Introduction
Wernicke encephalopathy is characterized by the triad of ocular signs, cerebellar dysfunction, and confusion. It is a serious cranial neuropathy caused by vitamin B1 (thiamine) deficiency and is characterized by eye movement disorders, ataxia, memory impairment, and impaired consciousness. It is caused when thiamine supply is insufficient or malabsorption occurs, and it is mainly chronic. It frequently appears in alcoholics, but it can also occur due to hyperemesis gravidarum, chronic malnutrition, Crohn’s disease, malignant neoplasms, gastrointestinal resection surgery (including bariatric surgery), anorexia nervosa, chemotherapy-induced hyperemesis, and AIDS [
1-
3].
Bilateral hearing impairment associated with Wernicke encephalopathy is a seldom-documented occurrence, with its precise occurrence rate remaining unknown and only isolated instances being reported [
3-
6]. Previous studies examining Wernicke encephalopathy cases featuring hearing deficits have commonly observed lesions affecting the bilateral medial thalamus, with occasional instances of lesions in the inferior colliculus [
3]. This paper presents a case study involving a 57-year-old male who experienced a sudden onset of sensorineural hearing loss and vertigo, both of which were successfully resolved following treatment with high-dose intravenous thiamine therapy.
Case Report
On March 21, 2024, a 57-year-old man visited our hospital via the emergency department with suddenly-developed bilateral deafness and dizziness. He felt severe dizziness suddenly and was transferred via the primary outpatient clinic. During the time of transfer, he felt perceptual deafness in both ears. For about 10 years, he has experienced tinnitus resembling the sound of chirping crickets and buzzing insects. He stated that he got some degree of hearing impairment in both ears after military service in his twenties but could hear TV sounds and engage in telephone conversations in every day. His dizziness did not conform to vertigo, characterized by a spinning sensation, but rather manifested as a general sense of imbalance. His brother reported that a patient got chronic alcoholism and has been consuming alcohol frequently; however, his alcohol intake has decreased over the past week before admission.
In the neurological examination, the patient exhibited an alert mental status and clear consciousness. Korean Mini-Mental State Examination-2 (K-MMSE-2) revealed that he was partially oriented about time and place, but apathy and a subtle memory recall deficit were noticed (K-MMSE-2 score: 18). Because of bilateral perceptual deafness hindering verbal communication, he relied on written communication. Both ear canal and tympanic membrane were normal. No spontaneous nystagmus was observed in the neutral eye position. Attempts to examine gaze-evoked nystagmus through voluntary eye movements proved unsuccessful, as he displayed inability to move both eyes in any direction—up, down, left, or right. Finger-to-nose test showed left dysmetria and he showed ataxic gait.
To rule out central lesion of both sudden deafness, dizziness and ophthalmoplegia, carotid bifurcation three-dimensional computed tomography (3D CT) angiography as well as brain diffusion magnetic resonance imaging (MRI) were taken. CT showed asymmetric diffuse attenuation of the right middle cerebral artery M3 segment, suggestive of arteriosclerotic change rather than vasospasm but did not show any evidence of aneurysm or stenosis as well as mass-like lesion in the brain. MRI showed symmetrically increased signal intensity on T2-weighted/fluid-attenuated inversion recovery (T2/FLAIR) at the dorsomedial thalami (
Fig. 1D and E), inferior tectal plate (inferior colliculus) (
Fig. 1B), and periaqueductal grey matter within the dorsal midbrain (
Fig. 1A). It also showed diffusion-weighted image (DWI) high signal intensity in bilateral dorsomedial thalami and inferior tectal plate of dorsal midbrain (
Fig. 1B, D, and E). A few tiny and small nodular T2 hypersignal intensities were in both white matters. MRI suggested abnormal findings of Wernicke encephalopathy and minimal chronic ischemic changes (
Fig. 1). On blood tests, aspartate aminotransferase, direct bilirubin, and γ-glutamyl transpeptidase were slightly increased.
We concluded that his diagnosis was central deafness of sudden onset in both ears and dizziness, which resulted from Wernicke encephalopathy. On blood tests, a level of vitamin B1 (thiamine) was moderately lowered (15.4 µg/L; normal range, 28.0 to 85.0 µg/L). High-dose intravenous thiamine therapy commenced with intravenous administration of thiamine hydrochloride at a dosage of 500 mg three times a day.
On the day after high-dose intravenous thiamine therapy (hospital day 2), his symptoms of hearing, dizziness, and ophthalmoplegia were significantly improved. The fixation of extraocular muscles was improved but gaze-evoked nystagmus was found in all directions. He still showed left dysmetria on the finger-to-nose test. He could listen and talk freely in quiet as well as noisy environments. The dizziness has improved to the extent that he could walk unaided but ataxic gait still remained slightly. Pure tone audiometry revealed high-frequency sensorineural hearing loss in both ears (weighted four-frequency average: 38 dB HL in right ear and 28 dB HL in left) (
Fig. 2). Speech reception threshold was 30 dB HL in both ears and word recognition score was 60% at the presenting level of 60 dB in both ears. Most comfortable loudness level was 60 dB in both ears and uncomfortable level was 90 dB in both ears. Interestingly, the tolerance of pure tone was increased up to 120 dB, contrary to uncomfortable level of speech. Acoustic reflex appeared in both ears to ipsi- as well as contralateral stimulation at the loudness level of 85 to 100 dB HL. Transient otoacoustic emission as well as distortion product otoacoustic emission were partially abnormal in both ears, which might result from both high frequency hearing loss. The estimated hearing threshold based on auditory brainstem response and auditory steady-state response were correlated with threshold of pure tone audiometry. Auditory brainstem response using click sound showed that all waveform were clearly defined waves I to V but the latencies of wave V and interwave latency differences of wave I–V were abnormally delayed in right ear at the level of 90 dB nHL (the latencies of wave V were 6.41 ms in right ear and 6.12 ms in left and the interwave latency differences of wave I–V were 4.46 ms in right ear and 4.41 ms in left). Because of ophthalmoplegia, video-nystagmography (VNG) did not show that any eye movements did not occur in spontaneous nystagmus, positional nystagmus, head-shaking nystagmus, saccade, smooth pursuit, and optokinetic nystagmus tests (
Fig. 3). However, reflexive eye movements were shown in video head impulse test (vHIT), which revealed reduced gain without overt/covert corrective saccade in all semicircular canals, especially both vertical ones. Suppression head impulse (SHIMP) test also showed reduced gain without anticompensatory saccade in both lateral semicircular canals (
Fig. 4). Cervical vestibular evoked myogenic potential (cVEMP) and electrocochleography (ECoG) were within normal limit in both ears.
After 4 days of high-dose intravenous thiamine therapy, oral administration of thiamine hydrochloride at a dosage of 10 mg three times a day. He was discharged from the hospital on hospital day 6 and was getting vitamin B1 (thiamine), vitamin B12 (mecobalamin) and choline alfoscerate orally. On 1 months after the discharge (April 24, 2024), pure tone and speech audiometry did not show any interval change (weighted four-frequency average: 43 dB HL in right ear and 31 dB HL in left; speech reception threshold: 30 dB HL in both ears, word recognition score was 60% at the presenting level of 70 dB in right ears and was 80% at the presenting level of 60 dB in left ears). VNG revealed that there was no spontaneous nystagmus, gaze-evoked nystagmsus, head-shaking nystagmus, or positional/positioning nystagmus. There was no abnormality in saccade, smooth pursuit and optokinetic nystagmus tests. Bithermal caloric tests showed both vestibular weakness (6°/s for warm and 0°/s for cold in right ear; 0°/s for warm and 7°/s for cold irrigation in left ear). On vHIT, the gain was improved without overt/covert corrective saccade in five semicircular canals, except left lateral one. However, SHIMP test still showed reduced gain without anticompensatory saccade in both lateral semicircular canals. cVEMP and ECoG were within normal limit in both ears.
On 2 months after the discharge, he did not any audio-vestibular symptom, except both tinnitus, which persisted for about 10 years. He reported that his hearing had fully recovered to its pre-illness level. Follow-up of audio-vestibular tests was planned 2 months later.
Discussion
Because simultaneous bilateral sudden hearing loss is exceedingly rare, its evaluation process necessitates a meticulous examination to rule out known causal factors, particularly those warranting or treatable specific treatment. Bilateral sudden hearing loss typically arises from peripheral auditory organ lesions rather than central nervous system impairments [
7]. This phenomenon results from the transmission of sound stimuli in one ear via the auditory nerve to the brainstem, followed by the crossing of nerves at the trapezoid body and inferior colliculus, ultimately reaching the bilateral auditory cortex in the temporal lobe. Consequently, bilateral lesions affecting the brainstem or temporal lobe may lead to hearing deficits on both sides, albeit rarely observed. Notably, bilateral hearing loss in Wernicke encephalopathy represents a particularly uncommon manifestation, with its exact prevalence uncertain and sporadic cases documented. Because complete symptom triad (ophthalmoplegia, gait ataxia, and confusion) of Wernicke encephalopathy is observed in as few as one fifth of cases, the diagnostic protocols such as The European Federation of Neurological Societies (EFNS) guidelines advocate for a more inclusive approach, necessitating the presence of at least two out of four indicative signs (including dietary deficiencies, ocular manifestations, cerebellar dysfunction, and either altered mental status or mild cognitive impairment) [
8].
Previous studies on Wernicke encephalopathy-associated hearing loss have often identified lesions in the bilateral medial thalamus, with occasional involvement of the inferior colliculus [
3]. In our case, mild high-signal intensity lesions on MRI were observed in the dorsomedial thalami and inferior tectal plate. Many reports on Wernicke encephalopathy-associated hearing loss stated that the degree of hearing loss varied from mild to profound, and the type of audiogram also varied, including up-slope, down-slope, and trough shape [
1,
4,
5,
9-
12]. A comprehensive review of the literature revealed a total of 25 documented cases of Wernicke encephalopathy-associated sudden hearing loss across the world, including two cases in Korea [
2,
3,
5,
6,
10,
12-
14]. Lim, et al. [
10] reported a case of 54-year-old female with chronic malnutrition resulted from chemotherapy, which complaint poorer word discrimination out of proportion to pure tone loss. Bae, et al. [
3] reported a case of 74-year-old male with chronic malnutrition complicated after enterectomy, which complaint total perceptual deafness.
Ocular motor and vestibulo-ocular manifestations in Wernicke encephalopathy exhibit variability across reported cases. Notable findings encompass: 1) horizontal, bilateral gaze-evoked nystagmus; 2) bilateral hypofunction observed during bithermal caloric irrigation; 3) abnormal results on sinusoidal rotation chair test; 4) abnormal head impulse test primarily affecting the lateral semicircular canal; 5) ranging from normal to abnormal performance in saccadic movements, smooth pursuit, and optokinetic nystagmus tests; 6) normal subjective visual vertical; and 7) intact vestibular evoked myogenic potentials. Our cases showed that gain was reduced in horizontal (on SHIMP) as well as vertical semicircular canals (on vHIT) in both ears. Interestingly, the gain of vertical canals was more reduced than that of horizontal canals in vHIT, although many reports stated selective impairment of the horizontal semicircular canal, sparing of the vertical canals [
15,
16]. Our case emphasizes that SHIMP test can be as essential as vHIT for the diagnosis and should be applied in all patients with suspected Wernicke encephalopathy. In our case, despite the presence of ophthalmoplegia, gazeevoked nystagmus developed due to several reasons: 1) While ophthalmoplegia in Wernicke encephalopathy is often associated with lesions in the midbrain affecting the oculomotor nuclei, other brainstem structures involved in eye movement control may be spared or affected differently, leading to gazeevoked nystagmus. 2) In Wernicke encephalopathy, damage to the cerebellum can result in dysregulation of eye movements, including the development of nystagmus. 3) The overall disruption of neural signaling and coordination within the brain due to Wernicke encephalopathy can affect the control mechanisms for eye movements and result in abnormal patterns of eye movement, including nystagmus, even in the presence of ophthalmoplegia. 4) In some cases, gaze-evoked nystagmus may represent a compensatory mechanism to overcome the limitations imposed by ophthalmoplegia. However, since definitive conclusions cannot be derived from a single case, it is essential to compile related cases and conduct further analyses in future research.
In our case, cVEMP was not affected, consistent with the fact that otolith organs are not typically involved in Wernicke encephalopathy. While vestibular dysfunction can occur in Wernicke encephalopathy, it is more related to central vestibular pathways rather than direct involvement of the otolith organs in the inner ear. Kattah, et al. [
17] explained that information from the otolith organs may be processed abnormally in the projections from the medulla to cerebellar nodulus. They suggested that this could be one of the hypotheses for vertical nystagmus in Wernicke encephalopathy.
With the advancement of domestic living conditions, instances of nutritional deficiencies have become less conspicuous in Korea, resulting in a scarcity of reports or literature on the subject since the 1980s. Consequently, there is a notable absence of statistical data regarding the prevalence of thiamine deficiency in Korea. However, in countries such as Canada, Belgium, and Ireland, approximately 30% to 40% of hospitalized elderly patients or those living independently in their senior years are reportedly afflicted by thiamine deficiency. Similarly, in the United States, approximately 5% of the elderly population aged 60 and above are reported to experience thiamine deficiency. In a recent analysis conducted by the Health Insurance Review and Assessment Service (HIRA) in Korea, focusing on nutritional deficiencies and the treatment landscape for obesity over a five-year span (2017–2021), it was reported that the number of patients with thiamine deficiency increased notably by 13% in 2021 compared to 2017. Moreover, the study highlights that not only the prevalence but also the duration of medical visits and associated expenses were notably higher in cases of thiamine deficiency compared to other nutritional disorders. Because many patients with Wernicke encephalopathy may not be evaluated by neuro-otologists in most clinical situations, hearing loss or vestibular abnormalities cannot be noticed especially in non-encephalopathic cases of Wernicke encephalopathy, which may be difficult to diagnose.
In conclusion, neuro-otologists should know that sudden deafness of central type can occur in Wernicke encephalopathy or thiamine deficiency because thiamine deficiency can be easily developed. Thiamine deficiency can be frequently found in chronic alcoholics, but it can also occur in patients with chronic malnutrition, such as Crohn disease or malignant neoplasms. The gastrointestinal resection surgery, such as bariatric surgery, can be one of the main reasons for thiamine deficiency. As well as audiological tests, vHIT and SHIMP test should be applied in all patients suspected for Wernicke encephalopathy or thiamine deficiency.