scholarly journals Anti Iglon5 Syndrome: What We Know So Far? A Non-Systematic Review

2020 ◽  
Author(s):  
Caroline Figueiredo da Silva ◽  
Gustavo Figueiredo da Silva ◽  
Washigton Luiz Gomes de Medeiros Junior ◽  
Marcus Vinícius Magno Gonçalves
Keyword(s):  
Current Knowledge ◽  
Immune Therapy ◽  
Neuronal Loss ◽  
Autoimmune Response ◽  
Cervical Cord ◽  
Protein Accumulation ◽  
Antibody Testing ◽  
Neurodegenerative Process ◽  
Upper Cervical ◽  
Neuropathological Finding

The objective of this review is to do an overview about the current knowledge of Anti Iglon5 Syndrome, a disease that was first described in 2014. The IgLON proteins are a family of cell adhesion molecules and the presence of antibodies against IgLON5 are crucial for diagnosis of Anti IgLON5 Syndrome. This syndrome has an expanded clinical spectrum that involves prominent sleep disorder, progressive bulbar dysfunction, gait instability with abnormal eye movements reminiscent and cognitive deterioration sometimes associated with chorea. The main neuropathological finding is the neuronal loss with hyperphosphorylated tau (p-Tau) protein accumulation at hypothalamus, brainstem tegmentum, hippocampus, periaqueductal gray matter, medulla oblongata and upper cervical cord. The exact pathogenesis is still unclear and involves a neurodegenerative process and autoimmune response. The early diagnosis is important to avoid unnecessary tests and prevent complications. Important resources for diagnosis are the antibody testing of serum and CSF for IgLON5-IgG. The mortality of anti IgLON5 syndrome is high and new studies published described a good response to immune therapy. However, the response to immune therapy depends of some clinical and analytical characteristic. In addition, future studies are needed to thoroughly study the aspects of pathogenesis and treatment of this important pathological syndrome.

scholarly journals Anti -Iglon5 Syndrome: What we know so far? A non-systematic review

2021 ◽  
Author(s):  
Gustavo Figueiredo da Silva ◽  
Caroline Figueiredo da Silva ◽  
Washigton Luiz Gomes de Medeiros Junior ◽  
Marcus Vinícius Magno Gonçalves
Keyword(s):  
Systematic Review ◽  
Current Knowledge ◽  
Immune Therapy ◽  
Case Series ◽  
Neuronal Loss ◽  
Autoimmune Response ◽  
Cervical Cord ◽  
Protein Accumulation ◽  
Antibody Testing ◽  
Pubmed Database

Background: The first report of Anti-IgLON5 syndrome was in 2014. AntiIgLON5 antibodies have a prevalence of 12 in 150,000 patients per year. However, considering the unreported patients, the prevalence can be much higher. Objectives: Provide an overview of the current knowledge of Anti- IgLON5 syndrome. Design and setting: Narrative review. Methods: Non- systematic review on Pubmed database. Results: The IgLON proteins are a family of cell adhesion molecules and the presence of antibodies against IgLON5 is crucial for the AntiIgLON5 Syndrome diagnosis. This syndrome has an expanded clinical spectrum that involves prominent sleep disorder, progressive bulbar dysfunction, gait instability with abnormal eye movements reminiscent, and cognitive deterioration sometimes associated with chorea. The main neuropathological finding is the neuronal loss with hyperphosphorylated tau protein accumulation at the hypothalamus, brainstem tegmentum, hippocampus, periaqueductal gray matter, medulla oblongata, and upper cervical cord. The exact pathogenesis is still unclear and involves a neurodegenerative process and autoimmune response. Early diagnosis is important to avoid unnecessary tests and prevent complications. Important resources for diagnosis are the antibody testing of serum and cerebrospinal fluid for IgLON5-IgG. The Anti-IgLON5 syndrome mortality is high and new studies published described a good response to immune therapy, however, depends on some clinical and analytical characteristics. Conclusions: The Anti-Iglon5 syndrome is a pathology still poorly studied and described in the medical literature (only in case series, for example), being a syndrome probably underdiagnosed. Future studies are needed to thoroughly analyze the aspects of pathogenesis and treatment of this important pathological syndrome.

Fluid Biomarkers Indicative of Neurodegenerative Diseases

2016 ◽  
Author(s):  
Henrik Zetterberg ◽  
Jonathan M. Schott
Keyword(s):  
Central Nervous System ◽  
Neurodegenerative Diseases ◽  
Microglial Activation ◽  
Psychiatric Symptoms ◽  
Neuronal Loss ◽  
Protein Accumulation ◽  
Time Line ◽  
The Past ◽  
Neurodegenerative Process ◽  
Disease Specific

A major unifying feature of neurodegenerative diseases (NDDs) is excessive neuronal loss. Depending on when and where this occurs, patients may express distinct neurological and psychiatric symptoms. Neurodegeneration is accompanied by protein aggregation, inflammation, and microglial activation that may be drivers of the disease or in some circumstances may be protective reactions to the neurodegenerative process. A key development over the past decade has been our ability to leverage these accompanying central nervous system changes to develop clinically impactful biomarkers of specific NDDs. This has been crucial in helping us develop an understanding the time line of progression of these diseases, in their early diagnosis and to help target patients appropriately in therapeutic clinical trials, This chapter gives an overview of both established and novel fluid biomarkers for neurodegeneration, protein accumulation, inflammation, and microglial activation across different neurodegenerative diseases. Common as well as disease-specific biomarker changes in cerebrospinal fluid and blood are emphasized.

scholarly journals *Autopsy of a suspected venous circulatory disturbance localized in the medulla oblongata and upper cervical cord accompanied with an aneurysm

2008 ◽  
Vol 48 (8) ◽  
pp. 568-574
Author(s):  
Katsuhisa Masaki ◽  
Masaharu Ohno ◽  
Hironobu Maeda ◽  
Tetsuo Hamada ◽  
Toru Iwaki ◽  
...  
Keyword(s):  
Medulla Oblongata ◽  
Cervical Cord ◽  
Circulatory Disturbance ◽  
Upper Cervical

scholarly journals SETBP1 accumulation induces P53 inhibition and genotoxic stress in neural progenitors underlying neurodegeneration in Schinzel-Giedion syndrome

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Federica Banfi ◽  
Alicia Rubio ◽  
Mattia Zaghi ◽  
Luca Massimino ◽  
Giulia Fagnocchi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Neuronal Death ◽  
Neuronal Loss ◽  
Genotoxic Stress ◽  
Protein Product ◽  
Neural Progenitors ◽  
Cell Identity ◽  
Neurodegenerative Process ◽  
Parp 1 ◽  
Shed Light

AbstractThe investigation of genetic forms of juvenile neurodegeneration could shed light on the causative mechanisms of neuronal loss. Schinzel-Giedion syndrome (SGS) is a fatal developmental syndrome caused by mutations in the SETBP1 gene, inducing the accumulation of its protein product. SGS features multi-organ involvement with severe intellectual and physical deficits due, at least in part, to early neurodegeneration. Here we introduce a human SGS model that displays disease-relevant phenotypes. We show that SGS neural progenitors exhibit aberrant proliferation, deregulation of oncogenes and suppressors, unresolved DNA damage, and resistance to apoptosis. Mechanistically, we demonstrate that high SETBP1 levels inhibit P53 function through the stabilization of SET, which in turn hinders P53 acetylation. We find that the inheritance of unresolved DNA damage in SGS neurons triggers the neurodegenerative process that can be alleviated either by PARP-1 inhibition or by NAD + supplementation. These results implicate that neuronal death in SGS originates from developmental alterations mainly in safeguarding cell identity and homeostasis.

Responses of Medullary Dorsal Horn Neurons to Corneal Stimulation by CO2 Pulses in the Rat

1999 ◽  
Vol 82 (5) ◽  
pp. 2092-2107 ◽  
Author(s):  
Harumitsu Hirata ◽  
James W. Hu ◽  
David A. Bereiter
Keyword(s):  
Thalamic Nucleus ◽  
Receptive Fields ◽  
Male Rats ◽  
Cervical Cord ◽  
Type I ◽  
Type Ii ◽  
Upper Cervical ◽  
The Difference ◽  
Evoked Activity ◽  
Stimulation Of

Corneal-responsive neurons were recorded extracellularly in two regions of the spinal trigeminal nucleus, subnucleus interpolaris/caudalis (Vi/Vc) and subnucleus caudalis/upper cervical cord (Vc/C1) transition regions, from methohexital-anesthetized male rats. Thirty-nine Vi/Vc and 26 Vc/C1 neurons that responded to mechanical and electrical stimulation of the cornea were examined for convergent cutaneous receptive fields, responses to natural stimulation of the corneal surface by CO2 pulses (0, 30, 60, 80, and 95%), effects of morphine, and projections to the contralateral thalamus. Forty-six percent of mechanically sensitive Vi/Vc neurons and 58% of Vc/C1 neurons were excited by CO2 stimulation. The evoked activity of most cells occurred at 60% CO2 after a delay of 7–22 s. At the Vi/Vc transition three response patterns were seen. Type I cells ( n = 11) displayed an increase in activity with increasing CO2 concentration. Type II cells ( n = 7) displayed a biphasic response, an initial inhibition followed by excitation in which the magnitude of the excitatory phase was dependent on CO2 concentration. A third category of Vi/Vc cells (type III, n = 3) responded to CO2 pulses only after morphine administration (>1.0 mg/kg). At the Vc/C1 transition, all CO2-responsive cells ( n = 15) displayed an increase in firing rates with greater CO2 concentration, similar to the pattern of type I Vi/Vc cells. Comparisons of the effects of CO2 pulses on Vi/Vc type I units, Vi/Vc type II units, and Vc/C1 corneal units revealed no significant differences in threshold intensity, stimulus encoding, or latency to sustained firing. Morphine (0.5–3.5 mg/kg iv) enhanced the CO2-evoked activity of 50% of Vi/Vc neurons tested, whereas all Vc/C1 cells were inhibited in a dose-dependent, naloxone-reversible manner. Stimulation of the contralateral posterior thalamic nucleus antidromically activated 37% of Vc/C1 corneal units; however, no effective sites were found within the ventral posteromedial thalamic nucleus or nucleus submedius. None of the Vi/Vc corneal units tested were antidromically activated from sites within these thalamic regions. Corneal-responsive neurons in the Vi/Vc and Vc/C1 regions likely serve different functions in ocular nociception, a conclusion reflected more by the difference in sensitivity to analgesic drugs and efferent projection targets than by the CO2 stimulus intensity encoding functions. Collectively, the properties of Vc/C1 corneal neurons were consistent with a role in the sensory-discriminative aspects of ocular pain due to chemical irritation. The unique and heterogeneous properties of Vi/Vc corneal neurons suggested involvement in more specialized ocular functions such as reflex control of tear formation or eye blinks or recruitment of antinociceptive control pathways.

Input patterns and pathways from the six semicircular canals to motoneurons of neck muscles. I. The multifidus muscle group

1994 ◽  
Vol 72 (6) ◽  
pp. 2691-2702 ◽  
Author(s):  
Y. Shinoda ◽  
Y. Sugiuchi ◽  
T. Futami ◽  
N. Ando ◽  
T. Kawasaki
Keyword(s):  
Semicircular Canals ◽  
Input Pattern ◽  
Muscle Group ◽  
Cervical Cord ◽  
Multifidus Muscle ◽  
Postsynaptic Potentials ◽  
Upper Cervical ◽  
Neck Motoneurons ◽  
Homogeneous Pattern ◽  
Stimulation Of

1. The pattern of connections between the six semicircular canals and neck motoneurons of the multifidus muscle group was investigated by recording intracellular potentials from motoneurons in the upper cervical cord of anesthetized cats. 2. Synaptic potentials were recorded in motoneurons of the rectus capitis posterior (RCP) muscle at C1, the obliquus capitis inferior (OCI) muscle at C1 and C2, and the cervical multifidus muscle (Multi) at C4 in response to electrical stimulation of individual ampullary nerves of the six semicircular canals. Excitatory or inhibitory postsynaptic potentials (EPSPs or IPSPs, respectively) were evoked by separate stimulation of individual ampullary nerves in all of the neck motoneurons. Virtually all of the neck motoneurons received convergent inputs from the six ampullary nerves. 3. Motoneurons that supplied a single muscle had a homogeneous pattern of input from the six semicircular canals. There were two patterns of input from the six semicircular canals to motoneurons of the multifidus muscle group. RCP and Multi motoneurons were excited by stimulation of the bilateral anterior canal nerves (ACNs) and the contralateral lateral canal nerve (LCN) and inhibited by stimulation of the bilateral posterior canal nerves (PCNs) and the ipsilateral LCN. This input pattern is similar to that previously observed in other dorsal extensor muscles, whereas the other input pattern observed in OCI motoneurons is entirely new. OCI motoneurons at C1 and C2 were excited by stimulation of the ipsilateral ACN, PCN, and the contralateral LCN and inhibited by stimulation of the contralateral ACN, PCN, and the ipsilateral LCN. 4. Most postsynaptic potentials (PSPs) were disynaptic, but there were trisynaptic inhibitory connections between the contralateral ACN and PCN and OCI motoneurons, and between the contralateral PCN and RCP motoneurons. 5. The pathways for mediating these inputs from different semicircular canals to neck motoneurons were determined by making lesions in the lower medulla. Transection of the ipsilateral medial longitudinal fascicle (MLF) abolished the following potentials: all disynaptic PSPs in RCP motoneurons except the disynaptic EPSPs from the ipsilateral ACN, and in OCI motoneurons, disynaptic PSPs from the bilateral LCNs, and disynaptic IPSPs from the contralateral PCN. Complete bilateral section of the MLF did not affect the disynaptic EPSPs from the ipsilateral ACN in RCP motoneurons, the disynaptic EPSPs from the ipsilateral ACN and PCN in OCI motoneurons, nor the trisynaptic IPSPs from the contralateral ACN and PCN in COI motoneurons and from the contralateral PCN in RCP motoneurons.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Severe and regionally-widespread increases in tissue urea in the human brain represent a novel finding of pathogenic potential in Parkinson’s disease dementia

2021 ◽  
Author(s):  
Melissa Scholefield ◽  
Stephanie J. Church ◽  
Jingshu Xu ◽  
Stefano Patassini ◽  
Federico Roncaroli ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
High Performance ◽  
Current Knowledge ◽  
Neuronal Loss ◽  
Middle Temporal Gyrus ◽  
Parkinson’S Disease Dementia ◽  
Pathogenic Potential ◽  
Age Related ◽  
Liquid Chromatography Tandem Mass

Abstract Background: Widespread elevations in brain urea have, in recent years, been reported in certain types of age-related dementia, notably Alzheimer’s disease (AD) and Huntington’s disease (HD). Urea increases in these diseases are substantive, and approximate in magnitude to levels present in uraemic encephalopathy. In AD and HD, elevated urea levels occur across the entire brain, and not only in regions heavily affected by neurodegeneration. However, measurements of brain urea have not hitherto been reported in Parkinson’s disease dementia (PDD), a condition defined by changes in thinking and behaviour in someone with a diagnosis of Parkinson's disease, which shares neuropathological and symptomatic overlap with both AD and HD. This study aims to address this gap in the current knowledge of PDD.Methods: Here we report measurements of tissue urea from nine neuropathologically-confirmed regions of the brain in PDD and post-mortem-delay-matched controls, in regions that included the cerebellum, motor cortex, sensory cortex, hippocampus, substantia nigra, middle temporal gyrus, medulla oblongata, cingulate gyrus, and pons, by applying ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Case-control differences were determined using multiple t-tests followed by correction with 10% false discovery rate.Results: We found urea concentrations to be substantively elevated in all nine regions, the average increase being 3-4-fold. Urea concentrations were remarkably consistent across regions in both cases and controls, with no clear distinction between regions heavily affected by neuronal loss in PDD compared to less severely affected areas. These urea elevations mirror those found in uraemic encephalopathy, where equivalent levels are generally considered to be pathogenic. These urea elevations also reflect those previously reported in AD and HD. Conclusions: Increased urea is a widespread metabolic perturbation in brain metabolism common to PDD, AD, and HD, at levels equal to those seen in uremic encephalopathy. This presents a novel pathogenic mechanism in PDD, which is shared with two other neurodegenerative diseases.

Four Convergent Patterns of Input from the Six Semicircular Canals to Motoneurons of Different Neck Muscles in the Upper Cervical Cord

1996 ◽  
Vol 781 (1 Lipids and Sy) ◽  
pp. 264-274 ◽  
Author(s):  
Y. SHINODA ◽  
Y. SUGIUCHI ◽  
T. FUTAMI ◽  
S. KAKEI ◽  
Y. IZAWA ◽  
...  
Keyword(s):  
Semicircular Canals ◽  
Neck Muscles ◽  
Cervical Cord ◽  
Upper Cervical
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