Ataxias

Question 1

What is pathophysiology behind episodic ataxia type 2?

Answer 1

Episodic ataxia type 2 (EA2) is an autosomal dominant calcium channelopathy caused by a mutation in CACNA1A which encodes the Ca(v)2.1 subunit of the P/Q-type calcium channel and is primarily expressed in Purkinje cells.

Question 2

How does episodic ataxia type 2 present?

Answer 2

Spells are characterized by ataxia, which may be accompanied by vertigo, diplopia, dysarthria, and generalized weakness. Can be provoked by physical exertion or emotional stress.

Question 3

What would you look for on neurological exam between attacks in patients with episodic ataxia type 2?

Answer 3

Between spells, patients often demonstrate persistent nystagmus, often downbeating.

Question 4

How do you treat episodic ataxia type 2?

Answer 4

Acetazolamide and 4-aminopyridine are reported to decrease severity and frequency of spells.
How do they work?
Acetazolamide 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.

Question 5

How long do episodes of ataxia last in episodic ataxia type 2?

Answer 5

Attacks last hours to days

Question 6

What might you see on imaging in episodic ataxia type 2?

Answer 6

With disease progression, there might be slight atrophy of midline cerebellar structures.

Question 7

Half of patients with episodic ataxia type 2 will also have what other condition?

Answer 7

Migraines

Question 8

At what age does episodic ataxia type 2 present?

Answer 8

In childhood or early adulthood usually

Question 9

At what age does episodic ataxia type 1 usually present?

Answer 9

In early childhood

Question 10

What is the pathophysiology of episodic ataxia type 1?

Answer 10

It is autosomally inherited, caused by a mutation in the KCNA1 gene, which encodes the voltage-gated potassium channel KV1.1,

KV1.1 is expressed heavily in basket cells and interneurons that form GABAergic synapses on Purkinje cells. The channels aid in the repolarization phase of action potentials, thus affecting inhibitory input into Purkinje cells and, thereby, all motor output from the cerebellum. EA1 is an example of a synaptopathy.

Question 11

What is myokymia and in what condition is it seen?

Answer 11

Myokymia is an involuntary, spontaneous, localized quivering of a few muscles, or bundles within a muscle, but which are insufficient to move a joint. The term is commonly used to describe eyelid twitching. Seen in episodic ataxia type 1 between and during attacks.

Question 12

What are some other names by which episodic ataxia type 1 is known by?

Answer 12

This disorder is also known as episodic ataxia with myokymia (EAM), hereditary paroxysmal ataxia with neuromyotonia and Isaacs-Mertens syndrome.

Question 13

How does episodic ataxia type 1 usually present?

Answer 13

Attacks characterized by seconds to minutes-lasting attacks including gait incoordination, limb ataxia, truncal instability, dysarthria, nystagmus, tremor, and occasionally seizures, but also persistent neuromuscular symptoms like myokymia or neuromyotonia. These episodes can occur up to 30 times per day. Can be bought on by fatigue, caffeine, or emotional or physical stress.

Question 14

What condition frequently co-exists in patients with episodic ataxia type 1?

Answer 14

Epilepsy

Question 15

What are the treatment options for episodic ataxia type 1?

Answer 15

After diagnosis, EA is typically treated with anticonvulsant/antiseizure medication. Acetazolamide is one of the most common drugs in the treatment of EA1 and EA2, though it’s more effective in treating EA2.

Alternative medications used to treat EA1 include carbamazepine and valproic acid.

Question 16

what does CANVAS stand for?

Answer 16

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome

Question 17

What is the clinical picture of CANVAS?

Answer 17

CANVAS is a late-onset progressive ataxia, which tends to progress slowly. It is commonly characterised by imbalance, sensory neuronopathy (damage to the sensory nerves), bilateral vestibulopathy (damage to the balance portions of both inner ears), and chronic cough.

Question 18

At what age does CANVAS tend to present?

Answer 18

middle age

Question 19

What features should you look for in diagnosing CANVAS?

Answer 19

The diagnosis of CANVAS is challenging because patients will typically have a nonspecific presentation, most commonly with gait imbalance and falls, often worse in the dark. Less commonly, they may present with dysesthesias or oscillopsia. On physical examination, each of the three hallmark features of CANVAS can be demonstrated: cerebellar ataxia, non-length-dependent sensory neuronopathy (ganglionopathy), and bilateral vestibulopathy. In addition to the classic triad, other commonly associated signs and symptoms include postural hypotension, dysphagia, and chronic cough.