OBJECTIVE: To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. METHODS: The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). RESULTS: Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a "cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. CONCLUSION The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.
Humans ; Male ; Female ; Child, Preschool ; Infant ; Child ; Olivopontocerebellar Atrophies/genetics* ; Arginine-tRNA Ligase/genetics* ; Mutation ; Cerebellar Diseases

OBJECTIVE: To explore the genetic basis for a fetus with cerebellar dysplasia and widened lateral ventricles. METHODS: The couple have elected induced abortion after careful counseling. Skin tissue sample from the abortus and peripheral venous blood samples from both parents were collected for the extraction of genomic DNA, which was then subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: Prenatal ultrasonography showed increased nuchal translucency (0.4 cm) and widened lateral ventricles. Magnetic resonance imaging revealed infratentorial brain dysplasia. By DNA sequencing, the fetus was found to carry compound heterozygous variants c.1A>G and c.1564G>A of the RARS2 gene, which were inherited from its father and mother, respectively. Among these, c.1A>G was known to be pathogenic, but the pathogenicity of c.1564G>A was unreported previously. Based on the American College of Medical Genetics and Genomics guidelines, the c.1564G>A variant of RARS2 gene was predicted to be likely pathogenic(PM2+PM3+PP3+PP4). CONCLUSION The compound heterozygous variants c.1A>G and c.1564G>A of RARS2 gene contributed to the fetus suffering from pontocerebellar hypoplasia type 6, which expanded variant spectrum of RARS2 gene.
Female ; Fetus ; Genomics ; Humans ; Mutation ; Olivopontocerebellar Atrophies ; Pregnancy ; Whole Exome Sequencing

OBJECTIVE: To clarify the specificity of the ‘hot cross bun’ sign (HCBS) for multiple system atrophy (MSA) in adult cerebellar ataxia or parkinsonism. METHODS: The radiologic information systems at an academic center and affiliated veterans' hospital were queried using the keywords ‘hot cross bun,’ ‘pontocerebellar,’ ‘cruciate,’ ‘cruciform,’ ‘MSA,’ ‘multiple system atrophy,’ and ‘multisystem atrophy.’ Scans were reviewed by a neurologist and neuroradiologist to identify the HCBS. Subjects with the HCBS were reviewed by 2 neurologists to identify the most likely etiology of the patient's neurologic symptoms. RESULTS: Eleven cases were identified. Etiologies included MSA (4 probable, 2 possible), hereditary cerebellar ataxia (3/11), probable dementia with Lewy bodies (1/11), and uncertain despite autopsy (1/11). CONCLUSION: MSA was the most common etiology. However, 5 of the 11 patients did not have MSA. The most common alternate etiology was an undefined hereditary cerebellar ataxia (3/11).
Adult ; Autopsy ; Cerebellar Ataxia ; Dementia ; Hexachlorobenzene ; Humans ; Lewy Bodies ; Magnetic Resonance Imaging ; Multiple System Atrophy ; Neurologic Manifestations ; Olivopontocerebellar Atrophies ; Parkinsonian Disorders ; Radiology Information Systems ; Sensitivity and Specificity

Adult ; Female ; Humans ; Male ; Olivopontocerebellar Atrophies ; genetics ; Pedigree ; Young Adult

Acupuncture Therapy ; Aged ; Female ; Humans ; Olivopontocerebellar Atrophies ; therapy

AIMTo investigate the change of latency and interpeak latency of each component of BAEP (brainstem auditory evoked potential, BAEP) and its correlation with PV/PFV (pontine volume/posterior fossa volume, PV/PFV) ratio in OPCA (olivopontocerebellar atrophy, OPCA).

METHODSWe used Keypoint EMG/EP to determine waves I PL (peak latency, PL), III PL, V PL and I - III IPL (interpeak latency, IPL), III - V IPL, I - V IPL and used 1.5TMR 3D volume rendering software to determine PV (pontine volume, PV), CV(cerebellar volume, CV) and PFV (posterior fossa volume,PFV). Then calculated PV/PFV ratio, CV/PFV ratio and PV/ CV ratio in OPCA group and control group.

RESULTSCompared with control group, in OPCA group wave IIII PL, I - III IPL were significantly elongated (P < 0.05), III - V IPL was significantly shorten (P < 0.05), PV/PFV ratio was significantly decreased (P < 0.01); there was a positive correlation between III-V IPL and PV/PFV ratio (r = 0.83, P < 0.01).

CONCLUSIONIn patients with OPCA, III PL, I - III IPL of BAEP were elongated and III - V IPL of BAEP was shorten. III - V IPL became shorter when the volume of pontine decreased.

Adult ; Case-Control Studies ; Evoked Potentials, Auditory, Brain Stem ; physiology ; Female ; Humans ; Male ; Middle Aged ; Olivopontocerebellar Atrophies ; pathology ; physiopathology ; Pons ; pathology

INTRODUCTION

Spinocerebellar ataxia 7 (SCA7) is a slowly progressive autosomal dominant neurodegenerative disorder characterized clinically by cerebellar ataxia associated with cone-rod and retinal dystrophy. In the Philippines, only a few case reports are documented regarding spinocerebellar ataxias.

CLINICAL PRESENTATION

D.I. is an 1 8-year old female who presented with a 4-year history of progressive blurring of vision and ataxia. Pertinent findings in the neurologic examination include impaired visual acuity, optic disc pallor with bull's eye maculopathy, hyperreflexia, and ataxia.

DIAGNOSTIC WORK-UP

Cranial CT scan revealed mild atrophy of the midbrain and pons, and moderate cerebellar atrophy. Follow-up cranial MRI showed multiple non-enhancing punctuate foci of increased T2 signal involving the subcortical and periventricular white matter bilaterally seen in demyelinating disease, vasculitis as well as chronic migraine headaches, with no associated mass effect. Mild to moderate atrophy of the cerebellar hemispheres, pons and middle cerebellar peduncles bilaterally were seen. CSF analysis, CSF IgG and BAER results were normal. Flouroscein angiography confirmed the presence of Bull's eye maculopathy. Goldmann perimetry revealed bilateral central scotoma. Visual evoked potential was abnormal s uggestive of a pre-chiasmatic l esion. Electroretinogram findings were consistent with tapetoretinal degeneration.

TREATMENT AND FOLLOW UP

Treatment modalities for the spinocerebellar ataxias are supportive. Genetic counseling is recommended. Plans for molecular genetic testing for the patient and her family are currently underway.

Human ; Female ; Adolescent: 13-18 Yrs Old ; Olivopontocerebellar Atrophies ; Spinocerebellar Ataxias ; Spinocerebellar Ataxia Type 7

BACKGROUND: Ocular flutter is a rare horizontal eye movement disorder characterized by rapid saccadic oscillations. Excessive discharge of burst neurons, and/or loss of tonic excitation of pause cells cause ocular flutter in several neurologic diseases. Ocular flutter can be easily differentiated from other saccadic oscillations with the aid of electro-oculography (EOG) findings showing an absence of intersaccadic intervals. METHODS: We analyzed EOG findings of ocular flutter in four patients. RESULTS: Ocular flutter, which was shown as rapid, repetitive, horizontal, symmetrical, and sinusoidal movements without intersaccadic intervals on EOG, was confirmed in four patients. The etiology of each patient was olivopontocerebellar atrophy (1 case), meningoencephalitis (2 cases), and lithium intoxication (1 case). CONCLUSIONS: Ocular flutter can be present in numerous neurologic diseases. Characteristic EOG findings are useful in the diagnosis of ocular flutter.
Diagnosis ; Electrooculography ; Humans ; Lithium ; Meningoencephalitis ; Neurons ; Ocular Motility Disorders ; Olivopontocerebellar Atrophies ; Saccades

We report a case of spontaneous intracranial epidural hematoma following the intraoperative course of a patient who had undergone surgical removal of a thoracolumbar schwannoma in olivo-ponto-cerebellar atrophy. To our knowledge there is no reported case in which the thoracolumbar schwannoma removal was followed by such a complication. Mechanical events leading to this complication are unclear. Abnormal results of a neurological examination in the early postoperative period should suggest this possibility.
Hematoma, Epidural, Cranial* ; Humans ; Neurilemmoma* ; Neurologic Examination ; Olivopontocerebellar Atrophies ; Postoperative Period

PURPOSE: To demonstrate the MRI findings of olivopontocerebellar atrophy. MATERIALS AND METHODS: We retrospectively reviewed the MRI findings of eight patients who had been diagnosed by clinical manifestation and the peculiar pattern of atrophy and signal change on MRI. RESULTS: Seven patients had an atrophy of the olive, pons and cerebellum and increased signal change of the transverse pontine fiber, median raphe and middle cerebellar peduncle on T2WI. Of these, six patients had severe atrophy of the olive, pons and cerebellum and decreased signal change of the basal ganglia, red nucleus, substantia nigra or dentate nucleus on T2WI. Additionally, four of six patients had a cerebral atrophy. Except one patient who had an urinary incontinence, these 5 patients had not been associated with extrapyramidal or autonomic symptom. The other patient with relatively short duration of the disease had only cerebellar atrophy without signal change on T2WI . CONCLUSION: With progressing of the olivopontocerebellar atrophy, cerebral atrophy and decreased signal change of the basal ganglia, red nucleus, substantia nigra or dentate nucleus on T2WI is combined. Thus, MRI is essential in establishing the diagnosis and evaluating the severity of olivopontocerebellar atrophy.
Atrophy ; Basal Ganglia ; Brain* ; Cerebellar Nuclei ; Cerebellum ; Diagnosis ; Humans ; Magnetic Resonance Imaging* ; Olea ; Olivopontocerebellar Atrophies* ; Pons ; Red Nucleus ; Retrospective Studies ; Substantia Nigra ; Urinary Incontinence