Treatable causes of cerebellar ataxia

Ramirez‐Zamora, Adolfo; Zeigler, Warren; Desai, Neeja; Biller, José

doi:10.1002/mds.26158

Cited by 36 publications

(76 citation statements)

References 78 publications

(133 reference statements)

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“…CAs are neurological conditions resulting from cerebellar inflammation or damage due to various causes 1,3,4 . Recent global studies on ataxia report an overall prevalence rate of 26 cases in every 100,000 children 16 .…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide administration for a mouse model of cerebellar ataxia with neuroinflammation

Hong

Yoon

Nam

et al. 2020

Sci Rep

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Most cerebellar ataxias (cAs) are incurable neurological disorders, resulting in a lack of voluntary control by inflamed or damaged cerebellum. Although CA can be either directly or indirectly related to cerebellar inflammation, there is no suitable animal model of CA with neuroinflammation. In this study, we evaluated the utility of an intracerebellar injection of lipopolysaccharide (LpS) to generate an animal model of inflammatory CA. We observed that LPS administration induced the expression of pro-inflammatory molecules following activation of glial cells. In addition, the administration of LPS resulted in apoptotic purkinje cell death and induced abnormal locomotor activities, such as impaired motor coordination and abnormal hindlimb clasping posture. Our results suggest that intracerebellar LPS administration in experimental animals may be useful for studying the inflammatory component of CA. Cerebellar ataxias (CAs) are motor neuron diseases caused by pathological processes affecting the cerebellum or its associated pathways 1,2. They are characterised by symptoms such as abnormal coordination of balance, movement and gait. Currently, most CAs are incurable, with few exceptions, and only symptom alleviation is possible 3. CAs can be caused by genetic defects, sporadic neurodegenerative disorders, and acquired conditions (for example, infections, toxic reactions, alcohol, and vitamin deficiencies), but they can also arise for unknown reasons 1,3,4. In particular, many reports have shown a close relationship between cerebellar inflammation and CA 1,3,5. The activation of glial cells resulting in the production of pro-inflammatory molecules has been observed in many animal models of CA and is also evident in the cerebellums of patients with CA 6-9. Furthermore, cerebellar inflammation has been shown to induce the loss of Purkinje cells, which results in cerebellar dysfunction 1,7. Although the understanding of CA pathogenesis associated with genetic causes, cerebellar neurotoxicity, and physical damage has contributed to the development of some animal models of CA 1,3 , there is no suitable animal model to study CA following glial activation and neurotoxic cerebellar inflammation in vivo. Neuroinflammation plays a crucial role in the pathogenesis and progression of neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease 10. As a potent stimulator of neuroinflammation, lipopolysaccharide (LPS) has been used to mediate neurodegenerative progression 11. An accumulation of evidence has shown that LPS-induced neuroinflammation causes neuronal damage through activation of microglia and astrocytes, M1 microglial polarization and the release of pro-inflammatory mediators. For example, LPS injected into the substantia nigra induces microglia activation, which causes the degeneration of dopamine neurons that constitutes the pathological basis of Parkinson's disease 12. In addition, LPS causes an increase in amyloid beta, which results in demyelination and oligodendrocyte injury in mice brains, w...

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Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide administration for a mouse model of cerebellar ataxia with neuroinflammation

Hong

Yoon

Nam

et al. 2020

Sci Rep

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“…Carbamazepine, acetazolamide, valproic acid and lamotrigine have been reported to be effective for EA1. Acetazolamide and the potassium channel blocker 4-aminopyridine seems to be effective in EA2 29,30 .…”

Section: Symptomatic Treatmentmentioning

confidence: 98%

Current concepts in the treatment of hereditary ataxias

Neto

Pedroso

Kuo

et al. 2016

Arq. Neuro-Psiquiatr.

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Hereditary ataxias (HA) represents an extensive group of clinically and genetically heterogeneous neurodegenerative diseases, characterized by progressive ataxia combined with extra-cerebellar and multi-systemic involvements, including peripheral neuropathy, pyramidal signs, movement disorders, seizures, and cognitive dysfunction. There is no effective treatment for HA, and management remains supportive and symptomatic. In this review, we will focus on the symptomatic treatment of the main autosomal recessive ataxias, autosomal dominant ataxias, X-linked cerebellar ataxias and mitochondrial ataxias. We describe management for different clinical symptoms, mechanism-based approaches, rehabilitation therapy, disease modifying therapy, future clinical trials and perspectives, genetic counseling and preimplantation genetic diagnosis.

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“…Friedreich’s ataxia and spinocerenellar ataxias, known as SCAs) or acquired (such as immune mediated and paraneoplastic) [1]. …”

Section: Introductionmentioning

confidence: 99%

Cerebellar ataxia and sensory ganglionopathy associated with light-chain myeloma

et al. 2017

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BackgroundCerebellar ataxia with sensory ganglionopathy is a rare neurological combination that can occur in some hereditary ataxias including mitochondrial diseases and in gluten sensitivity. Individually each condition can be a classic paraneoplastic neurological syndrome. We report a patient with this combination who was diagnosed with light-chain myeloma ten years after initial presentation.Case presentationA 65-year-old Caucasian lady was referred to our Ataxia Clinic because of a 6-year history of progressive unsteadiness and a 2-year history of slurred speech. Past medical history included arterial hypertension. The patient was a non-smoker was not consuming alcohol excessively. There was no family history of ataxia.Neurological examination revealed prominent gaze-evoked nystagmus, heel to shin ataxia, gait ataxia, reduced reflexes and loss of vibration sensation in the legs.Cerebellar ataxia was confirmed using magnetic resonance spectroscopy of the cerebellum and sensory ganglionopathy using neurophysiological assessments including blink reflex study. A muscle biopsy that was arranged to explore the possibility of mitochondrial disease revealed amyloidosis. Urinalysis confirmed the presence of light chains. A bone marrow biopsy confirmed the diagnosis of light chain multiple myeloma.ConclusionsWhilst it could be argued that this could simply be a coincidence, the rarity of these conditions and the absence of an alternative aetiology for the neurological dysfunction argue in favour of a paraneoplastic phenomenon.Electronic supplementary materialThe online version of this article (doi:10.1186/s40673-016-0060-4) contains supplementary material, which is available to authorized users.

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Treatable causes of cerebellar ataxia

Cited by 36 publications

References 78 publications

Lipopolysaccharide administration for a mouse model of cerebellar ataxia with neuroinflammation

Lipopolysaccharide administration for a mouse model of cerebellar ataxia with neuroinflammation

Current concepts in the treatment of hereditary ataxias

Cerebellar ataxia and sensory ganglionopathy associated with light-chain myeloma

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