-
Tremor and Other Hyperkinetic Movements... 2018Autosomal dominant familial cortical myoclonic tremor and epilepsy (FCMTE) is characterized by distal tremulous myoclonus, generalized seizures, and signs of cortical... (Review)
Review
BACKGROUND
Autosomal dominant familial cortical myoclonic tremor and epilepsy (FCMTE) is characterized by distal tremulous myoclonus, generalized seizures, and signs of cortical reflex myoclonus. FCMTE has been described in over 100 pedigrees worldwide, under several different names and acronyms. Pathological changes have been located in the cerebellum. This systematic review discusses the clinical spectrum, treatment, pathophysiology, and genetic findings.
METHODS
We carried out a PubMed search, using a combination of the following search terms: cortical tremor, myoclonus, epilepsy, benign course, adult onset, familial, and autosomal dominant; this resulted in a total of 77 studies (761 patients; 126 pedigrees) fulfilling the inclusion and exclusion criteria.
RESULTS
Phenotypic differences across pedigrees exist, possibly related to underlying genetic differences. A "benign" phenotype has been described in several Japanese families and pedigrees linked to 8q (FCMTE1). French patients (5p linkage; FCMTE3) exhibit more severe progression, and in Japanese/Chinese pedigrees (with unknown linkage) anticipation has been suggested. Preferred treatment is with valproate (mind teratogenicity), levetiracetam, and/or clonazepam. Several genes have been identified, which differ in potential pathogenicity.
DISCUSSION
Based on the core features (above), the syndrome can be considered a distinct clinical entity. Clinical features may also include proximal myoclonus and mild progression with aging. Valproate or levetiracetam, with or without clonazepam, reduces symptoms. FCMTE is a heterogeneous disorder, and likely to include a variety of different conditions with mutations of different genes. Distinct phenotypic traits might reflect different genetic mutations. Genes involved in Purkinje cell outgrowth or those encoding for ion channels or neurotransmitters seem good candidate genes.
Topics: Epilepsies, Myoclonic; Humans; Phenotype
PubMed: 29416935
DOI: 10.7916/D85155WJ -
Cureus Nov 2022Paraneoplastic syndromes (PNS) are uncommon, distinct clinical complications of a primary tumor. Paraneoplastic cerebellar degeneration (PCD) is a PNS that is described... (Review)
Review
Paraneoplastic syndromes (PNS) are uncommon, distinct clinical complications of a primary tumor. Paraneoplastic cerebellar degeneration (PCD) is a PNS that is described as an autoimmune response targeting Purkinje cells in the cerebellum. Ovarian cancer (OC) is one of the most prevalent causes of cancer-related deaths in women. Anti-Yo is the most common onconeural antibody produced in the PCD immune response and is most typically found in ovarian and breast cancer patients. While the current literature highlights the predisposing genetic factors, diagnostic workflows, and treatment options, the pathophysiology of PCD, among other considerations, remains largely unestablished. This review aimed to systematically observe procedural solutions to facilitate an early diagnosis and improve the prognosis of patients with OC-associated PCD. To that end, we examined literature published from 01/01/2015-11/10/2022 indexed in PubMed by using the keywords "paraneoplastic, cerebellar degeneration" combined with "ovarian cancer." Inclusion criteria were met if PCD and OC diagnoses were made and if studies provided adequate patient information. After screening and assessing records for eligibility using the inclusion and exclusion criteria, 18 articles involving 102 patients were included. The typical patient observed in this sample was diagnosed with International Federation of Gynecology and Obstetrics (FIGO) Stage III, high-grade serous carcinoma. The diagnostic workup typically included a clinical evaluation for dysarthria (50%), ataxia (60%), and gait abnormalities (50%), along with multiple imaging modalities and serological findings (90%). Genetic screening for human leukocyte antigen (HLA) haplotype susceptibility for PCD and immune tolerance modulators regulation may also be recommended prior to starting treatment. Findings support the use of corticosteroids (35%) and intravenous immunoglobulin (IVIg) (40%) as viable treatment options for managing PCD in conjunction with systemic therapy for the primary malignancy. A diagnosis of PCD should be considered if a patient has had a malignancy in the past five years with the presence of explicit cerebellar symptoms. This clinical diagnosis can be further supplemented by serologic and radiologic findings. Recognizing PCD symptoms and scheduling genetic and proteomic testing may help with early diagnosis and better prognosis.
PubMed: 36483902
DOI: 10.7759/cureus.31154 -
Advanced Drug Delivery Reviews 2020Modeling of human organs has long been a task for scientists in order to lower the costs of therapeutic development and understand the pathological onset of human...
Modeling of human organs has long been a task for scientists in order to lower the costs of therapeutic development and understand the pathological onset of human disease. For decades, despite marked differences in genetics and etiology, animal models remained the norm for drug discovery and disease modeling. Innovative biofabrication techniques have facilitated the development of organ-on-a-chip technology that has great potential to complement conventional animal models. However, human organ as a whole, more specifically the human heart, is difficult to regenerate in vitro, in terms of its chamber specific orientation and its electrical functional complexity. Recent progress with the development of induced pluripotent stem cell differentiation protocols, made recapitulating the complexity of the human heart possible through the generation of cells representative of atrial & ventricular tissue, the sinoatrial node, atrioventricular node and Purkinje fibers. Current heart-on-a-chip approaches incorporate biological, electrical, mechanical, and topographical cues to facilitate tissue maturation, therefore improving the predictive power for the chamber-specific therapeutic effects targeting adult human. In this review, we will give a summary of current advances in heart-on-a-chip technology and provide a comprehensive outlook on the challenges involved in the development of human physiologically relevant heart-on-a-chip.
Topics: Drug Discovery; Heart; Humans; Induced Pluripotent Stem Cells; Lab-On-A-Chip Devices; Microtechnology; Myocytes, Cardiac; Tissue Engineering
PubMed: 31917972
DOI: 10.1016/j.addr.2019.12.002 -
Cerebellum (London, England) Dec 2023Current understanding of anti-Yo/PCA1 antibody-associated cerebellar ataxia is based on case reports and small case series. Our goal was to summarize clinical features,... (Review)
Review
Current understanding of anti-Yo/PCA1 antibody-associated cerebellar ataxia is based on case reports and small case series. Our goal was to summarize clinical features, highlighting atypical presentations and gaps of knowledge. Following the PRISMA guidelines, we systematically screened Pubmed/MEDLINE, Embase, Scopus, and Web of Science from inception to April 2022 for all case reports and series concerning anti-Yo antibody-associated cerebellar ataxia. We collected data on clinical presentation, investigation findings, and treatment outcomes. Of 379 included patients, 96% were female with gynecologic cancer (82%). Among men, 87% had an associated tumor, mainly of gastrointestinal origin. The median age was 60 years old. Pancerebellar ataxia was the main clinical feature, but extracerebellar findings were frequent during the disease course. Vertigo and imbalance can be present early in the disease course in about two thirds of patients, as a prodromal phase. Although neuroimaging usually is normal or shows cerebellar atrophy, inflammatory changes may also be present. More than half of the patients reported some improvement after immunotherapy. However, despite treatment, 84% of survivors were unable to walk unassisted on follow-up. Our study provides objective data and advances in current knowledge of anti-Yo antibody-associated cerebellar ataxia such as the description of prodromal symptoms, extracerebellar findings, and its presentations in males.
Topics: Male; Middle Aged; Humans; Female; Cerebellar Ataxia; Paraneoplastic Cerebellar Degeneration; Purkinje Cells; Cerebellar Diseases; Neoplasms; Autoantibodies; Disease Progression
PubMed: 36334195
DOI: 10.1007/s12311-022-01492-3 -
Nutrients Mar 2020Gluten-related neurological disorders (GRND) represent a spectrum of neurological manifestations that are triggered by gluten. In coeliac disease, a T-cell mediated... (Meta-Analysis)
Meta-Analysis
Gluten-related neurological disorders (GRND) represent a spectrum of neurological manifestations that are triggered by gluten. In coeliac disease, a T-cell mediated enteropathy is triggered by gluten in genetically predisposed individuals. The underlying pathological mechanism of the neurological dysfunction is not yet clear. The aim of this review is to collate existing neuropathological findings in GRND as a means of aiding the understanding of the pathophysiology. A systematic search of the Pubmed Database yielded 188 articles, of which 32 were included, containing 98 eligible cases with a description of pathological findings in GRND. In gluten ataxia, loss of Purkinje cells, atrophy, gliosis and astrocytosis were apparent, as well as diffuse lymphocytic infiltration and perivascular cuffing with lymphocytes. In patients with large-fiber neuropathy, nerve biopsies revealed axonopathy, loss of myelinated fibers and focal and perivascular infiltration by inflammatory cells. Inflammatory infiltrate was also observed in muscle in myopathy and in cerebrum of patients with encephalopathy and patients with epilepsy. Such changes were not seen in skin biopsies from patients with small fiber neuropathies. The findings from this systematic review suggest an immune mediated pathogenesis for GRND. Future research should focus on the characterization of the inflammatory cell infiltrates and identifying target epitopes.
Topics: Biomarkers; Disease Management; Disease Susceptibility; Glutens; Humans; Immunohistochemistry; Nervous System Diseases; Organ Specificity; Phenotype
PubMed: 32244870
DOI: 10.3390/nu12030822 -
Neuroscience and Biobehavioral Reviews Mar 2018The inhibitory tone that the cerebellum exerts on the primary motor cortex (M1) is known as cerebellar brain inhibition (CBI). Studies show CBI to be relevant to several...
The inhibitory tone that the cerebellum exerts on the primary motor cortex (M1) is known as cerebellar brain inhibition (CBI). Studies show CBI to be relevant to several motor functions, including adaptive motor learning and muscle control. CBI can be assessed noninvasively via transcranial magnetic stimulation (TMS) using a double-coil protocol. Variability in parameter choice and controversy surrounding the protocol's ability to isolate the cerebellothalamocortical pathway casts doubt over its validity in neuroscience research. This justifies a systematic review of both the protocol, and its application. The following review examines studies using the double-coil protocol to assess CBI in healthy adults. Parameters and CBI in relation to task-based studies, other non-invasive protocols, over different muscles, and in clinical samples are reviewed. Of the 1398 studies identified, 24 met selection criteria. It was found that methodological design and selection of parameters in several studies may have reduced the validity of outcomes. Further systematic testing of CBI protocols is warranted, both from a parameter and task-based perspective.
Topics: Cerebellum; Humans; Motor Cortex; Neural Inhibition; Neural Pathways; Transcranial Magnetic Stimulation
PubMed: 29208533
DOI: 10.1016/j.neubiorev.2017.11.018 -
Frontiers in Neuroscience 2019Hereditary spastic paraplegia (HSP) and hereditary ataxia (HA) are two groups of disorders characterized, respectively, by progressive dysfunction or degeneration of the...
Hereditary spastic paraplegia (HSP) and hereditary ataxia (HA) are two groups of disorders characterized, respectively, by progressive dysfunction or degeneration of the pyramidal tracts (HSP) and of the Purkinje cells and spinocerebellar tracts (HA). Although HSP and HA are generally shown to have distinct clinical-genetic profiles, in several cases the clinical presentation, the causative genes, and the cellular pathways and mechanisms involved overlap between the two forms. Genetic analyses in humans in combination with and studies using model systems have greatly expanded our knowledge of spinocerebellar degenerative disorders. In this review, we focus on the zebrafish (), a vertebrate model widely used in biomedical research since its overall nervous system organization is similar to that of humans. A critical analysis of the literature suggests that zebrafish could serve as a powerful experimental tool for molecular and genetic dissection of both HA and HSP. The zebrafish, found to be very useful for demonstrating the causal relationship between defect and mutation, also offers a useful platform to exploit for the development of therapies.
PubMed: 31920481
DOI: 10.3389/fnins.2019.01311