Review Question - QID 217071

This patient with progressive disinhibition, apathy, lack of empathy and sympathy, repetitive behaviors, loss of executive function, and parkinsonism (masked facies, pill-rolling tremor) most likely has the behavioral variant of frontotemporal dementia (FTD). This subtype of FTD is associated with Pick bodies, round intracellular aggregates of hyperphosphorylated tau protein.

FTD is the most common cause of dementia in patients younger than 60, with 85% of cases being sporadic. Patients with the behavioral variant of FTD often present with psychiatric symptoms, of which 6 six major symptoms are loss of sympathy and empathy, disinhibition, repetitive behaviors, hyperorality, apathy, and loss of executive function. Histologically, FTD is divided into three subtypes based on inclusions found in the brain: FUS (RNA-binding protein Fused in Sarcoma/Translocated in Liposarcoma), TDP-43 (TAR DNA-binding protein 43), and tau. The tau subtype is characterized by Pick bodies, intracellular cytoplasmic and glial aggregates of tau fibrils which deposit in both the cerebral cortex and deeper brain structures. In turn, damage from these aggregates leads to frontotemporal lobe degeneration and may also damage basal ganglia structures. This manifests clinically as dementia with executive dysfunction, as well as parkinsonism.

Incorrect Answers:
Answer 1: Beta-pleated sheets of PrP resistant to protease are found in Creutzfeldt-Jakob disease (CJD), a rapidly progressive dementia with myoclonus and ataxia. CJD usually progresses more rapidly than in this patient and leads to death within 9 months on average.

Answer 2: Gray matter plaques with extracellular beta-amyloid cores are found in Alzheimer disease (AD), the most common cause of dementia in the elderly. AD usually begins in posterior brain areas that affect language, spatial function, and memory. In this younger patient presenting with more psychiatric and behavioral changes, AD is less likely than FTD.

Answer 3: Intracellular accumulation of glucocerebroside is found in Gaucher disease, a lysosomal storage disorder caused by hereditary deficiency of glucocerebrosidase. Gaucher disease can cause late-onset dementia, vertical gaze palsy, and parkinsonism, as well as anemia, thrombocytopenia, hepatosplenomegaly, and painful bone lesions. In this patient without a family history of neurological disease, hepatosplenomegaly, or gaze disturbance, Gaucher disease is less likely.

Answer 4: Intracellular eosinophilic inclusions of alpha-synuclein characterize Lewy bodies, which are found in Parkinson disease and Lewy body dementia (DLB). The core features of DLB are repeated visual hallucinations, fluctuating levels of awareness and consciousness, rapid eye movement (REM) sleep disorder, and parkinsonism. Although this patient does have parkinsonism, he does not have visual hallucinations, REM sleep disorder, or fluctuating levels of awareness of consciousness, making DLB less likely.

Bullet Summary:
The behavioral variant of frontotemporal dementia is associated with early onset personality and behavioral changes, may be associated with parkinsonism, and is histologically characterized by Pick bodies, round intracellular aggregates of hyperphosphorylated tau protein.