Hot-cross bun sign in multiple system atrophy

A 75-year-old male presented with symmetric parkinsonism, dysarthria, and autonomic dysfunction. He first noticed stiffness in his legs and gait difficulties 7 years before diagnosis. Orthostatisms, high-pitched dysarthria and a slight bilateral upper limb ataxia developed later. No bulbar abnormalities, except for a slight horizontal gaze-evoked nystagmus were noticed. Therapy with L-dopa was unsuccessful.

Brain MRI revealed moderate global cerebral atrophy as well as severe atrophy of the infratentorial structures, especially both middle cerebellar peduncles (Fig. 1) and lower pons (Fig. 2), but also the cerebellum. The fourth ventricle was compensatory dilated (Figures 1, 3, 4, 5). Moderate volume loss of both putamina (Fig. 6) was also observed. A cruciform hyperintensity - Hot-cross bun sign (HCBS) was present in the pons on T2-weighted (Fig. 4) and FLAIR (Fig. 5) images, but could be well appreciated as a hypointense band on gradient T1-weighted images as well (Fig. 3). Additionally, in the left temporal white matter, a hyperintensity on T2-weighted (Fig. 4) and FLAIR (Fig. 1, 5) images, and hypointensity on T1- weighted images (Fig. 3), was seen, corresponding to a post-traumatic encephalomalacia secondary to a traumatic brain injury 2 years earlier.

Multiple system atrophy (MSA) is a rare, sporadic neurodegenerative disorder with a prevalence of 5 per 100.000 persons. Onset is commonly in the sixth decade of life, with a mean survival of 6 to 10 years. After relentless worsening of symptoms, death usually occurs due to bronchopneumonia, urosepsis or sudden nocturnal cardiorespiratory death. MSA is caused by abnormal deposits of misfolded α-synuclein in oligodendrocytes, which lead to cellular degeneration. [1–3]

The term MSA was coined in 1969 to encompass Shy-Drager Syndrome, where autonomic dysfunction predominates, striatonigral degeneration, where parkinsonism predominates (MSA-P) and olivopontocerebellar atrophy, where cerebellar ataxia predominates (MSA-C). Autonomic dysfunction and REM sleep behaviour disorder are often the first premotor symptoms, followed by cerebellar and parkinsonian features. A combination of bradykinesia with rigidity, tremor, or postural instability, is predominant in MSA-P subtype (60% of cases) whereas gait ataxia with cerebellar dysarthria, limb ataxia, or cerebellar oculomotor dysfunction, is predominant in MSA-C subtype (40% of cases). [1–3]

Clinical features, poor levodopa responsiveness and MRI findings aid in the probable diagnosis of MSA, however, post-mortem autopsy is required for definitive diagnosis. [1, 2] Both subtypes may manifest as atrophy and increased signal intensity on T2 weighted images in the region of the putamina, middle cerebellar peduncles, pons, or cerebellum. The basal ganglia, especially the putamen, are predominantly affected in MSA-P, and infratentorial structures in MSA-C.

The two subtypes may be distinguished with low sensitivity and high specificity on FLAIR and T2-weighted images. Putaminal rim sign is observed in MSA-P as an increased signal of the putaminal dorsolateral border, whereas HCBS usually presents in the MSA-C as a cruciform hyperintensity of the pons. [2–5]

The signature pattern of HCBS, named after spiced English confection, is believed to appear due to selective pontine nuclei neuronal loss and degeneration of the transverse pontocerebellar fibres, with sparing of corticospinal tracts and pontine tegmentum. [6–8] Though characteristic for MSA, it has been observed in spinocerebellar ataxia 2, 3, 7 and 8, HIV-related progressive multifocal encephalopathy, parkinsonism secondary to presumed vasculitis, variant Creutzfeldt-Jacobs disease and JC virus granule cell neuronopathy. [5–10]