Flail arm syndrome with cytoplasmic vacuoles in remaining anterior horn motor neurons: A peculiar variant of amyotrophic lateral sclerosis

Hino, Shuji; Sasaki, Shoichi

doi:10.1111/neup.12223

Cited by 7 publications

(4 citation statements)

References 20 publications

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“…Clinical sALS phenotypes that eventually allow for alternative interpretations, e. g., flail-arm or flail-leg syndrome [45][46][47]55], still require neuropathological confirmation [56,57].…”

Section: Discussionmentioning

confidence: 99%

Does Sporadic Amyotrophic Lateral Sclerosis Spread via Axonal Connectivities?

Braak

Neumann

Ludolph

et al. 2017

Neurology International Open

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IntroductionAmyotrophic lateral sclerosis (ALS) is characterized by rapid progressive paralysis of the striated skeletal musculature [1,2]. The present review focuses on sporadic disease (sALS), which constitutes the majority of cases without a known genetic mutation. Clinically similar but inherited (familial) forms that display very diverse pathologies [3][4][5][6][7] are not taken into account here.The pathological process underlying sALS entails abnormal changes of an endogenous and predominantly intranuclear protein, TDP-43 (transactive response DNA-binding protein 43). Following nuclear clearance, the protein remains delocalized in the cytoplasm of susceptible nerve cells, where it undergoes defective phosphorylation and conformational change followed by ubiquitination, which ultimately prevent its re-entry into the nuclear compartment [7][8][9][10][11].The pathomechanisms that lead to the dysfunction and death of involved cells are still unknown. Along with a "loss of function" attributable to the loss of intranuclear TDP-43 expression accompanied by disrupted RNA metabolism, a "gain of function" mechanism owing to a noxious effect on cells by toxic TDP-43 forms has been discussed [7,12] Which Nerve Cell Types Develop TDP-43-immunoreactive Inclusions in sALS?The abnormal nuclear clearance and development of cytoplasmic TDP-43-immunopositive inclusions are confined to a few types ABsTr AC TThe pathological process underlying sporadic amyotrophic lateral sclerosis (sALS) that is associated with the formation of cytoplasmic inclusions of a nuclear protein (TDP-43) is confined to only a few types of long-axoned projection neurons. The giant Betz pyramidal cells of the primary motor neocortex as well as large α-motor neurons of the lower brainstem and spinal cord become involved early. In the human brain, these 2 neuronal types are to a large extent interconnected by monosynaptic axonal projections. The cell nuclei of affected neurons gradually forfeit their normal expression of the protein TDP-43. In α-motor neurons, this nuclear loss is followed by the formation of insoluble TDP-43-immunopositive inclusions in the cytoplasm, whereas in Betz cells the loss of nuclear expression remains for an unknown period of time unaccompanied by somatodendritic and/or axoplasmic aggregations. It is possible that in cortical pyramidal cells (Betz cells) the nuclear clearing initially leads to the formation of an abnormal but still soluble cytoplasmic TDP-43 which may enter the axoplasm and, following transmission via direct synaptic contacts, induces anew TDP-43 dysregulation and aggregation in recipient neurons. The trajectory of the spreading pattern that consecutively develops during the course of sALS is consistent with the dissemination from chiefly cortical projection neurons via axonal transport through direct synaptic contacts leading to the secondary induction of TDP-43-containing inclusions within recipient nerve cells in involved subcortical regions. E136Braak H et al. Does Sporadic Amyotrophic Lateral … Neurolo...

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Section: Discussionmentioning

confidence: 99%

Does Sporadic Amyotrophic Lateral Sclerosis Spread via Axonal Connectivities?

Braak

Neumann

Ludolph

et al. 2017

Neurology International Open

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“…11 However, if clinical significance of positivity of IgM anti-GM1 antibody from FAS patients is identified, it may be help to differentiation between FAS and ALS. 2…”

Section: Annals Of Clinical Neurophysiology Volume 19 Number 1 Janumentioning

confidence: 99%

Flail arm syndrome with several issues related to the diagnostic process

Kim

Park

Yoon

et al. 2017

Ann Clin Neurophysiol

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Flail arm syndrome (FAS) has a similar clinical course 1 and pathological findings as amyotrophic lateral sclerosis (ALS). 2 It is important to distinguish the two diseases because FAS patients have significantly better survival rates compared with other typical ALS variants. 1,3 We report a FAS patient confirmed by clinical and electrophysiological findings based on review of literatures. We show the findings of polysomnography (PSG) in patient with FAS. We suggest that several issues related to the diagnostic process needed to be addressed. CASEA 50-year-old male presented with slowly progressive weakness and muscle wasting in his arms about two years ago. At the time of the first manifestation, weakness was noted in the right proximal arm accompanied by atrophy and identical symptoms occurred in the left arm after a one year.He had no remarkable medical history except for hypertension and there was no related family history. In neurological examination, bilateral weakness of the arms was scored as Medical Research Council grade I proximally and grade III in the distal muscles symmetrically, combined with muscle atrophy in the upper limb girdles. Both acromion processes of the scapular bone protruded beneath the skin. Both of his arms, forearms and hands were pronated. Fasciculation were absent in his all limbs and tongue. Sensory examination was normal Flail arm syndrome (FAS), known as one of the atypical amyotrophic lateral sclerosis (ALS) variants, has a similar clinical course and pathologic findings as ALS. Therefore it is difficult to differentiate between ALS and FAS at a glance. There are few reports involving individual analysis of FAS patients to date. The findings of polysomnography (PSG) in patient with FAS are not well known. We report a male FAS patient with review of literatures and several issues related to the diagnostic process.

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“…Klinische Präsentationsformen einer sALS, die unter Umständen abweichende Interpretationen zulassen, wie z. B. bei einem Flail-arm-oder Flail-leg-Syndrom [45 -47, 55], bedürfen noch einer detaillierten neuropathologischen Analyse [56,57].…”

Section: Schlussfolgerungenunclassified

Breitet sich die sporadisch auftretende amyotrophe Lateralsklerose über axonale Verbindungen aus?

et al. 2017

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ZusammenfassungDer pathologische Prozess einer sporadisch auftretenden amyotrophen Lateralsklerose (sALS) ist mit dem Auftreten zytoplasmatischer Einschlusskörper eines normalerweise im Zellkern vorkommenden Proteins (TDP-43) verbunden und ergreift nur wenige Arten langaxoniger Projektionsneurone. Die Riesenpyramidenzellen von Betz im primären motorischen Neokortex und die α-Motorneurone im unteren Hirnstamm und Rückenmark sind früh ergriffene Zellformen. Im zentralen Nervensystem des Menschen sind diese beiden Zellarten durch axonale Projektionen monosynaptisch verbunden. Im Verlauf einer sALS verlieren die Zellkerne affizierter Neurone graduell ihre Immunoreaktivität für TDP-43. Bei α-Motorneuronen entstehen unlösliche TDP-43-Einschlüsse im Zellleib, während in Betz-Zellen derartige Aggregatbildungen zunächst ausbleiben. Es erscheint daher möglich, dass in Betz-Zellen anfänglich eine im Zytoplasma noch lösliche Form des TDP-43 entsteht, die in das Axoplasma gerät, über direkte synaptische Kontakte übertragen wird und im nachfolgenden Neuron erneut die Dysregulation und Aggregation des TDP-43 auslöst. Das im Verlauf einer sALS entstehende Ausbreitungsmuster der Schädigungen ist mit der Vorstellung vereinbar, dass ein zellenschädigendes Agens über axonale Kontakte von kortikalen Projektionsneuronen auf nachfolgende Neuronen übertragen wird und dort den pathologischen Prozess erneut induziert.

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Flail arm syndrome with cytoplasmic vacuoles in remaining anterior horn motor neurons: A peculiar variant of amyotrophic lateral sclerosis

Cited by 7 publications

References 20 publications

Does Sporadic Amyotrophic Lateral Sclerosis Spread via Axonal Connectivities?

Does Sporadic Amyotrophic Lateral Sclerosis Spread via Axonal Connectivities?

Flail arm syndrome with several issues related to the diagnostic process

Breitet sich die sporadisch auftretende amyotrophe Lateralsklerose über axonale Verbindungen aus?

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