New-Onset Multiple System Atrophy With Hot Cross Buns Sign Presenting in a Patient With COVID-19 : American Journal of Physical Medicine & Rehabilitation

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New-Onset Multiple System Atrophy With Hot Cross Buns Sign Presenting in a Patient With COVID-19

Chung, Michael MD; Heckelmann, Eric MD; Zhou, Yi MD; Lin, Lei MD, PhD; Cuccurullo, Sara MD

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American Journal of Physical Medicine & Rehabilitation 102(4):p e54-e55, April 2023. | DOI: 10.1097/PHM.0000000000002108
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A 65-yr-old woman developed progressive dizziness, blurry vision, and ataxia after hospitalization for COVID-19 infection. Evaluation noted rightward nystagmus, resting tremor of the right hand, slowed finger tapping bilaterally, right dysmetria, and shuffling gait. Lumbar puncture was negative. Magnetic resonance imaging of the brain revealed moderate cerebellar and pontine volume loss with crossed hyperintensity of the pons, known as the “hot cross buns sign” (Fig. 1). Videonystagmography confirmed cerebellar etiology of her symptoms. The patient was diagnosed with multiple system atrophy (MSA) with parkinsonian features (MSA-P) and started on amantadine and carbidopa/levodopa. Vestibular rehabilitation and meclizine were also initiated. After 20 days of acute inpatient rehabilitation, there was significant improvement in vertigo, dysarthria, postural stability, gait, and activities of daily living. The patient was discharged home with outpatient vestibular therapy.

Axial magnetic resonance imaging revealing cerebellar and pontine volume loss with crossed hyperintensity of the pons, known as “hot cross bun sign.”

Hot cross buns sign refers to the crossed hyperintensity of the pons seen in an axial view of a T2-weighted magnetic resonance imaging and represents a degenerative process of the median pontine raphe nuclei and the transverse pontocerebellar tracts. This imaging finding reflects an underlying neurodegenerative disease and was traditionally associated with the cerebellar subtype of MSA (MSA-C). However, more recent studies show that hot cross buns sign may not be exclusive and has been found in other neurodegenerative conditions including MSA-P, spinocerebellar ataxia, neuromyelitis optica, and Creutzfeldt-Jakob disease.1

MSA is the most common cause of acquired cerebellar degeneration in adults, with an average age of onset of 56 yrs and an estimated prevalence of 2 to 5 per 100,000 people.2 The etiology of MSA is unclear and mostly presumed to be sporadic, although some reports have suggested various associations including familial patterns as well as chemical exposures including plastics, pesticides, and metals. When considering this patient’s clinical course and the close temporal relationship between the onset of COVID-19 and MSA, the authors propose that this case of MSA may be linked to COVID-19. This is supported by a postmortem study of COVID-19 patients where 86% of tissue samples had astrogliosis in all assessed regions of the brain, with activation of microglia and cytotoxic T-cell infiltration most pronounced in the brainstem and cerebellum.3 It is unclear whether COVID-19 infection induced new MSA or accelerated preexisting disease. Given the increasing evidence of neurologic sequelae of COVID-19 infection, it is important for clinicians to recognize neurodegenerative conditions such as MSA on imaging and to be aware of the possible relationship between COVID-19 and MSA.


1. Zhu S, Li H, Deng B, et al.: Various diseases and clinical heterogeneity are associated with “hot cross bun”. Front Aging Neurosci 2020;12:592212
2. Damon-Perrière N, Tison F, Meissner WG: Multiple system atrophy. Psychol Neuropsychiatr Vieil 2010;8:179–91
3. Matschke J, Lütgehetmann M, Hagel C, et al.: Neuropathology of patients with COVID-19 in Germany: a post-mortem case series. Lancet Neurol 2020;19:919–29
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