Classification
Megavitamin-B6 syndrome is characterized mainly by degeneration of dorsal root ganglion axons and cell bodies, although it also affects the trigeminal ganglia. It is classified as a sensory ganglionopathy due to involvement of these ganglia. In electrodiagnostic testing,
it has characteristic non-length-dependent abnormalities of sensory action potentials that occur globally, rather than distally decreasing of sensory nerve action potential amplitudes. Megavitamin-B6 syndrome is predominately a large fiber neuropathy characterized by sensory loss of joint position, vibration and ataxia. Although it has characteristics of small fiber neuropathy in severe cases where there is impairment of pain, temperature, and autonomic functions. Treatment
The primary treatment for megavitamin-B6 syndrome is to stop taking supplemental vitamin B6. Physical therapy, including vestibular rehabilitation, has been used in attempts to improve recovery following cessation of vitamin B6 supplementation. Medications such as amitriptyline have been used to help with neuropathic pain.In experimental tests using animal subjects, neurotrophic factors, specifically neurotrophin-3, were shown to potentially reverse the neuropathy caused from the vitamin B6 toxicity. With rats and mice, improvement has also been seen with 4-methylcatechol, a specific chicory extract, coffee and trigonelline. Prognosis
Other than with extremely high doses of vitamin B6, neurologic dysfunction improves following cessation of vitamin B6 supplementation and usually, but not always, resolves within six months.
Megavitamin-B6 syndrome has been reported in doses as low as 24 mg/day.Symptoms may also be dependent on the form of vitamin B6 taken in supplements. It has been proposed that vitamin B6 in supplements should be in pyridoxal or pyridoxal phosphate form rather than pyridoxine as these are thought to reduce the likelihood of toxicity. A tissue culture study, however, showed that all B6 vitamers that could be converted into active coenzymes (pyridoxal, pyridoxine and pyridoxamine) were neurotoxic at similar concentrations. It has been shown, in vivo, that supplementing with pyridoxal or pyridoxal phosphate increases pyridoxine concentrations in humans, meaning there are metabolic pathways from each vitamer of B6 to the all other forms. Consuming high amounts of vitamin B6 from food has not been reported to cause adverse effects.Early diagnosis and cessation of vitamin B6 supplementation can reduce the morbidity of the syndrome. Cause
While vitamin B6 is water-soluble, it has a half-life of 25–33 days and accumulates in the body where it is stored in muscle, plasma, the liver, red blood cells and bound to proteins in tissues. Potential mechanisms
The common supplemental form of vitamin B6, pyridoxine, is similar to pyridine which can be neurotoxic. Pyridoxine has limited transport across the blood–brain barrier explaining why the central nervous system is spared. Cell bodies of motor fibers are located within the spinal cord that is also restricted by the blood-brain barrier explaining why motor impairment is rare.