The behavioural variant frontotemporal dementia phenocopy syndrome is a distinct entity - evidence from a longitudinal study.

BACKGROUND: This study aimed to i) examine the frequency of C9orf72 expansions in a cohort of patients with the behavioural variant frontotemporal dementia (bvFTD) phenocopy syndrome, ii) observe outcomes in a group of phenocopy syndrome with very long term follow-up and iii) compare progression in a cohort of patients with the phenocopy syndrome to a cohort of patients with probable bvFTD. METHODS: Blood was obtained from 16 phenocopy cases. All met criteria for possible bvFTD and were labeled as phenocopy cases if they showed no functional decline, normal cognitive performance on the Addenbrooke's Cognitive Examination-Revised (ACE-R) and a lack of atrophy on brain imaging, over at least 3 years of follow-up. In addition, we obtained very long term follow-up data in 6 cases. A mixed model analysis approach determined the pattern of change in cognition and behaviour over time in phenocopy cases compared to 27 probable bvFTD cases. RESULTS: All 16 patients were screened for the C9orf72 expansion that was present in only one (6.25%). Of the 6 cases available for very long-term follow-up (13 - 21 years) none showed progression to frank dementia. Moreover, there was a decrease in the caregiver ratings of behavioural symptoms over time. Phenocopy cases showed significantly slower rates of progression compared to probable bvFTD patients (p < 0.006). CONCLUSION: The vast majority of patients with the bvFTD phenocopy syndrome remain stable over many years. An occasional patient can harbor the C9orf72 expansion. The aetiology of the remaining cases remains unknown but it appears very unlikely to reflect a neurodegenerative syndrome due to lack of clinical progression or atrophy on imaging

Acute urinary retention in a 23-year-old woman with mild encephalopathy with a reversible splenial lesion: a case report

<p>Abstract</p> <p>Introduction</p> <p>Patients with clinically mild encephalitis/encephalopathy with a reversible splenial lesion present with relatively mild central nervous system disturbances. Although the exact etiology of the condition remains poorly understood, it is thought to be associated with infective agents. We present a case of a patient with mild encephalitis/encephalopathy with a reversible splenial lesion, who had the unusual feature of acute urinary retention.</p> <p>Case presentation</p> <p>A 23-year-old Japanese woman developed mild confusion, gait ataxia, and urinary retention seven days after onset of fever and headache. Magnetic resonance imaging demonstrated T2 prolongation in the splenium of the corpus callosum and bilateral cerebral white matter. These magnetic resonance imaging abnormalities disappeared two weeks later, and all of the symptoms resolved completely within four weeks. Except for the presence of acute urinary retention (due to underactive detrusor without hyper-reflexia), the clinical and radiologic features of our patient were consistent with those of previously reported patients with mild encephalitis/encephalopathy with a reversible splenial lesion. To the best of our knowledge, this is the first report of acute urinary retention recognized in a patient with mild encephalitis/encephalopathy with a reversible splenial lesion.</p> <p>Conclusion</p> <p>Our findings suggest that mild encephalitis/encephalopathy with a reversible splenial lesion can be associated with impaired bladder function and indicate that acute urinary retention in this benign disorder should be treated immediately to avoid bladder injury.</p

Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura

Publisher Copyright: © 2023, The Author(s).Migraine is a complex neurovascular disease with a range of severity and symptoms, yet mostly studied as one phenotype in genome-wide association studies (GWAS). Here we combine large GWAS datasets from six European populations to study the main migraine subtypes, migraine with aura (MA) and migraine without aura (MO). We identified four new MA-associated variants (in PRRT2, PALMD, ABO and LRRK2) and classified 13 MO-associated variants. Rare variants with large effects highlight three genes. A rare frameshift variant in brain-expressed PRRT2 confers large risk of MA and epilepsy, but not MO. A burden test of rare loss-of-function variants in SCN11A, encoding a neuron-expressed sodium channel with a key role in pain sensation, shows strong protection against migraine. Finally, a rare variant with cis-regulatory effects on KCNK5 confers large protection against migraine and brain aneurysms. Our findings offer new insights with therapeutic potential into the complex biology of migraine and its subtypes.Peer reviewe

Predictive factors for time to progression after hyperthermic mitomycin C treatment for high-risk non-muscle invasive urothelial carcinoma of the bladder: an observational cohort study of 97 patients

Hyperthermic mitomycin (HM) is a novel treatment modality for selected patients with high-risk non-muscle invasive bladder cancer (NMIBC). We sought to determine predictors of response to this therapy.A longitudinal, cohort study of 97 patients with high-risk NMIBC treated with ≥4 HM instillations on a prophylactic schedule was conducted. The primary outcome was time-to-progression survival; secondary outcomes were overall survival, cancer-specific survival, and adverse events. Descriptive statistics, Kaplan-Meier survival analyses, Cox proportional hazards modelling, and univariate and multivariable regression were performed.The presence of initial complete response (CR; no evidence of disease at first check video-cystoscopy and urine cytology) post-HM treatment was an independent predictor of good response to HM. Female patients and those without carcinoma in situ (CIS) also appeared to respond better to the intervention. The overall bladder preservation rate at a median of 27 months was 81.4%; 17/97 (17.5%) patients died during the course of the study.High-risk NMIBC patients can be safely treated with HM and have good oncological outcome. However, those without an initial CR have a poor prognosis and should be counselled towards adopting other treatment methodologies such as cystectomy. Female gender and lack of CIS may be good prognostic indicators for response to HM. © 2015 S. Karger AG, Basel