Progressive Ataxia and Palatal Tremor with Hypertrophic Olivary Degeneration

A 60-year-old man presented with a 2.5-year history of progressive gait imbalance and dysarthria, with recurrent falls in the past year. Neuro-ophthalmic examination showed mild rotatory pendular nystagmus and palatal tremor without oscillopsia or ear clicks. Cognition revealed MoCA 22/30 with deficits in attention, repetition, abstraction, and delayed recall; language showed paraphasic errors with preserved comprehension. On neurologic examination, he had bilateral dysmetria on finger-to-nose and heel-to-shin testing and had moderate ataxia on gait assessment, with an inability to tandem. MRI brain demonstrated bilateral inferior olivary hypertrophy. FDG-PET demonstrated moderate increased uptake along the left, greater than right, medulla, corresponding with the area of suspected inferior olivary hypertrophy on prior MRI-a pattern reported in hypertrophic olivary degeneration, including progressive ataxia and palatal tremor (PAPT). There was also diffuse asymmetric left cerebellar hypometabolism, which, while nonspecific in isolation, most likely represents a diaschisis phenomenon related to asymmetric involvement of the inferior olivary nuclei. This is particularly given the absence of an alternative contralateral right supratentorial cortical hypometabolism to account for it. No other degenerative pattern was seen on PET. Routine labs were unrevealing. A comprehensive ataxia panel (Blueprint Genetics) was negative, including POLG variants and SCA repeat expansions. No structural, pharmacologic, or genetic etiology was identified to explain the clinical syndrome, although a neurodegenerative cause cannot be entirely excluded. The findings are consistent with sporadic progressive ataxia with palatal tremor (PAPT), supported by imaging evidence of hypertrophic olivary degeneration. Management emphasized fall prevention and rehabilitation, with medication for oscillopsia deferred, given minimal visual symptoms.

Progressive Ataxia and Palatal Tremor with Hypertrophic Olivary Degeneration Arth Pahwa1 MD, MBA Aakash Shetty1 MBBS, FRCPC Imran Jivraj2 MD, FRCSC 1Department of Medicine, Division of Neurology, University of Alberta, Edmonton, Alberta, Canada 2Department of Ophthalmology & Visual Sciences, University of Alberta, Edmonton, Alberta, Canada Learning Objectives • Recognize clinical and eye-movement features of PAPT/OPT and their localizing value to the dentato–rubro–olivary (Guillain–Mollaret) pathway. • Identify MRI features of hypertrophic olivary degeneration (HOD) and understand their temporal evolution. • Formulate a differential diagnosis for palatal tremor (essential vs symptomatic • Present a case of sporadic Progressive Ataxia and Palatal Tremor and when to consider genetic testing for familial forms (e.g., POLG, SCA). Case Summary – History • 60-year-old man with 2.5 years of progressive gait imbalance and dysarthria, and 4 falls in the past year. • No diplopia, dysphagia, or oscillopsia. • There was no antecedent consistent with a previous stroke or demyelinating event. • Cognitive: new generalized anxiety and irritability. Mild short-term memory and word-finding issues; remained independent in IADLs. • Psychiatric: New generalized anxiety and irritability Case Summary - History • PMHx: hypertension, dyslipidemia, OSA (CPAP), anxiety. • Medications: ASA, citalopram, indapamide, perindopril, rosuvastatin. No exposure to drugs that could explain the current syndrome • Social: warehouse inventory specialist; nonsmoker; rare alcohol use. • No known family history of similar symptoms Case Videos • Please see the attached (X3) mp4 videos Examination • MoCA 22/30 (attention, repetition, abstraction, delayed recall impaired). • Neuroophthalmic: 2Hz fine rotatory pendular nystagmus with palatal tremor and no audible ear clicks. Normal smooth pursuits and vertical saccades with mild slowing of leftward horizontal saccades. • Motor/sensory: full strength, intact sensation, reflexes symmetric 2+, plantar responses flexor. • Coordination/gait: mild left heel-to-shin dysmetria; widebased gait; positive Romberg; cannot tandem. Imaging Bilateral subtle increased T2 and FLAIR signals in the inferior olivary nuclei slightly more pronounced on the right. Size and signal intensities of the remainder of the medulla pons are normal. Diagnosis • Based on the progressive ataxia, cognitive changes, oculopalatal tremor with bilateral hypertrophic olivary degeneration (HOD) was given a clinical diagnosis of Sporadic Progressive Ataxia and Palatal Tremor (PAPT). • Additional genetic testing and PET scan ordered. Imaging MRI – Axial T2 at medulla Inferior olivary hypertrophy (bilateral) (Insert image/video here) FDG-PET – Medulla Left > right uptake at inferior olive (Insert image/video here) FDG-PET (Jan 7, 2025): • • Moderate increased uptake along the left > right medulla corresponding to inferior olivary hypertrophy—pattern reported in HOD including PAPT (Korpela 2015; Dubinsky 1991). Diffuse asymmetric left cerebellar hypometabolism that most likely represents diaschisis related to asymmetric inferior olivary involvement, with no alternative contralateral right supratentorial cortical hypometabolism. Imaging Investigations • Routine labs unremarkable (e.g., HbA1c 5.4%, TSH 1.61) • Genetics: Blueprint Genetics Ataxia panel negative, including no pathogenic POLG variants and negative SCA repeat-expansion testing which have been previously reported in PAPT. Pathophysiology • Damage in the Guillain-Mollaret triangle leads to inferior olivary hypertrophy and synchronous oscillatory activity ~ 2Hz. • This propagates to the vestibular and brainstem oculomotor nuclei with modulatory input from the cerebellum Gottfried, O. (2022, September 26). X (formerly Twitter). https://x.com/OGdukeneurosurg/status/1574526794463576064 Pathophysiology • Denervation leads to hypersynchrony of the inferior olive, causing persistent rhythmic movements and acquired pendular nystagmus. 1. Deprived of input, the olive becomes overactive and hypertrophies due to glial hyperproliferation. 2. Over the years, those same cells slowly wear out and atrophy, so despite the early hypertrophy, they ultimately degenerate. *This combination leads to the term Hypertrophic Olivary Degeneration (HOD) • Palatal tremor/OPT arises from maladaptive rhythmic oscillations within the dentato–rubro–olivary network (Guillain–Mollaret triangle). – Most commonly, this is caused by ischemia • OPT is therefore caused by deafferentation (loss of input), trans-synaptic degeneration, and maladaptive reorganization • MRI: characteristic T2 hyperintensity and enlargement of the inferior olives (HOD). Differential Diagnosis for Palatal Tremor • Symptomatic palatal tremor/OPT – Usually from a structural lesion in the Guillain– Mollaret triangle (ischemic stroke, hemorrhagic stroke, tumour, demyelination) • This is often a delayed finding in the setting of stroke – Less likely without an antecedent ictus in our case Differential Diagnosis for Palatal Tremor • Essential palatal tremor – Tensor veil palatini; often ear clicks; MRI without HOD) — clinical/imaging mismatch. – EPT is an isolated focal tremor, and patients may report associated ear clicks. – Typically, there are no other neurological symptoms or signs, and imaging is normal. – Commonly recognized as a Functional Disorder. Progressive Ataxia and Palatal Tremor (PAPT) • A rare symptomatic palatal tremor syndrome that was initially described in 1985 • Further divided into – Sporadic forms • Increased T2 hyperintensity in the inferior olivary nucleus with hypertrophy • Most of them are thought to be neurodegenerative • Case reports associated with tauopathy – Familial forms • No significant olivary hypertrophy • Associated brainstem atrophy, cerebellar atrophy, and signs of corticospinal tract dysfunction • Include POLG-associated ataxia or Spinocerebellar Ataxia (SCA) • The Genetic Blueprint panel is negative in this case. Management/ Considerations • Rehabilitation & safety: gait aids for uneven surfaces (e.g., hiking poles/cane), targeted physiotherapy, fallprevention education. • Visual symptoms (if bothersome): consider gabapentin, memantine, or trihexyphenidyl for acquired pendular nystagmus, individualize to efficacy/tolerability. • Disease-modifying therapy: none established for degenerative PAPT; genetics for counseling • In this case, medication for oscillopsia was deferred given minimal symptoms; education and fall prevention prioritized. Permissions / PHI • All protected health information removed from images/videos. • Patient consent obtained for educational dissemination. References • • • • • • • • • • • • • Dubinsky, R.M., Hallett, M., Chiro, G.D., Fulham, M. and Schwankhaus, J., 1991. Increased glucose metabolism in the medulla of patients with palatal myoclonus. Neurology, 41(4), pp.557-557. Gottfried, O. (2022, September 26). X (formerly Twitter). https://x.com/OGdukeneurosurg/status/1574526794463576064 Hainline, C., Neophytides, A., Borja, M.J. and Galetta, S.L., 2017. Progressive ataxia and palatal tremor. Neurology: Clinical Practice, 7(4), p.e37. Korpela, J., Joutsa, J., Rinne, J.O., Bergman, J. and Kaasinen, V., 2015. Hypermetabolism of olivary nuclei in a patient with progressive ataxia and palatal tremor. Tremor and Other Hyperkinetic Movements, 5, p.342. Mongin, M., Delorme, C., Lenglet, T., Jardel, C., Vignal, C. and Roze, E., 2016. Progressive ataxia and palatal tremor: think about POLG mutations. Tremor and Other Hyperkinetic Movements, 6, p.382. Nicastro, N., Ranza, E., Antonarakis, S.E. and Horvath, J., 2016. Pure progressive ataxia and palatal tremor (PAPT) associated with a new polymerase gamma (POLG) mutation. The Cerebellum, 15(6), pp.829-831. Samuel, M., Torun, N., Tuite, P.J., Sharpe, J.A. and Lang, A.E., 2004. Progressive ataxia and palatal tremor (PAPT) Clinical and MRI assessment with review of palatal tremors. Brain, 127(6), pp.1252-1268. Shaikh, A.G., Hong, S., Liao, K., Tian, J., Solomon, D., Zee, D.S., Leigh, R.J. and Optican, L.M., 2010. Oculopalatal tremor explained by a model of inferior olivary hypertrophy and cerebellar plasticity. Brain, 133(3), pp.923-940. Silimon, N., Wiest, R. and Bassetti, C.L., 2023. Four new cases of progressive ataxia and palatal tremor (PAPT) and a literature review. Clinical and Translational Neuroscience, 7(4), p.32. Sperling, M.R. and Herrmann Jr, C., 1985. Syndrome of palatal myoclonus and progressive ataxia: two cases with magnetic resonance imaging. Neurology, 35(8), pp.1212-1212. Thurtell, M.J., 2015, October. Treatment of nystagmus. In Seminars in Neurology (Vol. 35, No. 05, pp. 522-526). Thieme Medical Publishers. Thurtell, M.J., Joshi, A.C., Leone, A.C., Tomsak, R.L., Kosmorsky, G.S., Stahl, J.S. and Leigh, R.J., 2010. Crossover trial of gabapentin and memantine as treatment for acquired nystagmus. Annals of Neurology, 67(5), pp.676-680. Tilikete, C. and Desestret, V., 2017. Hypertrophic olivary degeneration and palatal or oculopalatal tremor. Frontiers in neurology, 8, p.302.