Channelopathies

 

Glycine gated Cl channel

 

Strychnine blocks

- symptoms:

            - agitation, confusion

            - muscle spasms and stiffness

            - rhabdo, myoglobinuria, renal/resp failure

            - tetanus not a channelopathy

 

Kyperekplexia

- dominant inheritance > recessive

- rigidity with unexpected stimuli

- responds to clonazepam

 

Voltage gated Na channel

 

Multifocal motor neuropathy

- anti-GM1 antibodies block Na channels

- MMN and GBS can have this

 

Ciguatera toxin

- from dinoflagellates

- saxitoxin

- interferes with Na channels

- paralytic shellfish poisoning from mussels, crabs, oysters, lobster in NE US

- tetradotoxin from pufferfish

- neurotoxic shellfish poisoning from oysters, clams, mussels in SE US

- onset of paresthesias in 15min-12hrs (lips, tongues, limbs)

- "temperature reversal" - cold feels burning

- itchy, dental pain, muscle ache

- weakness can occur with respiratory failure

- decr LOC later

- always has GI upset, can have hypoTN, arrhythmia

- NCS like GBS

- Management: first 24h worst, supportive measures. Can continue persistent issues for years. IV mannitol sometimes used, with ?benefit.

 

Other biol poisons

- Black Mamba (K channel)

- rattlesnake venom (K channel)

- tarantula poison (K channel)

- scorpion against K, Na, Cl

- sea anemone, snail toxins(Na channel)

 

Familial erythromelalgia

- "reverse Raynauds"

- red feet > hands, pain

- cold improves

- autosomal dominant

- Na channel genetic cause

 

Neuromyotonia

- usually acquired

- continues peripheral nerve-caused muscle activation

- can lead to contractures

- also called Isaac's, Morvan's (with cognitive involvement, generalized myokymia (incorrect)

- onset can be GBS-like or slow neurodegenerative-like

- autoimmune - thymoma high incidence

- K channel antibodies in 25-50% (sometimes also seen in limbic encephalitis)

- anecdotal - PLEX, IVIG, steroids, cy

 

Episodic ataxia

- with myokymia usually

- K channel

- acetazolamide may be helpful

 

Episodic ataxia II

- onset in 2nd decade

- hours long spells

- Ca channel

- inter-attack signs

- acetazolamide may be helpful

- same gene as fam hemiplegic migraine and CADASIL

 

Lambert-Eaton Syndrome

- anti-VGCC antibodies

- underlying neoplasm in 2/3

- Ca channel blocked, preventing ACh release

- treatment is to control K channel

- fetal AChR has gamma subunit, adult form has epsilon subunit

 

Congenital myasthenic syndromes CAN be channelopathy or not.

- slow channel syndromes - Na channel remains open, sometimes because of prolonged ACh binding. Not fatiguable.

- fast channel syndromes - Na channel not open for enough time, or too long to open - ocular, bulbar disorder and fatiguability

 

Myotonic channelopathies

 

Myotonia congenita

- dominant or recessive

- warm up effect

- percussion myotonia

- Cl channel

 

Paramyotonia congenita (von Eulenburg)

- cold provokes

- weakness spells after myotonia

- not related to myotonia congenita

- Na channel

- worsens with K

- Mexiletene tx - Na block

 

Periodic paralysis

- hours to days

- rest post-work induces

- potassium not always elevated or lowered

- hyperkalemic form also induced by K load

- EMG helpful

- hypokalemic more severe - can worsen over years, worst in AM