Timothy C. Hain, MD• Page last modified: March 20, 2021
Wernicke Encephalopathy (Wernickes) is an uncommon cause of dizziness, ataxia, and diplopia. It may be grossly under diagnosed, as autopsy series suggest that prevalence may be as high as 1% of the general population (Lidoe et al, 1989; Vege et al, 1991).
Classically it is due mostly to thiamine deficiency occurring in starvation, alcoholism, and occasionally from hyperemesis, anorexia nervosa, and bariatric or other gastric procedures (Haymaker, 1969). It is mainly encountered in alcoholics. Thiamine is a water soluble vitamin, which is difficult to avoid unless one has a very restricted diet. Classically, this usually means persons whose main diet is ethanol. Other risk factors are a diet mainly consisting of white rice, dialysis, chronic diarrhea, and taking of high doses of diuretics.
Wernickes can often be averted by providing persons of uncertain nutritional status in the emergency department with a bolus of thiamine in their first intravenous fluid administration. If Wernickes is precipitated, one should supplement with large amounts of thiamine (see treatment section).
We saw a case ourselves in a woman who was on a "diet pepsi" diet. 4 months of diet Pepsi, with nothing else. The lack of vitamins presumably provoked her dizziness and upbeating nystagmus.
Although there are more than 1000 papers in Pubmed with "Wernicke" in their title, almost all of what we know about Wernickes and dizziness comes from a tiny number of case reports (e.g. see Kattah et al, 2018).
Although there is a recent trend to drop the "'s" in syndromes named after a person, we will keep it in this discussion in any case. In literature published in other countries, and particularly in France, Wernicke's syndrome sometimes goes under the name of "Gayet-Wernicke". Presumably a matter of national pride. Wernicke's name is also on "Wernicke's aphasia", which is a type of speech and comprehension disturbance found in lesions in "Wernicke's area", which is in auditory cortex in the temporal lobe. Beriberi is another name for medical consequences of thiamine deficiency. There are two main types -- wet and dry. Wet beriberi affects the heart, while dry affects the nervous system. Wernickes is a form of dry beriberi.
From a pathology perspective, the widespread parts of the brain that are mainly affected include the mammillary bodies, periaqueductal area, the lamina quadrigeminal. Lesions, often hemorraghic, extend throughout the periventricular area, and are most prevalent in the floor of the 4th ventricle and wall of the 3rd. Accompanying these autopsy findings, may be evidence of central pontine myelinolysis.
These lesions of Wernickes may be related to glutamate excitotoxicity.
Wernickes presents characteristically with acute onset of apparent ocular muscle weakness (usually resembling bilateral 6th), nystagmus, ataxia, and confusion. Soon after this may be seen a short term memory disturbance including confabulation (i.e. attempts to fill in gaps in memory with guesses), and hallucinations. The amnestic dementia is called Korsakoff's syndrome. (Haymaker, 1969)
Sometimes the "diagnosis" is made by observing some fragment of the above somewhat vague neurological findings as well as an apparent response to Thiamine. We are dubious that this is good reasoning -- as perhaps the person just got better on their own.
Similar conditions to Wernickes are found as a consequence of many damaging conditions in neurology, such as encephalitis, and there are numerous papers that report mistaking another neurological condition for Wernickes due to Thiamine deficiency. We do not think that it is all that important to know that Neurologists make mistakes, but perhaps it is useful to be reminded that not all that "walks like a duck, quacks like a duck, etc", is a duck.
MRI imaging often show high signal on both T2 and Flair in the periaqueductal region and tectal plate. (Sparacia et al, 2017)
Flair image bordering the 3rd ventricle in the dorsomedial thalami (Santos Andrade et al, 2010).
Santos Andrade et al (2010) provide many imaging examples of Wernickes. They state that MR abnormalities are classically reported as bilateral and symmetrical lesions around the third ventricle, in the dorsomedial portions of the thalami and the periaqueductal region of the midbrain, characterized by high signal on T2. The interested reader is referred to this excellent article for more examples.
Nystagmus in Wernickes
Wernickes is a multifocal brain disorder. Thus the mechanism of Wernickes is central, not peripheral. Loss of function is generally from damage to neurons in the brainstem, or in the case of the memory loss, in the mammillary bodies of the hippocampus. Because Wernickes is multifocal, there are no "hard and fast" rules about what you will see.
In Wernickes, there is often gaze-evoked nystagmus, and acutely there may be upbeating nystagmus. Because Wernicke patients generally have very poor smooth pursuit, presumably from cerebellar damage associated with alcoholism, they are also generally unable to suppress their nystagmus in the light, making it rather obvious even without video nystagmography.
Kattah et al (2018) reported on 2 patients as well as a literature review including 11 more patients (including other causes of upbeating nystagmus than Wernickes), and suggest that conversion of upbeating nystagmus to downbeating nystagmus suggests that the etiology of the original upbeating nystagmus was Wernickes. In the author's experience with a Wernicke's patient (only one of the 20 described above), the nystagmus has a peculiar increase on downgaze (one would expect the opposite). Presumably this would implicate the neural integrator which controls vertical gaze holding.
Downbeating nystagmus can also be provoked in Wernickes by a variety of other maneuvers including convergence, positional changes, mastoid vibration, head-shaking, and changes in head position (Kattah et al, 2018).
Salzer et al (2019) reported bilateral loss of the horizontal vestibulo-ocular reflex in Wernickes. Lee et al (2018) suggested that selective impairment of the horizontal VOR may be a "common finding". We doubt that this is sensitive to Wernickes however, as Wernickes is a multifocal disorder. Presumably this appears due to damage to the vestibular nucleus, and not the vestibular nerves (Lee et al, 2018). Perhaps this explains the fairly high prevalence of bilateral vestibular loss and downbeating nystagmus. It would seem to us that thiamine supplementation would be prudent in everyone with unexplained bilateral vestibular weakness.
There is a short window where thiamine supplementation may reverse acute Wernickes. However, once there are dead neurons and bleeding, this is a "cows have escaped from the barn" situation. There is no medication or therapy that will get them back.
The usual thiamine recommendation for acute Wernickes is 500 mg IV, as often as three times/day. The duration recommended is variable - -some suggesting as long as 1-2 months. Given the argument above, and lack of controlled study, this is may be more wishful thinking than useful treatment, after the first few days. Thiamine supplementation probably helpful in preventing Wernickes in those with nutritional issues. In this situation, thiamine deficiency might be called "beriberi" as noted above.
Ott et al (2020) have offered a review of the clinical chemistry of Thiamine. They promise a subsequent paper with therapeutic recommendations.
- Haymaker, Webb. Bing's local diagnosis in neurological diseases. Mosby, 1969
- Kattah, J. C., et al. (2018). "Conversion of upbeat to downbeat nystagmus in Wernicke encephalopathy." Neurology 91(17): 790-796.
- Lee, S. H., et al. (2018). "Vestibular Dysfunction in Wernicke's Encephalopathy: Predominant Impairment of the Horizontal Semicircular Canals." Front Neurol 9: 141.
- Lindboe, C. F. and E. M. Loberg (1989). "Wernicke's encephalopathy in non-alcoholics. An autopsy study." J Neurol Sci 90(2): 125-129.
- Ott, M. and U. Werneke (2020). "Wernicke's encephalopathy - from basic science to clinical practice. Part 1: Understanding the role of thiamine." Ther Adv Psychopharmacol 10: 2045125320978106.
- Salzer, J., et al. (2019). "[Bilateral loss of the horizontal vestibulo-ocular reflex in Wernicke encephalopathy - a specific and early clinical sign]." Lakartidningen 116.
- Santos Andrade, C., et al. (2010). "Non-alcoholic Wernicke's encephalopathy: broadening the clinicoradiological spectrum." Br J Radiol 83(989): 437-446.
- Sparacia, G., et al. (2017). "Magnetic resonance imaging in the assessment of brain involvement in alcoholic and nonalcoholic Wernicke's encephalopathy." World J Radiol 9(2): 72-78.
- Vege, A., et al. (1991). "Wernicke's encephalopathy in an autopsy material obtained over a one-year period." APMIS 99(8): 755-758.