Epilepsy with eyelid myoclonia (Jeavons syndrome): Generalized, focal, or combined generalized and focal epilepsy syndrome?

Epilepsy with eyelid myoclonia (EM) or Jeavons syndrome (JS) is an epileptic syndrome related to the spectrum of genetic generalized epilepsies (GGE). We report two untreated children on which EEGs were performed several hours after a generalized tonic-clonic seizure (GTCS). These showed a unilateral, nearly continuous posterior slowing. This slow-wave activity was associated with contralateral epileptiform activity in one case, while in the second case, it was associated with an ipsilateral activity. However, in the latter child, a few months later an independent focus on the contralateral side was observed. A diagnosis of focal occipital lobe epilepsy was proposed in both cases, and one child underwent a left occipital lobectomy at 3.5 years of age. Despite surgery, absences with EM persisted in this child, and a marked photosensitivity to photic stimulation was observed two years later. The focal slow wave activity of one occipital lobe several hours after a GTCS in these two subjects was in favor of a focal onset preceding the generalization. The EEG evidence for independent left and right posterior focus in these two cases, the persistence of EM, and the development of a marked photosensitivity to photic stimulation in the child who underwent an occipital lobectomy, allow us to suggest that JS is associated with a network of bi-occipital hyperexcitability that rapidly engages bilaterally to produce generalized seizures.

An "epileptic scent": Olfactory auras in tumor-related epilepsy.

OBJECTIVES: To characterize a profile for patients with tumor-related epilepsy presenting olfactory auras. MATERIALS AND METHODS: We conducted a monocentric, retrospective study on patients who underwent surgery in the Neurosurgery Unit of Udine University Hospital (Udine, Italy), between the 1st of January 2010 and the 1st of January 2019, for primary brain tumors (PBTs) involving the temporal lobe and the insula. All patients were affected by tumor-related epilepsy; the study group presented olfactory auras as well. We collected neuroradiological, neuropsychological and neurophysiological data from patients' medical charts. RESULTS: The subtraction analysis of MRI data shows maximum lesion overlay in left olfactory cortex, left and right hippocampus, left amygdala, right rolandic operculum, right inferior frontal gyrus and right middle temporal gyrus. The presence of olfactory auras did not influence seizure outcome (p = 0.500) or tumor recurrence after surgery (p = 0.185). The type of auras (elementary vs. complex), also, did not influence seizure control (p = 0.222). DISCUSSION: In presence of olfactory auras, anterior and mesial temporal regions are mainly involved, such as olfactory cortex, amygdala, and anterior hippocampus, together with right rolandic operculum, right inferior frontal gyrus and right middle temporal gyrus, suggesting their possible role in the genesis of olfactory auras. Post-surgical seizure outcome and disease relapse are not influenced by neither the presence nor the type of olfactory auras. CONCLUSIONS: Olfactory auras are rare event, however they may be often underestimated by the patients and under-investigated by the clinicians, even when their occurrence can represent a useful localizing tool.

Meningioma-Related Epilepsy: A Happy Ending?

(1) Background: More than one-third of patients with meningiomas experience at least one seizure during the course of their disease, and in the 20-50% of cases, seizure represents the onset symptom. After surgery, up to 30% of patients continue to have seizures, while others may experience them later; (2) Methods: The study analyzed retrospectively the risk factors for pre-operative seizures in a large cohort of 358 patients who underwent surgery for newly diagnosed brain meningioma; (3) Results: We identified age, peritumor edema, and location as risk factors for seizure at the onset. Patients with seizures differed from patients without seizures for the following characteristics: younger average age, lower pre-operative Karnofsky Performance Status (KPS), location on the convexity, lower Simpson Grade, lower incidence of pre-operative neurological deficits, and higher incidence of pre-operative peritumor edema. After 24 months, 88.2% of patients were classified as Engel class Ia, and no correlation with disease progression was observed; (4) Conclusions: Meningioma-related epilepsy has generally a positive outcome following surgery and it seems not to be linked to disease progression, even if further studies are needed.

Effect of Dexmedetomidine versus Propofol on Intraoperative Seizure Onset During Awake Craniotomy: A Retrospective Study.

OBJECTIVE: The effect of dexmedetomidine (DEX) compared with propofol on intraoperative seizures (IOSs) detected using electrocorticography during awake craniotomy for resection of brain tumors is unknown. This investigation aimed to compare IOS rate in patients receiving DEX versus propofol as sedative agent. METHODS: In this retrospective single-center study, awake craniotomies performed from January 2014 to December 2019 were analyzed. All IOSs detected by electrocorticography along with vital signs were recorded. RESULTS: Of 168 adults enrolled in the study, 58 were administered DEX and 110 were administered propofol. IOSs occurred more frequently in the DEX group (22%) versus the propofol group (11%) (P = 0.046). A higher incidence of bradycardia was also observed in the DEX group (P < 0.001). Higher incidence of hypertension and a higher mean heart rate were recorded in the propofol group (P = 0.006 and P < 0.001, respectively). No serious adverse events requiring active drug administration were noted in either group. At univariate regression analysis, DEX demonstrated a tendency to favor IOS onset but without statistical significance (odds ratio = 2.36, P = 0.051). Patients in both groups had a similar epilepsy outcome at the 1-year postoperative follow-up. CONCLUSIONS: IOSs detected with electrocorticography during awake craniotomy occurred more frequently in patients receiving DEX than propofol. However, patients receiving DEX were not shown to be at a statistically significant greater risk for IOS onset. DEX is a valid alternative to propofol during awake craniotomy in patients affected by tumor-related epilepsy.

Performing real time neuropsychological testing during awake craniotomy: are dexmedetomidine or propofol the same? A preliminary report.

PURPOSE: In awake surgery, the patient is sedated, but is also required to be sufficiently alert and collaborative during extensive neurocognitive testing. In the present preliminary report of a retrospective single-center study, a continuous series of 168 patients who underwent awake surgery for brain tumor located near eloquent areas, was investigated to observe the effect of dexmedetomidine (n = 58) compared with propofol (n = 110) on vigilance and collaboration required to perform extensive intra-operatory Real Time Neuropsychological Testing (RTNT). METHODS: We assigned a score to each patient, by using a scale that combines vigilance and collaboration in a 5 levels score (the higher score denoting higher level). RESULTS: The median interquartile range was significantly lower (range 3-5) for the dexmedetomidine group compared to the propofol one (range 4-5, p = .044). Patients with intra-operative seizures (p = .014) and/or electrocorticographic slow/epileptiform activity (p = .042), and patients in the propofol group who showed increased heart rate (p = .032) were those who obtained the lower scores (lower vigilance and collaboration level). CONCLUSION: The study shows that the effect of dexmedetomidine or propofol -based conscious sedation on ability to perform Real Time Neuropsychological Testing during awake surgery for supratentorial tumor resection is different. Although both permit high mean levels of vigilance and collaboration, the patient who received dexmedetomidine was more likely to show lower vigilance and collaboration during RTNT.

Pre- and Post-surgical Poor Seizure Control as Hallmark of Malignant Progression in Patients With Glioma?

Background: Regarding brain tumor-related epilepsy (BTRE), there is an increasing number of evidence about a relationship between epileptogenesis and oncogenesis. A recent study suggests a role of post-surgery seizure outcome on the survival of patients with low-grade glioma (LGG), underlying the need for a targeted and aggressive epilepsy treatment. Objective: This study aims at investigating the possible correlation between pre- and post-surgical seizure control and tumor progression in patients who underwent surgery for LGG. Methods: We performed a retrospective analysis of patients affected by LGGs and BTRE, in a single high-volume neurosurgical center. Seizure control was assessed before surgery and at 3 years of follow-up. Patients with histological progression in high-grade glioma (HGG) have been evaluated. Clinical features, pre-surgical electroencephalograms (EEGs), and electrocorticography (ECoG) have been analyzed. Results: Among 154 subjects, we collected 32 patients who presented a tumor progression in HGG during the follow-up period. The majority had poor seizure control both pre- and post-surgery, never being in Engel class Ia throughout the whole history of their disease. Almost all patients with poor seizure control had pathological ECoG recording. Clinical features of seizures did not correlate with seizure outcome. On the univariate analysis, the age, the post-operative Engel class, and the extent of resection (EOR) were the prognostic factors significantly associated with oncological outcome; nevertheless, on multivariate analysis, Engel class significance was not confirmed, and the only predicting factor were age and EOR. Conclusions: Although not confirmed on multivariate analysis, post-surgical seizure control could be a relevant factor to consider during follow-up of BRTE, in particular, when gross total resection is not achieved. Pathological findings on the ECoG may suggest a "hidden" propensity to malignant progression, strictly related to the persistent neuronal hyper-excitability. Further studies with longer follow-up period are needed to confirm our observations.

Seizures, Epilepsy, and NORSE Secondary to Autoimmune Encephalitis: A Practical Guide for Clinicians.

The most recent International League Against Epilepsy (ILAE) classification has included "immune etiology" along with other well-known causes of epilepsy. This was possible thanks to the progress in detection of pathogenic neural antibodies (Abs) in a subset of patients, and resulted in an increased interest in identifying potentially treatable causes of otherwise refractory seizures. Most autoimmune encephalitides (AE) present with seizures, but only a minority of cases evolve to long-term epilepsy. The risk of epilepsy is higher for patients harboring Abs targeting intracellular antigens (T cell-mediated and mostly paraneoplastic, such as Hu, CV2/CRMP5, Ma2, GAD65 Abs), compared with patients with neuronal surface Abs (antibody-mediated and less frequently paraneoplastic, such as NMDAR, GABAbR, LGI1, CASPR2 Abs). To consider these aspects, conceptual definitions for two entities were provided: acute symptomatic seizures secondary to AE, and autoimmune-associated epilepsy, which reflect the different pathophysiology and prognoses. Through this manuscript, we provide an up-to-date review on the current state of knowledge concerning diagnosis and management of patients with Ab-mediated encephalitis and associated epilepsy. Special emphasis is placed on clinical aspects, such as brain magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) specificities, electroencephalographic (EEG) findings, cancer screening and suggestions for a rational therapeutic approach.

Risk Assessment by Pre-surgical Tractography in Left Hemisphere Low-Grade Gliomas.

Background: Tracking the white matter principal tracts is routinely typically included during the pre-surgery planning examinations and has revealed to limit functional resection of low-grade gliomas (LGGs) in eloquent areas. Objective: We examined the integrity of the Superior Longitudinal Fasciculus (SLF) and Inferior Fronto-Occipital Fasciculus (IFOF), both known to be part of the language-related network in patients with LGGs involving the temporo-insular cortex. In a comparative approach, we contrasted the main quantitative fiber tracking values in the tumoral (T) and healthy (H) hemispheres to test whether or not this ratio could discriminate amongst patients with different post-operative outcomes. Methods: Twenty-six patients with LGGs were included. We obtained quantitative fiber tracking values in the tumoral and healthy hemispheres and calculated the ratio (HIFOF-TIFOF)/HIFOF and the ratio (HSLF-TSLF)/HSLF on the number of streamlines. We analyzed how these values varied between patients with and without post-operative neurological outcomes and between patients with different post-operative Engel classes. Results: The ratio for both IFOF and SLF significantly differed between patient with and without post-operative neurological language deficits. No associations were found between white matter structural changes and post-operative seizure outcomes. Conclusions: Calculating the ratio on the number of streamlines and fractional anisotropy between the tumoral and the healthy hemispheres resulted to be a useful approach, which can prove to be useful during the pre-operative planning examination, as it gives a glimpse on the potential clinical outcomes in patients with LGGs involving the left temporo-insular cortex.

What's behind drawing for an artist with left temporal lobe epilepsy? A multimodal neurophysiological study.

There are few studies in literature reporting drawing as a strong trigger of praxis-induced focal seizures. The aim of the present case report was describing a case of focal epilepsy with praxis induced EEG activation, due to a cavernoma, in the left middle anterior temporal lobe by using a multimodal approach. We combined video-EEG, showing that drawing increased a sustained monomorphic delta activity localized on left anterior temporal region (F7-T1a), diffusing to the vertex (Fz) and the fronto-polar electrodes (F3), with DTI data, showing that the left uncinate fasciculus, connecting the temporal pole to the orbitofrontal cortex, significantly differed from controls. fMRI confirmed that drawing increased activation in these areas. The congruence between findings supports the role of the left uncinated fasciculus linking the temporal lobe to the orbitofrontal cortex in the present focal epilepsy mainly facilitated by drawing.

Epilepsia partialis continua revealing idelalisib-associated PML-IRIS: clinical and pathological features.

Idelalisib, a selective phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor, is a newly approved second-line drug for patients with chronic lymphocytic leukemia. Recent clinical trials have suggested a possible association between idelalisib treatment and development of progressive multifocal leukoencephalopathy (PML) due to John Cunningham virus (JCV) reactivation. Nevertheless, clinical course and radiological and pathological features of idelalisib-induced PML still need to be clarified. We provide here the first clinicopathological description of idelalisib-associated PML in a patient who developed epilepsia partialis continua (EPC) as the first manifestation of the disease. Since EPC could present without electroencephalogram alterations, it is crucial to recognize the clinical features of this epileptic condition. EPC is characterized by the presence of repetitive, irregular, clonic jerking, often associated with hemiparesis and involvement of distal rather than proximal muscle groups. Moreover, we highlight the importance of brain biopsy in selected cases when there is a high clinical suspicion of PML, despite negative JCV testing in the cerebrospinal fluid. The pathological finding of prominent inflammatory infiltrate observed here was consistent with a diagnosis of immune reconstitution inflammatory syndrome (IRIS). IRIS is often associated with PML as a paradoxical worsening of clinical symptoms due to an overreacting immune response, in the context of previous immunosuppression. The unprecedented pathologic observation of IRIS in idelalisib-associated PML provides further insights into the pathogenesis of this rare neurological side effect.

Investigational therapies for the treatment of narcolepsy.

INTRODUCTION: Narcolepsy is a chronic sleep disorder characterized by a pentad of excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic/hypnopompic hallucinations, and disturbed nocturnal sleep. While non-pharmacological treatments are sometimes helpful, more than 90% of narcoleptic patients require a pharmacological treatment. Areas covered: The present review is based on an extensive Internet and PubMed search from 1994 to 2017. It is focused on drugs currently in development for the treatment of narcolepsy. Expert opinion: Currently there is no cure for narcolepsy, with treatment focusing on symptoms control. However, these symptomatic treatments are often unsatisfactory. The research is leading to a better understanding of narcolepsy and its symptoms. New classes of compounds with possible applications in the development of novel stimulant/anticataplectic medications are described. H3 receptor antagonists represent a new therapeutic option for EDS in narcolepsy. JZP-110, with its distinct mechanism of action, would be a new therapeutic option for the treatment of EDS in the coming years. In the future, hypocretin-based therapies and immune-based therapies, could modify the clinical course of the disease. However, more information would be necessary to completely understand the autoimmune process and also how this process can be altered for therapeutic benefits.