Downbeat Nystagmus: Etiology and Comorbidity in 117 Patients
Abstract & Commentary
By Erik J. Kobylarz, MD, PhD Assistant Professor of Neurology and Neuroscience, Weill Cornell Medical College, Cornell University Dr. Kobylarz reports no financial relationship relevant to this field of study.
Synopsis: With improved diagnostic techniques, the etiologic spectrum of downbeat nystagmus can be further refined.
Source: Wagner JN, Glaser M, Brandt T, et al. Downbeat nystagmus: aetiology and comorbidity in 117 patients. J Neurol Neurosurg Psychiatry 2008;79:672-677.
Wagner and colleagues retrospectively reviewed 117 cases of downbeat nystagmus (DBN) to determine whether retrospective analysis of this large dataset with improved diagnostic techniques would reduce the large number of cases that are diagnosed as "idiopathic," and to better define the etiologies for this unusual physical finding.
The investigators reviewed medical records of all patients in their Neurological Dizziness Unit diagnosed with DBN over a 14-year period, only including patients with documented brain MRIs. The evaluation of these cases included a detailed medical and family history (including vertigo and gait unsteadiness), standardized neurological, neuro-otological and neuro-ophthalmological examination (including detailed oculomotor and vestibular examinations) and electronystagmography, brainstem auditory evoked potentials, audiogram, EMG/NCV (electromyogram/nerve conduction velocity), and serum and CSF assays, if appropriate.
In 72 patients (62%), a specific etiology for DBN could be identified ("secondary DBN"). The most common causes included cerebellar degeneration (n=23), cerebellar ischemia (n=10), and craniocervical malformations with cerebellar ectopia (n=8). In 45 patients (38%), no cause was found ("idiopathic DBN"). For both idiopathic and secondary DBN, there was a high comorbidity with bilateral vestibulopathy (36%) as well as an association with polyneuropathy and cerebellar ataxia, even without identified cerebellar pathology on MRI. Patients with idiopathic DBN (mean age = 67 years) were older than those with secondary DBN (mean age = 59 years, p<0.001).
DBN is still often classified as idiopathic despite improved diagnostic techniques. However, this group further classified idiopathic DBN into three subgroups: "pure" DBN (n=17), "cerebellar" DBN (cerebellar signs without cerebellar pathology on MRI, n=6), and "syndromatic" DBN with at least two of the following characteristics: bilateral vestibulopathy, cerebellar signs (i.e., limb ataxia and dysarthria), and peripheral neuropathy (n=16). They concluded that the latter could be caused by a multisystem neurodegenerative process.
Commentary
DBN is the most common form of acquired involuntary ocular oscillations of central origin that is very often associated with other oculomotor disorders, such as impairment of horizontal and vertical smooth pursuit, vertical optokinetic reflex, and/or visual fixation suppression of the horizontal vestibulo-ocular reflex. This disorder can be caused by vestibulocerebellar, and rarely bilateral, paramedian brainstem lesions. The pathophysiology of DBN remains controversial. Proposed mechanisms include asymmetrical peripheral vestibular input, central imbalance of the vertical vestibulo-ocular system, and a mismatch of the coordinated saccadic burst generator and the neural eye velocity-position integrator. The diverse etiology of DBN includes craniocervical malformations, cerebellar degeneration, vascular lesions, inflammatory disease, and medication intoxication (e.g., anticonvulsants, lithium). Patients most commonly present with gait unsteadiness or horizontal vertigo (idiopathic 89%, secondary 81%).
The authors conclude that in their retrospective study, despite improved diagnostic means, the percentage of patients with so-called "idiopathic" DBN remains high (38%). These results are consistent with prior studies with smaller sample sizes.1,2 However, there were several major findings of this particular study. Wagner et al found an association of idiopathic and secondary DBN with bilateral vestibulopathy, which suggests a common pathophysiologic mechanism. In addition, they found that cerebellar ataxia and dysarthria commonly occur concurrently with DBN, which could be a result of the proposed cerebellar Purkinje cell dysfunction. They suggest that the lack of MRI findings with "idiopathic" DBN could be due to the early stage of the disease process, and that follow-up studies might be revealing. They also recommend further genetic and molecular studies to determine why DBN, particularly the idiopathic type, is a disorder of the elderly, and which gene defect(s) may predispose patients to developing this eye movement disorder.
References
1. Cogan DG. Arch Ophthalmol 1968;80:757-768.
2. Bronstein AM, Miller DH, Rudge P, et al. J Neurol Sci 1987;81:173-184.
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