A Parkinson Plus Case.

A 78 years-old woman presented with rapidly progressive Parkinsonism despite treatment. Parkinsonian symptoms consist of left upper extremity trembling and bilateral upper extremities cogwheel rigidity. She also referred gait disturbance with frequent falls and sporadic visual hallucinations for one year. The patient had cognitive decline but no criteria for dementia. The blood test and lumbar puncture revealed no abnormalities. 

Imaging Findings

MRI evaluation was required for further evaluations. T1, T2 fast spin eco, T2 FLAIR and T2* GRE weighted images (WI) were obtained.

Axial T2 fast spin echo and axial T2 FLAIR images showed mild brain atrophy and hyperintense foci in the periventricular and subcortical white matter related to chronic small vessel ischemic disease

At basal ganglia level, axial T2 FLAIR and T2* GRE demonstrate marked bilateral putamina hypointensity and putamina lateral slitlike hyperintensity. (Fig. 1)  At a lower level, T2WI revealed a cruciform shaped hyperintensity on the pons. (Fig. 2) This pons hyperintensity is labelled “the cross bun sign”.

Sagittal T1WI demonstrates mild cerebellar atrophy with relative sparing of brainstem. (Fig. 3) Nevertheless, middle cerebellar peduncle and pons were not atrophic.

Probable multiple system atrophy (MSA) was considered.

Multiple system atrophy (MSA) is a neurodegenerative disorder classified under the Parkinson Plus syndromes. It is a synucleinopathy. [1]

MSA is classified into two subtypes depends on its clinical manifestations. Nowadays autonomic failure is included in both MSA-P and MSA-C, it is no longer specific of Shy-Drager syndrome. [1][2]

• MSA-P or striatonigral degeneration has predominant Parkinsonism symptoms.

• MSA-C or olivopontocerebellar atrophy has predominant cerebellar symptoms.

Histology makes the definitive diagnosis.[2][3] Imaging has an important role in the diagnosis approach. A combination of clinical manifestations and imaging features should confirm a probable MSA. Some imaging features can overlap among them and with other diseases, such as idiopathic Parkinson’s disease (IPD). However, there are characteristic features to distinguish them. MRI is the preferred modality of imaging. [1][2][3][4]

• MSA-P has a predominance affectation of basal ganglia. Putamen nuclei are the most frequently involved. Characteristic imaging features include putaminal atrophy. Other abnormalities, such as hypointensity of the putaminal body (compared with ipsilateral globus pallidus), slitlike hyperintensity of the putaminal lateral border or hemisphere atrophy, can also be seen in IPD. When the severity of these features are moderate to severe support MSA-P diagnosis. [4] Note that the slitlike hyperintensity of the putaminal border may be normal on 3T scans. [5]
• MSA-C has infratentorial structures predominance. Imaging features supporting MSA-C include atrophy of cerebellum and brainstem, high signal intensity on T2WI of middle cerebellar peduncles and a cruciform hyperintensity T2WI on the pons resembling a hot cross bun. [1][2][3][4]. A study has demonstrated that T2* GRE imaging is superior to conventional T2WI in detecting the hot cross bun sign. [6]

The hot cross bun sign pathological substrate is gliosis and atrophy of the pontine neurons and pontine fibers with preservation of the pontine neurons and pontine fibers with preservation of the pyramidal tract and pontine tegmentum. It can be seen on other neurological disorders such as spinocerebellar ataxias (SCA), progressive multifocal leukoencephalopathy, paraneoplastic cerebellar degeneration, leptomeningeal metastases, bilateral middle cerebral peduncle infarction, cerebrotendinous xanthomatosis, and Creutzfeldt-Jakob disease, but is most commonly seen in MSA-C. [2][4][7]

MSA doesn’t respond to Parkinson´s disease treatment and inevitably progresses to death in 7 to 10 years from the time of diagnosis. [1][2]

Written informed patient consent for publication has been obtained.

• Teaching points:
  • Compatible clinical manifestations and imaging are required to consider MSA.
  • MRI is the imaging modality of choice in MSA diagnosis.
  • The pons Cross bun sign and bright middle cerebellar peduncle are not specific but support MSA-C diagnosis.