An unusual neurological syndrome of crawling gait, dystonia, pyramidal signs, and limited speech

Arif, Beenish; Grünewald, Anne; Fatima, Amara; Ramı́rez, Alfredo; Ali, Arif; Brüggemann, Nobert; Wuerfel, Jens; Rolfs, Arndt; Lohmann, Katja; Malik, Akbar; Klein, Christine; Naz, Sadaf

doi:10.1002/mds.23860

Cited by 5 publications

(4 citation statements)

References 12 publications

(13 reference statements)

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“…Atcay ji-hes mice exhibit a stiff-legged gait that is reminiscent of human dystonic gait (for example, see videos accompanying (Arif et al, 2011)). The gait is associated with prolonged hind-limb and tail extension during the stance and swing phases of gait accompanied by toe-walking, a pattern that differs markedly from the normal gait seen in wild-type littermate controls (Figure 1A, Movies 1 and 2).…”

Section: Resultsmentioning

confidence: 99%

Alterations in cerebellar physiology are associated with a stiff-legged gait in Atcayji-hes mice

Luna-Cancalon

Sikora

Pappas

et al. 2014

Neurobiology of Disease

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Recent evidence suggests that dystonia, a movement disorder characterized by sustained involuntary muscle contractions, can be associated with cerebellar abnormalities. The basis for how functional changes in the cerebellum can cause dystonia is poorly understood. Here we identify alterations in physiology in Atcayji-hes mice which in addition to ataxia, have an abnormal gait with hind limb extension and toe walking, reminiscent of human dystonic gait. No morphological abnormalities in the brain accompany the dystonia, but partial cerebellectomy causes resolution of the stiff-legged gait, suggesting that cerebellar dysfunction contributes to the dystonic gait of Atcayji-hes mice. Recordings from Purkinje and deep cerebellar nuclear (DCN) neurons in acute brain slices were used to determine the physiological correlates of dystonia in the Atcayji-hes mice. Approximately 50% of cerebellar Purkinje neurons fail to display the normal repetitive firing characteristic of these cells. In addition, DCN neurons exhibit increased intrinsic firing frequencies with a subset of neurons displaying bursts of action potentials. This increased intrinsic excitability of DCN neurons is accompanied by a reduction in after-hyperpolarization currents mediated by small-conductance calcium-activated potassium (SK) channels. An activator of SK channels reduces DCN neuron firing frequency in acute cerebellar slices and improves the dystonic gait of Atcayji-hes mice. These results suggest that a combination of reduced Purkinje neuron activity and increased DCN intrinsic excitability can result in a combination of ataxia and a dystonia-like gait in mice.

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Section: Resultsmentioning

confidence: 99%

Alterations in cerebellar physiology are associated with a stiff-legged gait in Atcayji-hes mice

Luna-Cancalon

Sikora

Pappas

et al. 2014

Neurobiology of Disease

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“…Diabetes is among the most prevalent chronic diseases, and researchers predicted a near doubling of patients with DM by 2030 compared to gures obtained in 2000 [12]. PD is a disease with an increasing prevalence in the elderlies, and the projected prevalence cases for PD are predicted to increase during the next 40 years [13]. Accumulating evidence suggests that DM constitutes a risk factor associated with increased neurodegenerative diseases [5].…”

Section: Introductionmentioning

confidence: 99%

Long-Term Hyperglycemia Induces α-Synuclein Aggregation and Dopaminergic Neuronal Loss in Parkinson's Disease Mouse Model

Lv¹,

Lin²,

Sun³

et al. 2021

Preprint

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Background: Growing evidence suggest the association between Parkinson’s disease (PD) and diabetes mellitus (DM). On a cellular level, it was proven that long-term elevated levels of glucose might lead to nigrostriatal degeneration in PD models. However, the underlying mechanism is still unclear. Previously, we have elucidated the potential of type 2 diabetes mellitus (T2DM) in facilitating PD progression, involving aggregation of both alpha-synuclein (α-syn) and islet amyloid polypeptide (IAPP) in the pancreatic and brain tissues. However, due to the complicated effect of insulin resistance on PD onset, the actual mechanism of hyperglycemia-induced dopaminergic degeneration remains unknown. Methods: In the present study, we employed the type 1 diabetes mellitus (T1DM) model induced by streptozotocin (STZ) injection, to investigate the direct effect of elevated blood glucose level on nigrostriatal degeneration. Results: We found that STZ treatment induced more severe pathological alterations in the pancreatic islets and T1DM symptoms in α-syn-overexpression mice than that in wild type (WT) mice, one month and three months after STZ injections. Behavioral tests evaluating motor performance confirmed the nigrostriatal degeneration. Furthermore, we observed a marked decrease in dopaminergic profiles and an increase of α-syn accumulation and Serine 129 (S129) phosphorylation in STZ-treated α-syn mice compared with vehicle-treated mice. At last, we observed more severe neuroinflammation in the brain of the STZ-treated α-syn mice.Conclusion: Our results solidify the potential link between DM and PD, providing insights on how hyperglycemia induces nigrostriatal degeneration and contributes to pathogenetic mechanisms in PD.

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“…The clinical and radiological characteristics of these cases are presented in Table 1. The syndrome has sparked a world-wide interest: see, for instance, Garber (2008), Ghika (2008), Caglayan (2008, Thesis), Akpinar (2009), Le Fanu (2009), Held (2009, Kolb (2009, Thesis), Kutty (2010), Bornstein (2010), Pribut (2010), Downey (2010a, b), MacLellan et al (2011), Arif et al (2011).…”

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confidence: 99%

Development of Bipedal and Quadrupedal Locomotion in Humans from a Dynamical Systems Perspective

Tan¹

2012

Human Development - Different Perspectives

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An unusual neurological syndrome of crawling gait, dystonia, pyramidal signs, and limited speech

Abstract: We describe an unusual movement disorder syndrome reminiscent of but distinct from Uner Tan syndrome.

Cited by 5 publications

References 12 publications

Alterations in cerebellar physiology are associated with a stiff-legged gait in Atcayji-hes mice

Alterations in cerebellar physiology are associated with a stiff-legged gait in Atcayji-hes mice

Long-Term Hyperglycemia Induces α-Synuclein Aggregation and Dopaminergic Neuronal Loss in Parkinson's Disease Mouse Model

Development of Bipedal and Quadrupedal Locomotion in Humans from a Dynamical Systems Perspective

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