| Affiliation |
(AGL) Chairman, Department of Ophthalmology, The Methodist Hospital, Houston, Texas; Professor of Ophthalmology, Weill Cornell Medicine, New York City, New York; (VJ) Class of 2022, Baylor College of Medicine, Houston, Texas |
| Transcript |
Today, we are going be talking about the Wernicke syndrome. Wernicke (syndrome) is a deficiency state created by lack of Vitamin B1, and there are a number of circumstances where this could occur - even in a developed nation like the United States: the most common being, of course, the classic alcoholic patient who is not eating enough (Vitamin)-B enriched food and develops Wernicke (syndrome) because they're substituting empty calories of alcohol for a nutritious diet. However, you should have be aware that there are a number of non-alcohol related causes of the Wernicke syndrome and include anything that decreases the intake such as anorexia, bulimia, or hyperemesis gravity' in pregnancy, vomiting, or absorption problems which the most common is bariatric surgery. So, we should be thinking about Wernicke (syndrome) not just in alcoholic patients but in any patient where there could be decreased intake of vitamins or nausea or vomiting or poor absorption from most commonly bariatric surgery. The classic presentation to us in ophthalmology is either an acute or subacute nystagmus and it can be of any waveform but it's often upbeat or downbeat and any type and pattern of ophthalmic lesion - unilateral or bilateral but it's often looks like a six no palsy but it can be a horizontal gaze palsy and I and O, a sixth, and it can be vertical. So, the combination of an acute subacute nystagmus or ophthalmic lesion or both should prompt consideration for the Wernicke syndrome. and normally we would just give them thymine if they're at an at-risk population. Don't wait for the values to come back on the thymine. Don't wait on the imaging study. Don't wait on other approaches because the risk of giving someone thymine is super low. Now the traditional triad for the Wernicke (syndrome) includes mental status change and confusion but they can have other neurologic signs or symptoms because the other vitamins might also be decreased. So, don't let the presence of decreased vision or peripheral neuropathy which often accompanies B1 or B9 folate deficiencies sway you from treating the patient for Wernicke's because many of the same co-morbidities that caused the B1 to be deficient also can produce B12 and folate deficiency. So, loss of vision doesn't change our differential. It still could be Wernicke. Peripheral neuropathy doesn't change our differential. Aataxia doesn't change our differential. Weakness or numbness in the periphery doesn't change the differential. So, even though mental status change, memory loss, nystagmus, and ophthalmoplegia are characteristic features, they're not - they don't all have to be present and they can be present in other combinations and can be dissociated with the vision loss.; Normally, we want to give very high doses of B1 and using a parenteral approach. Intravenous, I prefer up to 300 to 500 milligrams of thymine for the first three days until we get some turnaround, and usually it turns around pretty quick. So it's both a diagnostic and a therapeutic test, and we want to make sure we're giving concomitant magnesium. The MRI scans often show hyper-intense signal density that involves the periaqueductal grey, accounting for the ophthalmic lesion and nystagmus, as well as the mammillary bodies and the medial thalami. But the absence of the MRI findings should not dissuade you from giving Vitamin B1 to patients suspected of having the Wernicke. In addition, one of the things that's dangerous about patients who have nausea or vomiting, like hyperemesis gravidarum, or are dehydrated/losing weight from bariatric surgery is that there's a temptation to give intravenous fluids, and what we don't want to do is pour glucose into the system, because if we pour glucose like D5W onto this patient who already has thymine deficiency will make them worse.; We have many neurologic manifestations from B1 deficiency, and, ironically, the thymine related pathways spell out ATP. So, the three thymine dependent pathways that you should be aware of are alpha ketoglutarate dehydrogenase, which is in the Krebs cycle, the transketolase pathway which is in the ribose 5-phosphate shunt, and pyruvate dehydrogenase. So, as you know pyruvate produces the entry molecule into the Krebs cycle which is Acetyl-CoA, and, if you don't have Acetyl-CoA, you cannot make acetylcholine, and core components of the myelin. So, we need that pyruvate dehydrogenase to produce pyruvate to enter into the Krebs cycle. In addition, the transketolase pathway is a building pathway or an anabolic pathway. The transketolase pathway is involved in the Ribose 5-Phosphate shunt which allows us to construct neurotransmitters, DNA, as well as redox agents like NADPH. So, the absence of transketolase will cause shutdown not only on the energy producing side - the glycolysis side - but in the building pathway for both ribonucleic acids and neurotransmitters. Finally, alpha-ketoglutarate dehydrogenase which is involved in the conversion of ketoglutarate into the Krebs cycle, where we not only get ATP but the glutarate is important for the formation of glutamate. That's important for the formation of GABA and Aspartate. Those inhibitory neurotransmitters (glutamate, GABA, and aspartate) are super important and if you disinhibit them you might get nystagmus. So, in summary, when you are dealing with a patient who has suspected Wernicke syndrome from Vitamin B1 deficiency regardless of origin - alcoholic bariatric surgery, anorexia nervosa, or hyperemesis gravity - just give them B1. Don't wait for the lab. Don't wait for the MRI. Just hit them hard with parenteral high-dose thymine and add magnesium as a cofactor. Don't give them glucose D5W without giving the thymine. Remember the three key pathways: alpha-ketoglutarate, transketolase, and pyruvate dehydrogenase, which ironically spells out ATP. |
