Case

Clinical course

A 67-year-old man was admitted to our hospital presenting gait disturbance and facial dystonia. His wife noted that he showed nonfluent speech having difficulty in naming objects and abnormal behavior such as hyperphagia for the first time 6 years previously. Thereafter, tremor in the lower limbs, more dominantly in the left leg, gait disturbance and postural instability insidiously progressed for 4 years. Since the age of 65, he has shown personality change and memory impairment. He had been known to be a very gentle and quiet person, but now often showed temperament. His memory worsened and cognitive function continued to decline. One year previously, he began to develop stooped posture and left shuffled gait which gradually worsened. By then, his movements slowed considerably, his gait became unsteady, and he fell frequently. A trial of levodopa (200 mg/ day) was prescribed dose subsequently increased to 600 mg per day over one year. However, no objective signs of improvement showed despite increased dose of levodopa, and involuntary facial dystonia began to develop.

Neurological examination taken after the levodopa medication revealed severe facial dystonia. Involuntary facial grimacing usually sustained around both eyes accompanied with hypertonicity in facial muscles and deep facial folds. His speech was more difficult because of simultaneous contraction of facial muscles. Body bradykinesia, axial rigidity and rest tremor in both limbs, and rest tremor in both arms and legs, which was more severe on the left limbs, were shown. The motor score of the Unified Parkinson’s Disease Rating Scale (UPDRS) scored 59. Despite no definite supranuclear palsy, optokinetic nystagmus was not found. Motor power was intact and sensory examination was normal. There was no pathologic reflex on both feet despite increased overall deep tendon reflexes. The patient could not stand without assistance and fell down frequently.

After the discontinuation of levodopa, motor score of UPDRS dropped to 38 points and facial dystonia completely disappeared. There was bilateral symmetric parkinsonism on the proximal parts. When answering questions or having conversation, he showed groping speeches, intermittent palilalia and severe anomia. However, single word comprehension was preserved. A month later, levodopa administration restarted and doses were gradually increased to 150 mg per day. This increased medication caused reemergence of his facial dystonia. Motor score of UPDRS worsened to 45 points.

Results of routine laboratory investigations for dementia with Parkinsonism and gene (MAPT and progranulin) study for FTD were normal. Fourteen months later, at the age of 68 years, he became completely unable to walk even with assistance. His upward and downward gazes were absent and he finally showed supranuclear palsy.

Neuropsychologic evaluation

Results of neuropsychologic assessment performed 3 years previously showed naming difficulty (12.1 percentile) and severely impaired frontal executive function (2.68 percentile). Verbal and visual memory, attention, and visuospatial function were still preserved. Follow-up neuropsychologic assessment in our laboratory also showed a more significant decline in Boston naming test result (4.85 percentile) and frontal executive function (0.02 percentile) than the past examination. In addition, the performance of visuospatial function evaluated with the Rey Complex Copy test and memory ability evaluated with auditory verbal learning test marked several standard deviations below those of normal control subjects. Because of facial dystonia, he seldom spoke during hospitalization. He underwent the Korean version of the Western Aphasia Battery (KWAB) after the discontinuation of levodopa. Language was severely impaired, based on KWAB test results. Speech was non-fluent and marked by anomia. Comprehension was normal but repetition was impaired. Mini-Mental State Examination scored decreased to 26 from 29 in 2 years. His neuropsychologic results were summarized in Table 1.

Neuroimaging studies

Magnetic resonance images of the brain showed markedly bilateral frontotemporal lobe, midbrain and cereballar atrophy (Figure 1). ¹⁸F-fluorodeoxyglucose positron emission tomography showed hypometabolism definitely in the bilateral frontotemporal area (Figure 2). Lesser hypometabolic deficits were observed in the left parietal lobe. ¹²³I-metaiodobenzylguanidine scintigraphy revealed normal early and delayed H/M ratios (early H/M ratio: 1.91, delayed H/M ratio: 2.38).

Discussion

Language problem of the patient insidiously and slowly progressed once started. In addition, anomia and impaired repetition, which were documented by KWAB, were supportive of the diagnostic features of PNFA.2 Therefore, this initially led us to clinically suspect his condition as FTD. On the other hand, the MAPT and progranulin, the most popular genes in the FTD,13 were not found.

Despite the lack of typical clinical symptoms of PSP in the early stage, this patient showed some positive features that conform to the criteria,1 which are symmetric proximal parkinsonism, retrocolic posture, poor response of levodopa, and early onset cognitive impairment including frontal dysfunction. Over the six years from the symptom onset, gait disturbance and falling gradually became more severe and extraocular movement impairment began to show (from initial negative optokinetic nystagmus to supranuclear palsy eventually). These findings led to the diagnosis of clinically probable PSP.

Facial dystonia in this patient was thought to be a motor complication from levodopa therapy and could be considered as a form of levodopa-induced dyskinesia (LID). The development of LID in Parkinson’s disease usually depends on neuroplastic changes in the basal ganglia circuitry caused by degeneration of nigrostriatal dopaminergic neurons after the prolonged levodopa treatment.14 In contrast, the rarity of dyskinesias in PSP is associated with multilevel damage in the nigrostriatal and striatopallidal systems.15 Abnormal movements of this patient included facial dystonia, which occurred when the patient was on levodopa medication.

In conclusion, we presented a PSP patient with FTD-like behavioral problems. Although LIFD was rarely reported in PSP, our case suggested that LIFD could be considered as an atypical feature of PSP.

Figure 1.

Brain MRI. MRI shows diffuse cerebral cortex (especially bilateral fr-onto-temporal lobe), brain stem and cerebellar atrophy. In particular, midbrain atrophy is shown.

Figure 2.

F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) image. The FDG-PET showed decreased metabolism in caudate nucleus, bilateral frontal, temporal and parietal cortex, especially lower FDG uptake in the left hemisphere.

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Figure & Data

References

Citations

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