Human exposure seems to be most common via consumption of commonly harvested shellfish such as clams, oysters, and mussels, although it has been proposed that exposure to lower levels of brevetoxins can take place following the consumption of certain planktivorous fish. Toxins will typically be found in the flesh of shellfish for up to 2–8 weeks following a HAB event, however there have been reports of toxin retention for nearly one year post-bloom. Notably, brevetoxins are tasteless and odorless and cannot be eradicated by rinsing, cleaning, cooking, freezing, or application of acid. To date, there is no reasonable means of preventing the uptake of toxins by shellfish, nor of removing the toxins from shellfish after harvest. Biochemistry/Toxicology
Brevetoxins are a group of greater than ten lipid-soluble cyclic polyethers that bind to a specific site on the voltage-gated sodium channel (VGSC), leading to an influx of sodium ions into the cell. This results in activation of nerves and spontaneous nerve cell membrane depolarization and firing. Due to their lipid-solubility, brevetoxins are able to pass through cell membranes and cross the blood-brain barrier. They are metabolized primarily by the liver and are excreted in the bile, although it is thought that urinary excretion plays a role in toxin clearance as well. Additionally, brevetoxins can bind a separate site on VGSCs, causing release of neurotransmitters (such as acetylcholine), resulting in tracheal smooth muscle contraction and widespread mast cell degranulation. Presentation and Diagnosis
Diagnosis of NSP is made based on clinical presentation as well as history findings including recent consumption of shellfish.
EA4
Also known as periodic vestibulocerebellar ataxia, type-4 episodic ataxia (EA4) is an extremely rare form of episodic ataxia differentiated from other forms by onset in the third to sixth generation of life, defective smooth pursuit and gaze-evoked nystagmus. Patients also present with vertigo and ataxia. There are only two known families with EA4, both located in North Carolina. The locus for EA4 is unknown. EA5: CACNB4
There are two known families with type-5 episodic ataxia (EA5).These patients can present with an overlapping phenotype of ataxia and seizures similar to juvenile myoclonic epilepsy. In fact, juvenile myoclonic epilepsy and EA5 are allelic and produce proteins with similar dysfunction.Patients with pure EA5 present with recurrent episodes of ataxia with vertigo. Between attacks they have nystagmus and dysarthria. These patients are responsive to acetazolamide. Both juvenile myoclonic epilepsy and EA5 are a result of mutations in CACNB4, a gene that encodes the calcium channel β4 subunit. This subunit coassembles with α-subunits and produces channels that slowly inactivate after opening.EA5 patients have a cysteine to phenylalanine mutation at position 104.Thus results in channels with 30% greater current than wild-type. As this subunit is expressed in the cerebellum, it is assumed that such increased current results in neuronal hyperexcitability
Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. EA6: SLC1A3
Type-6 episodic ataxia (EA6) is a rare form of episodic ataxia, identified initially in a 10-year-old boy who first presented with 30 minute bouts of decreased muscle tone during infancy.