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.

Frontal Intermittent Rhythmic Delta Activity Is a Useful Diagnostic Tool of Neurotoxicity After CAR T-Cell Infusion.

BACKGROUND AND OBJECTIVES: Chimeric antigen receptor (CAR) T-cell therapies have dramatically improved the prognosis of patients with relapsed or refractory hematologic malignancies; however, cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS) occur in ∼100 and 50% of patients, respectively. This study aimed to determine whether EEG patterns may be considered as diagnostic tools for ICANS. METHODS: Patients who received CAR T-cell therapy at Montpellier University Hospital between September 2020 and July 2021 were prospectively enrolled. Neurologic signs/symptoms and laboratory parameters were monitored daily for 14 days after CAR T-cell infusion. EEG and brain MRI were performed between day 6 and 8 after CAR T-cell infusion. EEG was performed again on the day of ICANS occurrence, if outside this time window. All collected data were compared between patients with and without ICANS. RESULTS: Thirty-eight consecutive patients were enrolled (14 women; median age: 65 years, interquartile range: [55-74]). ICANS was observed in 17 of 38 patients (44%) after a median time of 6 days after CAR T-cell infusion (4-8). The median ICANS grade was 2 (1-3). Higher C-reactive protein peak (146 mg/L [86-256], p = 0.004) at day 4 (3-6), lower natremia (131 mmol/L [129-132], p = 0.005) at day 5 (3-6), and frontal intermittent rhythmic delta activity (FIRDA, p < 0.001) on EEG between days 6 and 8 after infusion were correlated with ICANS occurrence. FIRDA was only observed in patients with ICANS (N = 15/17, sensitivity of 88%) and disappeared after ICANS resolution, usually after steroid therapy. Except for hyponatremia, no other toxic/metabolic marker was associated with FIRDA (p = 0.002). The plasma concentration of copeptin, a surrogate marker of antidiuretic hormone secretion, assessed at day 7 after infusion, was significantly higher in patients with (N = 8) than without (N = 6) ICANS (p = 0.043). DISCUSSION: FIRDA is a reliable diagnostic tool for ICANS, with a sensitivity of 88% and a negative predictive value of 100%. Moreover, as this EEG pattern disappeared concomitantly with ICANS resolution, FIRDA could be used to monitor neurotoxicity. Finally, our study suggests a pathogenic pathway that starts with increased C-reactive protein, followed by hyponatremia and eventually ICANS and FIRDA. More studies are required to confirm our results. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that FIRDA on spot EEG accurately distinguishes patients with ICANS compared with those without after CAR T-cell therapy for hematologic malignancy.

Perampanel in 12 patients with Unverricht-Lundborg disease.

OBJECTIVE: Perampanel (PER) was used in 12 patients with Unverricht-Lundborg disease (ULD) to evaluate its efficacy against myoclonus and seizures. METHODS: We treated 11 patients with EPM1 mutations (6 F, 5 M, aged 13-62 years) and a 43-year-old man with de novo KCNC1 mutation. PER was introduced by 2 mg steps at 2-4 week intervals until 6 mg/day, with a possible dose reduction or dose increase. RESULTS: Ten patients had a clear clinical response of myoclonus, and five were able to reduce concomitant therapy. Improvement was noted sometimes as soon as with 2 mg/day. Epileptic seizures stopped on PER in the six patients who still had experienced generalized tonic-clonic or myoclonic seizures (100%). Some abatement of efficacy on myoclonus was seen in two patients who still retained some benefit. Weight gain was reported in six patients (50%). Psychological and behavioral side-effects were observed in six patients (50%) and led to withdrawal of PER in three cases and dose reduction in three, with abatement of the problems. SIGNIFICANCE: This study provides evidence that for ULD patients, PER may show marked efficacy even in severe cases, particularly against myoclonus, but also against seizures. PER should thus be tried in ULD patients whose seizures are not satisfactorily controlled. Its use is limited because of psychological and behavioral side effects, with higher doses of approximately 6 mg/day or greater likely risk factors.

Cost-effectiveness analysis of epilepsy surgery in a controlled cohort of adult patients with intractable partial epilepsy: A 5-year follow-up study.

OBJECTIVE: Despite its well-known effectiveness, the cost-effectiveness of epilepsy surgery has never been demonstrated in France. We compared cost-effectiveness between resective surgery and medical therapy in a controlled cohort of adult patients with partial intractable epilepsy. METHODS: A prospective cohort of adult patients with surgically remediable and medically intractable partial epilepsy was followed over 5 years in the 15 French centers. Effectiveness was defined as 1 year without a seizure, based on the International League Against Epilepsy (ILAE) classification. Clinical outcomes and direct costs were compared between surgical and medical groups. Long-term direct costs and effectiveness were extrapolated over the patients' lifetimes with a Monte-Carlo simulation using a Markov model, and an incremental cost-effectiveness ratio (ICER) was computed. Indirect costs were also evaluated. RESULTS: Among the 289 enrolled surgery candidates, 207 were operable-119 in the surgical group and 88 in the medical group-65 were not operable and not analyzed here, 7 were finally not eligible, and 10 were not followed. The proportion of patients completely seizure-free during the last 12 months (ILAE class 1) was 69.0% in the operated group and 12.3% in the medical group during the second year (p < 0.001), and it was respectively 76.8% and 21% during the fifth year (p < 0.001). Direct costs became significantly lower in the surgical group the third year after surgery, as a result of less antiepileptic drug use. The value of the discounted ICER was 10,406 (95% confidence interval [CI] 10,182-10,634) at 2 years and 2,630 (CI 95% 2,549-2,713) at 5 years. Surgery became cost-effective between 9 and 10 years after surgery, and even earlier if indirect costs were taken into account as well. SIGNIFICANCE: Our study suggests that in addition to being safe and effective, resective surgery of epilepsy is cost-effective in the medium term. It should therefore be considered earlier in the development of epilepsy.

Mixed myoclonic-absence status epilepticus in juvenile myoclonic epilepsy.

Myoclonic status epilepticus or mixed absence-myoclonic status is uncommon in juvenile myoclonic epilepsy (JME), often precipitated by sleep deprivation, withdrawal of medication, or inadequate antiepileptic drugs (Thomas et al., 2006; Crespel et al., 2013). Such episodes respond well to benzodiazepines or valproate (Crespel et al., 2013). We present the video-EEG of a 24-year-old woman with JME and bipolar disorder. She had a confusional state five days after withdrawal of clonazepam (14 mg/d) and introduction of oxazepam (200 mg/d), followed by catatonic stupor with subtle myoclonus of the face and the arms. The EEG showed absence status (figures 1, 2), which stopped after IV injection of clonazepam (1 mg) (figure 3). Consciousness returned to normal [Published with video sequence and figures (1)].

Sleep before and after temporal lobe epilepsy surgery.

PURPOSE: Patients with epilepsy often complain of non-restorative sleep. This is the consequence of the acute effect of seizures and the chronic effect of epilepsy responsible for disrupting sleep architecture. Other factors such as antiepileptic drugs (AEDs), also play a role in the alteration of sleep organization. The aim of this study was to evaluate the specific effect of seizures and interictal epileptiform abnormalities (IEAs) on sleep, in particular to see whether reducing seizure frequency by epilepsy surgery might improve sleep organization in these patients. METHODS: Eleven patients with refractory mesial temporal lobe epilepsy, who underwent surgical treatment and who were seizure free at the follow-up, were included in the study. Treatment with AEDs was not significantly modified before the second year of follow-up. Patients were evaluated before surgery, at 1-year and 2-year follow-up visits with a videoEEG monitoring (24h/24). At each follow-up visit, interictal epileptiform abnormalities and sleep macrostructure parameters were assessed. RESULTS: All patients showed a reduction of their IEAs. At 1-year follow-up, total sleep time and REM sleep increased significantly (p=0.032 and p=0.006, respectively). At 2-year follow-up, an important increase of REM sleep was observed (p=0.028). Most significant variations were noted 1 year after surgery. No significant variations were observed between the first and the second year after surgery. CONCLUSIONS: Surgical treatment of temporal lobe epilepsy may improve sleep macrostructure by reducing the number of seizures and of IEAs. These results indirectly confirm the role of epilepsy in disrupting sleep organization chronically.

Parasagittal transinsular electrodes for stereo-EEG in temporal and insular lobe epilepsies.

OBJECTIVE: Direct invasive EEG recordings of the insula - due to its particular anatomical position, deeply seated between both opercula - can only be performed with intracerebral electrodes. To date, the technique most commonly used for insular stereoelectroencephalography (SEEG) is the orthogonal-transopercular electrode approach with the Talairach methodology. We propose another technique utilizing MRI with transinsular parasagittal electrodes and a posterior entry point. This avoids passing through the opercula and sylvian vessels running over the insular surface. METHODS: Nine patients, whose seizures implicated the insula, underwent brain surgery. Under general anesthesia with a Leksell frame, 3D-T(1) SPGR MRI with gadolinium enhancement was achieved. Surgical planning was performed using the StealthStation with an entry point in the parieto-occipital junction setting the target for the first contact of the lead at the most anterior part of the insula. The trajectory was manipulated in order to have at least 4 contacts per electrode track within the insular cortex. All patients had a postoperative MRI to verify the exact position of each contact. RESULTS: Insular seizures were recorded in all patients. There was neither intracranial bleeding nor infection. In all of the cases, except 1, the seizures recorded were found to be propagations of the primary epileptic zone located in the temporal lobe, either in the mesial structures or the superior temporal gyrus. Eight patients were operated, 7 with an antero-mesial temporal lobectomy and 1 with dysplasia of the superior temporal gyrus. No insular resections were performed. CONCLUSION: We report a novel technique for insular SEEG with parasagittal electrodes, parallel to the insular cortex, with an entry point at the parieto-occipital junction. This technique is based entirely on use of MRI, and avoids passing through the opercula and sylvian vessels.

Discrepancies between preoperative stereoencephalography language stimulation mapping and intraoperative awake mapping during resection of focal cortical dysplasia in eloquent areas.

BACKGROUND/AIMS: To compare the reliability of preoperative stereoencephalography (SEEG) and intraoperative electrostimulation regarding functional mapping, and to select the indication for surgery for focal cortical dysplasia (FCD) in language areas. METHODS: The authors present the case of a 21-year-old, right-handed female, suffering from chronic pharmacologically resistant epilepsy since the age of 8. MRI showed a subcortical hypersignal on FLAIR and T(2) sequences at the posterior end of the left superior temporal sulcus compatible with an FCD. SEEG invasive monitoring was performed to precisely identify the epileptogenic zone (EZ) and for functional language mapping. RESULTS: The stimulation of the contacts implicated in the EZ through SEEG leads induced language disturbances, which were not reproducible. Surgery was performed under local anesthesia with awake corticosubcortical mapping. Direct intraoperative stimulation in the EZ, including FCD, did not induce language disturbances. Thus, EZ could be removed completely without any postoperative language deficit. CONCLUSIONS: The present case suggests that when language disturbances which occur during invasive SEEG functional mapping, in eloquent areas, are not reproducible, resection can be considered using intraoperative electrical mapping, without inducing permanent language impairment. This may be explained by a certain degree of plasticity and reshaping of functional areas associated with a congenital lesion and chronic epilepsy.

Cough syncope misinterpreted as epileptic seizure.

Cough syncopes are rare but may be one of the cause of sudden loss of consciousness. We recorded under video-EEG monitoring a typical syncope triggered by voluntary coughing (video) and Valsava maneuvre in a patient referred for the diagnosis of generalized tonic-clonic seizures. There were no signs of active epilepsy. The attacks were associated with overweight, obstructive sleep apnea and heavy consumption of cigarettes. [Published with video sequences].

Comparison of carbamazepine and oxcarbazepine effects on aminothiol levels.

OBJECTIVE: The aim of our study was to investigate the effects of carbamazepine (CBZ) and oxcarbazepine (OXCBZ) on aminothiol levels, including homocysteine (Hcy), cysteine, and cysteinylglycine, in chronically treated patients. METHODS: Epileptic patients receiving CBZ or OXCBZ were recruited as part of routine clinical practice. Demographic data and concomitant medications were recorded from the patient medical file. RESULTS: Sixty patients were included in the study; 30 patients were treated with CBZ and 30 with OXCBZ. Median Hcy level was significantly higher in CBZ-treated patients (20.6 micromol/l) than in OXCBZ-treated patients (14.0 micromol/l, p < 0.0001). No correlation was evidenced between antiepileptic drugs or metabolite levels and Hcy levels for each group. CONCLUSIONS: Less change observed with OXCBZ compared with CBZ on aminothiol levels could constitute an advantage for OXCBZ treatment in patients with other factors influencing Hcy levels and/or at high risk for cardiovascular diseases.

Ictal SPECT in a case of pure musicogenic epilepsy.

A 39-year-old, right-handed woman had seizures for two years which were always triggered by exposure to various types of music: the first occurred while she listened to a tune she particularly liked, Con Te Partiro, by Andrea Boccelli. Other triggering factors were various types of music such as supermarket background music and polyphonic singing or instrumental music played by family members. The seizures had a stereotyped course: she felt anxious, tearful, then occurred slight obtundation, during which she smacked her lips and moved restlessly. There was no complete loss of consciousness, but some degree of amnesia. She never experienced a generalized tonic-clonic seizure, but reported rare spontaneous feelings of déjà-vu that had begun at the same time as the induced seizures. There were no other spontaneous attacks; only one seizure was apparently provoked, not by music but by a loud background noise in her office. She was a music lover and a singer. Interictal EEG showed independent slow waves over the temporal regions. Several seizures with EEG localisation over the right temporal region were elicited after several minutes of exposure to music. Monoauricular stimulation with the same music produced a seizure when applied to the left ear but was ineffective when applied to the right ear. Ictal SPECT demonstrated right temporal hyperperfusion. MRI was normal. On high dose of carbamazepine, seizure frequency decreased. The addition of topiramate resulted in full seizure control. Musicogenic epilepsy is a rare form of reflex epilepsy. Pure cases, when patients do not experience unprovoked seizures, are exceptional. Our report confirms the implication of the right temporal lobe in this epilepsy.

Abnormal neuroimaging in patients with benign epilepsy with centrotemporal spikes.

PURPOSE: Neuroimaging procedures are usually unnecessary in benign epilepsy of childhood with centrotemporal spikes (BECTS) but are often performed before a specific diagnosis has been reached. By definition, BECTS occurs in normal children; however, recent reports have shown that it also can affect children with static brain lesions. We evaluated the prevalence of abnormal neuroimaging in BECTS and assessed whether the lesions had influenced the clinical and EEG expression of this epilepsy. RESULTS: Among 98 consecutive cases first referred between 1984 and 1999, neuroimaging had been performed in 71 (72%) [magnetic resonance imaging (MRI), 20; computed tomography (CT), 59; MRI+CT, eight]. In ten (14.8%), neuroradiologic procedures were abnormal: enlargement of lateral venticles in five cases including a shunted hydrocephalus in two (no etiology in one, neonatal intraventricular hemorrhage in one), a moderate ventricular dilation in one (neonatal distress), a slight ventricular dilation and hypersignal intensities in the white matter in one (premature birth at 27 weeks), and a moderate enlargement of the right temporal horn in one. A right hippocampal atrophy, a biopercular polymicrogyria, a cavum septum pellucidum, a small cystic lesion located in the epiphysis, and an agenesis of the corpus callosum with macrocrania also were observed once each. The outcome was benign in all, in accordance with the overall prognosis of BECTS. CONCLUSIONS: This study confirms that neuroimaging may be abnormal in patients with BECTS and shows that the presence of brain lesions has no influence on the prognosis. Conversely, BECTS can be diagnosed in patients with brain lesions with or without significant neurologic history or abnormalities.