Schizophrenia syndrome due to C9ORF72 mutation case report: a cautionary tale and role of hybrid brain imaging!

BACKGROUND: Frontal variant frontotemporal dementia is a common cause of presenile dementia. A hexanucleotide expansion on chromosome 9 has recently been recognized as the most common genetic mutation cause of this illness. This sub-type tends to present psychiatrically with psychosis being a common presenting symptom before the onset of cognitive changes or brain atrophy. A few case series have been published describing the prominence of early psychotic symptoms, and lack of clear brain atrophy on clinical brain imaging imposing a challenge in reaching early accurate diagnosis. In this report, we present a case whereby the diagnosis of Schizophrenia syndrome was made and the patient was treated for years with multiple interventions for that syndrome before reaching the accurate diagnosis of Frontal variant frontotemporal dementia due to hexanucleotide expansion on chromosome 9. This diagnosis was confirmed after genetic testing and findings on a hybrid Positron Emission Tomography/Magnetic Resonance Imaging scanning. A 60-year-old female diagnosed with schizophrenia at age 50 after presenting with delusions and hallucinations, which proved to be refractor to several lines of pharmacological and non-pharmacological interventions including electroconvulsive therapy. Patient had a history of post-partum psychosis in her 20s. She was referred to cognitive neurology due to progressive decline in function. While clinical structural brain imaging data were not adequate to support an alternative neurological diagnosis, careful inquiry elicited a history of psychotic illness followed by progressive decline in a sister. Genetic testing confirmed hexanucleotide expansion on chromosome 9 mutation. The patient was offered a state-of-the-art FD-Glucose Positron Emission Tomography/Magnetic Resonance Imaging scan available at our centre. While volumetric Magnetic Resonance Imaging scan did not show volume loss in frontotemporal areas, the hybrid scan showed regionally specific deficit in FD-Glucose Positron Emission Tomography affecting medial superior frontal, insula, inferior temporal, thalamus, and anterior cingulate cortex consistent with behavioral variant frontotemporal dementia. CONCLUSIONS: This case highlights the importance of considering Frontal variant frontotemporal dementia due to hexanucleotide expansion on chromosome 9 when facing relatively late-onset, refractory schizophrenia-like syndrome. Careful history from all available sources to elicit family history of similar presentation is very important. Genetic testing and functional brain imaging can aid in confirming the diagnosis and potentially streamlining the management of these cases.

Rigid-body motion correction in hybrid PET/MRI using spherical navigator echoes.

Integrated positron emission tomography and magnetic resonance imaging (PET/MRI) is an imaging technology that provides complementary anatomical and functional information for medical diagnostics. Both PET and MRI are highly susceptible to motion artifacts due, in part, to long acquisition times. The simultaneous acquisition of the two modalities presents the opportunity to use MRI navigator techniques for motion correction of both PET and MRI data. For this task, we propose spherical navigator echoes (SNAVs)-3D k-space navigators that can accurately and rapidly measure rigid body motion in all six degrees of freedom. SNAVs were incorporated into turbo FLASH (tfl)-a product fast gradient echo sequence-to create the tfl-SNAV pulse sequence. Acquiring in vivo brain images from a healthy volunteer with both sequences first compared the tfl-SNAV and product tfl sequences. It was observed that incorporation of the SNAVs into the image sequence did not have any detrimental impact on the image quality. The SNAV motion correction technique was evaluated using an anthropomorphic brain phantom. Following a stationary reference image where the tfl-SNAV sequence was acquired along with simultaneous list-mode PET, three identical PET/MRI scans were performed where the phantom was moved several times throughout each acquisition. This motion-up to 11° and 14 mm-resulted in motion artifacts in both PET and MR images. Following SNAV motion correction of the MRI and PET list-mode data, artifact reduction was achieved for both the PET and MR images in all three motion trials. The corrected images have improved image quality and are quantitatively more similar to the ground truth reference images.

An investigation of changes in regional gray matter volume in cardiovascular disease patients, pre and post cardiovascular rehabilitation.

Cognitive function decline secondary to cardiovascular disease has been reported. However, little is known about the impact of coronary artery disease (CAD) on the aging brain macrostructure or whether exercise training, in the context of cardiovascular rehabilitation, can affect brain structure following a coronary event. This study employed voxel-based morphometry of high resolution structural MRI images to investigate; 1) changes in regional gray matter volume (GMV) in CAD patients compared to age-matched controls, and 2) the effects of a six-month exercise-based cardiovascular rehabilitation program on CAD-related GMV decline. Compared to controls, significant decreases in regional GMV were found in the superior, medial and inferior frontal gyrus; superior and inferior parietal gyrus; middle and superior temporal gyrus and in the posterior cerebellum of CAD patients. Cardiovascular rehabilitation was associated with the recovery of regional GMV in the superior frontal gyrus, superior temporal gyrus and posterior cerebellum of the CAD patients as well as the increase in GMV in the supplementary motor area. Total and regional GMV correlated with fitness level, defined by the maximal oxygen consumption (VO2max), at baseline but not after cardiovascular rehabilitation. This study demonstrates that cardiovascular disease can adversely affect age-related decline in GMV; and that these disease-related effects could be mitigated by moderate levels of exercise training as part of cardiovascular rehabilitation.