Figure 1

Longitudinal cognitive, motor, functional, and neuropsychiatric data in an illustrative case in the VSM-20 kindred with c9FTD/ALS. (a) Graphs of longitudinal scores on the Mini-Mental State Exam (MMSE) (maximum of 30) and Kokmen Short Test of Mental Status (STMS) (maximum of 36) of a patient from ages 50 to 57. (b) Global scores on the Clinical Dementia Rating (CDR) scale (maximum of 3) and CDR sum of the boxes (CDR-SOB) (maximum of 18) from ages 50 to 57. (c) Longitudinal summed scores for each assessment on the motor subtest of the Unified Parkinson's Disease Rating Scale (UPDRS) (maximum of 108) from ages 50 to 57. (d) Longitudinal scores and Neuropsychiatric Inventory (NPI) from ages 50 to 55. (At age 57, the patient was estranged from his wife.) The NPI-Present score represents the summed score for the presence (score = 1) or absence (score = 0) of each domain across the 12 domains (maximum of 12), and the NPI-Severity score represents the summed score for the severity rating by the informant (mild = 1, moderate = 2, and severe = 3) for each domain across the 12 domains (maximum of 36). Given that scores of less than 24 on the MMSE and of less than 29 on the STMS are viewed as abnormal, this patient has declined minimally on these screening/global measures of mental status. He has hovered in the very mild (0.5) to mild (1) range on the global CDR, whereas the CDR-SOB score shows the accumulating functional impairment across the six domains measured on the CDR. The UPDRS graph reflects that, at age 50, the patient had subtle parkinsonism that increased in severity through age 52 and that has registered scores of around 30 to 33 in the past five years. His parkinsonian features began as left hemiparkinsonism, which has since evolved to an asymmetric akinetic-rigid syndrome without tremor. None of his parkinsonian features responded to carbidopa-levodopa (750 mg of levodopa per day in divided doses). As reflected in the NPI graph, apathy, depression, and appetite/eating change have been confirmed by his wife to have been present throughout his course (he has gained more than 50 pounds over his illness due to hyperphagia), and the severity of most features has increased in recent years. The dips in frequency and severity on the NPI at age 52 may reflect the effects of quetiapine, which was commenced at age 51. However, despite upward titrations of this agent and many other pharmacologic adjustments, his neuropsychiatric morbidity continues to escalate. c9FTD/ALS, frontotemporal dementia or amyotrophic lateral sclerosis (or both) linked to chromosome 9; VSM-20, Vancouver-San Francisco-Mayo Clinic family 20.