Periodic sharp wave complexes identify a distinctive phenotype in Creutzfeldt-Jacob disease.

OBJECTIVE: The aim of our study was to evaluate the diagnostic and prognostic value of Electroencephalogram (EEG), brain Magnetic Resonance Imaging (MRI) and cerebrospinal fluid features, currently representing Creutzfeldt-Jacob Disease (CJD) diagnostic criteria. METHODS: A retrospective study on rapidly progressive dementia patients admitted at the Neurology Clinic of the University of Rome "Tor Vergata" between 2015 and 2020 was conducted. We evaluated clinical, EEG, cerebrospinal fluid and neuroradiological findings. RESULTS: Our analysis included 13 patients with probable CJD and 18 patients with non-CJD rapidly progressive dementia. Periodic sharp wave complexes were observed in 7/13 CJD and in 4/18 non-CJD patients (p =.151). The sub-analysis according to the EEG features revealed that CJD patients with earlier periodic sharp wave complexes had a significantly lower average survival time (p =.003), a shorter time to admission (p =.003) and lower levels of cerebrospinal fluid p-tau (p =.008) compared to CJD patients without periodic sharp wave complexes. Finally, they did not show signs of signal alteration on Fluid Attenuated Inversion Recovery images. CONCLUSIONS: Despite the lowest diagnostic specificity and sensibility among the CJD criteria, periodic sharp wave complexes could identify a distinctive phenotype hallmarked by a faster evolution, a reduced survival time and specific MRI and cerebrospinal fluid features. SIGNIFICANCE: The early presence of the typical EEG pattern may play a prognostic role in CJD.

Cognitive functioning, cerebrospinal fluid Alzheimer's disease biomarkers and cerebral glucose metabolism in late-onset epilepsy of unknown aetiology: A prospective study.

Epilepsy is increasing, being more common in older adults, with more than 20% of late-onset cases with unknown aetiology (LOEU). Although epilepsy was associated with cognitive impairment, few studies evaluated the trajectories of cognitive decline in patients with LOEU. The present study aimed at assessing biomarkers of Alzheimer's disease (AD) in patients with LOEU and evaluating their cognitive performance for 12 months. For this study, 55 patients diagnosed with LOEU and 21 controls were included. Participants underwent cognitive evaluation and cerebrospinal fluid (CSF) biomarker analysis (ß-amyloid42 , tau proteins) before starting anti-seizure medication and then repeated the cognitive evaluation at the 12-month follow-up. A subgroup of LOEU patients and controls also performed 18 F-fluoro-2-deoxy-D-glucose positron emission tomography (18 F-FDG PET) before starting anti-seizure medication. At baseline, LOEU patients showed lower Mini-Mental State Examination (MMSE) score, worse cognitive performance in several domains, lower ß-amyloid42 and higher tau proteins CSF levels than controls. Significantly reduced glucose consumption was observed in the right posterior cingulate cortex and left praecuneus areas in LOEU patients than controls, and this finding correlated with memory impairment. In the longitudinal analysis, a significant decrease in MMSE and an increase in verbal fluency scores were found in LOEU patients. These findings evidence that LOEU patients have a significant cognitive impairment, and alteration of cerebral glucose consumption and CSF AD biomarkers than controls. Moreover, they showed a progressive global cognitive decline at follow-up, although verbal fluency was preserved. Further studies are needed to better understand the pathophysiological aspects of LOEU and its association with AD.

Nocturnal Hypoxia and Sleep Fragmentation May Drive Neurodegenerative Processes: The Compared Effects of Obstructive Sleep Apnea Syndrome and Periodic Limb Movement Disorder on Alzheimer's Disease Biomarkers.

BACKGROUND: Sleep disorders may cause dysregulation in cerebral glucose metabolism and synaptic functions, as well as alterations in cerebrospinal fluid (CSF) biomarker levels. OBJECTIVE: This study aimed at measuring sleep, CSF Alzheimer's disease (AD) biomarkers, and cerebral glucose consumption in patients with obstructive sleep apnea syndrome (OSAS) and patients with periodic limb movement disorder (PLMD), compared to controls. METHODS: OSAS and PLMD patients underwent 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET), polysomnographic monitoring, and lumbar puncture to quantify CSF levels of amyloid-ß42 (Aß42), total tau, and phosphorylated tau. All patients were compared to controls, who were not affected by sleep or neurodegenerative disorders. RESULTS: Twenty OSAS patients, 12 PLMD patients, and 15 controls were included. Sleep quality and sleep structure were altered in both OSAS and PLMD patients when compared to controls. OSAS and PLMD patients showed lower CSF Aß42 levels than controls. OSAS patients showed a significant increase in glucose uptake in a wide cluster of temporal-frontal areas and cerebellum, as well as a reduced glucose consumption in temporal-parietal regions compared to controls. PLMD patients showed increased brain glucose consumption in the left parahippocampal gyrus and left caudate than controls. CONCLUSION: Sleep dysregulation and nocturnal hypoxia present in OSAS patients, more than sleep fragmentation in PLMD patients, were associated with the alteration in CSF and 18F-FDG PET AD biomarkers, namely reduction of CSF Aß42 levels and cerebral glucose metabolism dysregulation mainly in temporal areas, thus highlighting the possible role of sleep disorders in driving neurodegenerative processes typical of AD pathology.

Levetiracetam, lamotrigine and carbamazepine: which monotherapy during pregnancy?

OBJECTIVE: Epilepsy treatment during pregnancy is still challenging. The study is aimed at comparing the efficacy and safety of carbamazepine (CBZ), lamotrigine (LTG) and levetiracetam (LEV) monotherapies during pregnancy in women with focal (FE) or generalized (GE) epilepsy. METHODS: A multicentre retrospective study was conducted to evaluate seizures frequency and seizure freedom (SF) rate during 3 months before pregnancy, each trimester of gestation and post-partum period in women on monotherapy with CBZ, LTG and LEV. RESULTS: Fifty-seven pregnancies (45 FE, 12 GE) on monotherapy (29 CBZ, 11 LTG, 17 LEV) were included. A significant reduction of seizure frequency was found in the first trimester of pregnancy as compared with that one before pregnancy (p = 0.004), more evident in GE (p = 0.003) and in LEV group (p = 0.004). The SF rate significantly increased in the first trimester in comparison to that one before pregnancy and persisted in the post-partum period in the whole sample (p < 0.001) and in women on LEV (p = 0.004). Besides, 88.57% of SF women before pregnancy remained unchanged during gestation and the post-partum period. One major heart malformation in CBZ and no major malformations in LTG and LEV groups were found. CONCLUSIONS: A better clinical outcome during pregnancy emerged since the first trimester in comparison to the before-pregnancy period, mostly evident in women with GE and LEV therapy, reinforcing the hypothesis of a protective role of pregnancy versus seizures. SF before pregnancy represents a significant predictive factor of good clinical outcome during gestation and the post-partum period. Compared to CBZ, LTG and LEV showed a better safety profile.

Comparison of the effectiveness and tolerability of perampanel and brivaracetam: a real-world, observational, retrospective study.

Perampanel (PER) and brivaracetam (BRV) are third-generation antiseizure medications. The aim of the present retrospective, double-centre study was to compare the effectiveness and tolerability between PER and BRV in adult patients with epilepsy. We reviewed the clinical charts of patients affected by epilepsy, admitted to the Epilepsy Centre at the University Hospital of Rome "Tor Vergata" and the Cardarelli Hospital in Naples, who started BRV or PER as add-on treatment for controlling seizures with a follow-up of 12 months. Seizure freedom, >50% seizure reduction, retention rate, and adverse events reported during follow-up were compared between the two drugs. Moreover, we considered the effects of both drugs in specific subsets of patients: age ≥60 years, male or female, in patients with genetic generalized epilepsy, and considering previous treatment with levetiracetam (LEV). Forty-three patients treated with BRV and 64 patients treated with PER were included in this study and followed at both sites for 12 months. Similar effectiveness was observed between BRV and PER, with similar rates of seizure freedom (30% vs 31%) and >50% seizure reduction (32% vs 34%) during follow-up. Moreover, PER and BRV discontinuation rates, due to ineffectiveness or adverse events, were similar. Groups of patients who started BRV or PER as first add-on treatments were also compared but no differences in effectiveness or tolerability were identified. Lastly, BRV was shown to be more effective in patients who were not previously treated with LEV. This retrospective study reveals comparable effectiveness and tolerability between PER and BRV also when used as first add-on treatments, in patients with epilepsy.

Cognitive performances in patients affected by late-onset epilepsy with unknown etiology: A 12-month follow-up study.

INTRODUCTION: Epilepsy has a growing frequency, particularly in the elderly. Several triggers may cause late-onset epilepsy; however, more than 20% of epilepsies, manifesting in the elderly, has an unknown etiology. Although cognition is frequently altered in patients affected by epilepsy, there is a paucity of studies specifically evaluating cognition in patients affected by late-onset epilepsy. The aim of the present study was to assess the cognitive profile of patients affected by late-onset epilepsy with an unknown etiology and followed for 12 months. METHODS: Patients affected by diagnosed late-onset epilepsy with unknown etiology were included in this observation. All patients were evaluated at the time of diagnosis (baseline) and at follow-up (12 months later). We distributed patients in subgroups based on seizure type (focal seizures [FS], secondarily generalized seizures [SGS], primarily generalized seizures [GS]) and antiepileptic drug (AED) regimen (mono- vs. polytherapy). Cognition was evaluated through standardized neuropsychological testing. RESULTS: Fifty-eight patients were included in this observation and distributed in three groups: 29 affected by FS, 14 affected by SGS, 15 affected by GS. Forty-five patients were in monotherapy, and 13 in polytherapy. The most frequent treatments were levetiracetam (n = 12), valproic acid (VPA) (n = 9), carbamazepine (n = 9), and oxcarbazepine (n = 7). We documented a significant decrease of Mini-Mental State Examination (MMSE) and memory scores at follow-up in the whole group. Verbal learning decreased exclusively in VPA users. CONCLUSION: Patients affected by late-onset epilepsy with unknown etiology showed a significant decline of cognition at follow-up, independently from number and efficacy of AEDs received. These results deserve verification in larger longitudinal cohorts.

Lacosamide may improve cognition in patients with focal epilepsy: EpiTrack to compare cognitive side effects of lacosamide and carbamazepine.

Carbamazepine (CBZ) is a first generation anti-seizure drug, considered as first choice therapy in focal epilepsy but associated with cognitive side effects. Lacosamide (LCM) is a third-generation anti-seizure drug approved for treating focal epilepsy. This case series documented the comparable efficacy of LCM and CBZ as first add on treatments in patients affected by uncontrolled focal seizures. LCM showed an increase in EpiTrack scores, which measure cognitive abilities, at follow-up compared to CBZ. This preliminary data may represent the basis for future prospective studies aimed at comparing the long-term cognitive side effects of LCM and CBZ.

Efficacy and tolerability of perampanel and levetiracetam as first add-on therapy in patients with epilepsy: A retrospective single center study.

Perampanel (PER) is a third generation antiepileptic drug (AED), recently approved as add-on therapy in both focal and generalized seizures. Levetiracetam (LEV) is a second generation AED, widely used in patients with epilepsy because of its favorable safety and efficacy profiles. Perampanel and LEV treatments have been associated with the occurrence of similar adverse events (AEs) (sleepiness, irritability, depression, anxiety, aggressiveness). The aim of the present retrospective single center study was to verify the efficacy and tolerability of PER and LEV used as first add-on therapy in patients with epilepsy affected by secondarily generalized seizures. We collected data from 15 patients treated with PER and 26 patients treated with LEV and followed at our site with follow-up visits at 3, 6, and 12months. This retrospective study documented the comparable efficacy of PER and LEV as first add-on treatments in patients affected by uncontrolled secondarily generalized seizures. However, more patients withdrawn LEV because of AEs compared with PER at the 3- and 12-month follow-up visits. The better tolerability of PER observed in this study could be related to the low therapeutic dose of PER prescribed when it is used as first adjunctive treatment for better controlling secondarily generalized seizures.