Episodic ataxia: attacks of unsteadiness, causes and treatment

Ataxia means a lack of coordination, usually showing as unsteadiness when walking, clumsy movements and slurred speech. Ataxia UK describes ataxia as an umbrella term for a group of neurological disorders affecting balance, coordination and speech. Most people think of ataxia as constant. In episodic ataxia, the problem comes in bouts. The Genomics Education Programme (GeNotes) describes it as a rare form of hereditary ataxia in which a central nervous system channelopathy presents with distinct episodes of incoordination and imbalance.

A channelopathy is a problem with the tiny channels that let charged particles in and out of nerve cells. In episodic ataxia, genes that are involved in neurotransmission and neuronal excitability are affected. This is why attacks can start and settle completely, and why some people feel close to normal in between.

GeNotes says eight subtypes have been described clinically, although there is significant overlap between them and genetic confirmation is advised. Ataxia UK notes that there are several types but that types 1 and 2 are the best understood, and both occur in families and are inherited in an autosomal dominant manner.

GeNotes describes the core features during an episode as ataxia, dysarthria (slurred or unclear speech) and nystagmus (involuntary eye movements). Other features can include sweating, vertigo, headache, muscle stiffness or weakness, rippling of the muscle (myokymia), dystonia, tremor, double vision, hemiplegia, nausea, vomiting and tinnitus.

Between attacks some people have no symptoms, but GeNotes notes that interictal features such as ataxia, myokymia or gaze-evoked nystagmus may be present and can be progressive, that epilepsy or intellectual disability can be present, and that joint contractures can develop as a complication. Brain imaging may show cerebellar vermis atrophy.

A recognisable trigger is common. GeNotes lists emotional stress, physical exertion, environmental temperature, caffeine, alcohol and sudden movement. Ataxia UK's guidance for clinicians advises helping people to identify and avoid common triggers such as stress, caffeine, alcohol and excessive physical exertion.

Diagnosis starts with the clinical story: repeated, stereotyped attacks with a clear start and finish, a family history, and a normal or near-normal examination between attacks in some people. GeNotes states that episodic ataxia is primarily a clinical diagnosis, so the absence of a causative variant on genomic testing does not exclude it.

Genetic testing is used to confirm the type. GeNotes says the genomic testing currently available will identify a causative variant in the majority of those assessed. It highlights that the choice of test matters: whole genome sequencing may not detect multi-exon deletions or duplications, which are picked up by a technique called MLPA, and that the NHS panel R66 Paroxysmal central nervous system disorders includes sequencing and MLPA of the known episodic ataxia genes. Because genes involved in other conditions, including progressive ataxia syndromes, metabolic conditions, epilepsy syndromes and mitochondrial conditions, can also present with episodic features, a broader differential is considered when features are atypical.

There is no cure, but attacks can often be reduced. Ataxia UK's clinical guidance says that acetazolamide, a carbonic-anhydrase inhibitor, is used as a first-line drug for the prevention or reduction in frequency of episodic ataxia attacks, and recommends it as first line in types 1 and 2, although not all patients respond. GeNotes notes that symptomatic drug management may involve off-licence prescription of acetazolamide or anti-epileptic medications.

The guidance is candid about side effects and monitoring. It says long-term acetazolamide is associated with dose-related side effects such as kidney stones, gastrointestinal symptoms, tingling, muscle twitching and fatigue, and advises patients to keep hydrated to prevent kidney stones and to have annual ultrasound screening of the urinary tract. A previous sulphonamide allergy is not an absolute contraindication but needs caution and surveillance.

If acetazolamide does not help in episodic ataxia type 2, the guidance says to consider 4-aminopyridine as a second-line drug on a named patient basis, noting that at the time of its writing it was not licensed for episodic ataxia in the UK. Dichlorphenamide, which some clinicians used previously, is no longer available in the UK.

Day-to-day management centres on understanding your own triggers, pacing activity, and planning for the possibility of an attack, for example when driving or working at heights. Your neurologist can advise on safety for your circumstances. Because attacks can be unpredictable, many people find a diary of attacks and possible triggers helpful when reviewing treatment.

Because the types described by GeNotes are inherited in an autosomal dominant pattern, a child of an affected parent has a 1 in 2 (50%) chance of inheriting the gene variant. GeNotes also notes that incomplete penetrance occurs, which means not everyone who has the variant develops the condition, and that de novo variants (new in the individual) have been reported. Clinical genetics services can discuss testing for relatives and options in pregnancy.

Suspected episodic ataxia is usually assessed by a neurologist, with referral to a specialist ataxia service and clinical genetics where available. Ataxia UK lists specialist ataxia centres on its website, and GeNotes points clinicians to the NHS England National Genomic Test Directory for the relevant panel (R66, paroxysmal central nervous system disorders).

A private neurology opinion can speed up an initial assessment or brain imaging, but treatment decisions such as acetazolamide monitoring and genetic testing sit best within a coordinated specialist service. Whoever you see, ask them to share their findings with your GP and NHS neurologist.