Bilateral lesions of the middle cerebellar peduncles, resulting in the middle cerebellar peduncle sign, are uncommon and can be seen either in isolation (rare) or along with other regions of involvement.

Despite their relative rarity, they have a fairly long list of potential causes (see below) ^1-4. Among these, neurodegenerative diseases are probably most common.

Pathology

The middle cerebellar peduncles are composed of white matter that connects the cerebellar hemispheres to the contralateral pontine nuclei ⁵. Therefore, many of the causes of lesions in this location are related to white matter pathology. They are supplied by branches of the anterior inferior cerebellar artery and the superior cerebellar artery.

For additional discussion of region anatomy refer to middle cerebellar peduncles.

Etiology

Most of the entities listed do not usually cause isolated bilateral middle cerebellar peduncular lesions and as such care must be taken in identifying other areas of involvement.

• neurodegenerative diseases

  • multiple systemic atrophy - cerebellar type (MSA-C)

  • fragile X-associated tremor/ataxia syndrome (FXTAS) ⁶

  • CARASIL: with involvement of pons, known as the arc sign ⁷

  • ​spinocerebellar ataxia

  • neuronal intranuclear hyaline inclusion disease

  • CLCN2-related leukoencephalopathy ⁹

• metabolic diseases

  • adrenoleukodystrophy

  • Wilson disease

  • acquired non-wilsonian hepatocerebral degeneration

  • hypoglycemic encephalopathy

  • extrapontine myelinolysis

• neoplasms

  • primary CNS lymphoma

  • brainstem glioma

  • leptomeningeal carcinomatosis

• cerebrovascular disease

  • anterior inferior cerebellar artery (AICA) infarction

  • superior cerebellar artery infarction

  • Wallerian degeneration secondary to pontine infarction ^4,8

  • posterior reversible encephalopathy syndrome (PRES)

• inflammatory and demyelinating diseases

  • myelin oligodendrocyte glycoprotein​ antibody-associated disease (MOGAD) ¹⁰

  • multiple sclerosis (MS)

  • acute disseminated encephalomyelitis (ADEM)

  • Behçet disease

  • Erdheim-Chester disease ²

  • neuromyelitis optica spectrum disorder (NMOSD) ⁴

  • progressive multifocal leukoencephalopathy (PML) ⁵

• toxins and drugs

  • cyclosporin-A encephalopathy

  • heroin-induced leukoencephalopathy

• infective

  • acute cerebellitis ^11,12

  • HIV encephalopathy

  • JC virus granule cell neuronopathy

  • Zika virus encephalitis in adults

Radiographic features

Although potentially visible on CT, in most instances this is an MRI feature.

MRI

The majority of patients presenting with bilateral middle cerebellar peduncle lesions have high T2 signal without suppression on FLAIR, with matching low signal on T1 weighted images ⁴. This will usually have facilitated diffusion on ADC maps.

Diffusion restriction (low ADC values) may be seen acutely in infarction, lymphoma and acute cerebellitis ^4,12. Enhancement is usually absent although some enhancement may be seen in lymphoma ⁴.