Mutations in the Progranulin gene (PGRN) recently have been discovered to be associated with frontotemporal dementia (FTD) linked to 17q21 without identified MAPT mutations. The range of mutations of PGRN that can result in the FTD phenotype and the clinical presentation of patients with PGRN mutations have yet to be determined. We examined 84 FTD patients from families not known previously to have illness linked to chromosome 17 for identified PGRN and MAPT mutations and sequenced the coding exons and the flanking intronic regions of PGRN. We compared the prevalence, clinical characteristics, magnetic resonance imaging and 18-fluoro-deoxyglucose positron emission tomography results, and neuropsychological testing of patients with the PGRN R493X mutation with those patients without identified PGRN mutations. We discovered a new PGRN mutation (R493X) resulting in a stop codon in two patients. This was the only PGRN mutation identified in our sample. The patients with the PGRN R493X mutation had a rapid illness course and had predominant right-sided atrophy and hypometabolism on magnetic resonance imaging and 18-fluoro-deoxyglucose positron emission tomography. The affected father of one of the patients with the PGRN R493X mutation showed frontal and temporal atrophy without neurofibrillary tangles on neuropathological examination. Our judgment that this mutation results in a heterogeneous clinical presentation has been confirmed in an international in press study of a much large sampling of patients.? ? Many patients with FTD come to our evaluations still driving. To evaluate driving competency and the relationship between neuropsychiatric symptoms and driving behavior in frontotemporal dementia (FTD) patients, we studied 15 patients with a diagnosis of FTD and 15 healthy controls using a driving simulation task. The FTD patients received more speeding tickets, ran more stop signs and were involved in more off-road crashes and collisions than the controls. The patients' overall average speed was significantly higher. Driving performance was correlated with agitated behavior. Based on this finding that behavioral changes characteristic of FTD patients have an impact on their driving skills leading to inappropriate driving behavior, we now caution that all patients with a diagnosis of FTD should cease driving.? ? Finally, we recently reviewed neurotransmitter deficiencies and neurotransmitter-based treatments for FTDD patients. Patients with FTD show deficiencies in the serotonin and dopamine neurotransmitter systems, while the acetylcholine system appears relatively intact. Antidepressant treatment significantly improves behavioral symptoms in FTD, but most studies are small and uncontrolled. Serotonergic treatments appear to improve the behavioral but not cognitive symptoms of FTD. Studies of neurotransmitter deficiencies in FTD can be helpful in developing treatments. Treatment studies on FTD are scarce, given the prevalence and severity of this illness. Larger, well-controlled treatment studies are required to reach more definitive conclusions about treatment efficacy. Multicenter studies are likely the best way to complete treatment studies in a timely manner.
| Huey, Edward D; Garcia, Charisse; Wassermann, Eric M et al. (2008) Stimulant treatment of frontotemporal dementia in 8 patients. J Clin Psychiatry 69:1981-2 |
| Huey, Edward D; Zahn, Roland; Krueger, Frank et al. (2008) A psychological and neuroanatomical model of obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci 20:390-408 |
| de Simone, V; Kaplan, L; Patronas, N et al. (2007) Driving abilities in frontotemporal dementia patients. Dement Geriatr Cogn Disord 23:1-7 |
| Spina, S; Murrell, J R; Huey, E D et al. (2007) Clinicopathologic features of frontotemporal dementia with progranulin sequence variation. Neurology 68:820-7 |
| Huey, Edward D; Probasco, John C; Moll, Jorge et al. (2007) No effect of DC brain polarization on verbal fluency in patients with advanced frontotemporal dementia. Clin Neurophysiol 118:1417-8 |
| Spina, Salvatore; Murrell, Jill R; Huey, Edward D et al. (2007) Corticobasal syndrome associated with the A9D Progranulin mutation. J Neuropathol Exp Neurol 66:892-900 |
| Momeni, Parastoo; Rogaeva, Ekaterina; Van Deerlin, Vivianna et al. (2006) Genetic variability in CHMP2B and frontotemporal dementia. Neurodegener Dis 3:129-33 |
| Huey, Edward D; Putnam, Karen T; Grafman, Jordan (2006) A systematic review of neurotransmitter deficits and treatments in frontotemporal dementia. Neurology 66:17-22 |
| Henkel, Karsten; Danek, Adrian; Grafman, Jordan et al. (2006) Head of the caudate nucleus is most vulnerable in chorea-acanthocytosis: a voxel-based morphometry study. Mov Disord 21:1728-31 |
| Bowen, Raffick A R; Drake, Steven K; Vanjani, Rachna et al. (2006) Markedly increased vitamin B12 concentrations attributable to IgG-IgM-vitamin B12 immune complexes. Clin Chem 52:2107-14 |
Showing the most recent 10 out of 11 publications
