Mania triggered by levodopa treatment in a patient with frontotemporal dementia caused by A C9orf72 repeat expansion: A case report

Involvement of striatal motoric subregions in familial frontotemporal dementia with parkinsonism harboring the C9orf72 repeat expansions

“…In our study, all FTDP patients presented with bradykinesia and rigidity, moreover, we found the overlapping structural, metabolic, and dopamine transport functional alterations of the striatal motor subdivisions in in vivo imaging findings, suggesting that TDP-43 pathological deposition may exist in motor subregions to cause functional deterioration. Our findings were partially in line with the only two previous study, which revealed the hypometabolism and dopamine depletion in the striatum as a whole in FTDP patients with C9 repeat expansions 10,24 . These results likely add some support information to our hypothesis wherein C9orf72 repeat expansions may cause the pathological aggregation of TDP-43 in the striatal motor regions, leading to the degeneration and severe loss of dopaminergic neurons, which contribute to parkinsonism in FTDP patients.…”

“…Notably, this patient showed inconsistent results with non-significant hypometabolism and significantly decreased VMAT2 uptake in the striatal motor regions. Similar to previous studies, the dopaminergic PET might more easily identify the striatal dysfunction associated with parkinsonism compared with FDG-PET 10,26 . Given the limited evidence, further investigation of striatal motor subdivisions in larger FTDP cohorts with C9orf72 repeat expansions need to be undertaken.…”

“…We detected alterations at the level of striatal motoric subregions in FTDP patients with C9orf72 repeat expansions and analyzed their roles in parkinsonism. Some previous studies have suggested non-specific subcortical or striatal impairment without any functional distinction [9][10][11] . It is generally acknowledged that the striatum has connections with the cortex and plays an important role in the striato-cortical circuitry, which has been characterized by several functionally segregated subcircuits that are adjacent, but anatomically different 16 .…”

“…Atrophy, hypermetabolism, and dopaminergic dysfunction with a predominant rostral-caudal gradient in the striatum had firmly been confirmed in Parkinson's disease (PD) [6][7][8] . Few research studies in FTDP patients with C9orf72 mutation have revealed the involvement of the striatum based on neuropathological and imaging analysis [9][10][11] , however, it is ambiguous whether the pattern of striatum involvement is different between C9orf72related FTDP and Parkinson's disease. It is worth noting that the striatum has been involved in multiple functions, including motor control, motivated behavior, social emotion, and cognition, and is widely integrated with motor, limbic, associative networks [12][13][14] .…”

Bipolar Disorder and Manic-Like Symptoms in Alzheimer’s, Vascular and Frontotemporal Dementia: A Systematic Review

“…Dextroamphetamine has shown potential efficacy in reducing apathy and disinhibition in eight patients with bvFTD [ 109 ] and a single administration of methylphenidate (40 mg) effectively reduced abnormal risk-taking behavior in a small sample of bvFTD patients [ 110 ]. However, mania has been triggered by levodopa in a patient with a C9orf72 mutation associated bvFTD [ 111 ], suggesting that caution is needed in the introduction of dopaminergic treatments in subjects with FTD.…”