Serial Examination and Evolution of Horizontal Gaze Palsy in Thiamine Deficiency

Neurology consult of patient with hearing loss following vertical band sleeve gastroplasty. See associated video: https://collections.lib.utah.edu/details?id=1512438

Serial Examination and Evolution of Horizontal Gaze Palsy in Thiamine Deficiency Nyce, M. , Chisholm J., Szmanda J., Kattah JC Any questions or comments , please address to Jorge C Kattah, M.D. [e-mail] BACKGROUND • The bilateral medial vestibular nucleus and prepositus hypoglossi nucleus may be the earliest brainstem nuclei affected in thiamine deficiency • If identified in time, patients at this early stage may be nonencephalopathic. Timely treatment would likely restore function rapidly • The typical Wernicke's Encephalopathy (WE) triad of encephalopathy, ataxia and nystagmus is infrequent • The Caine's criteria suggest that nutritional deficiency and two triad components increased diagnostic sensitivity substantially 1. Choi KD, Oh SY, Kim HJ, Kim JS. The vestibulo-ocular reflexes during head impulse in Wernicke's encephalopathy. J Neurol Neurosurg Psychiatry 2007;78:1161-1162 2. Kattah JC, Dhanani S, Pula JH, Mantokoudis G, Therani AS, Newman Toker DE. Vestibular signs in non-encephalopathic Wernicke's disease. Neurol Clin Practice 2013;3:460-467. 3. Caine D, Halliday GM, Krill JJ, Harper CG. Operational criteria for the classification of chronic alcoholics: identification of Wernicke's encephalopathy. Journal of neurology, neurosurgery, and psychiatry 1997;62:51-60. BACKGROUND • Rapid response to timely administration of thiamine usually restores neurologic function in patients with nutritional depletion • Studies that involved a large number of thiamine deficient patients in the past, identified improvement of gaze palsy, abducens palsy and nystagmus in patients with thiamine deficiency 1. De Wardener H. E., Lennox B. Cerebral beriberi (Wernicke's encephalopathy); review of 52 cases in a Singapore prisoner-of-war hospital. Lancet 1947;1:11-17. 2. Victor M, Adams R, Collins G. The Wernicke Korsakoff Syndrome: F. A. Davis Company, 1971. Acute External Ophthalmoplegia is Uncommon in WE • Reported in one of the first three patients described by Carl Wernicke in 1881. • Not present in 245 patients reported by Victor, Adams and Collins in 1978 • Present in a recent report , but sparing UP GAZE. See below Won Jae Kim, Myung Mi Kim. Korean J Ophthalmol 2017;31(4):372-374 https://doi.org/10.3341/kjo.2017.0014 Patient Presentation • 64 year- old Caucasian woman with a vertical band sleeve gastroplasty performed in 1990. After her operation, she was never able to eat well; in the early summer, 2019, she developed recurrent daily vomiting , became hypokalemic and required potassium supplementation. She was admitted to the Internal Medicine Department on 09-08-2019 with an acute encephalopathy; even though she was awake, she answered slowly, could not provide a history, and was disoriented. In addition, her husband felt that new hearing loss contributed to her confusion. She could not stand or sit without support. A Neurology consult was sought to investigate a cause for her encephalopathy. CLINICALLY ENCEPHALOPATHIC. COULD NOT SIT WITHOUT ASSISTANCE Attempt to look RIGHT Straight Gaze and attempted up gaze Left Gaze Initially, lack of cooperation was the presumed cause for her inability to move the eyes. However, she followed other simple motor commands correctly, thus it became clear that she had a total right greater and partial left gaze palsy. She did not have vertical eye movements ( not photographed) . Pupils were spared and there was no ptosis. In gaze right, she had absent saccades , pursuit and VOR, the left medial rectus contracted about 5 degrees to the right, the right abducens did not contract. In left gaze, saccades and pursuit were absent, the left VOR showed slow movement to the Left gaze (which was restricted) .A serum level of thiamine was obtained, and intravenous replacement began immediately. She received 500 mg, i.v., three times daily for three days Ophthalmoplegia. CLINICAL COURSE 24 HOUR EXAMINATION: AFTER INTRAVENOUS THIAMINE VIDEO FIRST SECTION: NOTE IMPROVED LEFT GAZE., NOTE NORMAL RANGE OF MOTION IN LEFT GAZE. OBSERVE LEFT GAZE HOLDING FAILURE: GAZE PARETIC NYSTAGMUS. RIGHT GAZE IMPROVED SLIGHTLY 72 HOUR EXAMINATION, 48 AFTER INITIIATION OF THIIAMINE ADMINISTRATION VIDEO SECOND SECTION ; NOTE LEFT GAZE PARETIC NYSTAGMUS. SHE NOW HAS FULL ROM IN RIGHT GAZE AND GAZE PARETIC NYSTAGMUS. THERE IS NO PHORIA DETECTED WITH RED GLASS TEST. THE HORIZONTAL HEAD IMPULSE TEST IS ABNORMAL, AND THE VERTICAL NORMAL 5 DAYS AFTER DAILY ADMINISTRATION OF THIAMINE: NORMAL RIGHT AND LEFT GAZE, RESOLUTION OF BILATERAL GAZE PARETIC NYSTAGMUS. ORTHOPHORIC WITH CROSSCOVER EXAMINATION IN STRAIGHT, LATERAL AND VERTICAL GAZE POSITIONS. THE HEAD IMPULSE TEST APPEARS CLINICALLY NORMAL BECAUSE THERE ARE COVERT SACCADES , THE HORIZONATAL VOR GAIN IS BILATERALLY DECREASED 3 MONTH EXAM : THE ENCEPHALOPATHY RESOLVED . SHE HAS ONLY A VAGUE RECOLLECTION OF THE EVENTS THAT TRANSPIRED DURING HER ADMISSION. THE HORIZONTAL VOR GAIN IS BILATERALLY DECREASED. SHE WALKS WITH A WIDE BASE SHORT DISTANCES HEARING LOSS CLINICAL COURSE CENTRAL HEARING LOSS THE SPEECH DISCRIMINATION SCORES WERE VERY POOR. BEYOND THE ANTIICPATED FOR THE PURE TONE TRESHOLDS Outpatient audiogram completed on 12/4/19 Inpatient audiogram completed on 9/19/19 Word Recognition Testing Inpatient (9/19/19) Outpatient (12/4/19) Right Ear 20% at 90 dBtesting HL wasRight Ear with 84%recorded (good) atNU-6 80 dB HL lists *All(very wordpoor) recognition completed word Left Ear 34% (very poor) at 90 dB HL Binaural 54% (poor) at 85 dB HL Left Ear 88% (good) at 80 dB HL HEARING LOSS ASSOCIATED WITH WE SUMMARY PANEL A September 2019 • Moderately severe hearing loss in low frequencies • Severe hearing loss in high frequencies • Speech discrimination: Right 20 %, Left 34% PANEL B December 2019 • Improved low frequency hearing loss (~ 30 Db Improvement) • Severe hearing loss in high frequencies • Speech discrimination: Right: 84%, Left 88% High frequency was probably pre-existent , at least to some extent HEARING LOSS IN WE • First described in the last 25 years , probably unrecognized, may contribute to the encephalopathy • Audiometry when measured shows low and high frequency loss • Signal changes in the inferior colliculus have been reported (not seen in this case). The second most common site affected is the medial thalami • In experimental primate thiamine deficiency the most common targets are the inferior colliculi and the medial vestibular nuclei Witt, et al Intermittent thiamine deficiency in the rhesus monkey. I. Progression of neurological signs and neuroanatomical lesions. Annals of neurology 1983;13:376-395. Walker MA, Zepeda R, Afari HA, Cohen AB. Hearing loss in Wernicke encephalopathy. Neurol Clin Pract 2014;4:511-515. DISCUSSION HEARING LOSS AND SPEECH DISCRIMINATION • There are a handful of reports of hearing loss and near deafness in Wernicke's Encephalopathy. One case documented palinacousis (echoing of the patient's own and others voice), during the acute stage of WE • The usual documented targets of thiamine deficiency relevant to hearing loss include the medial geniculate bodies and the inferior colliculi • In our case, low-frequency hearing loss and speech discrimination was acutely affected, and improved with treatment. Is this a primary cochlear deficit? The substantial word recognition deficit suggests central localization (cochlear nuclei, inferior colliculi and medial geniculate body) 1. Zhang S Q, et al. Acute bilateral deafness as the fist symptom of Wernicke's Encephalopathy. AJNR, 2012: 33: E44-E45 2. Walker MA. Hearing Loss in Wernicke's Encephalopathy . Neurol Clin Pract 2014; 1: 511-515 3. Nguyen J, T. , et al Wernicke's encephalopathy, hearing loss and palinacousis. In Med J. 2019;49:536-539 VESTIBULAR LOSS CLINICAL COURSE Normal gain: 0.7 Note that the vHIT was performed after the ophthalmoplegia resolved. The patient was orthophoric in all gaze positions prior to testing. The latest Video does not show corrective saccades in response to decreased VIR gain, They Are covert vHIT: 12 -04-2019 : Note decreased horizontal and normal vertical VOR gain Bilateral Vestibular Loss Clinical Course • It is possible to diagnose thiamine deficiency in the early stage in a patient at risk for malnutrition and immediate treatment may prevent the development of the full triad. (Always check serum levels before treatment). In consideration of possible serious mimickers such as encephalitis, toxic states, paraneoplastic syndromes, etc.; routinely pre-treatment serum thiamine levels will be helpful in decision making . If normal, you must focus on a different diagnosis. • Utilize Caine's diagnostic criteria. We expand on this concept and suggest that any patient with malnutrition , acute, symmetric bilateral vestibular loss or bilateral gaze paretic nystagmus should be evaluated for thiamine deficiency. • Our patient had the complete WE triad, though nystagmus was not present because of the horizontal gaze palsy, she developed it in follow up, this was previously pointed in the Victor M, et al, series. Our patient's chronic B1 deficiency may be the reason for persistently impaired medial vestibular nuclei function. The last video does not show the corrective saccade (they are covert), the average gain is ~ 0.5 DWI MRI 09-11-2019 Note increased DWI signal in medial thalami, there were also increased periaqueductal changes, the findings were present in axial T2 FLAIR as well. Did not see changes in the sixth nerve , medial vestibular or prepositus hypoglossi nuclei , no change noted after contrast administration Summary: Ocular Motor, Vestibular and Auditory findings • Rapid response to timely administration of thiamine usually restores neurologic function in patients with nutritional depletion • Large WE series in the past identified improvement of gaze palsy, abducens palsy and nystagmus • Here , we documented the transition from near complete external ophthalmoplegia without ptosis to normal vertical gaze and bilateral horizontal gaze paretic nystagmus • The sequence of horizontal gaze deficits suggest compromise of the bilateral abducens nuclei; initially minimal left adduction was possible (5 degrees), this suggest that cholinergic abducens neurons were probably more affected initially than glutamatergic interneurons within the sixth nerve nucleus • Once there was improvement of the sixth nerve nucleus neurons, it was superseded by gaze holding failure and once ocular motor function improved , we found evidence of bilateral vestibular loss. • Central hearing loss and speech discrimination impairment may be an underestimated contributor to the acute encephalopathy 1. De Wardener H. E., Lennox B. Cerebral beriberi (Wernicke's encephalopathy); review of 52 cases in a Singapore prisoner-of-war hospital. Lancet 1947;1:11-17. 2. Victor M, Adams R, Collins G. The Wernicke Korsakoff Syndrome: F. A. Davis Company, 1971.