An intronic GAA repeat expansion in the FGF14 gene was recently identified as a common cause of autosomal dominant GAA-FGF14 ataxia (SCA27B). We aimed to characterize in detail the clinical and video-oculographic features in our cohort of SCA27B patients. We genotyped the FGF14 GAA repeat expansion in 52 patients with unsolved late-onset cerebellar ataxia. Brain MRI and nerve conduction study, as well as video-oculographic (VOG) assessment, were performed. Eight patients (15.4%) with pathogenic GAA repeat expansion in the FGF14 gene were found. The median age at onset was 51 years (range—23–63 years). Sensory axonal neuropathy was found in 5/8 patients. Cerebellar atrophy was observed in 5/8 patients, and in one case, pontocerebellar atrophy was found. All tested patients had impaired smooth pursuit, 5/6 patients had impaired vestibulo-ocular reflex suppression, nystagmus, and an increased number of square wave jerks, 4/6 patients had horizontal gaze-evoked nystagmus, 3/6 had spontaneous downbeat nystagmus, and 1/6 had an upbeat one. Video head impulse test gain was lower than 0.8 on both sides in 2/4 patients, along with the presence of overt saccades. Further studies in different cohorts are needed to complete the phenotype of the FGF14-related disorders.

ЦЕЛЬ ИССЛЕДОВАНИЯ Оценить частоту встречаемости спиноцеребеллярной атаксии 8-го типа (СЦА8) у пациентов с прогрессирующими мозжечковыми атаксиями, описать клинические особенности фенотипа у пациентов с СЦА8. МАТЕРИАЛ И МЕТОДЫ Генотипирование CTA/CTG-повторов в гене ATXN8OS проведено 411 пациентам с дегенеративными атаксиями методом фрагментного анализа. Предварительно были исключены СЦА 1, 2, 3 и 6-го типов, атаксия Фридрейха. Всем пациентам выполнена МРТ головного мозга, оценка по шкале для обследования и оценки атаксии (SARA), для скрининга когнитивных нарушений использовали Монреальскую шкалу оценки когнитивных функций. РЕЗУЛЬТАТЫ Выявлены 6 (1,5%) пациентов с СЦА8 — носители экспансии в гене ATXN8OS (91—152 CTA/CTG-повторов). Все случаи были спорадическими. Возраст дебюта варьировал от 14 до 42 лет. У всех пациентов отмечалась медленно прогрессирующая мозжечковая атаксия, глазодвигательные нарушения, дизартрия, пирамидный синдром, у двух больных — когнитивные нарушения. У одной пациентки клиническая картина соответствовала мультисистемной атрофии мозжечкового типа (атаксия, ортостатическая гипотензия, атрофия мозжечка и ствола мозга). МРТ головного мозга у всех пациентов выявила атрофию мозжечка. ЗАКЛЮЧЕНИЕ СЦА8 является редкой формой аутосомно-доминантной атаксии с преобладанием классического фенотипа. Все выявленные случаи СЦА8 были спорадическими, что необходимо учитывать при планировании генетического тестирования у пациентов с СЦА.

Anti-glutamic acid decarboxylase (GAD) antibody-associated ataxia is a rarely diagnosed but potentially curable disease associated with autoimmune damage to and death of Purkinje cells in the cerebellar cortex. In Russia, the authors have provided for the first time descriptions of three own observations of this disease, which had a number of clinical features, such as slow progression, mild ataxia, stroke-like episodes with stem symptoms, concomitant gluten sensitivity, onset of ataxia after hepatitis C with cerebellar hemiataxia and hemiatrophy. In the all patients, the diagnosis was verified based on the determination of high anti-GAD antibody titers in serum and cerebrospinal fluid. All the patients lacked intrathecal synthesis of oligoclonal antibodies; protein levels and cytosis were normal. Pulse therapy with methylprednisolone at a total dose of 3–5 g led to a slight reduction in ataxia in one case (a female patient with subacute onset of the disease); the treatment was ineffective in two other cases (patients with a primary chronic course). The paper analyzes the literature covering the pathogenesis and clinical presentations of this type of ataxia, and difficulties in its diagnosis and treatment.

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.

Hereditary spastic paraplegia (HSP) and spinocerebellar ataxia (SCA) are heterogeneous groups of neurodegenerative disorders with the main clinical manifestations including progressive pyramidal syndrome and cerebellar ataxia. The differential diagnosis of these diseases is difficult owing to the significant genetic and phenotypic polymorphism. The use of massive parallel sequencing (MPS) technologies makes it possible to assess the genetic basis of specific clinical syndromes and to clarify the systematization of these overlapping phenotypes. We examined 70 patients with degenerative cerebellar ataxias who were admitted to the clinic with one of the suspected forms of SCA. Mutation screening included panel sequencing on the Illumina MiSeq platform. In the group of patients with SCA phenotypes, four individuals (5.7%) were identified—carriers of mutations in the HSP genes: SPG5—1 patient, SPG7—1 patient, and SPG11—2 patients. Seven mutations were identified: CYP7B1 (SPG5) gene—p.R63X and p.R486C mutations; SPG7 gene—c.1047dupC (p.G352Rfs*43) and splice site mutation c.1779+1G>T, which was described by us for the first time. Two patients with SPG11 carried a compound heterozygous nonsense mutation p.Q811X in the SPG11 gene; other mutations were c.7168dupC (p.P2390fs) and c.733_734del (p.M245fs). The presented data confirm the concept that HSP and SCA represent a single continuum of spinocerebellar degenerations with a significant phenotypic overlap. To verify the diagnosis in patients with cerebellar and pyramidal syndrome of degenerative genesis, MPS methods should be used.