A 55-year-old woman is brought to the office by her husband for evaluation of strange behavior. She has been spending large amounts of money to buy expensive clothes and jewelry. The patient has also offered sex to unknown men in the neighborhood and has become increasingly indifferent toward her family, about whom she used to care deeply. She usually drinks 1 or 2 glasses of wine on weekends but lately has been drinking 2 or 3 glasses almost every day. When asked about these changes during the interview, the patient states that she has not noticed any change in her behavior. Vital signs are normal. The general physical and neurologic examinations are normal. This patient's condition is most likely due to abnormal accumulation of which of the following?

Question

A 55-year-old woman is brought to the office by her husband for evaluation of strange behavior.  She has been spending large amounts of money to buy expensive clothes and jewelry.  The patient has also offered sex to unknown men in the neighborhood and has become increasingly indifferent toward her family, about whom she used to care deeply.  She usually drinks 1 or 2 glasses of wine on weekends but lately has been drinking 2 or 3 glasses almost every day.  When asked about these changes during the interview, the patient states that she has not noticed any change in her behavior.  Vital signs are normal.  The general physical and neurologic examinations are normal.  This patient's condition is most likely due to abnormal accumulation of which of the following?

Quizplus · Accepted Answer

This patient with disinhibition (eg, soliciting sex from strangers), loss of empathy toward her family, complex compulsive behaviors (eg, excessive shopping), and hyperorality (eg, increase in drinking wine) likely has frontotemporal dementia (FTD). FTD is characterized by degeneration of the prefrontal cortex, which progresses to include the anterior temporal lobes. The disease process results in accumulation of different neurotoxic proteins, including: Tau, a protein associated with neuronal microtubules that normally takes part in microtubule stabilization. In patients with FTD, tau becomes hyperphosphorylated and disassociates from the microtubules, which may lead to instability and disrupted axonal transport. It also forms paired helical filaments, which create intracellular tangled clumps of tau proteins predominantly in the frontal and temporal lobes, as well as the hippocampi. Tau-related neurofibrillary tangles are also found in patients with Alzheimer dementia. TDP-43 (transactive response DNA-binding protein 43), a protein that normally functions as a transcription inhibitor or a DNA repair protein. Abnormal ubiquitination leads to immunoreactive inclusions of TDP-43. Pathologic TDP-43 is also found in patients with amyotrophic lateral sclerosis. (Choices A and C) CAG trinucleotide (polyglutamine) repeats can lead to neurotoxic protein formation. When this occurs in the ataxin genes, it can lead to spinocerebellar ataxia. When it occurs in the huntingtin protein, it leads to Huntington disease, which can present with prominent changes in mood or cognition. However, both spinocerebellar ataxia and Huntington disease also typically present with significant gait abnormalities (ie, ataxia). (Choice B) Extracellular accumulation of beta-amyloid occurs in Alzheimer disease. Alzheimer disease commonly presents with early and prominent memory impairment with language deficits and spatial disorientation. Although personality changes can occur, they typically occur later in the disease process. This patient's early personality changes are more characteristic of FTD. (Choice D) Excessive prion accumulation causes Creutzfeldt-Jakob disease. Although behavioral changes are common, dementia is rapidly progressive and associated with myoclonus and/or seizures. Educational objective: Frontotemporal dementia presents with early personality change, executive dysfunction, compulsivity, and hyperorality. It is associated with neurofibrillary tangles due to abnormal tau proteins (also seen in Alzheimer dementia) and pathologically ubiquitinated TDP-43 (also seen in amyotrophic lateral sclerosis). __________ References: Towards a TDP-43-based biomarker for ALS and FTLD. (http://www.ncbi.nlm.nih.gov/pubmed/29460270)

A 55-Year-Old Woman Is Brought to the Office by Her