Episodic Ataxia Type 1 and 2 (Familial Periodic Ataxia/Vertigo)

Brandt, Thomas; Strupp, Michael

doi:10.1159/000259262

Cited by 56 publications

(23 citation statements)

References 31 publications

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“…26,44 Thus, one hypothesis is that attacks are secondary to abnormally high intracellular pH values and that it is by reducing this pH level that ACTZ may prevent attacks. 11 Lower pH values reduce potassium conductance of the cell membrane and have an effect on the activation and inactivation of sodium and calcium channels, respectively. 30 Thus, the excitability and resting activity of neurons are restored.…”

Section: Acetazolamidementioning

confidence: 99%

Episodic Ataxia Type 2

Strupp¹,

Zwergal²,

Brandt³

2007

Neurotherapeutics

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162

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Summary: Episodic ataxia type 2 (EA 2) is a rare neurological disorder of autosomal dominant inheritance resulting from dysfunction of a voltage-gated calcium channel. It manifests with recurrent disabling attacks of imbalance, vertigo, and ataxia, and can be provoked by physical exertion or emotional stress. In the spell-free interval, patients present with central ocular motor dysfunction, mainly downbeat nystagmus. A slow progression of cerebellar signs accompanied by a slight atrophy of midline cerebellar structures is commonly observed during the course of the disease. EA 2 is caused most often by the loss of function mutations of the calcium channel gene CACNA1A, which encodes the Ca V 2.1 subunit of the P/Q-type calcium channel and is primarily expressed in Purkinje cells. To date, more than 30 mutations have been described. Two effective treatment options have been established for EA 2: acetazolamide (ACTZ), which probably changes the intracellular pH and thereby the transmembraneous potential, and 4-aminopyridine (4-AP), a potassium channel blocker. Approximately 70% of all patients respond to treatment with ACTZ, but the effect is often only transient. In an open trial, 4-AP prevented attacks in five of six patients with EA 2, most likely by increasing the resting activity and excitability of the Purkinje cells. These findings were confirmed by experiments in animal models of EA 2. Many aspects of the pathophysiology (e.g., induction of the attacks) and treatment of EA 2 (e.g., mode of action of ACTZ and 4-AP) still remain unclear and need to be addressed in further animal and clinical studies.

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Section: Acetazolamidementioning

confidence: 99%

Episodic Ataxia Type 2

Strupp¹,

Zwergal²,

Brandt³

2007

Neurotherapeutics

Self Cite

162

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“…They are caused by mutations in the potassium and calcium channel genes, KCNA1 and CACNA1A. 1,2 Mutations in CACNB4 and SLC1A3 cause EA5 and EA6. 3,4 Further, mutations in PRRT2 have been identified in a single patient who also presents with hemiplegic migraines 5 and in two brothers with familial paroxysmal kinesigenic dystonia in addition to learning disabilities, absences and EA.…”

Section: Introductionmentioning

confidence: 99%

A novel locus for episodic ataxia:UBR4 the likely candidate

et al. 2013

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Episodic ataxias (EAs) are rare neurological channelopathies that are characterized by spells of imbalance and a lack of co-ordination. There are seven clinically recognized EAs and multiple isolated cases. Five disease-causing genes have been identified to date. We describe a novel form of autosomal dominant EA in a large three-generation Irish family. This form of EA presents in early childhood with periods of unsteadiness generalized weakness and slurred speech during an attack, which may be triggered by physical tiredness or stress. Linkage analysis undertaken in 13 related individuals identified a single disease locus (1p36.13-p34.3) with a LOD score of 3.29. Exome sequencing was performed. Following data analysis, which included presence/absence within the linkage peak, two candidate variants were identified. These are located in the HSPG2 and UBR4 genes. UBR4 is an ubiquitin ligase protein that is known to interact with calmodulin, a Ca 2 þ protein, in the cytoplasm. It also co-localizes with ITPR1 a calcium release channel that is a major determinant of mammal co-ordination. Although UBR4 is not an ion channel gene, the potential for disrupted Ca 2 þ control within neuronal cells highlights its potential for a role in this form of EA.

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“…Beide Typen werden den sog. "Kanalopathien" zugeordnet.Beim Typ 2 liegt eine Mutation des zerebralen P/QTyps des Kalziumkanals α1 vor, die auf dem Chromosom 19p lokalisiert ist [9]. Zur Anfallsprophylaxe hat sich Azetazolamid bewährt.…”

Section: Familiäre Episodische Ataxieunclassified

Episodisch auftretendes Schwindelgef�hl

Schmäl

Stoll

2003

HNO

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While an acute loss of unilateral vestibular function (for example in case of neuritis vestibularis or temporal bone fracture) leads to long-term vertigo, this paper deals with the phenomenon of episodic vertigo (duration: seconds up to hours).Both peripheral-vestibular and central disturbances can be responsible for this symptom. The aim of this paper is to present otological and neurological diseases which can lead to episodic attacks of vertigo.

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Episodic Ataxia Type 1 and 2 (Familial Periodic Ataxia/Vertigo)

Cited by 56 publications

References 31 publications

Episodic Ataxia Type 2

Episodic Ataxia Type 2

A novel locus for episodic ataxia:UBR4 the likely candidate

Episodisch auftretendes Schwindelgef�hl

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