Cerebellar degeneration is a group of diseases that manifests as progressive ataxia, that finally led to death without specific treatment. We report here two patients with cerebellar degeneration, who had shown an improvement and less progressive course, which is associated with panax ginseng intake. Patient 1 was a 60-year-old woman with multisystem atrophy (MSA) type C with 5 year history of ginseng ingestion. Patient 2 was a 54-year-old woman with spinocerebellar ataxia (SCA) type 6, who had a history of ginseng intake for 30 months. Both the patients showed atrophic change in the cerebellum by brain magnetic resonance imaging. Cerebellar functions had been semi-quantified by International Cooperative Ataxia Rating Scale (ICARS) and monitored before and after the ginseng ingestion every 6 to 12 months. In Patient 1 with MSA type C, ICARS had improved from 21 to 17.5 ± 1.8 in the following 5 years. In Patient 2 with SCA, ICARS also showed an improvement from 22 to 6.0 ± 1.0 over 30 months. However, when she stopped taking ginseng, it progressed up to 13 points in two years. These observations provide a potential disease-modifying effect of ginseng on patients with cerebellar degeneration.
Cerebellar Ataxia ; Cerebellar Diseases

BACKGROUND AND PURPOSE: Autosomal recessive cerebellar ataxias constitute a highly heterogeneous group of neurodegenerative disorders. This study was carried out to determine the clinical and genetic causes of ataxia in two families from Pakistan. METHODS: Detailed clinical investigations were carried out on probands in two consanguineous families. Magnetic resonance imaging was performed. Exome sequencing data were examined for likely pathogenic variants. Candidate variants were checked for cosegregation with the phenotype using Sanger sequencing. Public databases including ExAC, GnomAD, dbSNP, and the 1,000 Genome Project as well as ethnically matched controls were checked to determine the frequencies of the alleles. Conservation of missense variants was ensured by aligning orthologous protein sequences from diverse vertebrate species. RESULTS: Reverse phenotyping identified spinocerebellar ataxia, autosomal recessive 1 [OMIM 606002, also referred to as ataxia oculomotor apraxia type 2 (AOA2)] and ataxia telangiectasia (OMIM 208900) in the two families. A novel homozygous missense mutation c.202 C>T (p.Arg68Cys) was identified within senataxin, SETX in the DNA of both patients in one of the families with AOA2. The patients in the second family were homozygous for a known variant in ataxia-telangiectasia mutated (ATM) gene: c.7327 C>T (p.Arg2443Ter). Both variants were absent from 100 ethnically matched control chromosomes and were either absent or present at very low frequencies in the public databases. CONCLUSIONS: This report extends the allelic heterogeneity of SETX mutations causing AOA2 and also presents an asymptomatic patient with a pathogenic ATM variant.
Alleles ; Apraxias* ; Ataxia Telangiectasia ; Ataxia* ; Cerebellar Ataxia ; DNA ; Exome ; Genome ; Humans ; Magnetic Resonance Imaging ; Movement Disorders ; Mutation, Missense ; Neurodegenerative Diseases ; Pakistan ; Phenotype ; Population Characteristics ; Spinocerebellar Ataxias ; Vertebrates

BACKGROUND: Spinocerebellar ataxia (SCA) type 8 (SCA8) is an inherited neurodegenerative disorder caused by the expansion of untranslated CTA/CTG triplet repeats on 13q21. The phenomenology of SCA8 is relatively varied when compared to the other types of SCAs and its spectrum is not well established. CASE REPORT: Two newly detected cases of SCA8 with the nonataxic phenotype and unusual clinical manifestations such as dopaminergic-treatment-responsive parkinsonism and amyotrophic lateral sclerosis (ALS) are described herein. Family A expressed good dopaminergic treatment-responsive parkinsonism as an initial manifestation and developed mild cerebellar ataxia with additional movements, including dystonic gait and unusual oscillatory movement of the trunk, during the disease course. The proband of family B presented as probable ALS with cerebellar atrophy on brain MRI, with a positive family history (a brother with typical cerebellar ataxia) and genetic confirmation for SCA8. CONCLUSIONS: Our findings support that the non-ataxic phenotypes could be caused by a mutation of the SCA8 locus which might affect neurons other than the cerebellum.
Amyotrophic Lateral Sclerosis* ; Atrophy ; Brain ; Cerebellar Ataxia ; Cerebellum ; Gait ; Humans ; Neurodegenerative Diseases ; Neurons ; Parkinson Disease* ; Parkinsonian Disorders ; Phenotype* ; Siblings ; Spinocerebellar Ataxias ; Spinocerebellar Degenerations ; Trinucleotide Repeats

The spinocerebellar ataxia type 7 is an autosomal dominant neurodegenerative disorder with expansion of unstable CAG trinucleotide repeats in a gene on chromosome 3p, and is classified as autosomal dominant cerebellar ataxia type II. Extrapyramidal findings are uncommonly recognized in autosomal dominant cerebellar ataxia type II. A 27-year-old woman showed progressive ataxia, visual disturbance and torticollis. We report a case of genetically confirmed spinocerebellar ataxia type 7 with extrapyramidal finding.
Adult ; Ataxia ; Cerebellar Ataxia ; Female ; Genes, vif ; Humans ; Neurodegenerative Diseases ; Spinocerebellar Ataxias* ; Torticollis* ; Trinucleotide Repeats

The spinocerebellar ataxia are a heterogeneous group of neurodegeneative disorders varying in both clinical manifestations and mode of inheritance. Recently, CAG trinucleotide repeats have been identified in inherited neurodegenerative disease such as dentrorubopallidoluysian atrophy, spinocerebellar ataxia type 1 (SCA1), Machado-Joseph disease (MJD) and SCA3. Individuals with SCA3 are phenotypically similar to those with SCA1 and, like MJD, the locus is linked to genetic markers on chromosome 14q24.3-qter. We experienced 38 year old man who presented with slowly progressive cerebellar dysfunction. Family history was not remarkable. We could not observe orofacial fasciculation, ophthalmoplegia, optic atrophy, peripheral neuropathy, amyotrophy, or dystonia. We peformed genomic polymerase chain reaction (PCR) analysis with patient's blood samples using the following primers: MJD52 (5'-CCAGTGAC TACTTTGATTCG-3') and MJD25 (3'-AAGTGTAGGTACACTTTCCGGT-5'). We found that his gene contained expanded CAG repeats (CAG repeat number was 69). We reported a clinically suspected sporadic case of genetically confirmed SCA3 who shared a similar genetic mutation with MJD and similar clinical presentation with SCA1. To our knowledge, this is the first case report on SCA3 in Korea. We think that the further genetic study with his family members should be done to evaluate mode of inheritance in this case.
Adult ; Ataxia ; Cerebellar Diseases ; Dystonia ; Fasciculation ; Genetic Markers ; Humans ; Korea ; Machado-Joseph Disease* ; Neurodegenerative Diseases ; Ophthalmoplegia ; Optic Atrophy ; Peripheral Nervous System Diseases ; Polymerase Chain Reaction ; Spinocerebellar Ataxias* ; Trinucleotide Repeats ; Wills*

Aged ; Female ; Humans ; Male ; Myoclonic Cerebellar Dyssynergia ; complications ; Vagus Nerve ; Vagus Nerve Diseases ; etiology

Dominantly inherited spinocerebellar ataxias (SCAs) are a group of the heterogenous neurodegenerative diseases that are characterized by chronic progressive cerebellar ataxia associated with various combinations of other neurological signs. Clinical classification is difficult because of the phenotypic overlap. With the evolution of molecular genetics, the loci and mutations for many of the ataxias have been identified, allowing more definitive molecular classification. We experienced 42 years-old man who presented with progressive both lower leg weakness, dysarthria, ataxia, ophthalmoplegia, and nystagmus. The family history was remarkably suspicious. We could not observe the upper extremity weakness, definite evidences of peripheral neuropathy and myopathy in electrodiagnosis. No abnormal findings in blood chemistry and brain MRI. We performed polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE) analysis, found that his gene contained expanded CAG repeats (CAG repeat number was 72). Although no effective treatment exists for most the ataxic syndromes, the accurate diagnosis and the genetic counseling are often important to the patient's family for prognostication.
Adult ; Ataxia ; Brain ; Cerebellar Ataxia ; Chemistry ; Classification ; Diagnosis ; Dysarthria ; Electrodiagnosis ; Electrophoresis, Polyacrylamide Gel ; Genetic Counseling ; Humans ; Leg ; Machado-Joseph Disease* ; Magnetic Resonance Imaging ; Molecular Biology ; Muscular Diseases ; Neurodegenerative Diseases ; Ophthalmoplegia ; Peripheral Nervous System Diseases ; Polymerase Chain Reaction ; Spinocerebellar Ataxias* ; Upper Extremity

Clinically, multiple system atrophy is difficult to differentiate from other basal ganglia disorders such as idiopathic Parkinson's disease or other types of cerebellar ataxia. The "hot cross bun"sign is a radiological sign which, it has been claimed, is highly specific for multiple system atrophy, and we describe four cases in which this sign occurred. In one patient, multiple system atrophy was clinically diagnosed, but in the other three, the respective clinical diagnosis was spinocerebellar ataxia type 1, type 2 (genetically), and old cerebellar hemorrhage. We therefore suggest that the hot cross bun sign reflects degeneration of transverse pontocerebellar fibers and is not a pathognomic sign of multiple system atrophy.
Basal Ganglia Diseases ; Cerebellar Ataxia ; Diagnosis ; Hemorrhage ; Humans ; Magnetic Resonance Imaging* ; Movement Disorders* ; Multiple System Atrophy ; Parkinson Disease ; Spinocerebellar Ataxias

Early onset cerebellar ataxia with retained tendon reflexes is clinical syndrome characterized by progressive cerebelar ataxia of unknown etiology with an onset within the first two decades. This disorder was distinguished from Friedreich's ataxia by the preservation of the tendon reflexes. We have experienced a case of early onset cerebellar ataxia with retained tendon reflexes which was diagnosed by clinical features, eletrophysiologic studies, and MRI scan. This 8 year-old male patient had suffered from gait ataxia with delayed growth and development since 3 years of age. A brief review of the related literatures was also made.
Ataxia ; Cerebellar Ataxia ; Child ; Friedreich Ataxia ; Gait Ataxia ; Growth and Development ; Humans ; Magnetic Resonance Imaging ; Male ; Reflex, Stretch* ; Spinocerebellar Degenerations* ; Tendons*

Early onset cerebellar ataxia with retained tendon reflexes is clinical syndrome characterized by progressive cerebelar ataxia of unknown etiology with an onset within the first two decades. This disorder was distinguished from Friedreich's ataxia by the preservation of the tendon reflexes. We have experienced a case of early onset cerebellar ataxia with retained tendon reflexes which was diagnosed by clinical features, eletrophysiologic studies, and MRI scan. This 8 year-old male patient had suffered from gait ataxia with delayed growth and development since 3 years of age. A brief review of the related literatures was also made.
Ataxia ; Cerebellar Ataxia ; Child ; Friedreich Ataxia ; Gait Ataxia ; Growth and Development ; Humans ; Magnetic Resonance Imaging ; Male ; Reflex, Stretch* ; Spinocerebellar Degenerations* ; Tendons*