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JPMA. the Journal of the Pakistan... Apr 2021Hypertrophic olivary degeneration is a kind of trans-synaptic degeneration, caused by the interruption of dentato rubro olivary pathway. Magnetic resonance imaging (MRI)...
Hypertrophic olivary degeneration is a kind of trans-synaptic degeneration, caused by the interruption of dentato rubro olivary pathway. Magnetic resonance imaging (MRI) has been the best modality to show the signals of olivary nucleus hypertrophy. It appears on T2-weighted magnetic resonance imaging as hyper-intensities. Here we present a unique case of a 27-year-old male with traumatic brain injury causing multiple intracranial haemorrhages and functional impairment, which was revealed on computerised tomography. Tracheotomy and thoracic drainage were performed immediately. Anti-infection therapy, brain protection, and comprehensive arousal therapy were part of the intervention along with a comprehensive rehabilitation programme including occupational therapy, balance training, coordination, bed mobility training, and strengthening exercises. A holistic diagnostic approach can reduce the chances of misdiagnosing post-traumatic Hypertrophic Olivary Degeneration cases. We concluded that a comprehensive physical rehabilitation programme and medical treatment works best to heal the lesion and its resulting traumatic symptoms in cases of Hypertrophic Olivary Degeneration cases.
Topics: Adult; Brain Injuries, Traumatic; Humans; Hypertrophy; Magnetic Resonance Imaging; Male; Olivary Nucleus
PubMed: 34125782
DOI: 10.47391/JPMA.1124 -
Journal of Child Neurology Oct 2023It is well established that extreme prematurity can be associated with cerebellar lesions potentially affecting the neurologic prognosis. One of the commonly observed...
Differentiating Genetic Forms of Pontocerebellar Hypoplasia From Acquired Lesions Resembling Pontocerebellar Hypoplasia: Clinical, Neurodevelopmental, and Imaging Insight From 19 Extremely Premature Patients.
It is well established that extreme prematurity can be associated with cerebellar lesions potentially affecting the neurologic prognosis. One of the commonly observed lesions in these cases is pontocerebellar hypoplasia resulting from prematurity, which can pose challenges in distinguishing it from genetically caused pontocerebellar hypoplasia. This confusion leads to unacceptable and prolonged diagnostic ambiguity for families as well as difficulties in genetic counseling. Therefore, it is crucial to identify the clinical and neuroradiologic features allowing to differentiate between acquired and genetic forms of pontocerebellar hypoplasia in order to guide clinical practices and improve patient care. In this regard, we report in the present manuscript the clinical, developmental, and radiologic characteristics of 19 very premature children (gestational age <28 weeks, now aged 3-14 years) with cerebellar lesions and discuss the causal mechanisms. Our findings support the notion that a combination of specific clinical and radiologic criteria is essential in distinguishing between acquired and genetic forms of pontocerebellar hypoplasia.
Topics: Child; Humans; Olivopontocerebellar Atrophies; Magnetic Resonance Imaging; Cerebellar Diseases; Cerebellum
PubMed: 37731326
DOI: 10.1177/08830738231201926 -
Brain & Development May 2023The inositol polyphosphate 4-phosphatase intracellular signaling pathway is susceptible to genetic or epigenetic alterations that may result in major neurological...
BACKGROUND
The inositol polyphosphate 4-phosphatase intracellular signaling pathway is susceptible to genetic or epigenetic alterations that may result in major neurological illnesses with clinically significant pons and cerebellum involvement.
CASE REPORTS
A seven-year-old girl with pontocerebellar hypoplasia, resistant myoclonic epilepsy with axial hypotonia, microcephaly, atypical facial appearance, nystagmus, ophthalmoplegia, hyperactive tendon reflexes, spasticity, clonus, extensor plantar response, contractures in wrists and ankles and growth retardation, whole-exome sequencing was performed and a homozygous "NM_001134225.2:c.646C > T, p.(Arg216Ter)" variant was found in the INPP4A gene.
CONCLUSION
INPP4A mutations should be kept in mind in cases with severely delayed psychomotor development, progressive microcephaly, resistant myoclonic epilepsy, isolated cerebellum, and pons involvement.
Topics: Female; Humans; Child; Microcephaly; Olivopontocerebellar Atrophies; Nervous System Malformations; Mutation; Epilepsies, Myoclonic
PubMed: 36759255
DOI: 10.1016/j.braindev.2023.01.006 -
Brain Pathology (Zurich, Switzerland) May 2024Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder that presents with variable combinations of autonomic dysfunction, cerebellar ataxia,...
Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder that presents with variable combinations of autonomic dysfunction, cerebellar ataxia, parkinsonism, and pyramidal signs. The inferior olivary nucleus is targeted in MSA, with a phenotype of olivopontocerebellar atrophy in particular, and involvement of the olivocerebellar tract is well known. However, degeneration of the olivospinal tract has not been studied in MSA. We examined 97 spinal cords from consecutively autopsied patients with MSA. Myelin staining revealed that 22 cords (22.7%) had small, bilateral, triangular-shaped tract degeneration in the boundary of the anterior and lateral funiculi, which appeared continuously from C1 to C5. The anatomical pathway of the degenerated tract was consistent with the description of the olivospinal tract provided by Helweg in 1888. The MSA patients showing degeneration of this tract were younger at disease onset (average: 56.4 ± 8.7 years, range: 42-74), and had longer disease duration (average: 10.1 ± 4.8 years, range: 2-25) and more severe olivopontocerebellar changes compared to other MSA patients. Quantitative analyses revealed that patients with olivospinal tract degeneration had a lower neuronal density in the inferior olivary nucleus compared to other patients. Microglial density in this tract was negatively correlated with the neuronal density in the inferior olivary nucleus. The densities of glial cytoplasmic inclusions in the inferior olivary nucleus and in the olivospinal tract were strongly correlated with each other. Neurologically healthy controls (n = 22) and disease controls with Lewy body disease (n = 30), amyotrophic lateral sclerosis (n = 30), and progressive supranuclear palsy (n = 30) did not present the olivospinal tract degeneration. Our results indicate an impairment of the neural connection between the inferior olivary nucleus and the spinal cord in MSA patients, which may develop in a descending manner.
Topics: Adult; Humans; Multiple System Atrophy; alpha-Synuclein; Cervical Cord; Olivopontocerebellar Atrophies
PubMed: 37972988
DOI: 10.1111/bpa.13226 -
American Journal of Medical Genetics.... Oct 2020Mutations in the MBOAT7 gene have been described in 43 patients, belonging to 18 families, showing nonspecific clinical features (intellectual disability [ID], seizures,...
Mutations in the MBOAT7 gene have been described in 43 patients, belonging to 18 families, showing nonspecific clinical features (intellectual disability [ID], seizures, microcephaly or macrocephaly, and mild to moderate cerebellar atrophy) that make the clinical diagnosis difficult. Here we report the first Italian patient, a 22.5-year-old female, one of the oldest reported, born to apparently consanguineous parents. She shows severe ID, macrocephaly, seizures, aggressive outbursts, hyperphagia. We also documented progressive atrophy of the cerebellar vermis, that appeared not before the age of 7. The whole-exome sequencing of the trio identified a novel homozygous variant c.1057_1058delGCinsCA (p.Ala353His) in the MBOAT7 gene. The variant is considered to be likely pathogenic, since it is absent from population database and it lies in a highly conserved amino acid residue. This disorder has a neurometabolic pathogenesis, implicating a phospholipid remodeling abnormalities. A brain hydrogen-magnetic resonance spectroscopy (H-MRS) examination in our patient disclosed a peculiar neurometabolic profile in the cerebellar hemispheric region. This new finding could address the clinical suspicion of MBOAT7-related disorder, among the wide range of genetic conditions associated with ID and cerebellar atrophy. Moreover, the documented progression of cerebellar atrophy and the worsening of the disease only after some years open to the possibility of a therapeutic window after birth.
Topics: Acyltransferases; Adolescent; Adult; Cerebellum; Child; Consanguinity; Exome; Female; Genetic Predisposition to Disease; Homozygote; Humans; Intellectual Disability; Male; Membrane Proteins; Olivopontocerebellar Atrophies; Pedigree; Exome Sequencing; Young Adult
PubMed: 32744787
DOI: 10.1002/ajmg.a.61773 -
Archivos Argentinos de Pediatria Feb 2022The latest method of next-generation sequencing has allowed the characterization and identification of genetic variants associated to diverse pathologies. In this...
The latest method of next-generation sequencing has allowed the characterization and identification of genetic variants associated to diverse pathologies. In this article, we present the case of female patient with a mutation of the RARS2 gene that encodes the enzyme for arginyl tRNA synthetase for coding of proteins. This genetic alteration manifests in pontocerebellar hypoplasia type 6, with a prevalence of<1/1,000,0000, characterized by a cerebellum and pons that are smaller in size and are associated with severe neurodevelopmental delay. The analysis of the case of this patient provides better knowledge of diseases of genetic origin; specifically, regarding genetic diseases of autosomal recessive patterns of inheritance from non-consanguineous parents. The impact of these studies; specially within the family, social, economic and genetic aspects helps provide a better quality of life for these patients and their family.
Topics: Arginine-tRNA Ligase; Colombia; Consanguinity; Female; Humans; Magnetic Resonance Imaging; Mutation; Parents; Quality of Life
PubMed: 35068129
DOI: 10.5546/aap.2022.e39 -
Acta Neurologica Belgica Feb 2023
Topics: Humans; Cerebellar Diseases; Mutation; India; Olivopontocerebellar Atrophies; AMP Deaminase
PubMed: 34826127
DOI: 10.1007/s13760-021-01800-4 -
Genetics and Molecular Biology Aug 2020The spinocerebellar ataxia type 2 is a neurodegenerative disease with autosomal dominant inheritance; clinically characterized by progressive cerebellar ataxia, slow...
The spinocerebellar ataxia type 2 is a neurodegenerative disease with autosomal dominant inheritance; clinically characterized by progressive cerebellar ataxia, slow ocular saccades, nystagmus, ophthalmoplegia, dysarthria, dysphagia, cognitive deterioration, mild dementia, peripheral neuropathy. Infantile onset is a rare presentation that only has been reported in four instances in the literature. In the present work a boy aged 5 years 7 months was studied due to horizontal gaze-evoked nystagmus, without saccades, ataxic gait, dysarthria, dysphagia, dysmetria, generalized spasticity mainly pelvic, bilateral Babinsky. The mother aged 27 years-old presented progressive cerebellar ataxia, dysarthria, dysmetria, dysdiadochokinesis, limb ataxia and olivopontocerebellar atrophy. The molecular analysis was made by identifying the expansion repeats in tandem by long PCR to analyze the repeats in the ATXN2 gene. We found an extreme CAG expansion repeats of ~884 repeats in the child. We describe a Mexican child affected by SCA2 with an infantile onset, associated with a high number of CAG repeats previously no reported and anticipation phenomenon.
PubMed: 32870233
DOI: 10.1590/1678-4685-gmb-2019-0325 -
Neuropediatrics Dec 2020Pontocerebellar hypoplasia (PCH) is an autosomal recessive neurodevelopmental and neurodegenerative disorder characterized by cerebellar and pontine hypoplasia,...
Pontocerebellar hypoplasia (PCH) is an autosomal recessive neurodevelopmental and neurodegenerative disorder characterized by cerebellar and pontine hypoplasia, progressive microcephaly, and developmental delay. Ten types of PCH have been described; PCH type 2A (PCH2A) due to a mutation in is the most frequent. Seizures have been reported in the large majority of patients. The probability of epilepsy developing increases with age, along with difficulties in differentiating seizures from dyskinetic movements. The aim of the present report was to describe the clinical symptoms and electroencephalogram (EEG) changes over time in three patients of Israeli Arab origin with PCH2A. All three, including two siblings and their first cousin, were homozygous for the p.A304S mutation. The patients demonstrated profound psychomotor retardation, severe spasticity and contractures, choreoathetoid movements, and seizures. The magnetic resonance imaging (MRI) scans and EEGs were reviewed by an experienced neuroradiologist and epileptologist, respectively. The MRI scans revealed a dragonfly-like cerebellar pattern in all patients. Despite the normal early EEG findings, all patients had characteristic features of epilepsy, with tonic seizures starting in the first days to months followed by focal to bilateral tonic-clonic seizures in early childhood which continued to adolescence. In conclusion, patients with PCH2A due to the missense mutation p.A304S in exhibit profound psychomotor delay, movement disorders, and intractable epilepsy. An evolution of EEG abnormalities and seizure semiology occurs over time. Similar to several other genetic epileptic encephalopathies, the normal early EEG tracing does not rule out the later occurrence of epilepsy.
Topics: Adolescent; Brain; Child; Disease Progression; Electroencephalography; Female; Humans; Olivopontocerebellar Atrophies
PubMed: 32629522
DOI: 10.1055/s-0040-1714126 -
Neurology May 2020
Topics: ATPases Associated with Diverse Cellular Activities; Ataxia; Female; Humans; Metalloendopeptidases; Middle Aged; Mutation; Olivopontocerebellar Atrophies; Palatal Muscles; Tremor
PubMed: 32317346
DOI: 10.1212/WNL.0000000000009409