FDG-PET findings and alcohol-responsive myoclonus in a patient with Unverricht-Lundborg disease

The aim of this report is to describe clinical, EEG, and neuroimaging findings in a patient with UnverrichtLundborg disease (ULD), the most common form of progressive myoclonus epilepsy (PME). A 23-year-old male with genetically confirmed ULD had a phenotype consisting of myoclonus, generalized seizures, intellectual disability, ataxia, and dysarthria. Myoclonus and gait disturbance were strongly ameliorated by alcohol consumption. EEG revealed a posterior dominant rhythm with alpha variant, mild bilateral slowing, and anterior-predominant epileptiform abnormalities. Brain MRI showed mild cerebellar atrophy. FDG-PET revealed hypometabolism more prominent in the posterior brainstem, thalami, frontal and parietal lobes. This report confirms that alcohol may ameliorate myoclonus in a subset of patients with PME, including genetically confirmed ULD. In addition, the presence of FDG-PET hypometabolism predominant in the frontoparietal region and thalami has not been previously described in ULD, yet is consistent with previous brain morphometry studies showing motor cortex and thalamic atrophy in ULD, and brings into question the possibility of a shared metabolic pattern with other PMEs, notably Lafora disease. (c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

The central region of the msp gene of Treponema denticola has sequence heterogeneity among clinical samples, obtained from patients with periodontitis

<p>Abstract</p> <p>Background</p> <p><it>Treponema denticola </it>is an oral spirochete involved in the pathogenesis and progression of periodontal disease. Of its virulence factors, the major surface protein (MSP) plays a role in the interaction between the treponeme and host. To understand the possible evolution of this protein, we analyzed the sequence of the <it>msp </it>gene in 17 <it>T. denticola </it>positive clinical samples.</p> <p>Methods</p> <p>Nucleotide and amino acid sequence of MSP have been determined by PCR amplification and sequencing in seventeen <it>T. denticola </it>clinical specimens to evaluate the genetic variability and the philogenetic relationship of the <it>T. denticola msp </it>gene among the different amplified sequence of positive samples. In silico antigenic analysis was performed on each MSP sequences to determined possible antigenic variation.</p> <p>Results</p> <p>The <it>msp </it>sequences showed two highly conserved 5' and 3' ends and a central region that varies substantially. Phylogenetic analysis categorized the 17 specimens into 2 principal groups, suggesting a low rate of evolutionary variability and an elevated degree of conservation of <it>msp </it>in clinically derived genetic material. Analysis of the predicted antigenic variability between isolates, demonstrated that the major differences lay between amino acids 200 and 300.</p> <p>Conclusion</p> <p>These findings showed for the first time, the nucleotide and amino acids variation of the <it>msp </it>gene in infecting <it>T. denticola</it>, <it>in vivo</it>. This data suggested that the antigenic variability found in to the MSP molecule, may be an important factor involved in immune evasion by <it>T. denticola</it>.</p

Cellular Targets of HIV-1 Protease: Just the Tip of the Iceberg?

Human immunodeficiency virus 1 (HIV-1) viral protease (PR) is one of the most studied viral enzymes and a crucial antiviral target. Despite its well-characterized role in virion maturation, an increasing body of research is starting to focus on its ability to cleave host cell proteins. Such findings are apparently in contrast with the dogma of HIV-1 PR activity being restricted to the interior of nascent virions and suggest catalytic activity within the host cell environment. Given the limited amount of PR present in the virion at the time of infection, such events mainly occur during late viral gene expression, mediated by newly synthesized Gag-Pol polyprotein precursors, rather than before proviral integration. HIV-1 PR mainly targets proteins involved in three different processes: those involved in translation, those controlling cell survival, and restriction factors responsible for innate/intrinsic antiviral responses. Indeed, by cleaving host cell translation initiation factors, HIV-1 PR can impair cap-dependent translation, thus promoting IRES-mediated translation of late viral transcripts and viral production. By targeting several apoptotic factors, it modulates cell survival, thus promoting immune evasion and viral dissemination. Additionally, HIV-1 PR counteracts restriction factors incorporated in the virion that would otherwise interfere with nascent virus vitality. Thus, HIV-1 PR appears to modulate host cell function at different times and locations during its life cycle, thereby ensuring efficient viral persistency and propagation. However, we are far from having a complete picture of PR-mediated host cell modulation, which is emerging as a field that needs further investigation

Ictal characteristics of psychogenic nonepileptic seizures: what we have learned from video/EEG recordings - a literature review.

Psychogenic nonepileptic seizures (PNES) are highly prevalent in selected populations, with a strong impact in terms of morbidity and social cost. The gold standard for PNES diagnosis is video/EEG recording of a typical attack. However this technique is costly and not always available. In addition, many patients are treated with antiepileptic drugs for several years before undergoing video/EEG recording. The diagnosis is further complicated by concomitant epileptic seizures in some patients with PNES. Therefore, a good knowledge of PNES semiology is important for early screening of patients for video/EEG recording and for correct interpretation of the examination. We reviewed the literature on video/EEG studies reporting ictal PNES semiology to identify features indicative of psychogenic or epileptic seizures. Several features appeared to be useful in the clinical setting

Cortical myoclonic tremor induced by fixation-off sensitivity An unusual cause of insomnia

Fixation-off sensitivity (FOS) refers to seizures or EEG abnormalities elicited by the elimination of central vision/fixation, even in the presence of light. Typically, a paroxysmal discharge occurs within 1\u20133 seconds of eye closure, persists throughout the eye-closed state, and disappears immediately on eye opening. FOS occurs mainly in childhood occipital epilepsies.1 It has also been reported in generalized and focal epilepsies of structural/unknown etiology, eyelid myoclonia with absences, and rarely in non-epileptic individuals. We describe a patient with FOS associated with cortical myoclonic tremor (CMT) so intense and severe at wake\u2013sleep transition to cause sleep-onset insomnia as the main complaint

Narcolepsy Type 1 and Idiopathic Generalized Epilepsy: Diagnostic and Therapeutic Challenges in Dual Cases

The aim of this study is to describe the possible co-occurrence of narcolepsy type 1 and generalized epilepsy, focusing on diagnostic challenge and safety of dual treatments

Phenotype variability of GLUT1 deficiency syndrome: Description of a case series with novel SLC2A1 gene mutations

Glucose transporter type 1 (GLUT1) deficiency due to SLC2A1 mutations causes a wide spectrum of neurologic disorders ranging from severe encephalopathy with developmental delay, epilepsy, ataxia, and acquired microcephaly to atypical less severe variants. Early diagnosis is crucial for prompt initiation of a ketogenic diet. Recognizing GLUT1 deficiency syndrome (GLUT1DS) may be challenging and results in delayed diagnosis. Here we describe the clinical and molecular findings of patients with SLC2A1 mutations referred to our adult Epilepsy Center. Patients with a clinical history suggestive of GLUT1DS were screened for SLC2A1 mutations. Blood samples were collected from probands and first-degree relatives. A lumbar puncture was performed in two patients in fasting state, and cerebrospinal fluid and blood glucose measurement were undertaken at the same time. Since 2010, 19 GLUT1DS probands have been screened for SLC2A1 mutations. We identified four different SLC2A1 mutations in three sporadic cases and one family. Three mutations (c.130_135delTACAAC, c.342_343insA, and c.845A > G) were novel, whereas one was previously reported in the literature associated with a different phenotype (c.497_499delTCG). Here we describe a small case series of patients with sporadic and familial GLUT1DS presenting with a broad phenotypic heterogeneity which is likely to be responsible for the considerable delay in diagnosis

Predictors of Health-Related Quality of Life and Adjustment to Prostate Cancer During Active Surveillance

Abstract Background Active surveillance (AS) is emerging as an alternative approach to limit the risk of overtreatment and impairment of quality of life (QoL) in patients with low-risk localised prostate cancer. Although most patients report high levels of QoL, some men may be distressed by the idea of living with untreated cancer. Objective To identify factors associated with poor QoL during AS. Design, setting, and participants Between September 2007 and March 2012, 103 patients participated in the Prostate Cancer Research International Active Surveillance (PRIAS) QoL study. Mental health (Symptom Checklist-90), demographic, clinical, and decisional data were assessed at entrance in AS. Health-related QoL (HRQoL) Functional Assessment of Cancer Therapy-Prostate version and Mini-Mental Adjustment to Cancer outcomes were assessed after 10 mo of AS. Outcome measurements and statistical analysis Multivariate logistic regression models were used to identify predictors of low (<25th percentile) HRQoL, adjustment to cancer, and a global QoL index at 10 mo after enrolment. Results and limitations The mean age of the study patients was 67 yr (standard deviation: \ub17 yr). Lack of partner (odds ratio [OR]: 0.08; p = 0.009) and impaired mental health (OR: 1.2, p = 0.1) were associated with low HRQoL (p = 0.006; area under the curve [AUC]: 0.72). The maladaptive adjustment to cancer (p = 0.047; AUC: 0.60) could be predicted by recent diagnosis (OR: 3.3; p = 0.072). Poor global QoL (overall p = 0.02; AUC: 0.85) was predicted by impaired mental health (OR: 1.16; p = 0.070) and time from diagnosis to enrolment in AS 18 core specimens (OR: 0.89; p = 0.029) were predictors of better QoL. Limitations of this study were the small sample size and the lack of a control group. Conclusions Factors predicting poor QoL were lack of a partner, impaired mental health, recent diagnosis, influence of clinicians and lower number of core samples taken at diagnostic biopsy. Educational support from physicians and emotional/social support should be promoted in some cases to prevent poor QoL

Prostate cancer patients on active surveillance: is physical activity associated with health-related quality of life?

The benefits of physical activity (PA), even of low intensity, on disease progression, urinary symptoms, psychological wellbeing, and health-related quality of life (HRQoL) of prostate cancer (PCa) patients have been documented by several studies (Richman 2011; Chipperfield 2014; Thorsen 2008). To our knowledge, there are no studies investigating the effects of PA on HRQoL among PCa patients in Active Surveillance (AS). The present research aimed to study the relationship between the level of PA performed by patients in AS and their HRQoL