ABSTRACT
Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, autosomal recessive neurodegenerative disorder caused by biallelic AAGGG/ACAGG repeat expansion (AAGGG-exp/ACAGG-exp) in RFC1. The recent identification of patients with CANVAS exhibiting compound heterozygosity for AAGGG-exp and truncating variants supports the loss-of-function of RFC1 in CANVAS patients. We investigated the pathological changes in 2 autopsied patients with CANVAS harboring biallelic ACAGG-exp and AAGGG-exp. RNA fluorescence in situ hybridization of the 2 patients revealed CCTGT- and CCCTT-containing RNA foci, respectively, in neuronal nuclei of tissues with neuronal loss. Our findings suggest that RNA toxicity may be involved in the pathogenesis of CANVAS. ANN NEUROL 2024;95:607-613.
Subject(s)
Bilateral Vestibulopathy , Cerebellar Ataxia , Peripheral Nervous System Diseases , Humans , Cerebellar Ataxia/genetics , In Situ Hybridization, Fluorescence , RNA , SyndromeABSTRACT
We developed a diagnostic method for repeat expansion diseases using a long-read sequencer to improve currently available, low throughput diagnostic methods. We employed the real-time target enrichment system of the nanopore GridION sequencer using the adaptive sampling option, in which software-based target assignment is available without prior sample enrichment, and built an analysis pipeline that prioritized the disease-causing loci. Twenty-two patients with various neurological and neuromuscular diseases, including 12 with genetically diagnosed repeat expansion diseases and 10 manifesting cerebellar ataxia, but without genetic diagnosis, were analyzed. We first sequenced the 12 molecularly diagnosed patients and accurately confirmed expanded repeats in all with uniform depth of coverage across the loci. Next, we applied our method and a conventional method to 10 molecularly undiagnosed patients. Our method corrected inaccurate diagnoses of two patients by the conventional method. Our method is superior to conventional diagnostic methods in terms of speed, accuracy, and comprehensiveness.
ABSTRACT
A 39-year-old man exhibited ocular flutter and cerebellar ataxia following a subacute disturbance of consciousness and partial seizure. He was diagnosed with autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy by tissue- and cell-based antibody assays. Brain single-photon emission computed tomography detected a significant increase in blood flow in the fastigial nucleus, a critical region for eye saccade control. Immunotherapies diminished the ocular flutter and reduced hyperperfusion in the fastigial nucleus. This case suggests that autoimmune GFAP astrocytopathy can cause ocular flutter and provides strong imaging evidence supporting the hypothesis that ocular flutter is caused by hyperactivity or disinhibition of the fastigial nucleus.
Subject(s)
Astrocytes , Intermediate Filaments , Adult , Glial Fibrillary Acidic Protein , Humans , MaleABSTRACT
A 19-year-old woman developed high fever, headache, and nausea after taking Loxoprofen for pharyngitis, followed by disturbed consciousness and nuchal stiffness. The patient and her mother had a history of Raynaud's phenomenon. Cerebrospinal fluid (CSF) examination indicated a diagnosis of aseptic meningitis and revealed high levels of Q albumin and IgG index. Anti-RNP antibodies were positive in serum and CSF. Her symptoms disappeared immediately after cessation of Loxoprofen and a drug lymphocyte stimulation test was negative, confirming a diagnosis of non-steroidal anti-inflammatory drugs (NSAIDs)-induced aseptic meningitis. It should be kept in mind that an immune abnormality such as serum and CSF anti-RNP antibodies may play a role in development of NSAIDs-induced aseptic meningitis. A history of usage of NSAIDs and a thorough examination of collagen diseases are useful for identification of the origin of aseptic meningitis in a young woman.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/cerebrospinal fluid , Meningitis, Aseptic/diagnosis , Meningitis, Aseptic/etiology , Phenylpropionates/adverse effects , Ribonucleoproteins/immunology , Acetaminophen/administration & dosage , Adult , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Autoimmune Diseases/complications , Autoimmune Diseases/diagnosis , Autoimmunity , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Diagnosis, Differential , Drug Substitution , Female , Humans , Treatment Outcome , Young AdultABSTRACT
We herein describe a case of acute spinal subdural hematoma (SSDH) during the administration of high-dose corticosteroids and intravenous heparin for the treatment of active lupus nephritis. After SSDH was promptly diagnosed using magnetic resonance imaging (MRI), the patient recovered well with conservative treatment involving the discontinuation of heparin sodium. Although SSDH is a rare complication, it should be considered as a cause of neurological manifestations in patients with active systemic lupus erythematosus.
