The continuous increase in the stroke thrombolysis rate and decrease in door-to-needle time in many countries were also associated with an increased risk of using thrombolytic therapy in stroke mimics (15). Patients with WKE as a stroke mimic have been reported before, but this is the first case we know of simulating an acute left hemispheric lesion with an atypical clinical presentation with right-side hemiparesis and aphasia, conjugate gaze palsy limited toward an apparent left frontal lobe lesion and lack of ataxia (16). Retrospectively, the memory deficits were surely present from the start, but they were difficult to assess due to language problems. Even though motor deficits have been described in WKE, they usually presented as tetraparesis, since the lesions are generally bilateral (17, 18). In cases where hemiparesis was reported, it was not associated with other signs of hemispheric deficits, presenting more often with diplopia, complex ophthalmoplegia or ataxia, and mimicking a vertebro-basilar stroke. Other reports of aphasia or unilateral hemiparesis are very few, with one case with acute onset of aphasia and limb ataxia in which the diagnosis was not supported by specific MRI changes and the second one presented with an acute confusional state, double vision and slight hemiparesis with normal speech and language (19). In the second case, typical WKE lesions in the medial thalamus and contrast enhancement of the mamillary bodies were associated with a small area of restricted diffusion of the left precentral gyrus, but that could have been a postictal marker, as the patient also presented generalized tonic-clonic seizures (20). Another case presented with stroke-like left occipitotemporal cortical lesions similar to those encountered in mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (21).
The correlation between alcohol consumption and the decrease in thiamine availability has long been established. It has been proven that alcohol harms thiamine absorption and storage (22). Additionally, in alcoholic patients, the phosphorylation of thiamine is impaired in both the central and peripheral nervous systems (23). Thiamine is a key cofactor for three enzymes: transketolase, pyruvate dehydrogenase (PDH), and alpha-ketoglutarate dehydrogenase (α-KGDH) which have complex implications in metabolic circuits with roles in adenosine triphosphate (ATP), neurotransmitters (acetylcholine, glutamate, gamma-aminobutyric acid) and myelin synthesis. Decreases in the activity of PDH and α-KGDH can result in reduced ATP synthesis, increased oxidative stress, glutamate-mediated excitotoxicity, apoptosis, and various degrees of inflammation, which in turn can contribute to cell damage and death (24–26). Histologically, cytotoxic and vasogenic edema are present initially, and necrosis ensues if the deficit persists. Impaired energy metabolism induces dysfunction of the cell electrolyte homeostasis and accumulation of lactate, alanine, and glutamate at cytotoxic levels, processes that result in cytotoxic edema. In conjunction with the low pH and glutamate excitotoxicity, ATP depletion also damages the astrocytes, and the brain-blood barrier becomes dysfunctional, with associated vasogenic edema (23, 24, 27).
The MRI is of particular importance in the diagnosis of WKE and differential diagnosis. It usually reveals bilateral and T2/FLAIR hyperintensities, with a symmetrical distribution affecting the medial thalami, mamillary bodies, and periaqueductal region. As was the situation in our case, anomalies in these areas are typical and can help in establishing the correct diagnosis even if extensive cerebral involvement is also present (25, 28). Additionally, similar lesions in the brainstem, cerebellum, thalamus, red nuclei, caudate nuclei, splenium, and cerebral cortex have been described in the literature in alcoholic and nonalcoholic patients (11, 29). Atrophy of the mamillary bodies may be absent initially but is a typical finding (30).
DWI/ADC can show variable patterns. Cytotoxic edema in ischemic stroke presents with a high DWI signal, with corresponding low ADC, but up to 6.8% of acute ischemic stroke can be DWI negative. (31). Unlike acute ischemic stroke, in WKE, this high DWI signal does not always correspond to irreversible neuronal damage, and part of DWI hyperintensity could be due to the T2 shine-through effect (25, 28). In both stroke and WKE, the mechanism of the cytotoxic edema is impaired cellular energy metabolism, which restricts membrane transport of water and electrolytes. Nevertheless, in WKE, the slow development of metabolic dysfunction allows the cells to adapt and increases survival time. Additionally, the pentose phosphate shunt pathway, which has a neuroprotective role in acute ischemia, seems to remain functional in WKE even when the thiamine deficit is severe, constituting a metabolic reserve for the affected cells (32, 33).
DWI may show only slightly increased signal intensities within the thalami and periaqueductal area, but no significant changes in signal intensity in the other affected brain areas (33). In most cases of acute ischemic stroke in the corresponding areas of high DWI, there are decreased ADC values. In WKE patients the ADC in lesional areas has a variable pattern, from normal to various degrees of reduction, but generally less than that in most cases of ischemic stroke, although there is no clear cutoff value to differentiate them (25, 28).
MRI can also reveal areas with high ADC signal and variable DWI signal, which reflect vasogenic edema secondary to the dysfunction of the blood-brain barrier (BBB) (34). Contrast enhancement can be present in approximately half of the cases, revealing the areas where the BBB is severely disrupted (25). These MRI anomalies tend to regress with adequate treatment (35–38).
In our patient, lesions were also present in the high frontal cortex bilaterally, a distribution that is rarely encountered. Available data suggest that patients with cortical lesions have a worse prognosis, especially when contrast enhancement is present (39). Despite the severe clinical and radiological findings at admission, he made an excellent, even if delayed, recovery with complete remission of motor, language, and cognitive deficits in approximately eight weeks.