Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028738 (nystagmus)
 7,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. Families with autosomal dominant EA represent at least two distinct clinical syndromes. One clinical type of EA (MIM 160120) includes individuals who have episodes of ataxia and dysarthria lasting seconds to minutes. In addition, myokymia (rippling of muscles, diagnosable by electromyography) is evident during and between attacks. Since K+ channel genes are candidate genes for EA, we tested markers near known K+ channel genes for linkage. Using a group of Genethon markers from one such region--chromosome 12p--we found evidence of linkage in four EA/myokymia families. A maximum combined lod score of 13.6 was obtained at theta = 0, with the marker D12S99. A human Ca++ channel gene, CACNL1A1, and three human K+ channel genes--KCNA5, KCNA6, and KCNA1--map close to D12S99, but the Ca++ channel gene is unlikely to be the site of the defect, because crossovers have been observed to occur between the disease gene and a CA-repeat marker located close to this gene. Studies of a large EA family with a different clinical phenotype (MIM 108500), which lacks myokymia but is associated with nystagmus, have excluded the gene causing that disease from the chromosome 12p locus.
 ...
PMID:A gene for episodic ataxia/myokymia maps to chromosome 12p13. 794 48

Cerebellar ataxia is a frequent and often disabling syndrome severely impairing motor functioning and quality of life. Patients suffer from reduced mobility, and restricted autonomy, experiencing an even lower quality of life than, e.g., stroke survivors. Aminopyridines have been demonstrated viable for the symptomatic treatment of certain forms of cerebellar ataxia. This article will give an outline of the present pharmacotherapy of different cerebellar disorders. As a current key-therapy for the treatment of downbeat nystagmus 4-aminopyridine (4-AP) is suggested for the treatment of downbeat nystagmus (5-10 mg Twice a day [TID]), a frequent type of persisting nystagmus, due to a compromise of the vestibulo-cerebellum. Studies with animals have demonstrated, that a nonselective blockage of voltage-gated potassium channels (mainly Kv1.5) increases Purkinje- cell (PC) excitability. In episodic ataxia type 2 (EA2), which is frequently caused by mutations of the PQ-calcium channel, the efficacy of 4-AP (5-10 mg TID) has been shown in a randomized controlled trial (RCT). 4-AP was well tolerated in the recommended dosages. 4-AP was also effective in elevating symptoms in cerebellar gait ataxia of different etiologies (2 case series). A new treatment option for cerebellar disease is the amino-acid acetyl-DL-leucine, which has significantly improved cerebellar symptoms in three case series. There are on-going randomized controlled trials for cerebellar ataxia (acetyl-DL-leucine vs placebo; ALCAT), cerebellar gait disorders (SR-form of 4-AP vs placebo; FACEG) and EA2 (sustained-release/SR-form of 4-AP vs acetazolamide vs placebo; EAT2TREAT), which will provide new insights into the pharmacological treatment of cerebellar disorders.
 ...
PMID:Aminopyridines and Acetyl-DL-leucine: New Therapies in Cerebellar Disorders. 3018 58