Episodic ataxia (EA) is a rare hereditary autosomal dominant disorder which is caused by genetic defects that result in impairment of specific nerve fibers that carry messages to and from the brain to control the movement of the body. EA is defined by intermittent episodes or symptoms that can vary in duration and frequency, lasting from minutes to days, consisting of dizziness, unsteadiness, abnormal posturing, ringing in the ears, and at times paralysis on one side of the body.
Episodic ataxias are also known as “channelopathies”.
Episodes of ataxia and other symptoms can start anytime from early childhood to adulthood. Precipitating causes for EA attacks can be associated with environmental factors such as alcohol, emotional stress, illness, caffeine, physical activity, fatigue, exposure to paint thinners, and certain medications like phenytoin. The frequency and length of attacks vary and may range from several per day to one or several per year. Some affected individuals continue to experience ataxia and/or nystagmus or involuntary eye movements between episodes and these may worsen over time.
EA affected individuals may also experience progressive cerebellar degenerative conditions which are symptoms of either spinocerebellar ataxia or familial hemiplegic migraine.
Episodic ataxia is a genetic disorder, which means that it is an inherited disease.
The defective gene responsible for this condition is passed along from one generation to another generation by family members who are carriers if the defective genes. The genetic defect may also occur spontaneously. Genetic diseases take place when one of the body’s 20,000 genes does not work properly.
There are currently 8 known types of episodic ataxia and each type has various causes, symptoms, age of onset and even duration of attacks. The EA types are labeled using “EA” and the number in the order of their discovery, ie EA1, EA2, etc.
2What are the Causes and Symptoms of Episodic Ataxia?
Episodic ataxia may be caused by sequence changes in several different genes.
These causes vary per type of episodic ataxia. The different symptoms of EA are due to dysfunction of different areas.
Symptoms of episodic ataxia can vary depending on an individual and his/her family.
The most frequent symptoms are episodes of ataxia or problems with balance and coordination and dysarthria or unclear speech interspersed with periods of normal or nearly normal neurological function. The attacks may be brought about by rapid changes in posture, excitement, exercise, or, in some cases, high-carbohydrate meals.
Individuals with episodic ataxia have recurring episodes of symptoms such as ataxia or poor balance and coordination. During these bouts, many patients also experience migraine headaches, dizziness or vertigo, slurred speech, double or blurred vision, nausea and vomiting, and tinnitus or ringing in the ears. Paralysis that affects one side of the body, seizures, and muscle weakness, may also happen during attacks. Some individuals with EA tend to have myokymia, a muscle abnormality that occurs during or between episodes. This abnormality can cause stiffness, muscle cramping, and continuous, fine muscle twitching.
The major symptoms of episodic ataxia are ataxia and progressive, inter-attack weakness, ataxia, and dystonia. The symptoms are mostly of cerebellar origin. Purkinje cells, which integrate sensory and cortical inhibitory and excitatory inputs, can be found at the core of the cerebellum, There is a huge merging of synaptic activity onto each Purkinje cell, with input from noradrenergic fibers, mossy fibers, climbing fibers, and parallel fibers. Abnormalities in any of these components of the brain can cause ataxia and cerebellar dysfunction.
3Types of Episodic Ataxia
- Episodic ataxia type 1 (EA1)
CAUSE: due to sequence changes in KCNA1 gene that encodes a channel for potassium to move in and out of brain cells
SYMPTOMS: stiffness, ataxia or loss of coordination and balance, myokymia or muscle twitching, double vision, headache, contractions and tightening of muscles, difficulty speaking or breathing, or nausea
ONSET: childhood or teenage years
ATTACK DURATION: several seconds to several minutes per episode, episodes may occur several times in a day or only a few times a month
- Episodic ataxia type 2 (EA2)
CAUSE: due to sequence changes in CACNA1A gene that encodes a channel for calcium to move in and out of brain cells; episodes may be triggered by alcohol, caffeine, exertion, or stress
SYMPTOMS: similar to symptoms of EA1, involuntary jerky eye movement and ataxia may be experienced in between episodes, migraine, shrinking of vermis in the cerebellum
ONSET: childhood or teenage years
ATTACK DURATION: hours and can last for days
- Episodic ataxia type 3 (EA3)
CAUSE: found in one Mennonite family for which the genetic defect maps to 1q42
SYMPTOMS: dizziness, vertigo, ringing in the ears
ONSET: childhood to adulthood
ATTACK DURATION: minutes to hours
- Episodic ataxia type 4 (EA4)
SYMPTOMS: rapid eye movements, occasional epilepsy, and ringing in the ears
ONSET: between 3rd to 6th decade
ATTACK DURATION: brief
- Episodic ataxia type 5 (EA5) with seizures
SYMPTOMS: seizures, rapid eye movements, epilepsy
ONSET: childhood or teenage years
ATTACK DURATION: hours
- Episodic ataxia type 6 (EA6) associated with
SYMPTOMS: a migraine, hemiplegia, seizures
ONSET: age 5
ATTACK DURATION: hours to days
- Episodic ataxia type 7 (EA7) of adult onset in one family for which the genetic defect maps to 19q13
- Episodic ataxia type 8 (EA8) of infantile-onset in one family for which the genetic defect maps to 1p36.13-p.34.3
- Episodic ataxia with paroxysmal choreoathetosis and spasticity
- Episodic ataxia of late-onset after the 6th decade typically with no family history, slow progression, and poor responsiveness to acetazolamide
4How is Episodic Ataxia diagnosed?
A neurologist is a specialist who is the most helpful in diagnosing episodic ataxia.
The neurologist evaluates a patient’s medical history, the family’s medical history, and also possibly electromyography findings. After checking the medical history, a neurologist performs a thorough neurological examination to determine whether a patient showcases typical symptoms of episodic ataxia.
Genetic testing may also be another way to help diagnose EA and this is available on a research basis at different laboratories.
5How is Episodic Ataxia treated?
There is currently no known cure for episodic ataxia but there are several drugs that have been reported to improve symptoms. The attacks may respond to medicines such as acetazolamide (Diamox), topiramate (Topamax) or 4-aminopyridine (Ampyra). These drugs are to be taken under doctor’s prescription.