A novel scale for suspicion of psychogenic nonepileptic seizures: development and accuracy.

OBJECTIVE: The differential diagnosis between epileptic and psychogenic nonepileptic seizures (PNES) is challenging, yet suspicion of PNES is crucial to rethink treatment strategies and select patients for diagnostic confirmation through video EEG (VEEG). We developed a novel scale to prospectively suspect PNES. METHODS: First, we developed a 51-item scale in two steps, based upon literature review and panel expert opinion. A pilot study verified the applicability of the instrument, followed by a prospective evaluation of 158 patients (66.5% women, mean age 33 years) who were diagnosed for prolonged VEEG. Only epileptic seizures were recorded in 103 patients, and the other 55 had either isolated PNES or both types of seizures. Statistical procedures identified 15 items scored between 0 and 3 that best discriminated patients with and without PNES, with a high degree of consistency. RESULTS: Internal consistency reliability of the scale for suspicion of PNES was 0.77 with Cronbach's Alpha Coefficient and 0.95 with Rasch Item Reliability Index, and performance did not differ according to the patient's gender. For a cut-off score of 20 (of 45) points, area under the curve was 0.92 (95% IC: 0.87-0.96), with an accuracy of 87%, sensitivity of 89%, specificity of 85%, positive predictive value of 77%, and negative predictive value of 94% (95% IC) for a diagnosis of PNES. CONCLUSIONS: The scale for suspicion of PNES (SS-PNES) has high accuracy to a reliable suspicion of PNES, helping with the interpretation of apparent seizure refractoriness, reframing treatment strategies, and streamlining referral for prolonged VEEG.

The COVID-19 outbreak and PNES: The impact of a ubiquitously felt stressor.

OBJECTIVE: We aimed to assess frequency of functional seizures or psychogenic nonepileptic seizures (PNES) during the COVID-19 outbreak and to recognize possible factors associated with worsening in this population. METHODS: In this cross-sectional study conducted during the second phase of the pandemic, adult patients with PNES documented by video-EEG and followed up in two tertiary epilepsy centers responded to a structured telephone survey. Data were gathered on demographics, clinical features and frequency of PNES, history of psychiatric comorbidity, access to treatment, as well as on anxiety (GAD-7 items) and depressive symptoms (NDDI-E). RESULTS: Fifty-four patients (78% female; mean age of 31.36 years [SD = 10.6]) were contacted and 15 (28%) reported increased frequency of PNES during the pandemic. Higher scores of GAD-7 items (p < 0.001) and NDDI-E (p < 0.001) were associated with PNES worsening. There was strong evidence of a correlation between higher stress levels (p < 0.001) and poor sleep quality (p 0.005) with PNES aggravation. After regression, stress was the strongest predictor of PNES increased frequency. SIGNIFICANCE: Patients with functional neurological disorders are vulnerable during ubiquitously felt stressors. However, the atmosphere of uncertainty did not affect these patients equally. Patients with PNES showing symptoms of anxiety and depression are at higher risk of seizure worsening. Early identification of this subset of patients may prevent this detrimental outcome.

Neuropsychiatric features of the coexistence of epilepsy and psychogenic nonepileptic seizures.

OBJECTIVE: To investigate demographic, epidemiologic and psychiatric features suggestive of the coexistence epilepsy (ES) and psychogenic nonepileptic seizures (PNES) that may contribute to precocious suspicion of the association. METHODS: In this exploratory study, all patients older than 16 years admitted to prolonged video-electroencephalogram monitoring were evaluated about demographic, epileptological and psychiatric features. Detailed psychiatric assessment using M.I.N.I.-plus 5.0, Beck Anxiety Inventory, Beck Depression Inventory and the Childhood Trauma Questionnaire (CTQ) was performed. Data were collected previous to the final diagnosis and patients with ES-only, PNES-only or coexistence of ES/PNES were compared. RESULTS: Of 122 patients admitted to epilepsy monitoring unit, 86 patients were included and 25 (29%) had PNES. Twelve (14%) had PNES-only, 13 (15%) had ES/PNES and the remaining 61 (71%) had only ES. A coexistence of ES and PNES was associated with clinical report of more than one seizure type (p˂0.001), nonspecific white matter hyperintensities on MRI (p < .001) and a past of psychotic disorder (p = .005). In addition, these patients had significantly more emotional abuse and neglect (p < .002 and 0.001, respectively). Somatization (including conversion disorder) was the most common diagnosis in patients with PNES- only (83%) and co-existing of PNES and ES (69.2%), differentiating both from ES-only patients (p < .001). CONCLUSION: The high prevalence of this coexistence ES/PNES in this study reinforces a need to properly investigate PNES, especially in patients with confirmed ES who become refractory to medical treatment with antiepileptic drugs. The neuropsychiatric assessment may help to diagnostic suspicion and in the planning of therapeutic interventions.

Suicide risk, temperament traits, and sleep quality in patients with refractory epilepsy.

OBJECTIVES: The objective of the study was to access the suicide risk (SR) in patients with refractory epilepsy and its association with temperament and sleep quality. METHODS: A total of 50 consecutive patients referred for epilepsy surgery evaluation in the Porto Alegre Epilepsy Surgery Program were included. All patients had a detailed neurologic and psychiatric evaluation, including video-electroencephalogram (VEEG), high-resolution magnetic ressonance imaging (MRI), and neuropsychologic assessment. In addition, structured questionnaires were applied: module C of the MINI-plus (International Neuropsychiatric Interview-Brazilian version 5.0.0), Affective and Emotional Composite Temperament Scale (AFECTS), and Pittsburgh Sleep Quality Index (PSQI). RESULTS: Ten patients (20.0%) showed an increased SR. The most frequent location of the epileptic focus was in the temporal lobe (50%; n=25). Final diagnosis on VEEG comprised epilepsy in 74.0% (n=37), psychogenic nonepileptic seizures (PNES) in 8.0% (n=4), and both in 12%. Thirty patients (60.0%) received surgery indication. Mood disorders were the main psychiatric diagnosis, found in 19 subjects (70.4%), with major depressive disorder (MDD) encountered in 15 patients (55.6%). In the group, SR was more frequent in patients with sleep disorders (p=0.001) and elevated scores of high emotional sensitivity (p=0.003). CONCLUSION: In this cohort of patients with highly refractory epilepsy, there was a significant association between SR, sleep disorders, and high emotional sensitivity. Careful evaluation of these factors should be performed in these patients to fully access SR.

Variables associated with co-existing epileptic and psychogenic nonepileptic seizures: a systematic review.

PURPOSE: Epileptic seizures (ES) have many mimickers, perhaps the most relevant being psychogenic nonepileptic seizures (PNES). The picture is even more challenging when PNES are associated with ES in a given patient. The aim of this research paper was to delineate the demographic, epileptological and psychiatric profile of that specific population. METHODS: A systematic review was carried out from 2000 to 2015 for articles in English, French, Italian, Spanish and Portuguese in PUBMED and EMBASE. Cohort or case-control studies reporting prospective or retrospective original data comparing patients with co-existing ES and PNES with those who had PNES only and ES only have been included. In retained studies, the presence of PNES was confirmed by video-electroencephalography (V-EEG). Forty-eight abstracts were identified. RESULTS: Nine studies were retained. Most showed that female gender predominated in both groups with PNES. Patients with co-existing ES and PNES take higher number of antiepileptic drugs (AEDs) than PNES alone. Two studies showed association of concomitant ES and PNES with earlier age of seizure onset. Localizing EEG features and ES type were evaluated in only two studies and their association with either group was inconclusive. Somatoform, conversion or cluster B personality disorders were more frequent in subjects with PNES than with ES. DISCUSSION: Patients with concomitant ES and PNES are highly heterogeneous, challenging differentiation on clinical grounds. A diagnosis of conversion or somatoform, anxiety disorders, and the use of a higher number of AEDs than psychiatric medications may have an association with co-existing ES and PNES. Further studies are warranted to differentiate patients who only have PNES from those with co-existing ES and PNES.

Contribuição na prevenção da isquemia cerebral pelo cilostazol, um inibidor da fosfodiesterase III: revisão de literatura / Contribution to prevention of cerebral ischemia by cilostazol, a phosphodiesterase III inhibitor: a review

Esta revisão bibliográfica objetiva expor estas pesquisas sobre as ações do cilostazol no sistema nervoso central. O cilostazol é uma droga que demonstrou exercer inibição seletiva e potente da fosfodiesterase tipo III, ocasionando o aumento de adenosina cíclica -3',5'-monofosfato nas plaquetas, nas células endoteliais e nas células musculares lisas, sendo classificado como vasodilatador, antiagregante plaquetário e antitrombótico. É o fármaco de primeira escolha na claudicação intermitente devido à doença arterial obstrutiva periférica. Além disso, há evidências de que o cilostazol é eficaz no processo aterosclerótico cerebral, promovendo aumento do fluxo e volume sangüíneos e prevenindo infartos, especialmente lacunares e recorrentes, por diminuir a morte celular devido à apoptose e ao estresse oxidativo nas substâncias branca e parda.

This literature review aims at presenting the main possibilities for the clinical application of cilostazol in the central nervous system. Cilostazol, a selective phosphodiesterase type III inhibitor, increases adenosine 3',5'-cyclic monophosphate levels on platelets, endothelial and smooth muscle cells, having vasodilatory, antiplatelet and antithrombotic properties. Currently, it is the first-choice drug for intermittent claudication, due to peripheral occlusive vascular disease. In addition, there is evidence showing that cilostazol is efficacious in cerebral atherosclerotic process, resulting in increase of blood flow and volume and preventing infarctions, especially lacunar and recurrent, since it reduces cellular death due to apoptosis and oxidative stress in white and gray substances.

Potencial terapêutico para a prevenção e tratamento da nefropatia e neuropatia diabéticas: evidências do uso do cilostazol / Potential therapeutic approaches for prevention and treatment of diabetic nephropathy and neuropathy: evidences of cilostazol

O cilostazol é um inibidor seletivo da fosfodiesterase tipo III com ação vasodilatadora, antiagregante plaquetária e antitrombótica. É considerada a droga de primeira escolha na claudicação intermitente devido à doença arterial obstrutiva periférica. Vários estudos demonstraram melhora significativa na distância percorrida na caminhada sem dor e na qualidade de vida, sem aumentar o risco de sangramento. Essas ações também foram verificadas em pacientes diabéticos, pois o cilostazol não afeta o metabolismo da glicose. Estudos, principalmente experimentais, têm mostrado resultados satisfatórios na melhora do fluxo sangüíneo neural, na atividade da bomba de sódio e potássio, na resistência à insulina e na microalbuminúria. Neste artigo, apresentamos uma revisão do uso do cilostazol na prevenção e no tratamento das complicações do diabetes mellitus, como nefropatia e neuropatia. Ressalta-se a necessidade do controle adequado dos níveis glicêmicos, da hipertensão arterial sistêmica e do tabagismo. Um maior número de estudos clínicos é necessário para melhor compreensão desses efeitos benéficos.

Cilostazol, a selective phosphodiesterase type III inhibitor, has vasodilatory, antiplatelet, and antithrombotic actions, as well as being the first-choice drug for the intermittent claudication due to peripheral vascular disease. Main researches have demonstrated significant improvement for this situation, including patients with diabetes mellitus, concerning pain-free walking distance and quality-of-life, not rising the bleeding event risk. It does not affect the glucose metabolism even in patients suffering from diabetes. This paper aims to present a review on the discoveries of various studies, most of them experimental, on the prevention and treatment of diabetes mellitus complications, such as nephropathy and neuropathy, through the use of cilostazol, which demonstrated satisfactory results on the improvement in neural blood flow, on sodium-potassium ATPase activity, on insulin resistance, and microalbuminuria. However, strict controlling of glucose plasma levels, hypertension, and smoking habits, as well as more extended investigations on the matter are required to the better comprehension.

[Potential therapeutic approaches for prevention and treatment of diabetic nephropathy and neuropathy: evidences of cilostazol]. / Potencial terapêutico para a prevenção e tratamento da nefropatia e neuropatia diabéticas: evidências do uso do cilostazol.

Cilostazol, a selective phosphodiesterase type III inhibitor, has vasodilatory, antiplatelet, and antithrombotic actions, as well as being the first-choice drug for the intermittent claudication due to peripheral vascular disease. Main researches have demonstrated significant improvement for this situation, including patients with diabetes mellitus, concerning pain-free walking distance and quality-of-life, not rising the bleeding event risk. It does not affect the glucose metabolism even in patients suffering from diabetes. This paper aims to present a review on the discoveries of various studies, most of them experimental, on the prevention and treatment of diabetes mellitus complications, such as nephropathy and neuropathy, through the use of cilostazol, which demonstrated satisfactory results on the improvement in neural blood flow, on sodium-potassium ATPase activity, on insulin resistance, and microalbuminuria. However, strict controlling of glucose plasma levels, hypertension, and smoking habits, as well as more extended investigations on the matter are required to the better comprehension.