Clinical, Cortical, Subcortical, and White Matter Features of Right Temporal Variant FTD.

The distinct clinical and radiological characteristics of right temporal variant FTD have only been recently recognized. METHODS: Eight patients with right temporal variant FTD were prospectively recruited and underwent a standardised neuropsychological assessment, clinical MRI, and quantitative neuroimaging. RESULTS: Our voxelwise grey analyses captured bilateral anterior and mesial temporal grey matter atrophy with a clear right-sided predominance. Bilateral hippocampal involvement was also observed, as well as disease burden in the right insular and opercula regions. White matter integrity alterations were also bilateral in anterior temporal and sub-insular regions with a clear right-hemispheric predominance. Extra-temporal white matter alterations have also been observed in orbitofrontal and parietal regions. Significant bilateral but right-predominant thalamus, putamen, hippocampus, and amygdala atrophy was identified based on subcortical segmentation. The clinical profile of our patients was dominated by progressive indifference, decline in motivation, loss of interest in previously cherished activities, incremental social withdrawal, difficulty recognising people, progressive language deficits, increasingly rigid routines, and repetitive behaviours. CONCLUSIONS: Right temporal variant FTD has an insidious onset and may be mistaken for depression at symptom onset. It manifests in a combination of apathy, language, and behavioural features. Quantitative MR imaging captures a characteristic bilateral but right-predominant temporal imaging signature with extra-temporal frontal and parietal involvement.

Limbic Network and Papez Circuit Involvement in ALS: Imaging and Clinical Profiles in GGGGCC Hexanucleotide Carriers in C9orf72 and C9orf72-Negative Patients.

Background: While frontotemporal involvement is increasingly recognized in Amyotrophic lateral sclerosis (ALS), the degeneration of limbic networks remains poorly characterized, despite growing evidence of amnestic deficits, impaired emotional processing and deficits in social cognition. Methods: A prospective neuroimaging study was conducted with 204 individuals with ALS and 111 healthy controls. Patients were stratified for hexanucleotide expansion status in C9orf72. A deep-learning-based segmentation approach was implemented to segment the nucleus accumbens, hypothalamus, fornix, mammillary body, basal forebrain and septal nuclei. The cortical, subcortical and white matter components of the Papez circuit were also systematically evaluated. Results: Hexanucleotide repeat expansion carriers exhibited bilateral amygdala, hypothalamus and nucleus accumbens atrophy, and C9orf72 negative patients showed bilateral basal forebrain volume reductions compared to controls. Both patient groups showed left rostral anterior cingulate atrophy, left entorhinal cortex thinning and cingulum and fornix alterations, irrespective of the genotype. Fornix, cingulum, posterior cingulate, nucleus accumbens, amygdala and hypothalamus degeneration was more marked in C9orf72-positive ALS patients. Conclusions: Our results highlighted that mesial temporal and parasagittal subcortical degeneration is not unique to C9orf72 carriers. Our radiological findings were consistent with neuropsychological observations and highlighted the importance of comprehensive neuropsychological testing in ALS, irrespective of the underlying genotype.

Progressive Cerebrocerebellar Uncoupling in Sporadic and Genetic Forms of Amyotrophic Lateral Sclerosis.

BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is predominantly associated with motor cortex, corticospinal tract (CST), brainstem, and spinal cord degeneration, and cerebellar involvement is much less well characterized. However, some of the cardinal clinical features of ALS, such as dysarthria, dysphagia, gait impairment, falls, and impaired dexterity, are believed to be exacerbated by coexisting cerebellar pathology. Cerebellar pathology may also contribute to cognitive, behavioral, and pseudobulbar manifestations. Our objective was to systematically assess both intracerebellar pathology and cerebrocerebellar connectivity alterations in a genetically stratified cohort of ALS. METHODS: A prospective, multimodal neuroimaging study was conducted to evaluate the longitudinal evolution of intracerebellar pathology and cerebrocerebellar connectivity, using structural and functional measures. RESULTS: A total of 113 healthy controls and 212 genetically stratified individuals with ALS were included: (1) C9orf72 hexanucleotide carriers ("C9POS"), (2) sporadic patients who tested negative for ALS-associated genetic variants, and (3) intermediate-length CAG trinucleotide carriers in ATXN2 ("ATXN2"). Flocculonodular lobule (padj = 0.014, 95% CI -5.06e-5 to -3.98e-6) and crura (padj = 0.031, 95% CI -1.63e-3 to -5.55e-5) volume reductions were detected at baseline in sporadic patients. Cerebellofrontal and cerebelloparietal structural connectivity impairment was observed in both C9POS and sporadic patients at baseline, and both projections deteriorated further over time in sporadic patients (padj = 0.003, t(249) = 3.04 and padj = 0.05, t(249) = 1.93). Functional cerebelloparietal uncoupling was evident in sporadic patients at baseline (padj = 0.004, 95% CI -0.19 to -0.03). ATXN2 patients exhibited decreased cerebello-occipital functional connectivity at baseline (padj = 0.004, 95% CI -0.63 to -0.06), progressive cerebellotemporal functional disconnection (padj = 0.025, t(199) = -2.26), and progressive flocculonodular lobule degeneration (padj = 0.017, t(249) = -2.24). C9POS patients showed progressive ventral dentate atrophy (padj = 0.007, t(249) = -2.75). The CSTs (padj < 0.001, 95% CI 4.89e-5 to 1.14e-4) and transcallosal interhemispheric fibers (padj < 0.001, 95% CI 5.21e-5 to 1.31e-4) were affected at baseline in C9POS and exhibited rapid degeneration over the 4 time points. The rate of decline in CST and corpus callosum integrity was faster than the rate of cerebrocerebellar disconnection (padj = 0.001, t(190) = 6.93). DISCUSSION: ALS is associated with accruing intracerebellar disease burden as well as progressive corticocerebellar uncoupling. Contrary to previous suggestions, we have not detected evidence of compensatory structural or functional changes in response to supratentorial degeneration. The contribution of cerebellar disease burden to dysarthria, dysphagia, gait impairment, pseudobulbar affect, and cognitive deficits should be carefully considered in clinical assessments, monitoring, and multidisciplinary interventions.

Supra- and infra-tentorial degeneration patterns in primary lateral sclerosis: a multimodal longitudinal neuroradiology study.

BACKGROUND: Primary lateral sclerosis (PLS) is traditionally solely associated with progressive upper motor neuron dysfunction manifesting in limb spasticity, gait impairment, bulbar symptoms and pseudobulbar affect. Recent studies have described frontotemporal dysfunction in some patients resulting in cognitive manifestations. Cerebellar pathology is much less well characterised despite sporadic reports of cerebellar disease. METHODS: A multi-timepoint, longitudinal neuroimaging study was conducted to characterise the evolution of both intra-cerebellar disease burden and cerebro-cerebellar connectivity. The volumes of deep cerebellar nuclei, cerebellar cortical volumes, cerebro-cerebellar structural and functional connectivity were assessed longitudinally in a cohort of 43 individuals with PLS. RESULTS: Cerebello-frontal, -temporal, -parietal, -occipital and cerebello-thalamic structural disconnection was detected at baseline based on radial diffusivity (RD) and cerebello-frontal decoupling was also evident based on fractional anisotropy (FA) alterations. Functional connectivity changes were also detected in cerebello-frontal, parietal and occipital projections. Volume reductions were identified in the vermis, anterior lobe, posterior lobe, and crura. Among the deep cerebellar nuclei, the dorsal dentate was atrophic. Longitudinal follow-up did not capture statistically significant progressive changes. Significant primary motor cortex atrophy and inter-hemispheric transcallosal degeneration were also captured. CONCLUSIONS: PLS is not only associated with upper motor neuron dysfunction, but cerebellar cortical volume loss and deep cerebellar nuclear atrophy can also be readily detected. In addition to intra-cerebellar disease burden, cerebro-cerebellar connectivity alterations also take place. Our data add to the evolving evidence of widespread neurodegeneration in PLS beyond the primary motor regions. Cerebellar dysfunction in PLS is likely to exacerbate bulbar, gait and dexterity impairment and contribute to pseudobulbar affect.

Non-dipping nocturnal blood pressure correlates with obstructive sleep apnoea severity in normotensive subjects and may reverse with therapy.

BACKGROUND: Obstructive sleep apnoea (OSA) is strongly associated with systemic hypertension, but there are limited data on the relationship with blood pressure (BP) in normotensive subjects. Here, we examined the relationship of OSA with nocturnal BP in a documented diurnal normotensive cohort, explored potential intermediate pathways and assessed the effects on BP of continuous positive airways pressure (CPAP) therapy. METHODS: 65 males referred for assessment of possible OSA and normotensive on 24-hour BP monitoring underwent overnight inpatient polysomnography (age 41±7 years, body mass index (BMI) 34±6 kg·m-2, apnoea-hypopnoea index (AHI) 14 (interquartile range 5-26)). Urine and serum were assessed for markers of sympathetic activation, renin-angiotensin-aldosterone system activity, oxidative stress, endothelial function and systemic inflammation. In a subset of patients, 24-hour BP monitoring was repeated after CPAP therapy. RESULTS: Within this normotensive cohort, night-time systolic and diastolic BP and nocturnal BP dip were highest in the fourth OSA severity quartile (p<0.05). Nocturnal BP dip correlated with AHI (r=-0.327, p<0.05) and oxygen desaturation index (ODI) (r=-0.371, p<0.05), but only ODI was an independent predictor of BP dip (B=-0.351, p<0.01) and non-dipping status (B=0.046, p<0.05). Overnight urinary norepinephrine correlated with nocturnal systolic BP (r=0.387, p<0.01) with a trend towards correlation with systolic dipping (p=0.087). In 20 CPAP-treated patients, night-time systolic BP decreased (p<0.05) and mean nocturnal BP dip increased (p≤0.05). CONCLUSION: In this normotensive cohort, OSA severity was associated with higher nocturnal BP, which improved following CPAP therapy, and intermittent hypoxia was the most important OSA-related variable in this relationship.

First Autochthonous West Nile Lineage 2 and Usutu Virus Infections in Humans, July to October 2018, Czech Republic.

We present epidemiological, clinical and laboratory findings of five Czech patients diagnosed with autochthonous mosquito-borne disease-four patients with confirmed West Nile virus (WNV) and one patient with Usutu virus (USUV) infections, from July to October 2018, including one fatal case due to WNV. This is the first documented human outbreak caused by WNV lineage 2 in the Czech Republic and the first record of a neuroinvasive human disease caused by USUV, which illustrates the simultaneous circulation of WNV and USUV in the country.

Nondipping Nocturnal Blood Pressure Predicts Sleep Apnea in Patients With Hypertension.

STUDY OBJECTIVES: Systemic hypertension is highly prevalent in obstructive sleep apnea (OSA) but there are limited data on OSA prevalence in cohorts with hypertension comparing dippers and nondippers. We investigated this relationship in a clinic-based cohort of patients with hypertension who were not screened for any pretest possibility of OSA. METHODS: A total of 100 patients with hypertension aged (mean ± SD) 58 ± 10 years, body mass index 30.5 ± 6.1 kg/m2, and Epworth Sleepiness Scale score 6 ± 4 were included. All underwent overnight attended sleep studies and 24-hour ambulatory blood pressure monitoring. The primary study end-point was OSA prevalence based on the standard criteria of apnea-hypopnea index (AHI) ≥ 15 events/h in patients with dipping and nondipping nocturnal blood pressure. RESULTS: Results showed 10.5% of dippers and 43.5% of nondippers had an AHI ≥ 15 (chi-square P = .001). In univariate analysis, AHI correlated significantly with blood pressure dip (r = -.26, P < .05), as did ESS (r = -.28, P < .05). In linear regression, AHI predicted the magnitude of blood pressure dip (standardised ß = -.288, P = .03), whereas age, body mass index, systolic blood pressure and diastolic blood pressure did not. CONCLUSIONS: Patients with nondipping nocturnal blood pressure are at high risk of OSA, regardless of symptom profile, which supports the recommendation that such patients should be assessed for co-existing OSA.

[Is hepatitis E just an imported infection in the Czech Republic?].

The article deals with the issue of virus hepatitis E (VHE) whose increased incidence emerged in some Moravian districts in the monitored period from January 2004 to June 2005. The uncoated RNA virus, which is not taxonomically classified at present, is considered to be a causative agent of VHE. In the BIO-PLUS, the company with limited liability, 1 078 sera samples from various hospital and outpatient departments were tested by the ELISA method. The positive IgG and IgM VHE antibodies were found in 24 cases, that corresponded to the clinic condition of patient and to the biochemical findings showing an acute hepatitis. Other virus hepatitis (VHA, VHB, VHC) as well as further hepatotrophic infections were negative in all cases. Until recently the VHE was considered as an imported infection from endemic areas. However, only seven of our 24 positive cases showed a stay abroad, the traveller history was negative in the rest. In our work 18 VHE cases, diagnosed in the infection departments of the hospitals in Breclav and Prostejov, are analysed in details in the referred period.