Personality change and gait dysfunction.

Abstract

Awoman in her 50swas referred to a neurologist for a history of gait, balance, personality, and judgment changes over 4 years. Her family noted that her first symptoms appearedat age55,with subtle gait dysfunction and thenevident imbalance. By age57, there wasconcernoverprogressivewithdrawal fromsocial interchange,personality changes, and impairment of judgment. By age 59, she was experiencing bouts of inappropriate out-ofcontext laughter and tears, inattention, daytime fatigue, and frank memory impairment. She developed visuoperceptive changes and difficulties using the television remote control device. She developed obsessive checking behaviors. She started having swallowing difficultiesbutnonethelesshadunexpectedweightgain.Shedevelopedprogressivelyworse motoric problems,with stiffness, abnormal posturing, a left toepointing upward, and falls. Her medical history was significant only for restless legs syndrome, hypertension, hyperlipidemia,myopia, and adeviatednasal septum.Her family history revealed that her father was alive and well at approximately age 90 years, and her mother had died at approximately age 80 yearswith a history of neuropsychiatric disease and gait change. Therewas no history of tobacco, excess alcohol, or recreational drug use. General examination findings were noncontributory. Neurological examination revealed abnormal mental status, with full orientation and good registration, concentration, digit span, and language function but with poor calculations and constructions (Figure 1A) and decreased short-term memory. Nonetheless, her Mini-Mental State Examination score was 28 of 30. Cranial nerve examination revealed some decreased upgaze and mild facial masking. Motor examination revealed rigidity and dystonic posturing in the left arm and leg, imbalance on gait, decreased arm swing, and retropulsion but no significant tremor. Sensory examination findings were normal. Reflex examination showed mild left hyperreflexia with an upgoing left toe. Blood and urine laboratory study results were within normal limits. Cerebrospinal fluid was unremarkable except for biomarkers that showed a mid-range β-amyloid 42 level of 530 pg/mL and normal total tau and phosphotau levels of 182 and 25 pg/mL, respectively. Magnetic resonance imaging of the brain was reported as unremarkable (Figure 1B). Positron emission tomography (PET) imaging of the brain revealed right frontotemporoparietal hypometabolism with some sensorimotor sparing (Figure 1C), which was neither typical nor atypical of Alzheimer disease. Electroencephalography showed left frontotemporal sharp waves and slowing. She had continued progressive decline in cognition and motor function and died almost mute and bedridden in her early 60s after a 9-year course of illness. A B