Periodic Alternating Gaze Deviation Due to Paraneoplastic Cerebellar Degeneration

Many eye movement disorders can be seen in diseases involving the cerebellum, including nystagmus, abnormal smooth pursuit, and abnormal saccades. A rare eye movement disorder associated with cerebellar dysfunction is periodic alternative gaze deviation, which is thought to be a special case of periodic alternating nystagmus. It has never been reported in the context of paraneoplastic cerebellar degeneration. A 65-year-old woman presented to us in 2016 with the subacute onset of progressive cerebellar ataxia. She had a past history of ductal carcinoma involving both breasts in 2011 (invasive on the left involvement of 2/14 lymph nodes). It was believed that this was in remission following combined surgical, radiation, and chemotherapy. In 2015 she developed features of a sensory neuropathy followed later that year by progressive gait ataxia and bilateral hand tremor. This was followed by the development of bothersome tremulous movements of the upper lip worsened by speaking and vertical diplopia. Multiple investigations had failed to establish a cause of her symptoms. On examination she often closed her eyes during attempted oculomotor assessment; she showed difficulty maintaining ocular fixation with no definite square wave jerks, delayed initiation and hypometric saccades, particularly in upgaze, saccadic pursuit and a probable skew deviation. She had slow irregular tremulous movements of the upper lip and nostril region combining both side-to-side and up and down movements (Video 1). There was a scanning cerebellar-type dysarthria, no palatal abnormal movement, postural and action tremor of the upper limbs, combined with appendicular ataxia of all limbs and marked gait ataxia impairing arising from a chair and walking independently. Subsequent investigations revealed a poorly differentiated metastatic adenocarcinoma of breast origin. Over the following 3–4 years her symptoms progressed despite courses of chemotherapy as well as trials of prednisone, IVIG and plasma exchange. Her MRI showed progressive marked cerebellar atrophy (Fig. 1). In 2019 when she was seen in follow-up the abnormal facial movements present in 2016 were no longer evident. At this time and on four subsequent assessments over the following year she was noted to have abnormal eye movements consistent with periodic alternating gaze deviation (Video 2). Her tissue indirect immunofluorescence showed staining indicative of an unclassified neural-specific autoantibody consistent with a diagnosis of antibody-negative paraneoplastic cerebellar degeneration (Supplementary Material S1). Periodic alternating gaze deviation probably shares underlying pathophysiology with periodic alternating nystagmus (PAN).1 Periodic alternating gaze deviation may even be considered a variant of PAN with absent fast-phase eye movements but preserved slow phase movements driving the gaze deviation.1 In periodic alternating gaze deviation the eyes classically switch direction every 1–2 minutes, which is similar to the typical period of PAN.1, 2 Both PAN and periodic alternating gaze deviation are thought to be caused by instability of the brainstem velocity storage mechanism.1 Midline cerebellar dysfunction, in particular dysfunction of the nodulus and ventral uvula of the vestibulocerebellum, has been implicated in PAN and periodic alternating gaze deviation.1, 3 A recent report described a patient with paraneoplastic anti–kelch-like protein 11 rhombencephalitis with cerebellar nodulus involvement and resultant PAN.4 These rare neuro-ophthalmologic disorders have localizing value and can teach us about the physiology underlying eye movements. (1) Research Project: A. Conception, B. Organization, C. Execution, (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique, (3) Manuscript: A. Writing of the first draft, B. Review and Critique. S.A.C.: 1A, 1B, 1C, 3A, 3B F.J.T.: 1A, 1C, 3B W.P.M.: 1A, 1C, 3B A.E.L.: 1A, 1B, 1C, 3A, 3B Local research ethics board approval was not necessary for this case report, as per local policy. All ethical guidelines were followed. The patient (and her husband) gave verbal and written consent to have this video published. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. The authors declare that there are no funding sources or conflicts of interest relevant to this work. No specific funding was received for this work. Supplementary Material S1. List of laboratory investigations. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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