Objective
Most patients with Dravet syndrome (DS) have unremarkable neuroimaging studies. However, a small number of patients exhibit focal abnormalities that may modify the epilepsy phenotype. We ...report a case series of DS patients carrying SCN1A variants concurrent with additional focal brain lesions, aiming to provide details regarding their clinical course, electrographic findings, and imaging features.
Methods
We reviewed the electronic medical records of patients with developmental and epileptic encephalopathies in our center, from January 2000 to December 2022, identifying 90 patients with DS resulting from SCN1A variants. Of these, patients displaying focal brain lesions were eligible.
Results
Five patients (4 males and 1 female), with median age of 26 years, were included. All exhibited clinical and electroencephalographic features consistent with the DS spectrum. Sequencing analysis of the SCN1A gene identified pathogenic variants. Magnetic resonance imaging (MRI) revealed focal cortical dysplasia (FCD) in two patients, while the remaining three had cystic lesions. Three patients had previously undergone resective epilepsy surgery in other centers, with no improvement in seizure frequency. Neuropathology studies revealed the presence of FCD type IIA, intracranial teratomas, and dysembryoplastic neuroepithelial tumor (DNET).
Significance
When an individual with an established diagnosis of genetic epilepsy and a focal lesion on MRI is undergoing preoperative evaluation, it is crucial to conduct a comprehensive analysis to understand the relevance of the focal finding for the patient's phenotype and thus anticipate potential surgical outcomes. In instances where epilepsy in DS patients is influenced by a specific focal structural lesion, resective surgery should be carefully considered after precise pharmacological treatment, acknowledging the persistent influence of an SCN1A variant on expected outcomes.
This review aims to provide an updated perspective of epilepsy genetics and precision medicine in adult patients, with special focus on developmental and epileptic encephalopathies (DEEs), covering ...relevant and controversial issues, such as defining candidates for genetic testing, which genetic tests to request and how to interpret them. A literature review was conducted, including findings in the discussion and recommendations. DEEs are wide and phenotypically heterogeneous electroclinical syndromes. They generally have a pediatric presentation, but patients frequently reach adulthood still undiagnosed. Identifying the etiology is essential, because there lies the key for precision medicine. Phenotypes modify according to age, and although deep phenotyping has allowed to outline certain entities, genotype-phenotype correlations are still poor, commonly leading to long-lasting diagnostic odysseys and ineffective therapies. Recent adult series show that the target patients to be identified for genetic testing are those with epilepsy and different risk factors. The clinician should take active part in the assessment of the pathogenicity of the variants detected, especially concerning variants of uncertain significance. An accurate diagnosis implies precision medicine, meaning genetic counseling, prognosis, possible future therapies, and a reduction of iatrogeny. Up to date, there are a few tens of gene mutations with additional concrete treatments, including those with restrictive/substitutive therapies, those with therapies modifying signaling pathways, and channelopathies, that are worth to be assessed in adults. Further research is needed regarding phenotyping of adult syndromes, early diagnosis, and the development of targeted therapies.
Despite the increasing evidence of the benefit of corticosteroids for the treatment of moderate-severe coronavirus disease 2019 (COVID-19) patients, no data are available about the potential role of ...high doses of steroids for these patients. We evaluated the mortality, the risk of need for mechanical ventilation (MV), or death and the risk of developing a severe acute respiratory distress syndrome (ARDS) between high (HD) and standard doses (SD) among patients with a severe COVID-19. All consecutive confirmed COVID-19 patients admitted to a single center were selected, including those treated with steroids and an ARDS. Patients were allocated to the HD (≥ 250 mg/day of methylprednisolone) of corticosteroids or the SD (≤ 1.5 mg/kg/day of methylprednisolone) at discretion of treating physician. Five hundred seventy-three patients were included: 428 (74.7%) men, with a median (IQR) age of 64 (54–73) years. In the HD group, a worse baseline respiratory situation was observed and male gender, older age, and comorbidities were significantly more common. After adjusting by baseline characteristics, HDs were associated with a higher mortality than SD (adjusted OR 2.46, 95% CI 1.59–3.81,
p
< 0.001) and with an increased risk of needing MV or death (adjusted OR 2.35,
p
= 0.001). Conversely, the risk of developing a severe ARDS was similar between groups. Interaction analysis showed that HD increased mortality exclusively in elderly patients. Our real-world experience advises against exceeding 1–1.5 mg/kg/day of corticosteroids for severe COVID-19 with an ARDS, especially in older subjects. This reinforces the rationale of modulating rather than suppressing immune responses in these patients.
The role of immunosuppression among coronavirus disease 2019 (COVID‐19) patients has not been elucidated and management may be challenging. This observational study included confirmed COVID‐19 ...patients. The primary endpoint was the development of moderate–severe acute respiratory distress syndrome (ARDS). Time to moderate–severe ARDS, the need for mechanical or noninvasive ventilation (MV/NIV), death, and a composite of death or MV/NIV were secondary endpoints. Of 138 patients included, 27 (19.6%) were immunosuppressed (IS) and 95 (68.8%) were male, with a median (IQR) age of 68 (54–78) years. A significantly lower proportion of IS patients (25.9%) compared to non‐IS patients (52.3%) developed moderate–severe ARDS, in both unadjusted (0.32; 95% CI, 0.13–0.83; p = .017) and adjusted (aOR, 0.25; 95% CI, 0.08–0.80; p = .019) analyses. After stratifying by pathologies, only IS patients with autoimmune diseases remained significant (aOR 0.25; 95% CI, 0.07–0.98; p = .046). Nonsignificant trends toward a longer time to moderate or severe ARDS, a lower need for MV/NIV, and a lower risk of death or MV/NIV were detected among IS. In our cohort of COVID‐19 patients, nonsevere immunosuppression was associated with a lower risk of moderate–severe ARDS, especially among AD. This suggests a potential protective effect from a hypothesized hyper‐inflammatory response.
Immunosuppression (IS) and autoimmune disease (AD) are prevalent in patients with severe coronavirus disease 2019 (COVID-19), but their impact on its clinical course is unknown. We investigated ...relationships between IS, AD, and outcomes in patients hospitalized with COVID-19. Data on consecutive admissions for COVID-19 were extracted retrospectively from medical records. Patients were assigned to one of four cohorts, according to whether or not they had an AD (AD and NAD) or were immunosuppressed (IS and NIS). The primary endpoint was development of severe acute respiratory distress syndrome (ARDS); secondary endpoints included death, and a composite of mechanical ventilation (MV) or death. A total of 789 patients were included: 569 (72.1%) male, 76 (9.6%) with an AD, and 63 (8.0%) with IS. Relative to the NIS-NAD cohort, patients in the IS-AD cohort had a significantly reduced risk of severe ARDS (adjusted hazard ratio aHR 0.42; 95% confidence interval CI 0.23–0.80;
p
= 0.008). No significant relationships between IS or AD status and either death or the composite of MV and death were identified, although a trend towards higher mortality was identified in the IS-NAD cohort (aHR vs NIS-NAD 1.71; 95% CI 0.94–3.12;
p
= 0.081). Patients in this cohort also had higher median serum levels of interleukin-6 compared with IS-AD patients (98.2 vs 21.6 pg/mL;
p
= 0.0328) and NIS-NAD patients (29.1 pg/mL;
p
= 0.0057). In conclusion, among patients hospitalized with COVID-19, those receiving immunosuppressive treatment for an AD may have a reduced risk of developing severe ARDS.
The diagnostic criteria for progressive supranuclear palsy (PSP) incorporate two speech-language disturbances (SLDs), non-fluent/agrammatic primary progressive aphasia and progressive apraxia of ...speech, but overlook the inclusion of other SLDs, including dynamic aphasia (DA). Thus, there is a need to reappraise the broad spectrum of SLDs in PSP to include other presenting phenotypes. Here we report findings from the study of two elderly patients with PSP presenting with DA and irrepressible echolalia. Both patients had markedly impoverished verbal production, but their performance in other tasks (repetition and naming) and auditory comprehension were preserved or only mildly impaired. Experimental tests of DA revealed impaired word and sentence generation in response to verbal and non-verbal stimuli. Additional language and cognitive testing revealed different types of echolalia (mitigated, automatic, and echoing approval) as well as impaired inhibitory control and social cognition (mentalizing). Both patients had negative neuropsychiatric alterations (i.e., apathy, aspontaneity, and indifference/emotional flatness). Brain magnetic resonance imaging in both patients showed atrophy of the midbrain tegmentum and superior medial frontal cortex suggestive of PSP, yet further evaluation of the neural correlates using multimodal neuroimaging and neuropathological data was not performed. However, based on the already known neural basis of DA and echolalia in PSP and stroke, we suggest that, in the present cases, neurodegeneration in the midbrain tegmentum, superior medial frontal lobe, and caudate nucleus was responsible for DA and that decreased activity in these regions may play a permissive role for eliciting verbal echoing
disinhibition of the perisylvian speech-language network.
To assess efficacy and tolerability of stiripentol (STP) as adjunctive treatment in Dravet syndrome and non-Dravet refractory developmental and epileptic encephalopathies (DREEs).
Retrospective ...observational study of all children and adults with DREE and prescribed adjunctive STP at Hospital Ruber Internacional from January 2000 to February 2023. Outcomes were retention rate, responder rate (proportion of patients with ≥50% reduction in total seizure frequency relative to baseline), seizure freedom rate, responder rate for status epilepticus, rate of adverse event and individual adverse events, reported at 3, 6, and 12 months and at final visit. Seizure outcomes are reported overall, and for Dravet and non-Dravet subgroups.
A total of 82 patients (55 Dravet syndrome and 27 non-Dravet DREE) were included. Median age was 5 years (range 1-59 years), and median age of epilepsy onset was younger in the Dravet group (4.9 3.6-6 months) than non-Dravet (17.9 6-42.3, P < 0.001). Median follow-up time STP was 24.1 months (2 years; range 0.3-164 months) and was longer in the Dravet group (35.9 months; range 0.8-164) than non-Dravet (17 months range 0.3-62.3, P < 0.001). At 12 months, retention rate, responder rate and seizure free rate was 68.3% (56/82), 65% 48-77% and 18% 5.7-29%, respectively. There were no statistically significant differences between groups on these seizure outcomes. Adverse events were reported in 46.3% of patients (38/82), without differences between groups.
In this population of patients with epileptic and developmental encephalopathies, outcomes with adjunctive STP were similar in patients with non-Dravet DREE to patients with Dravet syndrome.
El presente estudio tiene por objetivo: evaluar la prevalencia de los riesgos laborales y su impacto en los trabajadores responsables de la gestión y reciclaje de residuos sólidos en una empresa ...privada, ubicada en la ciudad de Cuenca, Ecuador. La metodología es no experimental y de alcance descriptivo, analizando los riesgos y la gestión de residuos sólidos de los trabajadores. Los resultados determinan que la misión de recolección de residuos sólidos, representan un importante problema de seguridad y salud laboral en los trabajadores, su plan y política de prevención de riesgos laborales con la finalidad de minimizarlos, requieren un compromiso permanente en esta actividad laboral.
Background
Impulse control disorders (ICDs) have an increased frequency in patients with Parkinson's disease (PD), mainly because of treatment with dopamine agonists (DA). Factors related with the ...country of origin (culture, economy, healthcare politics) may impact phenomenology.
Objectives
To explore phenomenology of ICDs depending on the country.
Methods
A systematic review following PRISMA guidelines was performed using Pubmed database. Articles published up to 2018 in which the prevalence of ICDs was analyzed were selected.
Results
Thirty‐two studies from 22 countries worldwide were included. The highest prevalence of ICDs in each continent was found in UK (59%), USA (39.1%) and India (31.6%). Frequency of ICDs was higher in those studies with lower mean age, higher proportion of males, whenever a screening instrument was used and whenever prescription of DAs was more common. Prevalence of ICDs was higher in Western countries compared to Asian countries (20.8% vs. 12.8%, P < 0.001) as it was the proportion of patients treated with DAs (66% vs. 48.2%, P < 0.001). Hypersexuality was the most common ICD overall (up to 23.8%). The highest frequencies of compulsive buying and eating were found in Western countries. Gambling was less commonly diagnosed, but prevalence was relevant Japan (14%).
Conclusion
We observed a tendency towards a different ICD profile in different geographical areas, which may be attributable to socio‐economical, cultural or political influences in the phenomenology of these disorders. Acknowledging these differences could help their early detection, which is critical for prognosis.
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