Early onset frontotemporal dementia with psychiatric presentation due to the C9ORF72 hexanucleotide repeat expansion: a case report.

BACKGROUND: Frontotemporal dementia (FTD) may present with psychiatric symptoms, usually together with neurological ones and in cases with a family history of dementia. We describe the case of an FTD behavioural variant with a psychiatric presentation and a normal neurological examination, due to a C9Orf72 gene mutation. CASE PRESENTATION: The patient was a 57 years-old Caucasian woman with a recent onset of bizarre behaviours and mystic delusions. She had a negative clinical history for previous psychiatric disorders and treatments and this was her first admission to a Psychiatry Ward. A careful assessment was performed including, beyond psychiatric evaluation, the following: blood sampling, neurological examination (including electroencephalogram, electroencephalogram with zygomatic electrodes, Positron Emission Tomography, Cerebrospinal Fluid Analysis), carotid artery Doppler ultrasound, brain Magnetic Resonance Imaging - angio Magnetic Resonance Imaging. Blood sampling for the genetic assessment of mutations associated to primary dementias was performed as well: the genes investigated were FUS, C9Orf72, PSEN-1, PSEN-2. CONCLUSIONS: Serological tests were negative, neurological examination was normal, instrumental examinations showed theta waves in the posterior temporal areas bilaterally and frontotemporal cortical atrophy bilaterally. The genetic assessment of mutations associated revealed she carried a GGGGCC hexanucleotide repeat expansion (at least 80 repeats) in C9Orf72 intron 1. Patients carrying the C9Orf72 mutation are likely to receive a psychiatric diagnosis (mainly mood disorder or schizophrenia) prior to correct diagnosis; this may be particularly problematic for those patients with no neurological signs to orientate diagnosis. Understanding the manner in which such FTD variant may present as a psychiatric syndrome, with a negative neurological examination, is essential to provide the best treatment for patients, as soon as possible, especially when the behavioural anomalies interfere with their care.

Asenapine in clinical practice: preliminary results from a naturalistic observational study.

OBJECTIVE: Asenapine, a second-generation antipsychotic, seems to be an effective and tolerable alternative to other treatments for patients with manic or mixed episodes. The objective of our naturalistic observational study was to identify asenapine responders and remitters and to compare responders vs. non-responders and remitters vs. non-remitters, as far as clinical and socio-demographic features are concerned. MATERIALS AND METHODS: We recruited patients with diagnosis of manic episode in bipolar I (BD I) or schizoaffective disorder, with clinical indication to asenapine treatment. Patients' assessment was performed at baseline (T0), after 1 week (T1) and after 4 weeks (T2) of treatment, with the Young Mania Rating Scale (YMRS; T0,T1,T2) and Hamilton Rating Scale for Depression (HAM-D; T0, T2). According to YMRS scores, we classified patients as early improvers, treatment responders, and treatment remitters. RESULTS: A significant decrease was found in HAM-D scores from baseline to T2, with no significant difference between remitters and non-remitters or responders vs. non-responders.The YMRS score significantly improved from baseline to T2, with a significant difference between remitters and non-remitters, but not between responders and non-responders. No difference was found between responders and non-responders as far as socio-demographic and clinical variables, and questionnaire baseline scores are concerned. Remitters and non-remitters showed significant differences in baseline YMRS scores, which were lower in the first and in the type of current episode, which was more frequently moderate in the former than in the latter. CONCLUSIONS: Early improvers comprised 51% of subjects, responders comprised 91.9% and remitters comprised 59.4%. Elderly manic patients with neurological impairment and/or dementia may have poorer therapeutic outcomes. Our results suggest that: 1) decision regarding treatment discontinuation should be cautious in patients who fail to have an early response to asenapine; 2) different diagnosis (BDor schizoaffective disorder) does not seem to have a significant impact on asenapine efficacy; 3) remission with asenapine is more likely to happen for less severe manic episodes. Further naturalistic studies on larger samples are required to support our findings.