Journal of the Neurological Sciences 323 (2012) 77–79
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Journal of the Neurological Sciences
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Evolution of abnormal eye movements in Wernicke's encephalopathy: Correlationwith serial MRI findings
Kitae Kim a, Dong Hoon Shin a,⁎, Yeong-Bae Lee a, Kee-Hyung Park a, Hyeon-Mi Park a,Dong-Jin Shin a, Ji-Soo Kim b
a Department of Neurology, Gachon University Gil Medical Center, Incheon, South Koreab Department of Neurology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
⁎ Corresponding author at: Department of Neurology,ty, 1198, Guwol-Dong, Namdong-Gu, Incheon, 405‐760,3346; fax: +83 32 460 3344.
A 33-year-old woman with Wernicke's encephalopathy (WE) due to poor oral intake after allogeneic stemcell transplantation for acute myeloid leukemia showed a sequential development of bilateral gaze-evokednystagmus (GEN), rightward gaze palsy, and upbeat nystagmus. Initial MRIs obtained when she had GENonly showed a lesion involving the medullary tegmentum, and follow-up MRIs revealed additional lesionsin the pontine and midbrain tegmentum along with development of rightward gaze palsy, and finally bilat-eral medial thalamus lesions in association with upbeat nystagmus. The evolution of abnormal ocular motorfindings and serial MRI changes in our patient with WE provide imaging evidence on relative vulnerability ofthe neural structures, and on the progression of lesions and ocular motor findings in thiamine deficiency.
Wernicke's encephalopathy (WE) is characterized by a triad ofconfusion, ophthalmoplegia, and ataxia due to vitamin B1 (thiamine)deficiency [1]. Thiamine is a cofactor for three major enzymes (thepyruvate dehydrogenase complex, α-ketoglutarate dehydrogenase,and transketolase) that are involved in cellular energy metabolism[2]. Accordingly, thiamine deficiency is known to preferentially affectthe brain structures with high thiamine turnover rates and high rateof oxidative metabolism under normal physiological conditions,which include the medial dorsal thalamic nuclei, superior vermis ofthe cerebellum, periaqueductal region, and the pontine tegmentum[3–5].
In WE, abnormal ocular motor findings include gaze-evoked nys-tagmus (GEN), central positional nystagmus, abduction paresis,internuclear ophthalmoplegia, and horizontal or vertical gaze palsyto total ophthalmoplegia [1,6,7]. However, the evolution of abnormalocular motility has rarely been described in WE [7]. Furthermore, nostudy has attempted to correlate the evolutions between the abnor-mal ocular motilities and imaging findings. Herein, we describe serialchanges in ophthalmoplegia along with MRI findings in a patient withWE. This study provides imaging evidence on the pathophysiologyunderlying the evolution of ophthalmoplegia in WE.
Gil Hospital, Gachon Universi-South Korea. Tel.: +82 32 460
).
l rights reserved.
2. Case report
A 33-year-old woman underwent allogeneic stem cell transplan-tation (SCT) for acute myeloid leukemia in March 2012, which wasfollowed by intravenous cyclosporine A in order to preventgraft-versus-host reactions. Since then she had suffered from generalweakness and poor oral intake, and was referred to the neurologic de-partment for evaluation of progressive vertigo, oscillopsia, andtruncal ataxia 30 days after SCT. At that time, examination showedonly bilateral GEN without spontaneous nystagmus or limitation ofeye motion. Horizontal smooth pursuit, saccades, and head impulseappeared to be intact. The remainder of the neurological examinationwas normal except for the presence of truncal ataxia. Complete bloodcounts showed anemia (hemoglobin at 8.9 g/dL) and thrombocytope-nia (platelet counts of 45000/mm3), but routine blood chemistry andcerebrospinal fluid examination were unrevealing. Magnetic reso-nance imaging (MRI) disclosed a symmetric lesion involving the bi-lateral tegmentum of the medulla (Fig. 1). Even though we did notmeasure the serum thiamine level, the patient received intravenousinfusion of thiamine 50 mg per day with a consideration of WE.Four days after initiation of daily thiamine infusion, the patient con-tinued to report vertigo, oscillopsia, and ataxia, and examination re-vealed an interval development of rightward paresis of saccades andsmooth pursuit, which was partially overcome by passive head mo-tion (visually enhanced vestibulo-ocular reflex). Repeated MRIs atthat time revealed an extension of the lesion from the medulla tothe bilateral tegmentum of the pons and the midbrain. A week later,the vertigo and ataxia improved slightly with resolution of rightwardgaze paresis. However, the patient had newly developed upbeat
Fig. 1. Serial MRIs. A. The initial MRIs show an isolated lesion involving bilateral medullary tegmentum along with horizontal GEN. B. Four days later, the follow-up MRIs revealadditional lesions in the pons and midbrain with an expansion of the previous medullary lesion. C. Final MRIs, taken when the patient develop upbeat nystagmus, disclose newlesions in the bilateral medial thalami while the pre-existing lesions in the medulla, pons, and midbrain are almost resolved.
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nystagmus, and repeated MRI disclosed new lesions involving the bi-lateral medial thalami while the previous pontine and midbrain le-sions were almost resolved. Fifteen days after initiation of thiamineinjection, the vertigo and ataxia were almost resolved in the presenceof mild horizontal GEN.
3. Discussion
Our patient with WE showed a sequential development of hori-zontal GEN, rightward gaze paresis, and upbeat nystagmus alongwith serial changes in the MRI lesions.
Initial horizontal GEN was observed with the MRI lesion involvingthe medullary tegmentum. GEN may be ascribed to a deficient neuralintegrator that normally guarantees sustained eye position signals,thereby making it possible to hold the eyes steady in the eccentricgaze. The neural integrator for horizontal conjugate eye movementsresides in the nucleus prepositus hypoglossi, medial vestibular nucle-us, and flocculus. The initial medullary lesion observed on MRIs corre-sponds to the area of the nucleus prepositus hypoglossi and medialvestibular nucleus, and is well correlated with dysfunction of the neu-ral integrator as the mechanism of GEN.
The patient subsequently developed rightward gaze palsy alongwith additional MRI lesions involving both sides of the pontine andmidbrain tegmentum. Horizontal gaze palsy may be observed in le-sions involving the paramedian pontine reticular formation (PPRF)or the abducens nucleus. While selective damage to the PPRF givesrise to ipsiversive saccade palsy, lesions involving the abducens nu-cleus cause ipsiversive palsies of all saccades, smooth pursuit, andvestibulo-ocular reflex. Furthermore, saccades returning to the center
from the gaze in the opposite direction are also slow in the PPRF le-sions while these are relatively spared in lesions involving theabducens nucleus. Associated facial palsy is the rule in the abducensnuclear lesions since the facial fascicles encircle the nucleus beforethey exit the brainstem in the pontomedullary junction. In our patient,the paresis of the horizontal smooth pursuit and vestibulo-ocular reflexaswell as saccades suggests involvement of the abducens nucleus and/orthe PPRF [9]. The selective rightward gaze paresis indicates more severedamage to the right abducens nucleus/PPRF even though theMRI lesionsappeared to be symmetrical.
Finally, our patient developed upbeat nystagmus in associationwith new lesions in the bilateral medial thalami and with near com-plete resolution of the previous lesions in the medulla, pons, andmid-brain. Upbeat nystagmus mostly occurs in focal brainstem lesions,usually when the lesions are located in the medulla or brachiumconjunctivum [10–12]. However, upbeat nystagmus has also beenreported in lesions involving the thalamus [8,12]. In thalamic lesions,the upbeat nystagmus may be ascribed to concurrent damage to theinterstitial nucleus of Cajal that is a neural integrator for verticaland torsional eye motion and is located just below the thalamus,even though the resolution of the MRI did not allow the identificationof an INC lesion in our patient.
Our patient showed sequential involvement of the neural struc-tures, which are known to be vulnerable to thiamine deficiency,along with evolution of abnormal ocular motilities. The ocularmotor findings observed in our patient are similar to those in mon-keys with thiamine deficiency and in patients with WE [5]. In our pa-tient, even with intravenous supplementation of thiamine at a dose of50 mg per day, the ophthalmoplegia was aggravated along with the
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evolution of MRI lesions. Even though the recommended doses of thi-amine replacement have been varied for WE in the literature [13,14],the experience with our patient is in favor of the more higher doses.
This study provides imaging evidence on the neural structuresvulnerable to thiamine deficiency and of the neural substrates re-sponsible for each abnormal ocular motility observed in WE.
Conflict of interest
The authors report no conflicts of interest.
Appendix A. Supplementary data
Supplementary data to this article can be found online at http://dx.doi.org/10.1016/j.jns.2012.08.014.
References
[1] Harper CG, Giles M, Finlay-Jones R. Clinical signs in the Wernicke–Korsakoff com-plex: a retrospective analysis of 131 cases diagnosed at necropsy. J NeurolNeurosurg Psychiatry 1986;49:341-5.
[2] Todd KG, Butterworth RF. Mechanisms of selective neuronal cell death due to thi-amine deficiency. Ann N Y Acad Sci 1999;893:404-11.
[3] Rindi G, Patrini C, Comincioli V, Reggiani C. Thiamine content and turnover rates ofsome rat nervous regions, using labeled thiamine as a tracer. Brain Res 1980;181:369-80.
[4] Hawkins RA, Mans AM, Davis DW, Vina J, Hibbard L. Cerebral glucose use mea-sured with [14C] glucose labeled in the 1, 2, or 6 position. Am J Physiol Cell Physiol1985;248:C170-6.
[5] Cogan DG, Witt ED, Goldman-Rakic PS. Ocular signs in thiamine-deficient mon-keys and in Wernicke's disease in humans. Arch Ophthalmol 1985;103:1212-20.
[7] Choi KD, Oh SY, Kim HJ, Kim JS. The vestibulo-ocular reflexes during head impulsein Wernicke's encephalopathy. J Neurol Neurosurg Psychiatry 2007;78:1161-2.
[8] Shin BS, Oh SY, Kim JS, Lee H, Kim EJ, Hwang SB. Upbeat nystagmus changes todownbeat nystagmus with upward gaze in a patient withWernicke's encephalop-athy. J Neurol Sci 2010;298:145-7.
[9] Hirose G, Furui K, Yoshioka A, Sakai K. Unilateral conjugate gaze palsy due to a le-sion of the abducens nucleus: clinical and neuroradiological correlations. J ClinNeuroophthalmol 1993;13:54-8.
[10] Janssen J, Larner A, Morris H, Bronstein AM, Farmer SF. Upbeat nystagmus:clinicoanatomical correlation. J Neurol Neurosurg Psychiatry 1998;65:380-1.
[11] Pierrot-Deseilligny C, Milea D. Vertical nystagmus: clinical facts and hypotheses.Brain 2005;128:1237-46.
[12] Kim JS, Yoon B, Choi KD, Oh SY, Park SH, Kim BK. Upbeat nystagmus: clinicoanatomicalcorrelations in 15 patients. J Clin Neurol 2006;2:58-65.
[13] Ropper AH, Samuel MA. Adams and Victor's principles of neurology. 9th ed.McGraw-Hill Professional; 2009. p. 1113.
[14] Galvin R, Bråthen G, Ivashynka A, Hillbom M, Tanasescu R, Leone M. EFNS guide-lines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur JNeurol 2010;17:1408-18.
