Movement disorders in children with congenital Zika virus syndrome

BackgroundCongenital Zika Virus Syndrome (CZVS) denotes the neurologic and developmental sequelae of congenital infection of the Zika virus. While prior studies have detailed the associated clinical phenotypes, new findings continue to be identified. Abnormal postures and movements have been previously described in children with CZVS, but not in detail.ObjectiveTo examine a cohort of infants with CZVS and characterize the spectrum of motor abnormalities, especially movement disorders.DesignCross-sectional prospective study of 21 infants with confirmed CZVS.SettingSingle-center cohort of 32 patients with serologically confirmed CZVS cared for in a referral center in Brazil.Participants21 children (67% female), evaluated by two child neurologists and one movement disorders specialist, with clinical and laboratory diagnosis of CZVS aged between 16 and 30 months, with a mean age of 16 months at the time of the last examination.Main outcome(s) and measure(s)Prospective neurologic examination by a team of three neurologists, including one movement disorders specialist. Sixteen (76.2%) children had a longitudinal evaluation with a six-month interval. The same team of experts analyzed recorded videos of all patients to characterize motor abnormalities and movement disorders. Neuroimaging findings were also analyzed to correlate with clinical findings.ResultsTwenty (95.2%) patients presented with dystonic postures, including “125” posture of the fingers in 17 (80.1%), “swan neck” posture of the fingers in three (18.8%), oromandibular dystonia in nine (42.9%), extensor axial hypertonia in eight (38.1%) and internal rotation of the shoulder posture in two (9.5%). Four (19%) patients had tremor. All children had malformations of cortical development, and in 13 (61.9%), the pattern was consistent with a severe and diffuse gyral simplification. Seventeen children (81%) had calcification in the transition of grey and white matter, whereas 11 (52.4%) patients had basal ganglia calcifications.Conclusion and relevanceIn our series, dystonic postures and other extrapyramidal signs were frequent and potentially disabling. Although children with CZVS are assessed and treated for spasticity, dystonia and other movement disorders remain neglected. This study emphasizes that extrapyramidal findings may potentially influence optimal strategies for rehabilitation and management.     

Intracranial EEG-fMRI analysis of focal epileptiform discharges in humans

Purpose: Combining intracranial electroencephalography (iEEG) with functional magnetic resonance imaging (fMRI) is of interest in epilepsy studies as it would allow the detection of much smaller interictal epileptiform discharges than can be recorded using scalp EEG‐fMRI. This may help elucidate the spatiotemporal mechanisms underlying the generation of interictal discharges. To our knowledge, iEEG‐fMRI has never been performed at 3 Tesla (3T) in humans. We report our findings relating to spike‐associated blood oxygen level–dependent (BOLD) signal changes in two subjects. Methods: iEEG‐fMRI at 3T was performed in two subjects. Twelve channels of iEEG were recorded from subdural strips implanted on the left posterior temporal and middle frontal lobes in a 20‐year‐old female with bilateral periventricular gray matter heterotopia. Twenty channels of iEEG were recorded bilaterally from two subdural strips laid anterior–posterior along mesial temporal surfaces in a 29‐year‐old woman with bilateral temporal seizures and mild left amygdalar enlargement on MRI. Functional MRI (fMRI) statistical maps were generated and thresholded at p = 0.01. Key Findings: No adverse events were noted. A total of 105 interictal discharges were recorded in the posterior middle temporal gyrus of Subject 1. In Subject 2, 478 discharges were recorded from both mesial temporal surfaces (n = 194 left, 284 right). The right and left discharges were modeled separately, as they were independent. Subject 1 showed spike‐associated BOLD signal increases in the left superior temporal region, left middle frontal gyrus, and right parietal lobe. BOLD decreases were seen in the right frontal and parietal lobes. In Subject 2, BOLD signal increases were seen in both mesial temporal lobes, which when left and right spikes were modeled independently, were greater on the side of the discharge. In addition, striking BOLD signal decreases were observed in the thalamus and posterior cingulate gyrus. Significance: iEEG‐fMRI can be performed at 3T with low risk. Notably, runs of only 5 or 10 min of EEG‐fMRI were performed as part of our implementation protocol, yet a significant number of epileptiform discharges were recorded, allowing meaningful analyses. With these studies, we have shown that deactivation can be seen in individual subjects with focal epileptiform discharges. These preliminary observations suggest a novel mechanism through which focal interictal discharges may have widespread cortical and subcortical influences.     

24小时动态脑电图监测Tourette综合征癫痫样放电

目的：探讨Ｔｏｕｒｅｔｔｅ综合征（ＴＳ）癫痫样脑波的是临床意义。方法：利用动态脑电图仪对８６例ＴＳ患儿作２４小时监测。结果：８６例ＴＳ患儿中有１３例（１５．１％）监测到ＥＥＧ癫痫样放电。其中５例（６％）合并癫痫,８例（９．３％）无癫痫发作。结论：ＴＳ的癫痫样波一部分与癫痫有关,另一部分意义未明,可能遗传有关。     

Modulation of epileptiform EEG discharges in juvenile myoclonic epilepsy: an investigation of reflex epileptic traits

Purpose: Previous studies have suggested that cognitive tasks modulate (provoke or inhibit) the epileptiform electroencephalography (EEG) discharges (EDs) in patients with juvenile myoclonic epilepsy (JME). Their inhibitory effect was found to be especially frequent (64–90%). These studies arbitrarily defined modulation as a >100% increase or >50% decrease of the EDs compared with baseline, which may not sufficiently distinguish from spontaneous fluctuations. The aim of our study was to assess the modulation of EDs and the precipitation of myoclonic seizures by cognitive tasks and by conventional provocation methods, taking into account also the spontaneous fluctuation of EDs. Method: Sixty patients with JME underwent video‐EEG recordings including 50‐min baseline, sleep, hyperventilation, intermittent photic stimulation (IPS), and cognitive tasks. To account for spontaneous fluctuations of the EDs we divided the baseline period into 5‐min epochs and calculated the 95% confidence interval for the baseline EDs in each patient. Modulation was assumed when the number of EDs during any 5‐min test period was outside the 95% confidence interval. Key Findings: Using the arbitrary method, our results were similar to previous publications: Cognitive tasks seemed to inhibit the EDs in 94% of the patients, and to provoke them in 22%. However, when the spontaneous fluctuations were accounted for, inhibition was found in only 29% of the patients and provocation in 18%. A nonspecific effect of any cognitive task seemed to account for the observed significant inhibition in two‐thirds of the cases, but was observed in only one of the patients with significant provocation. Photoparoxysmal response was observed in 23% of the patients. When accounting for the spontaneous occurrence of EDs, IPS had provocative effect in 10% of the patients. Hyperventilation and sleep had provocative effect on EDs to an extent similar to the cognitive tasks (hyperventilation: 22%; sleep: 18%). The conventional provocation methods tended to be more efficient in patients who were not seizure free. Myoclonia were recorded most often during the cognitive tasks (10 patients). Significance: Spontaneous fluctuations of EDs account for most of the previously described inhibitory effect of the cognitive tasks. The provocative effect of the cognitive tasks is task‐specific, whereas the inhibitory effect seems to be related to cognitive activation in general.     

Clinical implications of interictal epileptiform discharges in cognitive functioning in CEC syndrome with evolution into epileptic encephalopathy

In epileptic encephalopathies (EE), interictal epileptiform discharges (IEDs) contribute to cognitive impairment. The EE process has been studied in a patient affected by epilepsy with occipital calcification and celiac disease (CEC syndrome) by combining the administration of brain area stimulus specific (visual and auditory) reaction times (RT) during continuous EEG monitoring with the off-line reconstruction of auditory and visual evoked potentials (EP). Visual RT and VEP were abnormal only if recorded concomitantly to the IEDs. Auditory RT and EP were normal. When the EE process is going on, IEDs transiently disrupt aspects of cortical functioning, contributing to the cognitive impairment.     

Seizures and EEG pattern in Kabuki syndrome

Purpose: Kabuki syndrome (KS) is a rare dysmorphogenic disorder that is characterized by multiple congenital abnormalities with central nervous system involvement. The diagnosis is clinical and a variable degree of mental retardation is always present. Epilepsy is frequently reported, but a typical electroclinical pattern has not been described. We describe the electroclinical features of eight KS non-Japanese patients with epilepsy. Methods: We analysed seizure characteristics and pattern EEG and clinical outcomes in eight KS patients. Results: All patients presented with focal seizures. A frontal epileptic status was present in two cases. We highlighted the fact that, during evolution, seven patients shared the same interictal EEG pattern, which was characterized by isolated or repetitive biphasic spikes or sharp waves, followed by a slow wave of medium and high voltage, predominantly localised in the fronto-central regions. The natural course of seizures is favourable. Conclusions: Our results showed a peculiar homogeneous electroclinical pattern in KS, characterized by focal seizures more frequently origin in fronto-central area which demonstrated that seizures are mostly focal in type and that a fronto-central origin is more frequently evident.     

Cyclic alternating pattern and interictal epileptiform discharges during morning sleep after sleep deprivation in temporal lobe epilepsy

PurposeSleep deprivation (SD) increases the occurrence of interictal epileptiform discharges (IED) compared to basal EEG in temporal lobe epilepsy (TLE). In adults, EEG after SD is usually performed in the morning after SD. We aimed to evaluate whether morning sleep after SD bears additional IED-inducing effects compared with nocturnal physiological sleep, and whether changes in sleep stability (described by the cyclic alternating pattern-CAP) play a significant role.MethodsAdult patients with TLE underwent in-lab night polysomnography (n-PSG) and, within 7 days from n-PSG, they underwent also a morning EEG after night SD (SD-EEG). We included only TLE patients in which both recordings showed IED. SD-EEG consisted of waking up patients at 2:00 AM and performing video EEG at 8:00 AM. For both recordings, we obtained the following markers for the first sleep cycle: IED/h (Spike Index, SI), sleep macrostructure, microstructure (NREM CAP rate; A1, A2 and A3 Indices), and SI association with CAP variables.ResultsThe macrostructure of the first sleep cycle was similar in n-PSG and morning SD-EEG, whereas CAP rate and SI were significantly higher in SD-EEG. SI increase was selectively associated with CAP phases.ConclusionsSD increases the instability of morning recovery sleep compared with n-PSG, and particularly enhances CAP A1 phases, which are associated with the majority of IED. Thus, higher instability of morning recovery sleep may account at least in part for the increased IED yield in SD-EEG in TLE patients.     

EEG frequency during spike-wave discharges may predict treatment outcome in patients with idiopathic generalized epilepsies

We report findings concerning the relationship between electroencephalography (EEG) frequency during spike-and-wave discharges (SWDs) and response to treatment in 21 patients with idiopathic generalized epilepsy (IGE). We studied patients whose EEG contained SWDs lasting at least 4 s. Among these patients, two groups could be distinguished on the basis of a subtle difference in EEG frequency during the first 2 s of the burst. The two groups differed markedly in their clinical response to medication, with the group becoming seizure-free during the next 1-2 years showing a spike-wave onset frequency of > 3.2 Hz, and those not seizure-free < 3.2 Hz (p = 0.0034, sensitivity 75% and specificity 92%). Given this strong effect in a relatively small group, further work is needed to clarify the predictive value of this frequency measure for clinical outcomes in absence epilepsies.     

睡眠性癫癎患者动态脑电图的研究

目的探讨睡眠性癫疒间患者的24h动态脑电图(AEEG)的表现及其诊断价值。方法对91例仅于睡眠中发作癫疒间的患者进行AEEG检查,并对检查结果进行分析。结果AEEG发现疒间性放电71例(78.0%),其中4例出现于清醒状态,41例出现于睡眠状态,26例清醒和睡眠时均有放电;在67例睡眠时有疒间性放电的患者中,34例仅出现在浅睡期,33例整个睡眠中均出现疒间性放电。清醒时有癫疒间波的患者癫疒间发作频率明显高于无异常放电患者和仅睡眠时有疒间性放电的患者(均P<0.05)。结论睡眠中癫疒间发作患者于睡眠中疒间性放电出现率明显高于白天清醒时。AEEG容易发现睡眠性癫疒间患者的发作期和发作间歇期以及自然睡眠状态下的疒间样波。     

Hemodynamic correlates of epileptiform discharges: an EEG-fMRI study of 63 patients with focal epilepsy

Using continuous EEG-correlated fMRI, we investigated the Blood Oxygen Level Dependent (BOLD) signal correlates of interictal epileptic discharges (IEDs) in 63 consecutively recruited patients with focal epilepsy. Semi-automated spike detection and advanced modeling strategies are introduced to account for different EEG event types, and to minimize false activations from uncontrolled motion. We show that: (1) significant hemodynamic correlates were detectable in over 68% of patients in whom discharges were captured and were highly, but not entirely, concordant with site(s) of presumed seizure generation where known; (2) deactivations were less concordant and may non-specifically reflect the consequential or downstream effects of IEDs on brain activity; (3) a striking pattern of retrosplenial deactivation was observed in 7 cases mainly with focal discharges; (4) the basic hemodynamic response to IEDs is physiological; (5) incorporating information about different types of IEDs, their durations and saturation effects resulted in more powerful models for the detection of fMRI correlates; (6) focal activations were more likely when there was good electroclinical localization, frequent stereotyped spikes, less head motion and less background EEG abnormality, but were also seen in patients in whom the electroclinical focus localization was uncertain. These findings provide important new information on the optimal use and interpretation of EEG-fMRI in focal epilepsy and suggest a possible role for EEG-fMRI in providing new targets for invasive EEG monitoring.     

Interictal epileptiform discharges relate to 1H-MRS-detected metabolic abnormalities in mesial temporal lobe epilepsy

PURPOSE: To examine whether the distribution of interictal epileptiform discharges (IEDs) recorded from foramen ovale electrodes (FOEs) correlates with metabolite levels in medial structures of the temporal lobes in patients with mesial temporal lobe epilepsy (MTLE). METHODS: We studied 34 patients with MTLE. The lateralization ratio of IEDs was calculated after counting IEDs recorded from FOEs during prolonged video-EEG monitoring. Metabolite ratio between N-acetylaspartate (NAA) and creatine (Cr) was calculated in each medial temporal structure. The correlation between the lateralization ratio of IEDs and metabolic ratio was evaluated. RESULTS: The asymmetry indexes of IEDs correlated with the asymmetry index of NAA/Cr ratio in the medial temporal structure (rho = -0.380; p = 0.027). Analysis of IEDs and metabolite ratio revealed a significant inverse relation in the contralateral side to the major epileptogenic focus (rho = -0.360; p = 0.037); however, this significance was not present in the ipsilateral side (rho = -0.018; p = 0.921). CONCLUSIONS: There is a correlation between the neuronal dysfunction or damage detected by MRS and the epileptic activity in the contralateral medial temporal structure. Our results suggest that the pathomechanism underlying the contralateral reduction of NAA/Cr ratio, frequently observed in patients with MTLE, might be related to the process of epileptogenesis generating the independent contralateral IEDs.     

睡眠中癎样放电对睡眠的影响

目的：观察不同睡眠时相中?样放电的情况,以及对不同发作类型患者生活品质（QOL ）的评价,探讨?样放电对癫?患者睡眠的影响以及睡眠对其Q O L的影响。方法：对132例癫?患者进行24 h录像脑电图（V‐EEG）及多项睡眠监测（PSG）检查,检测?样放电及分析睡眠结构。运用癫?患者生活质量量表‐31（QOLIE‐31）对不同发作类型患者进行QOL评估。结果：在全部132例患者中,非?性异常为32例（25．8％）,出现?样放电为52例（40．9％）,觉醒期及睡眠期?样放电检出率比较差异有显著意义（P＜0．05）。?样放电组和对照组相比NREM Ⅰ－Ⅱ期明显延长[分别为65．93（±9．1）％和58．67（±5．7）％],NREM Ⅲ期明显缩短[分别为17．78（±5．2）％和26．06（±8．2）％],差异均有统计学意义（P ＜0．05）;睡眠参数中?样放电组REM潜伏期明显延长,同时觉醒次数也增多。而非?性异常组REM 潜伏期、觉醒次数与正常对照组相比均有增加,但差异无统计学意义。不同发作类型睡眠结构差异无统计学意义。各种发作类型的患者各 QOL 指标均低于正常人群,差异有统计学意义（ P＜0．01）;全面性发作患者除药物影响外各指标均低于其他发作类型患者,差异有统计学意义;不同发作类型患者受到药物的影响无明显差异。结论：联合应用 V‐EEG及PSG可以更好地发现睡眠中?样放电,从而有助于确诊临床工作中难以发现的癫?。分析?样放电与睡眠时相之间的关系,以便指导临床癫?治疗,更好地控制癫?发作,改善患者QOL。     

Periodic lateralized epileptiform discharges: an initial electrographic pattern in reversible posterior leukoencephalopathy syndrome

Reversible posterior leukoencephalopathy (RPLE) is a unique clinicoradiological entity characterized by diverse neurological symptoms with bilateral posterior cerebral white matter edema. It is frequently associated with seizures but rarely with status epilepticus. Periodic lateralized epileptiform discharges (PLEDs) as an initial electrographic pattern in a patient with RPLE have never been reported. We discuss a 47-year-old woman with a newly diagnosed non-small cell carcinoma of the lung on etoposide who was admitted with encephalopathy. Initial EEG demonstrated PLEDs. She later developed nonconvulsive status epilepticus. Magnetic resonance imaging (MRI) revealed bilateral subcortical edema predominantly of the temporo-occipital lobes. Discontinuation of etoposide resulted in full clinical, electrical recovery within 10 days and significant radiological improvement within 15 days. Our case indicates the importance of identifying and addressing any modifiable etiologic factors of RPLE. We emphasize identification of the unique initial electrographic pattern of PLEDs, which may be a predisposing factor to status epilepticus or an indication of structural damage.     

Risk for developing epilepsy and epileptiform discharges on EEG in patients with febrile seizures

Purpose: The aim of the present study was to investigate the correlation between epileptiform discharges on EEGs after febrile seizures and the prognosis of patients in terms of the development of epilepsy and recurrence of febrile seizures. This study also evaluated the characteristics of epileptiform discharges and EEG changes on follow-up examination. Methods: This study consisted of 36 children who presented to our hospital with febrile seizures and whose electroencephalograms (EEG) showed epileptiform discharges. The development of epilepsy and the recurrence of febrile seizures were compared between the study group (n = 36) and the control group (n = 87), which included children with febrile seizure but with normal EEG findings. Results: No significant correlation was detected between the recurrence rate of febrile seizures in patients with normal EEG (23 out of 87, 26.4%) findings and that of patients whose EEGs showed epileptiform discharges (12 out of 36, 33.3%) [adjusted OR 0.67 (0.26–1.68)]. However, 9 (25.0%) out of 36 patients with epileptiform discharges on EEG had epilepsy compared to 2 patients (2.3%) in the control group. The correlation was statistically significant [crude OR 10.88 (2.47–47.88) and adjusted OR 8.75 (1.49–51.6)]. Conclusion: Epileptiform discharges on the EEGs of patients with febrile seizures are important predictive risk factors of the development of epilepsy.