An autopsy-confirmed case of progressive supranuclear palsy with predominant postural instability

Clinical differential diagnosis

As hypokinesia in the left upper limb and hypomimia had initially been present, the diagnosis of PD had first been suggested. This diagnosis was questionable right from the beginning, since prominent PI was among the patient’s initial complaints, which does not develop until late into the disease in typical PD. Furthermore, tremor, present in many patients with PD and some patients with PSP-P was absent in this patient throughout the clinical course. The clear lack of response to levodopa therapy despite evidence for presynaptic dopaminergic degeneration by SPECT imaging suggested postsynaptic dopaminoceptive dysfunction in this patient and affirmed the doubt at the diagnosis of PD [9, 21, 22]. There was no reason to suggest multiple system atrophy (MSA) because ataxia and autonomic dysfunction were absent [9, 22]. A corticobasal syndrome (CBS) might have been considered by year 9, since apraxic features occurred in both hands. However, neither dystonia, myoclonus, nor alien limb phenomenon as additional cortical features were present, the motor signs were strikingly symmetric by then, and the average survival time of CBS patient (7.9 years) had passed by far at this time, rendering the diagnosis of CBS unlikely [9, 21, 23]. Brain imaging did not show vascular lesions of the basal ganglia and brainstem suggestive of vascular parkinsonism. Slowing of vertical saccades allowed the diagnosis of possible PSP according to the NINDS-SPSP criteria in the 9^th year of his illness. With development of vertical SNGP, the patient fulfilled the criteria for probable PSP in the 11^th year [5]. Cognitive changes typically observed in PSP, including apathy and reduced verbal fluency were not observed until 10 years after onset in this patient [21, 24]. Predominant mesencephalic atrophy clearly below the threshold suggestive of PSP [25] has been demonstrated by MRI in the 12^th year Since data from prior MRI is not available, it cannot be verified if structural imaging had allowed to suggest PSP at an earlier time point than the clinical features. As typical for PSP, the patient developed dysphagia in the terminal phase and died of aspiration pneumonia. Compared to the average disease duration of PSP (8.7 years) [10], the patient experienced an exceptionally long disease duration of 15 years, but individual cases with survival as long as 16 years have been previously reported [3].

In summary, this clinically well documented case strengthens the concept that individual patients with definite PSP can present with predominant progressive PI (PSP-PI predominance type), as it had been previously proposed on the basis of a retrospective case series. This observation further expands the clinical spectrum of definite PSP and underlines the need to adapt the clinical diagnostic criteria to allow diagnosing syndromes suggestive for PSP, such as PSP-PI, as early as possible.