Type 1 Episodic Ataxia

Also Known As:

Episodic Ataxia, Type 1; Ataxia, Episodic, with Myokymia; Episodic Ataxia with Myokymia; Myokymia 1 With Or Without Hypomagnesemia; Myokymia with Periodic Ataxia; Paroxysmal Ataxia with Neuromyotonia, Hereditary

Networked: 56 relevant articles (2 outcomes, 2 trials/studies)

Relationship Network

Disease Context: Research Results

Nervous System Diseases: 14178
- Neurologic Manifestations: 7102
  - Dyskinesias: 7807
    - Ataxia: 6364
      - Type 1 Episodic Ataxia: 56
  - Neuromuscular Manifestations: 23
    - Myokymia: 136
      - Type 1 Episodic Ataxia: 56
Signs and Symptoms Pathological Conditions
- Signs and Symptoms
  - Neurologic Manifestations: 7102
    - Dyskinesias: 7807
      - Ataxia: 6364
        Type 1 Episodic Ataxia: 56
    - Neuromuscular Manifestations: 23
      - Myokymia: 136
        Type 1 Episodic Ataxia: 56

Related Diseases

1.	Channelopathies
2.	Epilepsy (Aura)
3.	Temporal Lobe Epilepsy
4.	Megalencephaly
5.	Type 2 Episodic Ataxia

Experts

1.	Hanna, Michael G: 7 articles (06/2022 - 04/2007)
2.	Kullmann, Dimitri M: 6 articles (01/2016 - 12/2006)
3.	Baloh, Robert W: 4 articles (06/2022 - 04/2002)
4.	Jen, Joanna C: 4 articles (06/2022 - 04/2002)
5.	Griggs, Robert C: 3 articles (06/2022 - 12/2010)
6.	Rajakulendran, Sanjeev: 3 articles (10/2013 - 04/2007)
7.	Schorge, Stephanie: 3 articles (10/2013 - 04/2007)
8.	Kullmann, D M: 3 articles (07/2010 - 10/2000)
9.	Bundy, Brian N: 2 articles (06/2022 - 04/2014)
10.	CINCH Investigators: 2 articles (06/2022 - 04/2014)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Type 1 Episodic Ataxia:

1.	PotassiumIBA 01/01/2020 - "One example is KCNA1 Potassium Voltage-Gated Channel Subfamily A Member 1 (KCNA1) (Kv1.1), an archetypal Shaker-type Kv channel, in which loss-of-function mutations cause episodic ataxia type 1 (EA1). " 08/01/2023 - "Episodic ataxia type 1 (EA1) is a rare autosomal potassium channelopathy, due to mutations in KCNA1. " 01/01/2018 - "Mutations in the KCNA1 gene encoding the voltage-gated potassium (K+) channel Kv1.1 have been linked to rare neurological syndromes, episodic ataxia type 1 (EA1) and myokymia. " 04/01/2007 - "Episodic ataxia type 1: a neuronal potassium channelopathy." 04/01/2004 - "Episodic ataxia type 1 with distal weakness: a novel manifestation of a potassium channelopathy."
2.	Carbamazepine (Tegretol)FDA LinkGeneric 01/01/2022 - "Case report: A novel loss-of-function pathogenic variant in the KCNA1 cytoplasmic N-terminus causing carbamazepine-responsive type 1 episodic ataxia." 01/01/2023 - "kcna1a mutant zebrafish model episodic ataxia type 1 (EA1) with epilepsy and show response to first-line therapy carbamazepine." 11/01/2008 - "Findings propose that potassium ion channelopathy may underlie disease for a group of infants or young children displaying idiopathic megalencephaly and early onset epilepsy or episodic ataxia type 1. Carbamazepine's remarkable protective effects on the neuronal plasticity in the hyperexcitable state should be further studied, and maybe this drug should be considered more in treatment of temporal lobe epilepsy and megalencephaly."
3.	Acetazolamide (Diamox)FDA LinkGeneric 11/01/2012 - "Some patients with episodic ataxia type 1 (EA1) will also describe improvement with acetazolamide. " 01/01/1998 - "Clinical details are given of different types of episodic ataxia: type 1, with myokymia, and attacks which usually last a few minutes, and may occur several times a day, and treatment with acetazolamide can reduce the number of attacks; type 2, with interictal nystagmus, and attacks which last for several hours to a day or more, and treatment with acetazolamide is very effective; paroxysmal choreoathetosis with episodic ataxia, with attacks lasting for about 20 min and occurring at varying intervals; and familial hemiplegic migraine, with transient hemiplegia presenting during the aura of a migraine headache, the symptoms improving on treatment with acetazolamide. " 01/01/2018 - "Antiepileptic drugs remain the treatment of choice for PKD and episodic ataxia type 1, benzodiazepines are often useful for PNKD, and episodic ataxia type 2 benefits from acetazolamide regardless of the genetic etiology. "
4.	Voltage-Gated Potassium Channels (Voltage-Gated Potassium Channel)IBA 01/01/2023 - "An activator of voltage-gated K+ channels Kv1.1 as a therapeutic candidate for episodic ataxia type 1." 01/01/2022 - "Episodic Ataxia Type 1 (EA1) is an inherited, autosomal dominant disease caused by sequence variants in KCNA1, which encodes the voltage-gated potassium channel, KCNA1 (Kv1.1). " 01/01/2018 - "Pathogenic variants in the KCNA1 gene, which encodes the voltage-gated potassium channel Kv1.1, are responsible for Episodic Ataxia Type 1 (EA1). " 01/30/2012 - "Mutations in the KCNA1 gene, which encodes for the α subunit of the voltage-gated potassium channel Kv1.1, cause episodic ataxia type 1 (EA1). " 10/01/2016 - "Episodic ataxia type 1 (EA1) is an autosomal dominant channelopathy caused by mutations in KCNA1, which encodes the voltage-gated potassium channel, Kv1.1. Eleven members of an EA family were evaluated with molecular and functional studies. "
5.	Potassium Channels (Potassium Channel)IBA 12/01/2010 - "Nerve excitability studies characterize Kv1.1 fast potassium channel dysfunction in patients with episodic ataxia type 1." 01/18/2016 - "The episodic ataxia type 1 mutation I262T alters voltage-dependent gating and disrupts protein biosynthesis of human Kv1.1 potassium channels." 03/01/2008 - "Episodic ataxia type 1 (EA1) is an autosomal-dominant neurological disease caused by point mutations in the potassium channel-encoding gene KCNA1. " 01/01/2015 - "In contrast it was reported that patients with episodic ataxia type 1 (genetic channelopathy with mutation of Kv1.1 channel gene) show prominent excitability changes exactly compatible with fast potassium channel blockade. " 07/27/2010 - "Episodic ataxia type 1 (EA1) is a monogenic channelopathy caused by mutations of the potassium channel gene KCNA1. "
6.	Ion Channels (Ion Channel)IBA 10/01/2013 - "Ion channel disorders: still a fascinating topic--news on episodic ataxia type 1." 04/01/2014 - "Episodic ataxia type 1 is considered a rare neuronal ion channel disorder characterized by brief attacks of unsteadiness and dizziness with persistent myokymia. " 10/01/2013 - "Heterozygous mutations in KCNA1 cause episodic ataxia type 1 (EA1), an ion channel disorder characterised by brief paroxysms of cerebellar dysfunction and persistent neuromyotonia. " 02/01/2001 - "This review evaluates the success of this approach in explaining the mechanisms of two forms of episodic ataxia that are known to be caused by mutations of ion channels: episodic ataxia type 1 (EA1, caused by K+ channel mutations) and episodic ataxia type 2 (EA2, caused by Ca2+ channel mutations). " 03/01/2009 - "Mutations in genes that interfere with K(v) ion channel function cause severe inherited diseases, such as episodic ataxia type 1, deafness, epilepsy, or cardiac arrhythmia. "
7.	Kv1.1 Potassium ChannelIBA 01/01/2023 - "Dominantly inherited missense mutations of the KCNA1 gene, which encodes the KV1.1 potassium channel subunit, cause Episodic Ataxia type 1 (EA1). " 01/01/2023 - "Additionally, we simulated the effects of known mutations in KCNA1 gene encoding the KV1.1 potassium channel subtype associated with episodic ataxia type 1 (EA1). " 01/01/2016 - "Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. " 06/15/2002 - "Episodic ataxia type 1 mutations in the human Kv1.1 potassium channel alter hKvbeta 1-induced N-type inactivation." 10/01/2013 - "Episodic ataxia type 1 (EA1) is caused by mutations in the KCNA1 gene encoding the fast potassium channel Kv1.1 and is characterized clinically by brief episodes of ataxia and continuous and spontaneous motor unit activity. "
8.	Calcium Channels (Calcium Channel)IBA 04/01/2002 - "Episodic ataxia type 1 (EA-1) is caused by missense mutations in the potassium channel gene KCNA1, whereas episodic ataxia type 2 (EA-2) is caused by missense and nonsense mutations in the calcium channel gene CACNA1A. " 11/01/1997 - "weakness), particularly in response to lowered serum potassium (hypokalemic periodic paralysis); despite the recently discovered etiology of the disease, the pathogenesis of the weakness is still unknown; iv) dominant mutations in a voltage-gated potassium channel expressed in the CNS cause episodic ataxia type 1 presumably by antagonizing repolarization of the cell membrane; v) dominant mutations in a neuronal calcium channel alpha-subunit may cause either episodic ataxia type II or familial hemiplegic migraine by a so far unknown pathomechanism; vi) the first mutation in an ion channel associated with an inherited form of epilepsy, nocturnal frontal lobe epilepsy, was found in the alpha(4)-subunit of a neuronal nicotinic acetylcholine receptor."
9.	Proteins (Proteins, Gene)FDA Link 03/01/2016 - "Herein, we critically evaluate the molecular and biophysical characteristics of the KV1.1 protein in comparison with others and discuss their role in the greater penetrance of KCNA1 mutations in humans leading to the neurological signs of episodic ataxia type 1 (EA1). " 04/01/2009 - "Interestingly, other mutations in the same protein cause the neurological disease episodic ataxia type 1. The authors show, using cells with heterologous expression of the wild-type and mutant channels, that the mutant channel is dysfunctional and speculate that Mg2+ wasting results from changes in apical membrane voltage along the nephron. "
10.	CalciumIBA 12/01/2000 - "Neuronal potassium channelopathies can cause familial benign neonatal convulsions and episodic ataxia type 1. Finally, neuronal calcium channelopathies can cause episodic ataxia type 2, familial hemiplegic migraine and spinocerebellar ataxia type 6. The clinical features, aetiology and pathogenesis of inherited voltage-gated ion channel disorders affecting muscle and the central nervous system are reviewed here." 01/01/2001 - "(1) Sodium channelopathies: familial generalized epilepsy with febrile seizures plus, hyperkalemic periodic paralysis, paramyotonias, hypokalemic periodic paralysis; (2) potassium channelopathies: benign infantile epilepsy, episodic ataxia type 1; (3) calcium channelopathies: episodic ataxia type 2, spinocerebellar ataxia type 6, familial hemiplegic migraine, hypokalemic periodic paralysis, central core disease, malignant hyperthermia syndrome, congenital stationary night blindness; (4) chloride channelopathies: myotonia congenitas; (5) ACh receptor channelopathies: autosomal dominant frontal lobe nocturnal epilepsy, congenital myasthenic syndromes; (6) glycine receptor channelopathies: hyperekplexia. "

Therapies and Procedures

1.	Therapeutics 01/01/2015 - "New insights into the pathogenesis and therapeutics of episodic ataxia type 1." 01/01/2023 - "kcna1a mutant zebrafish model episodic ataxia type 1 (EA1) with epilepsy and show response to first-line therapy carbamazepine."
2.	Feeding Methods 03/01/2016 - "Variants in CACNA1A that encodes the pore-forming α1-subunit of human voltage-gated Cav2.1 (P/Q-type) Ca(2+)channels cause several autosomal-dominant neurologic disorders, including familial hemiplegic migraine type 1, episodic ataxia type 2, and spinocerebellar ataxia type 6. To identify modifiers of incoordination in movement disorders, we performed a large-scale functional RNAi screen, using the Caenorhabditis elegansstrain CB55, which carries a truncating mutation in the unc-2gene, the worm ortholog for the human CACNA1A The screen was carried out by the feeding method in 96-well liquid culture format, using the ORFeome v1.1 feeding library, and time-lapse imaging of worms in liquid culture was used to assess changes in thrashing behavior. "