Conversion of upbeat to downbeat nystagmus in Wernicke encephalopathy

Abstract

ObjectiveTo explain (1) why an initial upbeat nystagmus (UBN) converts to a permanent downbeat nystagmus (DBN) in Wernicke encephalopathy (WE) and (2) why convergence and certain vestibular provocative maneuvers may transiently switch UBN to DBN.MethodsFollowing a literature review and study of our 2 patients, we develop hypotheses for the unusual patterns of vertical nystagmus in WE.ResultsOur overarching hypothesis is that there is a selective vulnerability and a selective recovery from thiamine deficiency of neurons within brainstem gaze-holding networks. Furthermore, since the circuits affected in WE are commonly paraventricular, especially medially, just under the floor of the fourth ventricle where lie structures important for control of vertical gaze, we suggest the patterns of involvement in WE also reflect a breakdown in vulnerable areas of the blood–brain barrier. Many of the initial deficits of our patients improved over time, but their DBN did not. Irreversible changes in paramedian tract neurons, which project to the cerebellar flocculus, may be the cause. Here we suggest that conversion of UBN to permanent DBN points to thiamine deficiency and may argue for a chronic, nonprogressive DBN/truncal ataxia syndrome. Finally, we posit that the transient switch of UBN to DBN reflects abnormal processing of otolith information about linear acceleration, and often points to a diagnosis of WE.ConclusionRecognizing the unusual patterns of transient switching and then permanent conversion of UBN to DBN in WE is vital since long-term disability from WE may be prevented by timely, parenteral high-dose thiamine.

Nystagmus characteristics of healthy controls

“…Episodic Ataxia (Type II) may be associated with interictal spontaneous down-beating nystagmus [15]. Spontaneous up-beating nystagmus is rare and has been described in Wernicke's encephalopathy [16] and lesions within the paramedian medulla [8]. Lying in the supine position may also provoke or enhance nystagmus generated by Chiari malformation or posterior fossa space occupying lesions [4,7,17,19,31,36].…”

Consensus Paper. Cerebellar Reserve: From Cerebellar Physiology to Cerebellar Disorders

“…Deficiency of thiamine results in glutamatergic neurotoxicity and subsequent cell damage, more vulnerably in the vestibular nuclei, causing the impairment in cerebellar function that is mediated by the brainstem vestibular nuclei. Fortunately, there is a therapeutic window over which supplementation of thiamine reverses the ocular motor dysfunction in patients with pre-encephalopathy stage of thiamine deficiency [88,89]. The molecular and physiological underpinnings of thiamine deficiency and secondary functional reserve have been identified.…”

Primary Position Upbeat Nystagmus with Low Serum Vitamin B12

“…Our patient uniquely demonstrated transition from upbeat nystagmus to downbeat nystagmus. There have been several reports of transition from upbeat to downbeat nystagmus due to Wernicke's encephalopathy and other diseases ( 16 - 21 ). Although the mechanisms underlying the change in the vertical nystagmus direction are unknown, some reports suggest the involvement of an imbalance in tonic vertical vestibuloocular signals and the influence of gravity over the time course ( 13 , 18 , 20 ).…”

“…Although the mechanisms underlying the change in the vertical nystagmus direction are unknown, some reports suggest the involvement of an imbalance in tonic vertical vestibuloocular signals and the influence of gravity over the time course ( 13 , 18 , 20 ). Others have suggested that improvement of metabolic brainstem lesions may unmask underlying downbeat nystagmus due to persisting cerebellar dysfunction ( 17 , 21 ). Kattah et al proposed that, in Wernicke's encephalopathy, the neurons that were selectively vulnerable to thiamin deficiency lying along the midline of the pons and medulla exhibited persistent impairment, leading to a shift toward downbeat nystagmus, after transiently damaged neurons in the medulla had recovered ( 21 ).…”