Florid Nonmotor Manifestations of a Pathologically proven Progressive Supranuclear Palsy.

Sir,

Progressive supranuclear palsy (PSP) is an atypical parkinsonism characterized by supranuclear gaze palsy and postural instability. After nonmotor symptoms (NMSs) were first recognized as constitutional features of those with Parkinson's disease, NMSs were also studied, revealing high frequency and great severity of NMSs such as a sleep problem, mood disturbance, gastrointestinal dysfunction, or urinary dysfunction in PSP.[1] Among various NMSs, psychosis is rare and less suggestive of PSP. Visual hallucination (VH) is also infrequently associated with the diagnosis of PSP.[2] However, NMS was not fully evaluated in the previous autopsied cases.

Here, we report an autopsy-proven case of PSP who presented with a lot of NMSs including psychosis and VH.

A 65-year-old female presented with cognitive decline and repeated falls 2.5 years before the visit. Cognitive impairment began at the age of 63 years, and cognitive function progressively deteriorated. Her family also complained about her psychotic problems such as delusion. The patient reported insomnia and urinary symptoms, including frequency, urgency, and nocturia. Parasomnia including rapid eye movement sleep behavior disorder was absent.

At the initial visit, the Seoul neuropsychological screening battery [Table 1] identified 8/30 in the Korean version of the mini–mental state examination (K-MMSE) and 49/144 in the caregiver-administered neuropsychiatric inventory questionnaire [Supplementary Table 1]. Follow-up levels of K-MMSE at 3, 10, 13, and 24 months after the first evaluation were 19/30, 14/30, 7/30, and 11/30, respectively. The family reported that cognitive function was worse in the evening.

Table 1

Detailed results of the Seoul Neuropsychological Screening Battery at the initial visit

Detailed results of the caregiver-administered neuropsychiatric inventory at the initial visit

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Neurological examination showed typical features of PSP [Supplementary Video 1]. Brain magnetic resonance imaging showed midbrain atrophy with the hummingbird sign and cortical atrophy [Figure 1a].

Figure 1

Brain magnetic resonance imaging and pathologic findings. (a) Brain magnetic resonance imaging showing prominent midbrain atrophy. (b) Immunohistochemical staining with antiphosphorylated tau antibody shows diffuse neutrophil threads and tufted astrocytes in the globus pallidus. (c) Globose tangles are seen in the substantia nigra. Immunohistochemical staining using antibodies against α-synuclein and transactive response DNA-binding protein 43 kDa (TDP-43) was negative. Braak neurofibrillary tangle stage = 1. Thal phase (amyloid plaques) = 2.Calibration bar= 100 μm

Treatment with levodopa was ineffective. The patient exhibited multiple NMSs on the Korean version of the NMSs scale [Supplementary Table 2] 2 years after the initial visit. The motor symptoms rapidly progressed, resulting in a wheelchair-bound state. The patient developed VH during treatment with levodopa, which was controlled with the addition of quetiapine. She became bedridden at the age of 68 years, was placed in a nursing home, and died of pneumonia at the age of 71 years. Autopsy was done 4 h after death, which was compatible with the pathologic diagnosis of PSP [Supplementary Table 3 and Figure 1b, c].[3]

Detailed results of the Korean version of the nonmotor symptoms scale 2 years after the initial visit

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Regional immunohistochemistry staining of phosphorylated Tau

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She had presented with a plethora of psychiatric symptoms. Although delusion was present in 3% of clinically diagnosed PSP,[4] only one case was reported to have schizophrenic symptoms as initial presentations in pathologically proven PSP.[5] Thus, this is the second pathologically proven PSP presenting with psychosis.

This patient seemed to share some clinical features with dementia with Lewy bodies (DLBs): VH and a nonlinear pattern of cognitive deterioration (serial MMSEs). However, some patients with PSP could have VH (5%–13%), albeit the correlation between VH and medications was unclear in the majority of the cases.[2] Moreover, MMSEs are insensitive to capture disease-specific domains such as frontal function.

Although florid NMSs, especially constipation and change in ability to taste or smell, are also reminiscent of PD or DLB, pathologic basis of some NMSs such as gastrointestinal symptoms is not firmly established in PSP, whereas α-synuclein pathologies are found outside the central nervous system, providing a better understanding of NMSs.

In conclusion, this is a pathologically proven PSP presenting with a variety of NMSs. Further studies are needed to investigate clinicopathologic correlation between tau pathologies and NMSs.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

This research was financially supported by the Ministry of Trade, Industry and Energy (MOTIE), and Korea Institute for Advancement of Technology (KIAT) through the International Cooperative R and D program.

Conflicts of interest

There are no conflicts of interest.