Mild Cognitive Impairment as the Initial Manifestation of Progressive Supranuclear Palsy.

Abstract

To the Editor: Progressive supranuclear palsy (PSP) is a major form atypical parkinsonism that should be differentiated from Parkinson's disease. Individuals with PSP typically present with an akinetic rigid syndrome with early postural instability, axial rigidity, and supranuclear gaze palsy.1, 2 Cognitive disorder in PSP is milder than Alzheimer's disease,3 featuring frontal executive dysfunction,4, 5 and appears with motor signs.1, 2 In contrast, it is rare that cognitive disorder occurs without motor disorder in PSP.2, 3 Such a patient was recently seen. A 73-year-old, previously healthy woman began to have memory problems (e.g., forgetful, forgetting to turn lights off, forgetting neighbors’ names) and infrequent delusional episodes (e.g., thinking that someone had stolen her wallet) for which she saw a general physician, who referred her to a memory clinic. She was taking no drugs that might affect cognitive or motor function. She was alert but slightly nervous and irritable. Her speech was fluent, and cranial nerve examinations, including extraocular muscle movement and eyelids, produced normal results. Her posture, including her neck, was normal. She had no tremor, rigidity, or akinesia of the neck, hands, or feet. Her gait was slightly slow for her age. Sensory examinations were unremarkable. She scored 20 out of 30 (normal > 24) on the Mini-Mental state Examination (MMSE) and 8 out of 18 (normal > 16) on the Frontal Assessment Battery (FAB). Laboratory data were normal. Brain magnetic resonance imaging (MRI) (Figure 1A) and brain 99mTc- L,L-ethyl cysteinate dimer single-photon emission computed tomography showed no remarkable changes. Metaiodobenzylguanidine myocardial scintigraphy results were normal (heart to mediastinum ratio on delayed images 3.35, normal > 2.0).6 Although hippocampal atrophy was not remarkable, she was diagnosed with mild cognitive impairment (MCI) due possibly to Alzheimer's disease. She was referred back to the local clinic, where 5 mg/d donepezil hydrochloride was started. Two years later, she was referred to the memory clinic again because of slow, short-stepped gait with assistance that had begun 1 year before. On examination, her cognitive function had deteriorated: MMSE score 14, FAB score 5. Delusions were not significant. Cranial nerve examination showed supranuclear vertical gaze palsy and dysarthria. She had no retropulsion. She had rigidity in her neck and upper extremities and marked akinesia bilaterally. She had no signs of aphasia, apraxia, limb dystonia, or alien hands. Brain MRI showed atrophy of the midbrain tegmentum (humming-bird sign or emperor penguin sign)7 (Figure 1B), and she was diagnosed with PSP1, 2 and referred back to the local clinic with instructions that she needed 300 mg/d of levodopa/carbidopa for gait difficulty. At the first visit, she had MCI alone without motor disorder. At the second visit, 2 years later, she had vertical gaze palsy and axial rigidity and akinesia. She did not have classical corticobasal syndrome during the course of the disease. Repeated brain MRI revealed midbrain atrophy and neurological signs. No similar cases had been previously reported to the knowledge of the authors except for a schizophrenia-like case8 and two cases of behavioral changes.9, 10 At the first memory screening, The woman described herein had marked frontal executive dysfunction as assessed according to the FAB. Prominent frontal dysfunction is a feature of PSP but not of Alzheimer's disease.3 A pathological lesion might have started in the frontal cortex and caused her frontal executive dysfunction. In conclusion, an elderly woman with PSP who presented with MCI without motor disorder is reported. MCI can be listed as a premotor feature of PSP. Conflict of Interest: None of the authors have any conflict of interest. Author Contributions: Ogata, Tateno: data acquisition, analysis, and interpretation. Sakakibara: study concept and design, acquisition of subjects and data, data analysis and interpretation, manuscript preparation. Tsuyusaki, Tateno, Aiba, Kishi, Inaoka, Terada, Doi: acquisition of subjects and data. Suzuki: critical review of data. Sponsor's Role: No sponsors.