By Dr. Dipanjan Bhattacharjee, MD
Intention of the manuscript
The present day management guidelines of Wernicke’s Encephalopathy (WE) are primarily centered around alcoholic patients. However, given the recent emergence of a plethora of reports of WE in a non-alcoholic background, these strategies need to be revised. Utilizing a case report of WE in a patient suffering from Hepatitis A, we have attempted to take another look at the management strategies of WE in patients, especially those without any history of alcoholism.
Key take-home messages of the manuscript
Firstly, WE amongst non-alcoholics may present with non-specific symptomatology, rather than the classical triad of ataxia, oculomotor abnormalities, and altered mentation. Secondly, even a suspicion of WE on the grounds of clinical findings necessitates prompt correction with intravenous thiamine supplementation, irrespective of the laboratory or radiological confirmation of the diagnosis of WE. Thirdly, even low dose thiamine supplementation of 100-200mg in the case of non-alcoholics can yield equi-efficacious results to that seen with higher thiamine doses (500mg thrice daily) administered to the alcoholics. Finally, thiamine supplementation should continue until the elimination of the pre-disposing factor in order to prevent any relapses.
Impact on clinical practice
Recent reports of a rise in the incidence of WE in a non-alcoholic background has served to illustrate the various precipitating conditions for WE. This bears extreme significance for the clinicians as the majority of the non-alcoholic WE patients may present to them with non-specific symptoms like nausea and vomiting along with the features of the underlying precipitating conditions, for instance, pancreatitis, peptic ulcer disease, starvation, chemotherapy and Hepatitis A as in our patient. Very often, all the features of WE’s clinical triad – ataxia, oculomotor abnormalities and altered mentation may not be present. This may end up confounding the diagnosis, leading to the physicians overlooking WE. Hence, it would be extremely pertinent for the physicians to be aware of the possibility of the development of WE even in the presence of any one of the features of the clinical triad of WE symptoms. Amongst the classical triad of WE, the one manifestation that could raise the suspicion of WE in a non-alcoholic patient background, would be altered mentation, which again concurs with the findings of an extensive 2015 systematic review of WE.
Additionally, the myriad presentations observed in non-alcoholic WE patients, raises the stakes of a meticulous history-taking, as it could easily serve up clues about the precipitating disease. Further, zeroing in on to the instigating condition of WE is of extreme significance as the treatment via thiamine supplementation has to continue until the precipitating condition has been eliminated. This is critical to preventing relapses as well as mitigating the progression of WE to Korsakoff’s psychosis.
It must be remembered that unlike alcoholic patients, arriving upon the diagnosis of WE in the case of non-alcoholic WE patients is not a straight-forward affair. Hence, even the slightest clinical suspicion of WE is grounds enough to initiate treatment with intravenous thiamine. Prompt thiamine supplementation is of utmost significance as the slightest delay could lead to an irreversible brain damage. Further, the unavailability of laboratory tests like serum thiamine and erythrocyte thiamine transketolase levels or imaging via computed tomography (CT) or magnetic resonance imaging (MRI) cannot be the reason for a delay in treatment. These investigations occupy a secondary position in the pecking order when compared to clinical evaluation for the diagnosis of WE. This could partly be due to the fact that the laboratory tests may not be truly reflective of the thiamine deficits in the brain. Moreover, radiological imaging may not be available, especially in resource-constrained settings. Among both, MRI has been observed to be more sensitive, especially in the case of non-alcoholics WE patients. Additionally, the site of brain lesions in non-alcoholic WE patients involving cerebellum, vermis, cranial nerve nuclei, red nuclei, dentate nuclei, caudate nuclei, splenium, and cortex differ from that of alcoholic WE patients, which may also provide a clue towards WE in atypical presentations. However, it must be re-emphasised that the radiological findings can act only in a substantiative capacity. Presently, the onus of the diagnosis of WE, more so in the case of non-alcoholic patients lies squarely on clinical evaluation.
Finally, it has been observed that a lower dose of thiamine (100-200mg thrice daily) may be sufficient in order to reverse the thiamine deficit in the case of non-alcoholic WE patients as compared to the higher 500mg thrice daily dose used in alcoholics. Despite there being no consensus yet, over the optimal thiamine dose in case of non-alcoholic WE patients, there is a line of thinking that believes that alcoholics are prone towards suffering from sub-clinical episodes of WE or excess glutamate discharge due to the co-existent alcohol withdrawal syndrome. This, in turn, produces a far greater brain damage, thereby necessitating a higher thiamine dose. However, as stated before, this is an area in WE management that is still open for further research.
Scope for future studies
In the imminent future, there is a need to carry out well-designed randomized controlled trials (RCTs) to ascertain the optimal dose and regimen of thiamine supplementation in case of non-alcoholic WE patients. Further, in light of the difficulties faced in establishing the diagnosis of the underlying precipitating conditions for WE in non-alcoholic patients, there may emerge a need for diagnostic algorithms in the near future. These formulaic approaches could help bypass the time delay arising from the arbitrariness of the clinical acumen of the physicians and help prevent relapses and progression of WE. Further, the role of thiamine prophylaxis is another gray area, which can offer scope for further studies.
Link to the original paper
Jayaprakash B, Rao KN, Patil N, Bhattacharjee D, Maden M, Rau NR.(2016) Wernicke’s Encephalopathy – ‘Pushing the Envelope’ of Patient’s Profile: A Case Report. Ann Neurosci. 2016;23:188-193. doi: 10.1159/000449186.