovered in 2019, under the form of abnormal biallelic expansion in the replication factor C subunit 1 (RFC1) in a population of late-onset ataxia. This pathological expansion was found in 100% of the familial form and 92% of sporadic ones when the triad was complete. But using the genetic criteria, the phenotype of CANVAS seems to expand, for exemple including patients with isolated neuronopathy. We propose here to review the clinical, electrophysiological, anatomical, genetic aspect of CANVAS in light of the recent discovery of the genetic aetiology, and discuss differential diagnosis, neuropathology and physiopathology.

Report of oscillopsia in ataxia patients correlates with activity, not vestibular ocular reflex gain

2021 ◽  
pp. 1-9
Author(s):  
Jennifer L. Millar ◽  
Michael C. Schubert
Keyword(s):  
Cerebellar Ataxia ◽  
Head Rotation ◽  
Gait Velocity ◽  
Head Impulse Test ◽  
Healthy Controls ◽  
Head Impulse ◽  
Ocular Reflex ◽  
Vestibular Ocular Reflex ◽  
Vestibulo Ocular Reflex ◽  
Reflex Gain

BACKGROUND: Patients with cerebellar ataxia report oscillopsia, “bouncy vision” during activity, yet little is known how this impacts daily function. The purpose of this study was to quantify the magnitude of oscillopsia and investigate its relation to vestibulo-ocular reflex (VOR) function and daily activity in cerebellar ataxia. METHODS: 19 patients diagnosed with cerebellar ataxia and reports of oscillopsia with activity were examined using the video head impulse test (vHIT), Oscillopsia Functional Index (OFI), and clinical gait measures. Video head impulse data was compared against 40 healthy controls. RESULTS: OFI scores in ataxia patients were severe and inversely correlated with gait velocity (r = –0.55, p <  0.05), but did not correlate with VOR gains. The mean VOR gain in the ataxic patients was significantly reduced and more varied compared with healthy controls. All patients had abnormal VOR gains and eye/head movement patterns in at least one semicircular canal during VHIT with passive head rotation. CONCLUSIONS: Patients with cerebellar ataxia and oscillopsia have impaired VOR gains, yet severity of oscillopsia and VOR gains are not correlated. Patients with cerebellar ataxia have abnormal oculomotor behavior during passive head rotation that is correlated with gait velocity, but not magnitude of oscillopsia.

scholarly journals Central and peripheral vestibular signs simultaneously present in a patient with instability: A case report

2019 ◽  
Vol 72 (1-2) ◽  
pp. 51-53
Author(s):  
Dusan Pavlovic
Keyword(s):  
Magnetic Resonance Imaging ◽  
Case Report ◽  
Magnetic Resonance ◽  
Cerebellar Ataxia ◽  
Head Impulse Test ◽  
Resonance Imaging ◽  
Head Impulse ◽  
Ocular Reflex ◽  
Vestibulo Ocular Reflex ◽  
Normal Head

Introduction. Cerebellar ataxia, neuropathy, vestibular areflexia syndrome is a rare neurodegenerative disease with instability as the main presenting symptom. Patients with this syndrome often present with central and peripheral vestibular signs. This slowly progressive disease usually starts after 60 years of age and it takes 11 years to diagnose it. Case Report. Here I present a 62-year-old woman with instability lasting for 7 years, but deteriorating in the last two years with two episodes of falls, diplopia when looking to the right, paresthesia in the extremities and clumsiness with hands. Clinical examination revealed dysarthria, positive Romberg test, left hand dysmetria, gaze evoked and downbeat nystagmus, positive head impulse test, absent vestibulo-ocular reflex at video head impulse test, no response to caloric stimulation, no smooth pursuit and dysmetric and prolonged saccades at videonystagmography, positive visually enhanced vestibulo ocular reflex test, normal head magnetic resonance imaging, subclinical signs of polyneuropathy at electroneurography and negative autoimmune and paraneoplastic cerebellar antibodies. Conclusion. Instability is the first symptom in patients with cerebellar ataxia, neuropathy, vestibular areflexia syndrome. Easy to perform, positive visually enhanced vestibulo-ocular reflex test points to a concomitant central and peripheral vestibular disorder. Negative autoimmune and paraneoplastic antibodies rule out other cerebellar diseases. However, normal head magnetic resonance imaging findings without expressed signs of peripheral sensory neuropathy are in concordance with a slowly progressive form of this syndrome.

Molecular Basis and Clinical Aspects of Hereditary Megakaryocyte and Platelet Membrane Glycoprotein Disorders

1996 ◽  
Vol 16 (02) ◽  
pp. 114-138 ◽  
Author(s):  
R. E. Scharf
Keyword(s):  
Genetic Basis ◽  
Molecular Mechanisms ◽  
Molecular Genetic ◽  
Platelet Membrane ◽  
Clinical Aspects ◽  
Membrane Glycoprotein ◽  
Membrane Glycoproteins ◽  
Membrane Expression ◽  
Receptor Complexes ◽  
Platelet Membrane Glycoprotein

SummarySpecific membrane glycoproteins (GP) expressed by the megakaryocyte-platelet system, including GPIa-lla, GPIb-V-IX, GPIIb-llla, and GPIV are involved in mediat-ing platelet adhesion to the subendothelial matrix. Among these glycoproteins, GPIIb-llla plays a pivotal role since platelet aggregation is exclusively mediated by this receptor and its interaction with soluble macromolecular proteins. Inherited defects of the GPIIb-llla or GPIb-V-IX receptor complexes are associated with bleeding disorders, known as Glanzmann's thrombasthenia, Bernard-Soulier syndrome, or platelet-type von Willebrand's disease, respectively. Using immuno-chemical and molecular biology techniques, rapid advances in our understanding of the molecular genetic basis of these disorders have been made during the last few years. Moreover, analyses of patients with congenital platelet membrane glycoprotein abnormalities have provided valuable insights into molecular mechanisms that are required for structural and functional integrity, normal biosynthesis of the glycoprotein complexes and coordinated membrane expression of their constituents. The present article reviews the current state of knowledge of the major membrane glycoproteins in health and disease. The spectrum of clinical bleeding manifestations and established diagnostic criteria for each of these dis-orders are summarized. In particular, the variety of molecular defects that have been identified so far and their genetic basis will be discussed.

CANVAS is a common form of late-onset hereditary ataxia

2020 ◽  
pp. 51-52
Author(s):  
Е.П. Нужный ◽  
Н.Ю. Абрамычева ◽  
Е.Г. Воробьева ◽  
Е.О. Иванова ◽  
Ю.А. Шпилюкова ◽  
...  
Keyword(s):  
Cerebellar Ataxia ◽  
Clinical Picture ◽  
Autosomal Recessive ◽  
Late Onset ◽  
Repeat Expansion ◽  
Hereditary Ataxia ◽  
Recessive Ataxia ◽  
Autosomal Recessive Ataxia

Синдром CANVAS (мозжечковая атаксия, невропатия и вестибулярная арефлексия) - аутосомно-рецессивная атаксия с поздним дебютом, обусловленная носительством биаллельной экспансии (AAGGG)n во 2-м интроне гена RFC1. До настоящего момента отсутствуют сведения о распространенности данного заболевания в российских семьях. Нами был проведен поиск биаллельной экспансии AAGGG-повторов у 35 российских пациентов с поздней мозжечковой атаксией. Верифицированы 5 пациентов (14,3%) с синдромом CANVAS и характерной клинической картиной. CANVAS (cerebellar ataxia, neuropathy and vestibular areflexia) is a late-onset autosomal recessive ataxia due to biallelic (AAGGG)n repeat expansion in the 2nd intron of the RFC1 gene. There is no information on the CANVAS prevalence in Russian families. We searched for biallelic expansion of AAGGG repeats in 35 Russian patients with late-onset cerebellar ataxia. Five patients (14.3%) with CANVAS syndrome and a characteristic clinical picture were verified.

Vestibulo-ocular reflex adaptation to moving virtual sound source

2013 ◽  
Vol 72 (3) ◽  
pp. 156-162
Author(s):  
Yumiko O. Kato ◽  
Koshi Mikami ◽  
Yasuhiro Miyamoto ◽  
Shoji Watanabe ◽  
Izumi Koizuka
Keyword(s):  
Sound Source ◽  
Ocular Reflex ◽  
Vestibulo Ocular Reflex
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