Faster Cortical Thinning and Surface Area Loss in Presymptomatic and Symptomatic C9orf72 Repeat Expansion Adult Carriers.

OBJECTIVE: C9orf72 expansion is the most common genetic cause of frontotemporal dementia (FTD). We examined aging trajectories of cortical thickness (CTh) and surface area in C9orf72 expansion adult carriers compared to healthy controls to characterize preclinical cerebral changes leading to symptoms. METHODS: Data were obtained from the Genetic Frontotemporal Dementia Initiative. T1-weighted magnetic resonance imaging scans were processed with CIVET 2.1 to extract vertex-wide CTh and cortical surface area (CSA). Symptomatic and presymptomatic subjects were compared to age-matched controls using mixed-effects models, controlling for demographic variables. Aging trajectories were compared between carriers and noncarriers by testing the "age by genetic status" interaction. False discovery rate corrections were applied to all vertex-wide analyses. RESULTS: The sample included 640 scans from 386 subjects, including 54 symptomatic C9orf72 carriers (72.2% behavioral variant FTD), 83 asymptomatic carriers, and 249 controls (age range = 18-86 years). Symptomatic carriers showed fairly symmetric reduction in CTh/CSA in most of the frontal lobes, in addition to large temporoparietal areas. Presymptomatic subjects had reduced CTh/CSA in more restricted areas of the medial frontoparietal lobes, in addition to scattered lateral frontal, parietal, and temporal areas. These differences were explained by faster cortical thinning linearly throughout adulthood in a similar anatomical distribution, with differences emerging in the early 30s. CSA reduction was also faster in mutation carriers predominantly in the ventrofrontal regions. INTERPRETATION: C9orf72 mutation carriers have faster cortical thinning and surface loss throughout adulthood in regions that show atrophy in symptomatic subjects. This suggests that the pathogenic effects of the mutation lead to structural cerebral changes decades prior to symptoms. ANN NEUROL 2020 ANN NEUROL 2020;88:113-122.

Clozapine Safety and Efficacy for Interictal Psychotic Disorder in Pharmacoresistant Epilepsy.

Since the middle of the 19th century, both neurologists and psychiatrists have linked psychosis and epilepsy. Clozapine, the most effective antipsychotic drug, alters electroencephalographic activity and carries a significant risk of causing seizures. Unfortunately, this risk limits the drug's potential use in treating pharmacoresistant psychosis in patients with epilepsy. We present a unique case in which we used clozapine successfully as a last resort treatment for chronic interictal psychosis in a 43-year-old woman with severe pharmacoresistant epilepsy and recurrent status epilepticus. Her psychotic symptoms improved markedly without an increase in the frequency of seizures despite gradual titration of the clozapine dose up to 300 mg daily. Her response demonstrates that, properly monitored, clozapine can be an effective treatment for psychosis even in patients with daily seizures.

Cognitive-Behavioral Therapy in Intensive Case Management: A Multimethod Quantitative-Qualitative Study.

Cognitive-behavioral therapy (CBT) has been shown to improve clinical outcomes in schizophrenia and severe and persistent mental illness, but access to it remains limited. One potential way to improve access to CBT is to provide it through intensive case management (ICM) teams. A 90-week quality improvement study was designed to assess if CBT could be implemented in ICM teams. Self-selected ICM clinicians (N=8) implemented CBT with their patients (N=40). These clinicians attended weekly seminars (36 h total) and group supervision (1.5 h/wk). Patient outcomes for this group were compared with those of other clinicians who did not attend the seminars [treatment as usual (TAU) clinicians (N=4)] and their patient population (N=49). Prescore and postscore on the Clinical Global Impressions scale and a quality-of-life scale (Montreal Life Skill Survey) were analyzed for completers in both groups (Clinical Global Impressions scores were analyzed for 25 patients in the CBT group and 29 patients in the TAU group). Weekly session reports by clinicians in the CBT group measured CBT interventions, session focus, and satisfaction with CBT. Qualitative data were obtained from clinicians in the CBT group. After 90 weeks, patients in the CBT group had fewer negative symptoms compared with patients in the TAU group. Our qualitative data describe 2 trajectories of patients: those who improved with CBT and those who did not, and they suggest factors that may impact patient trajectories in CBT. This study suggests that CBT can be used effectively in ICM teams working with patients suffering from severe and persistent mental illness.