Frontotemporal dementia with psychosis, parkinsonism, visuo-spatial dysfunction, upper motor neuron involvement associated to expansion of C9ORF72: a peculiar phenotype?

Gianluca Floris, Giuseppe Borghero, Antonino Cannas, Francesca Stefano, Emanuela Costantino, Maria R. Murru, Maura Brunetti, Gabriella Restagno, Bryan J. Traynor, Maria G. Marrosu, Adriano Chiò, Francesco Marrosu
2012 Journal of Neurology  
From 2006, a locus on chromosome 9p21 has been associated with a large proportion of ALS and FTD [1] [2] [3] . Recently, two independent groups have identified a hexanucleotide repeat expansion in noncoding region of the C9ORF72 gene as the cause of chromosome 9p21-linked ALS-FTD [4, 5] . We report the case of a 64-year-old man who presented with a 3-year history of delusional mystic thoughts, auditive, visual, and olfactory hallucinations, and hyperreligiosity. The patient later developed
more » ... essive apathy, dysphoric mood, hyperphagia, self-care reduction, and progressive cognitive decline with motor retardation. The man's father had died at age 68 after committing suicide, and his older brother developed parkinsonism associated with behavioral disturbances at age 60 and died 2 years later. Neuropsychological assessment of this patient, performed 3 years after the onset of neurological symptoms, demonstrated bradyphrenia, marked impairment of attention and executive functions, marked constructional apraxia, mild visual and verbal long-term memory deficit, mild anomia, emotional lability, fatuity, and mild utilization behavior. Blood exams, thyroid antibodies and hormones, vitamin B12, folic acid, and TPHA were all normal. Neurological examination revealed symmetric akinetic-rigid syndrome characterized by hypomimia, dysarthria, camptocormia with anterocollis, and diffuse bradykinesia. Brain MRI documented atrophy mainly frontotemporal but with consistent posterior region involvement (Fig. 1 ). Perfusion SPECT with 99 Tc-ethylene cystine dimer (ECD) showed a marked reduction of the uptake in the frontotemporal and parietal regions bilaterally (Fig. 1) . A few months after the first neurological assessment, the patient had a rapid progression to a severe dementia and developed marked pyramidal involvement of upper and lower limbs with an inability to walk. The patient became anarthric, dysphagic, and developed constipation. The nature of the dysarthria was both pseudobulbar and extrapyramidal. Lower motor neuron signs or symptoms were not present. Later the patient was admitted to a surgical department for intestinal sub-occlusion; during the hospitalization, a pulmonary embolism (PE) occurred. The patient died 4 years after the first neurological manifestations. Mutations of TARDBP, MAPT, and PGRN genes were excluded. The patient has been found positive for a GGGGCC hexanucleotide repeat expansion in the first intron of C9ORF72 gene (>50). Our patient developed a dementia with prominent behavioral disturbances at presentation, characterized mostly by psychosis with mystic themes. The neuropsychological evaluation Floris et al.
doi:10.1007/s00415-012-6444-3 pmid:22323211 pmcid:PMC4164047 fatcat:qkq3bha7zrdlbkavwckshyudiq