Clinical Manifestations And Magnetic Resonance Imaging Features Of Progressive Supranuclear Palsy

Background and Objective: Progressive supranuclear palsy (PSP) is rare, degenerative disorder of the brain. In the absence of clinical markers to diagnose PSP, neuropathological examination is the"gold standard"for diagnosis. PSP belongs to the tauopathies, and the characteristic pathologic changes include neurofibrillary tangles and astrocytic tufts affecting the most severely the basal ganglia, diencephalon and brainstem. However, in clinical practice, it is difficult to distinguish PSP from other neurodegenerative disorders, such as Parkinson's disease (PD), multiple system atrophy (MSA) in the early stage, when the clinical typical signs are not clearly evident. Recent findings suggest that magnetic resonance imaging (MRI) can contribute valuable information for the differential diagnosis of many neurodegenerative diseases including PSP. The aim of the present study was to analyze the clinical features of PSP and to identify the morphological differences of brainstem structures in patients with PSP, PD, parkinsonian variant of MSA (MSA-P) and cerebrellar variant of MSA (MSA-C) using MRI, providing the useful clues for the early diagnosis of PSP.Methods: Using a retrospective case notes review, we analyzed the clinical manifestations of 12 patients with PSP , and studied the MRI data from patients with PSP, PD (n=14), MSA-P (n=13), MSA-C (n = 11) and from the healthy controls (n=16) to compare their different features using visual and quantitative measurements. All patients underwent a systematic neurological examination including Hoehn-Yahr rating scale, the Mini Mental State Examination (MMSE) and/or the Montreal Cognitive Assessment (MoCA). Cranial MRI scan was applied in all subjects. Midbrain area, pons area, superior cerebellar peduncle (SCP) width as well as middle cerebellar peduncle (MCP) width were measured on T1-weighted or T2-weighted images. The ratio between pons and midbrain areas (m/p-ratio), and the MR parkinsonism index (MRPI) ([pons area/midbrain area]×[MCP width/SCP width]) were calculated.Results: Half of all patients with PSP presented with the gait disturbance and falls as the initial symptoms, and 67% of PSP patients experienced symptoms symmetrically, on both sides of the body. All PSP patients had the following clinical manifestations such as postural instability, frequent falling, axial dystonia, vertical supranuclear gaze palsy, psudobulbar palsy, pyramidal tract impairment and cognitive dysfunction. 83% of PSP patients were not sensitive to levodopa treatment. On mid-sagittal plane of brain MRI, all of PSP patients showed classical"hummingbird sign"indicating marked atrophy of the midbrain tegmentum. The average midbrain area was significantly smaller in patients with PSP than in those with PD, MSA-P and MSA-C and control subjects (P<0.001, respectively). The pons area was the smallest in the patients with MSA-C, but there was no difference in the average of pons area among patients with PSP, PD, MSA-P and the normal subjects (P>0.05, respectively). The SCP width was smaller in the PSP group compared with the other groups (P<0.01, respectively). The MCP width was smaller in the patients with PSP than those with PD or normal controls (P<0.01, respectively). The m/p-ratio was lower but the MRPI was higher in the PSP groups than those in the other groups. Furthermore, the values of either m/p-ratio or MRPI had no overlap between the PSP group and the other groups. On the contrary, all single measurements (i.e. midbrain area, pons area, SCP width as well as MCP width ) showed the partial overlaps between the PSP group and the other groups.Conclusion: When a patient presents with early and severe postural instability, falls, axial distonia, vertical supranuclear gaze palsy, psudobulbar palsy, pyramidal tract involvement and cognitive disturbance, the diagnosis of PSP should be considered. The visual and quantitative measurements of the brainstem structures using MRI are helpful for the diagnosis and the differential diagnosis of PSP. Midbrain atrophy is the major feature of PSP on the MRI. The m/p-ratio and MRPI seem to be better than the single measurements of brainstem structures in differentiating PSP from other neurodegenerative diseases.