scholarly journals Neuroimaging of Pediatric Cerebellum in Inherited Neurodegenerative Diseases

2021 ◽  
Vol 11 (18) ◽  
pp. 8522
Author(s):  
Luisa Chiapparini ◽  
Marco Moscatelli
Keyword(s):  
Neurodegenerative Disorder ◽  
Pediatric Population ◽  
Cerebellar Atrophy ◽  
Mitochondrial Diseases ◽  
Point Of View ◽  
Neuroaxonal Dystrophy ◽  
Cerebellar Hypoplasia ◽  
Degenerative Diseases ◽  
Cerebellar Ataxias ◽  
Magnetic Resonance Imaging Mri

In the study of cerebellar degenerative diseases, morphologic imaging (computed tomography, CT and magnetic resonance imaging, MRI) is the most common examination. From the clinical and genetic point of view, cerebellar degenerative diseases include heterogeneous conditions in which MRI may show isolated cerebellar atrophy or cerebellar atrophy associated with other cerebellar or supratentorial abnormalities. Neuroradiological progression is often observed. In congenital disorders of glycosylation (CDG), for example, MRI may be normal, may demonstrate mild cerebellar atrophy or, in the advanced stages of the disease, marked atrophy of the cerebellar hemispheres and vermis associated with the abnormal signal intensity of the cerebellar cortex and white matter and brainstem hypotrophy. In spinal cerebellar ataxias (SCAs), very rare in the pediatric population, MRI may demonstrate isolated cerebellar atrophy or cerebellar and brainstem atrophy. MRI shows characteristic findings in other diseases, strongly suggesting a distinct disorder, such as neuroaxonal dystrophy, ARSACS, ataxia-telangiectasia, or precise mitochondrial diseases. An example of neurodegenerative disorder with prenatal onset is pontocerebellar hypoplasia (PCH). PCH represents a group of neurodegenerative disorders characterized by microcephaly, early cerebellar hypoplasia, and variable atrophy of the cerebellum and ventral pons, genetically divided into several subtypes. Cerebellar hypoplasia visible on MRI is often the first sign that suggests the clinical diagnosis. In most cases, the PCH subtype may demonstrate a characteristic pattern distinguishable at MRI. Selective involvement of the cerebellum, sometimes accompanied by brainstem or supratentorial abnormalities in different combinations, may help restrict the differential diagnosis and may address the specific molecular screening.

scholarly journals The Natural History of Infantile Neuroaxonal Dystrophy

2020 ◽  
Author(s):  
Fadie D Altuame ◽  
Gretchen Foskett ◽  
Paldeep Atwal ◽  
Sarah Endemann ◽  
Mark Midei ◽  
...  
Keyword(s):  
Natural History ◽  
Neurodegenerative Disorder ◽  
Gastrointestinal Disease ◽  
Cerebellar Atrophy ◽  
Neuroaxonal Dystrophy ◽  
Fine Motor ◽  
Speech Impairment ◽  
Infantile Neuroaxonal Dystrophy ◽  
Significant Difference ◽  
History Of

Abstract Background: Infantile neuroaxonal dystrophy (INAD) is a rapidly progressive neurodegenerative disorder of early onset causing premature death. It results from biallelic pathogenic variants in PLA2G6, which encodes a calcium‐independent phospholipase A2. Objective: We aim to outline the natural history of INAD and provide a comprehensive description of its clinical, radiological, laboratory, and molecular findings. Materials and Methods: We comprehensively analyzed the charts of 28 patients: 16 patients from Riyadh, Saudi Arabia, 8 patients from North and South America and 4 patients from Europe with a molecularly confirmed diagnosis of PLA2G6‐associated neurodegeneration (PLAN) and a clinical history consistent with INAD.Results: In our cohort, speech impairment and loss of gross motor milestones were the earliest signs of the disease. As the disease progressed, loss of fine motor milestones and bulbar dysfunction were observed. Temporo-frontal function was among the last of the milestones to be lost. Appendicular spastic hypertonia, axial hypotonia, and hyperreflexia were common neurological findings. Other common clinical findings include nystagmus (60.7%), seizures (42.9%), gastrointestinal disease (42.9%), skeletal deformities (35.7%), and strabismus (28.6%). Cerebellar atrophy and elevations in serum AST and LDH levels were consistent features of INAD. There was a statistically significant difference when comparing patients with non-sense/truncating variants compared with missense/in-frame deletions in the time of initial concern (p = 0.04), initial loss of language (p = 0.001), initial loss of fine motor skills (p = 0.009), and initial loss of bulbar skills (p = 0.007).Conclusion: INAD is an ultra-rare neurodegenerative disorder that presents in early childhood, with a relentlessly progressive clinical course. Knowledge of the natural history of INAD may serve as a resource for healthcare providers to develop a targeted care plan and may facilitate the design of clinical trials to treat this disease.

scholarly journals The Natural History of Infantile Neuroaxonal Dystrophy

2020 ◽  
Author(s):  
Fadie D Altuame ◽  
Gretchen Foskett ◽  
Paldeep Atwal ◽  
Sarah Endemann ◽  
Mark Midei ◽  
...  
Keyword(s):  
Natural History ◽  
Neurodegenerative Disorder ◽  
Gastrointestinal Disease ◽  
Cerebellar Atrophy ◽  
Neuroaxonal Dystrophy ◽  
Fine Motor ◽  
Speech Impairment ◽  
Infantile Neuroaxonal Dystrophy ◽  
Significant Difference ◽  
History Of

Abstract Background Infantile neuroaxonal dystrophy (INAD) is a rapidly progressive neurodegenerative disorder of early onset causing premature death. It results from biallelic pathogenic variants in PLA2G6 , which encodes a calcium‐independent phospholipase A2. Objective We aim to outline the natural history of INAD and provide a comprehensive description of its clinical, radiological, laboratory, and molecular findings. Materials and Methods We comprehensively analyzed the charts of 28 patients: 16 patients from Riyadh, Saudi Arabia, 8 patients from North and South America and 4 patients from Europe with a molecularly confirmed diagnosis of PLA2G6 ‐associated neurodegeneration (PLAN) and a clinical history consistent with INAD. Results In our cohort, speech impairment and loss of gross motor milestones were the earliest signs of the disease. As the disease progressed, loss of fine motor milestones and bulbar dysfunction were observed. Temporo-frontal function was among the last of the milestones to be lost. Appendicular spastic hypertonia, axial hypotonia, and hyperreflexia were common neurological findings. Other common clinical findings include nystagmus (60.7%), seizures (42.9%), gastrointestinal disease (42.9%), skeletal deformities (35.7%), and strabismus (28.6%). Cerebellar atrophy and elevations in serum AST and LDH levels were consistent features of INAD. There was a statistically significant difference when comparing patients with non-sense/truncating variants compared with missense/in-frame deletions in the time of initial concern (p = 0.04), initial loss of language (p = 0.001), initial loss of fine motor skills (p = 0.009), and initial loss of bulbar skills (p = 0.007). Conclusion INAD is an ultra-rare neurodegenerative disorder that presents in early childhood, with a relentlessly progressive clinical course. Knowledge of the natural history of INAD may serve as a resource for healthcare providers to develop a targeted care plan and may facilitate the design of clinical trials to treat this disease.

scholarly journals Nanoscopic quantification of sub-mitochondrial morphology, mitophagy and mitochondrial dynamics in living cells derived from patients with mitochondrial diseases

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Weiwei Zou ◽  
Qixin Chen ◽  
Jesse Slone ◽  
Li Yang ◽  
Xiaoting Lou ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Optic Atrophy ◽  
Respiratory Function ◽  
Clinical Symptoms ◽  
Mitochondrial Dynamics ◽  
Cerebellar Atrophy ◽  
Mitochondrial Diseases ◽  
Living Cells ◽  
Mitochondrial Morphology ◽  
Mitochondrial Oxidative Phosphorylation

AbstractSLC25A46 mutations have been found to lead to mitochondrial hyper-fusion and reduced mitochondrial respiratory function, which results in optic atrophy, cerebellar atrophy, and other clinical symptoms of mitochondrial disease. However, it is generally believed that mitochondrial fusion is attributable to increased mitochondrial oxidative phosphorylation (OXPHOS), which is inconsistent with the decreased OXPHOS of highly-fused mitochondria observed in previous studies. In this paper, we have used the live-cell nanoscope to observe and quantify the structure of mitochondrial cristae, and the behavior of mitochondria and lysosomes in patient-derived SLC25A46 mutant fibroblasts. The results show that the cristae have been markedly damaged in the mutant fibroblasts, but there is no corresponding increase in mitophagy. This study suggests that severely damaged mitochondrial cristae might be the predominant cause of reduced OXPHOS in SLC25A46 mutant fibroblasts. This study demonstrates the utility of nanoscope-based imaging for realizing the sub-mitochondrial morphology, mitophagy and mitochondrial dynamics in living cells, which may be particularly valuable for the quick evaluation of pathogenesis of mitochondrial morphological abnormalities.

scholarly journals Inherited neuroaxonal dystrophy in dogs causing lethal, fetal-onset motor system dysfunction and cerebellar hypoplasia

2010 ◽  
Vol 518 (18) ◽  
pp. 3771-3784 ◽  
Author(s):  
John C. Fyfe ◽  
Raba' A. Al-Tamimi ◽  
Rudy J. Castellani ◽  
Diana Rosenstein ◽  
Daniel Goldowitz ◽  
...  
Keyword(s):  
Motor System ◽  
Neuroaxonal Dystrophy ◽  
Cerebellar Hypoplasia

scholarly journals Mitochondrial medicine - a key to solve pathophysiology of 21 century diseases

2008 ◽  
Vol 2 (1-2) ◽  
pp. 46-48
Author(s):  
Emina Kiseljaković ◽  
Radivoj Jadrić ◽  
Sabaheta Hasić ◽  
Lorenka Ljuboja ◽  
Jovo Radovanović ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Mitochondrial Diseases ◽  
Degenerative Diseases ◽  
Mitochondrial Genetics ◽  
Alzheimer Dementia ◽  
Scientific Investigations ◽  
Mitochondrial Medicine ◽  
The Past ◽  
Mitochondrial Defects

Over the past 13 years mitochondrial defects have been involved in wide variety of degenerative diseases - Parkinson disease, Alzheimer dementia, arteriosclerosis, ageing and cancer. Mitochondria are believed to control apoptosis or programmed cell death. Disturbance in mitochondrial metabolism has also been implicated in many common diseases such as congestive hart failure, diabetes and migraine. Scientific investigations have showed complexities in mitochondrial genetics, but at the same time, pathophysiology of mitochondrial diseases is still enigma. Mitochondria and their DNAs are opening the era of "mitochondrial medicine". What we today call "a mitochondrial medicine" is only a part of the whole panorama of diseases based on disordered mitochondrial function.

scholarly journals Spondyloarthritis in a Pediatric Population: Risk Factors for Sacroiliitis

2010 ◽  
Vol 37 (11) ◽  
pp. 2402-2408 ◽  
Author(s):  
MATTHEW L. STOLL ◽  
RAFIA BHORE ◽  
MOLLY DEMPSEY-ROBERTSON ◽  
MARILYNN PUNARO
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Physical Examination ◽  
Logistic Regression Analysis ◽  
Pediatric Population ◽  
Hip Arthritis ◽  
Magnetic Resonance Imaging Mri ◽  
Juvenile Spondyloarthritis ◽  
Texas Scottish Rite Hospital

Objective.Pediatric rheumatologists may have an opportunity to diagnose sacroiliitis in its early stages, prior to the development of irreversible radiographic changes. Early diagnosis frequently requires magnetic resonance imaging (MRI), the use of which is limited by expense and requirement for sedation. We set out to identify features of juvenile spondyloarthritis (SpA) associated with the highest risk of sacroiliitis, to identify patients who may be candidates for routine MRI-based screening.Methods.We reviewed the charts of 143 children seen at Texas Scottish Rite Hospital for Children diagnosed with SpA based on the International League of Associations for Rheumatology criteria for enthesitis-related arthritis or the Amor criteria for SpA. We performed logistic regression analysis to identify risk factors for sacroiliitis.Results.A group of 143 children were diagnosed with SpA. Consistent with the diagnosis of SpA, 16% had psoriasis, 43% had enthesitis, 9.8% had acute anterior uveitis, and 70% were HLA-B27+. Fifty-three children had sacroiliitis, of which 11 cases were identified by imaging studies in the absence of suggestive symptoms or physical examination findings. Logistic regression analysis revealed that hip arthritis was a positive predictor of sacroiliitis, while dactylitis was a negative predictor.Conclusion.Children with SpA are at risk for sacroiliitis, which may be present in the absence of suggestive symptoms or physical examination findings. The major risk factor for sacroiliitis is hip arthritis, while dactylitis may be protective. Routine screening by MRI should be considered in patients at high risk of developing sacroiliitis.

Trends in contrast media research the last 100 years

2021 ◽  
pp. 028418512110510
Author(s):  
Yousef W Nielsen ◽  
Henrik S Thomsen
Keyword(s):  
Magnetic Resonance Imaging ◽  
Computed Tomography ◽  
Contrast Media ◽  
Alimentary Tract ◽  
Adverse Reactions ◽  
Point Of View ◽  
Imaging Procedures ◽  
Resonance Imaging ◽  
Media Research ◽  
Magnetic Resonance Imaging Mri

This review focuses on the trends in contrast media (CM) research published in Acta Radiologica during the last 100 years, since the first edition in 1921. The main topics covered are the developments of iodine- and gadolinium-based CM. Other topics include manganese-based CM for magnetic resonance imaging (MRI) and barium for the investigation of the alimentary tract. From a historic point of view, special CM for use in cholegraphy and myelography are addressed in the review. Today, these imaging procedures are obsolete due to the development of computed tomography, MRI, and ultrasound. The historical use of radioactive thorium-based CM for angiography is also addressed. Furthermore, publications on adverse reactions to CM are reviewed.

Posterior Reversible Encephalopathy (PRES) in a Child with Severe Dengue

2019 ◽  
Vol 66 (3) ◽  
pp. 322-326
Author(s):  
Yogini Sawant ◽  
Suresh Birajdar ◽  
Hiren Doshi ◽  
Pooja Soni ◽  
Deepak Patkar ◽  
...  
Keyword(s):  
Pediatric Population ◽  
White Blood Cells ◽  
Neurological Complications ◽  
Severe Dengue ◽  
Mri Findings ◽  
Posterior Reversible Encephalopathy ◽  
Magnetic Resonance Imaging Mri ◽  
Mri Changes ◽  
Reversible Encephalopathy ◽  
Csf Examination

Abstract Among neurological complications associated with dengue, posterior reversible encephalopathy syndrome (PRES) has not been reported in pediatric population. We report a 10-year-old girl with severe dengue who developed PRES. The patient presented with hemorrhagic shock that required fluid resuscitation and inotropic support. She developed seizures with encephalopathy 2 days after recovering from the shock. Cerebrospinal fluid (CSF) examination was negative for dengue (no white blood cells in CSF with negative polymerase chain reaction for dengue). Her clinical features and magnetic resonance imaging (MRI) findings showed typical changes associated with posterior encephalopathy that reverted after resolution of hypertension. Repeat MRI after a month was normal. PRES should be considered as a possible differential diagnoses of dengue associated encephalopathy, especially in cases with normal CSF examination and characteristic MRI changes.

scholarly journals Emerging Evidences for an Implication of the Neurodegeneration-Associated Protein TAU in Cancer

2020 ◽  
Vol 10 (11) ◽  
pp. 862
Author(s):  
Stéphanie Papin ◽  
Paolo Paganetti
Keyword(s):  
Neurodegenerative Disorders ◽  
Neurodegenerative Disorder ◽  
Inverse Correlation ◽  
Epidemiologic Studies ◽  
Point Of View ◽  
Published Data ◽  
Cancer Resistance ◽  
Microtubule Network ◽  
Mapt Gene

Neurodegenerative disorders and cancer may appear unrelated illnesses. Yet, epidemiologic studies indicate an inverse correlation between their respective incidences for specific cancers. Possibly explaining these findings, increasing evidence indicates that common molecular pathways are involved, often in opposite manner, in the pathogenesis of both disease families. Genetic mutations in the MAPT gene encoding for TAU protein cause an inherited form of frontotemporal dementia, a neurodegenerative disorder, but also increase the risk of developing cancer. Assigning TAU at the interface between cancer and neurodegenerative disorders, two major aging-linked disease families, offers a possible clue for the epidemiological observation inversely correlating these human illnesses. In addition, the expression level of TAU is recognized as a prognostic marker for cancer, as well as a modifier of cancer resistance to chemotherapy. Because of its microtubule-binding properties, TAU may interfere with the mechanism of action of taxanes, a class of chemotherapeutic drugs designed to stabilize the microtubule network and impair cell division. Indeed, a low TAU expression is associated to a better response to taxanes. Although TAU main binding partners are microtubules, TAU is able to relocate to subcellular sites devoid of microtubules and is also able to bind to cancer-linked proteins, suggesting a role of TAU in modulating microtubule-independent cellular pathways associated to oncogenesis. This concept is strengthened by experimental evidence linking TAU to P53 signaling, DNA stability and protection, processes that protect against cancer. This review aims at collecting literature data supporting the association between TAU and cancer. We will first summarize the evidence linking neurodegenerative disorders and cancer, then published data supporting a role of TAU as a modifier of the efficacy of chemotherapies and of the oncogenic process. We will finish by addressing from a mechanistic point of view the role of TAU in de-regulating critical cancer pathways, including the interaction of TAU with cancer-associated proteins.

scholarly journals Compound heterozygous PLA2G6 loss-of-function variants in Swaledale sheep with neuroaxonal dystrophy

2020 ◽  
Author(s):  
Anna Letko ◽  
Ben Strugnell ◽  
Irene M. Häfliger ◽  
Julia M. Paris ◽  
Katie Waine ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Neuronal Degeneration ◽  
Neuroaxonal Dystrophy ◽  
Histopathological Analysis ◽  
Compound Heterozygous ◽  
Loss Of Function ◽  
Genome Region ◽  
Pathogenic Variants ◽  
Progressive Ataxia ◽  
Intron 2

Abstract Sporadic occurrences of neurodegenerative disorders including neuroaxonal dystrophy (NAD) have been previously reported in sheep. However, so far no causative genetic variant has been found for ovine NAD. The aim of this study was to characterize the phenotype and the genetic aetiology of an early-onset neurodegenerative disorder observed in several lambs of purebred Swaledale sheep, a native English breed. Affected lambs showed progressive ataxia and stiff gait and subsequent histopathological analysis revealed the widespread presence of axonal spheroid indicating neuronal degeneration. Thus, the observed clinical phenotype could be explained by a novel form of NAD. After SNP genotyping and subsequent linkage mapping within a paternal half-sib pedigree with a total of five NAD-affected lambs, we identified two loss-of-function variants by whole-genome sequencing in the ovine PLA2G6 gene situated in a NAD-linked genome region on chromosome 3. All cases were carriers of a compound heterozygous splice site variant in intron 2 and a nonsense variant in exon 8. Herein we present evidence for the occurrence of a familial novel form of recessively inherited NAD in sheep due to allelic heterogeneity at PLA2G6. This study reports two pathogenic variants in PLA2G6 causing a novel form of NAD in Swaledale sheep which enables selection against this fatal disorder.

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