Neuroradiological Findings in the Spinocerebellar Ataxias.

Background: The spinocerebellar ataxias (SCAs) are a group of autosomal dominant degenerative diseases characterized by cerebellar ataxia. Classified according to gene discovery, specific features of the SCAs - clinical, laboratorial, and neuroradiological (NR) - can facilitate establishing the diagnosis. The purpose of this study was to review the particular NR abnormalities in the main SCAs.

A patient with pontocerebellar hypoplasia type 6: Novel RARS2 mutations, comparison to previously published patients and clinical distinction from PEHO syndrome.

Pontocerebellar hypoplasia type 6 (PCH6) is a rare infantile-onset progressive encephalopathy caused by biallelic mutations in RARS2 that encodes the mitochondrial arginine-tRNA synthetase enzyme (mtArgRS). The clinical presentation overlaps that of PEHO syndrome (Progressive Encephalopathy with edema, Hypsarrhythmia and Optic atrophy). The proband presented with severe intellectual disability, epilepsy with varying seizure types, optic atrophy, axial hypotonia, acquired microcephaly, dysmorphic features and progressive cerebral and cerebellar atrophy and delayed myelination on MRI.

White matter DNA methylation profiling reveals deregulation of HIP1, LMAN2, MOBP, and other loci in multiple system atrophy.

Multiple system atrophy (MSA) is a fatal late-onset neurodegenerative disease. Although presenting with distinct pathological hallmarks, which in MSA consist of glial cytoplasmic inclusions (GCIs) containing fibrillar α-synuclein in oligodendrocytes, both MSA and Parkinson's disease are α-synucleinopathies. Pathologically, MSA can be categorized into striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA) or mixed subtypes.

Cross-examining candidate genes implicated in multiple system atrophy.

Multiple system atrophy (MSA) is a devastating neurodegenerative disease characterized by the clinical triad of parkinsonism, cerebellar ataxia and autonomic failure, impacting on striatonigral, olivopontocerebellar and autonomic systems. At early stage of the disease, the clinical symptoms of MSA can overlap with those of Parkinson's disease (PD). The key pathological hallmark of MSA is the presence of glial cytoplasmic inclusions (GCI) in oligodendrocytes.

Expanded PCH1D phenotype linked to EXOSC9 mutation.

Pontocerebellar Hypoplasia type 1 is a rare heterogeneous neurodegenerative disorder with multiple subtypes linked to dysfunction of the exosome complex. Patients with mutations in exosome subunits exhibit a generally lethal phenotype characterized by cerebellar and pontine hypoplasia in association with spinal motor neuropathy and multiple systemic and neurologic features. Recently, two variants in the novel PCH1 associated protein EXOSC9 p.

Coordination in adults with neurological impairment - A systematic review of uncontrolled manifold studies.

Background: Analysis of sensorimotor synergies has been greatly advanced by the Uncontrolled Manifold (UCM) approach. The UCM method is based on partitioning inter-trial variance displayed by elemental variables into 'good' (V) and 'bad' (V) variability that, respectively, indicate maintenance or loss of task stability. In clinical populations, these indices can be used to investigate the strength, flexibility, stereotypy and agility of synergistic control.

The 'Hot Cross Bun' Sign Is Not Always Multiple System Atrophy: Etiologies of 11 Cases.

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.

New Radiologic Findings of Hypertrophic Olivary Degeneration in 2 Patients with Brainstem Lymphoma.

Background: Hypertrophic olivary degeneration (HOD) is a rare neurological condition of trans-synaptic degeneration caused by disruption of the dentatorubro-olivary pathway. We present new radiologic findings of HOD in 2 cases of brainstem lymphoma.

Case Description: A 35-year-old woman (Case 1) and a 69-year-old man (Case 2) presented with remarkably similar clinical courses.

Neuroimaging Applications in Chronic Ataxias.

Magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and positron emission tomography (PET) are the main instruments for neuroimaging investigation of patients with chronic ataxia. MRI has a predominant diagnostic role in the single patient, based on the visual detection of three patterns of atrophy, namely, spinal atrophy, cortical cerebellar atrophy and olivopontocerebellar atrophy, which correlate with the aetiologies of inherited or sporadic ataxia. In fact spinal atrophy is observed in Friedreich ataxia, cortical cerebellar atrophy in Ataxia Telangectasia, gluten ataxia and Sporadic Adult Onset Ataxia and olivopontocerebellar atrophy in Multiple System Atrophy cerebellar type.

Clinics in diagnostic imaging (191). Multiple system atrophy-cerebellar type (MSA-C).

A 49-year-old Chinese man was evaluated for progressive uncoordinated movements, dysphagia and urinary symptoms. Magnetic resonance imaging demonstrated a cruciform pattern of T2-weighted hyperintensity within the pons and selective atrophy of the cerebellar hemispheres and pons. The clinical history and radiological findings were consistent with a diagnosis of multiple system atrophy-cerebellar type.

Converging Patterns of α-Synuclein Pathology in Multiple System Atrophy.

We aimed to determine patterns of α-synuclein (α-syn) pathology in multiple system atrophy (MSA) using 70-µm-thick sections of 20 regions of the central nervous system of 37 cases with striato-nigral degeneration (SND) and 10 cases with olivo-ponto-cerebellar atrophy (OPCA). In SND cases with the shortest disease duration (phase 1), α-syn pathology was observed in striatum, lentiform nucleus, substantia nigra, brainstem white matter tracts, cerebellar subcortical white matter as well as motor cortex, midfrontal cortex, and sensory cortex. SND with increasing duration of disease (phase 2) was characterized by involvement of spinal cord and thalamus, while phase 3 was characterized by involvement of hippocampus and amygdala.

Young-onset multiple system atrophy: Clinical and pathological features.

Background: The onset of multiple system atrophy (MSA) before age 40 years is referred to as "young-onset MSA." We identified clinical and pathological characteristics that might help with its early diagnosis and distinction from young-onset Parkinson's disease and late-onset MSA.

Methods: We reviewed the available clinical and pathological features in cases that fulfilled consensus criteria for diagnosis of probable MSA or had autopsy confirmed MSA with an onset before age 40 years and compared the clinical features with 16 autopsy confirmed cases with young-onset Parkinson's disease and a large published series of late-onset MSA from the European MSA Study Group.

A Chemical Biology Approach to Model Pontocerebellar Hypoplasia Type 1B (PCH1B).

Mutations of EXOSC3 have been linked to the rare neurological disorder known as Pontocerebellar Hypoplasia type 1B (PCH1B). EXOSC3 is one of three putative RNA-binding structural cap proteins that guide RNA into the RNA exosome, the cellular machinery that degrades RNA. Using RNAcompete, we identified a G-rich RNA motif binding to EXOSC3.

Sarcomeric disorganization and nemaline bodies in muscle biopsies of patients with EXOSC3-related type 1 pontocerebellar hypoplasia.

Introduction: Mutations in the EXOSC3 gene are responsible for type 1 pontocerebellar hypoplasia, an autosomal recessive congenital disorder characterized by cerebellar atrophy, developmental delay, and anterior horn motor neuron degeneration. Muscle biopsies of these patients often show characteristics resembling classic spinal muscle atrophy, but to date, no distinct features have been identified.

Methods: Clinical data and muscle biopsy findings of 3 unrelated patients with EXOSC3 mutations are described.

Three human aminoacyl-tRNA synthetases have distinct sub-mitochondrial localizations that are unaffected by disease-associated mutations.

Human mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) are key enzymes in the mitochondrial protein translation system and catalyze the charging of amino acids on their cognate tRNAs. Mutations in their nuclear genes are associated with pathologies having a broad spectrum of clinical phenotypes, but with no clear molecular mechanism(s). For example, mutations in the nuclear genes encoding mt-AspRS and mt-ArgRS are correlated with the moderate neurodegenerative disorder leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) and with the severe neurodevelopmental disorder pontocerebellar hypoplasia type 6 (PCH6), respectively.

Immunohistochemical and Molecular Investigations Show Alteration in the Inflammatory Profile of Multiple System Atrophy Brain.

Multiple system atrophy (MSA) is an adult-onset neurodegenerative disease characterized by aggregation of α-synuclein in oligodendrocytes to form glial cytoplasmic inclusions. According to the distribution of neurodegeneration, MSA is subtyped as striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA), or as combination of these 2 (mixed MSA). In the current study, we aimed to investigate regional microglial populations and gene expression in the 3 different MSA subtypes.

[Multisemic atrophy: a description of the clinical case of olivopontocerebellar atrophy against the background of stenosing atherosclerotic vascular lesions].

Features of the onset, the course of the disease causes difficulties in the early diagnosis and formulation of the correct diagnosis. Olivopontocerebellar atrophy is characterized by a broad polymorphism of clinical manifestations. There is a need to develop new methods of symptomatic and neuroprotective treatment, as well as the optimization of non-drug therapy.

Spatial correlation and segregation of multimodal MRI abnormalities in multiple system atrophy.

Objective: The variability of the severity and regional distribution of pathological process in basal ganglia (BG) and brainstem-cerebellar systems results in clinical heterogeneity and represents the motor subtype of multiple system atrophy (MSA). This study aimed to quantify spatial patterns of multimodal MRI abnormalities in BG and stem-CB regions and define structural MRI findings that correlate with clinical characteristics.

Methods: We simultaneously measured R2*, mean diffusivity (MD), and volume in the subcortical structures (BG, thalamus, brainstem-cerebellar regions) of 39 probable MSA and 22 control subjects.

Pontocerebellar hypoplasia type 1 for the neuropediatrician: Genotype-phenotype correlations and diagnostic guidelines based on new cases and overview of the literature.

Pontocerebellar hypoplasia type 1 (PCH1) is a major cause of non-5q spinal muscular atrophy (SMA). We screened 128 SMN1-negative SMA patients from Bulgaria for a frequent mutation -p.G31A in EXOSC3, and performed a literature review of all genetically verified PCH1 cases.

LRRK2 p.Ile1371Val Mutation in a Case with Neuropathologically Confirmed Multi-System Atrophy.

Background: Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are among the most common genetic causes of Lewy body Parkinson's disease (PD). However, LRRK2 mutations can also lead to a variety of pathological phenotypes other than typical PD, including relatively pure nigrostriatal cell loss without alpha-synuclein-positive Lewy bodies or Lewy neurites, progressive supranuclear palsy (PSP), and multiple system atrophy (MSA). The mechanisms behind this remarkable pleomorphic pathology are currently unclear.

The Relevance of Iron in the Pathogenesis of Multiple System Atrophy: A Viewpoint.

Iron is essential for cellular development and maintenance of multiple physiological processes in the central nervous system. The disturbance of its homeostasis leads to abnormal iron deposition in the brain and causes neurotoxicity via generation of free radicals and oxidative stress. Iron toxicity has been established in the pathogenesis of Parkinson's disease; however, its contribution to multiple system atrophy (MSA) remains elusive.

Whole exome sequencing diagnoses the first fetal case of Bainbridge-Ropers syndrome presenting as pontocerebellar hypoplasia type 1.

Background: Bainbridge-Ropers syndrome (BRPS) is a recently identified severe disorder characterized by failure to thrive, facial dysmorphism, and severe developmental delay, caused by de novo dominant loss of function mutation in the ASXL3 gene.

Case: We report here the first case of prenatal BRPS in a fetus presenting with arthrogryposis on ultrasound and for pontocerebellar hypoplasia type 1 (PCH1) following neuropathological examination. The diagnosis was done by whole exome sequencing that identified a novel de novo ASXL3 mutation.