Landau-Kleffner Syndrome: A Pharmacologic Study of Five Cases

Five children with Landau-Kleffner syndrome (epilepsy, acquired aphasia, and continuous spike-wave discharges during sleep), were treated with antiepileptic drugs (AEDs), sleep-modifying drugs, and corticosteroids. The pharmacologic profiles differed from those observed in focal epilepsies, resembling instead those of certain generalized epilepsies, such as West or Lennox-Gastaut syndromes. Phenobarbital (PB), carbamazepine (CBZ), and phenytoin (PHT) were ineffective or worsened the EEG and neuropsychological symptoms, whereas valproate (VPA), ethosuximide (ESM), and benzodiazepines were partially or transiently efficacious. Dextroamphetamine produced a dramatic but transient improvement in waking and sleep EEG in one of two children; aphasia did not change. Corticosteroid treatment resulted in improved speech, suppression of seizures, and normalization of the EEG in three of three children. Our own experience and data from the literature suggest that corticosteroids should be given in high doses as soon as the diagnosis is firmly established and should be continued in maintenance dose for several months or years to avoid escape. Early diagnosis, before mutism or global deterioration develops, appears to be essential for effective therapy with minimal neuropsychological sequelae.     

Cerebral Glucose Utilization During Sleep in Landau-Kleffner Syndrome: A PET Study

Three right-handed male children (aged 5, 6, and 11 years) with signs, symptoms and/or history of the syndrome of acquired aphasia-epilepsy (Landau-Kleffner syndrome) were studied during drug-induced, electroencephalographically (EEG)-monitored sleep by positron-emission tomography (PET) and the [18F]fluorodeoxyglucose (FDG) method. Our data demonstrate that in Landau-Kleffner syndrome, cerebral glucose utilization is not normal during sleep. The metabolic pattern varied between the children but the metabolic disturbances always predominated over the temporal lobes. They were right-sided, left-sided, or bilateral. In the two first patients, EEG recordings showed continuous spike-and-wave discharges during sleep and a right-greater-than-left asymmetry was observed in temporal areas. In patient 1, the asymmetry was associated with a relative increase of glucose utilization of the right posterior temporal region. In patient 2, the glucose utilization was relatively decreased in the left anterotemporal and left perisylvian regions. In patient 3, the sleep EEG showed no discharge and no significant asymmetry was observed; however, glucose utilization of both temporal lobes was decreased. Lower metabolic rates in subcortical structures than in cortex were also noted in the three children. This metabolic pattern may be related to the maturation of the central nervous system (CNS).     

EEG Abnormalities in Children with a First Unprovoked Seizure

Summary: We examined EEG findings from an ongoing study of 347 children with a first unprovoked seizure. EEGs were available in 321 (93%), and 135 (42%) had an abnormal EEG. EEG abnormalities included focal spikes (n = 77), generalized spike and wave discharges (n = 28), slowing (n = 43), and nonspecific abnormalities (n = 7). Abnormal EEGs were more common in children with remote symptomatic seizures (60%) than in those with idiopathic seizures (38%) (p < 0.003), more common in partial seizures (56%) than in generalized seizures (35%) (p < 0.001), and more common in children age >3 years (52%) than in younger children (12%) (p < 0.001). Records including both awake and sleep tracings were available in 148 (46%) cases. For 122 (38%) only awake tracings and for 51 (16%) only sleep tracings were available. Fifty-nine (40%) of the 148 patients with both an awake and asleep tracing had abnormal EEGs. Of 50 such EEGs with epileptiform abnormalities, 15 (30%) demonstrated the abnormality either only while awake (n = 8) or only while asleep (n = 7). Of 17 patients with EEG slowing, 8 showed slowing only in the awake tracing and 9 showed slowing in both the awake and asleep tracing. Children with even a single unprovoked seizure have a high incidence of EEG abnormalities. Obtaining a combined awake and sleep EEG significantly increases the yield of EEG abnormalities. In children with an idiopathic first seizure, EEG abnormalities are associated with an increased risk of seizure recurrence.     

Intracranial EEG Monitoring in Landau-Kleffner Syndrome Associated with Left Temporal Lobe Astrocytoma

Summary: A 3½-year-old boy developed partial complex seizures with right-sided motor activity, occasionally secondarily generalized at age 18 months. Initial EEG showed left-sided focal epileptiform discharges. Seizures became refractory to antiepileptic drugs (AEDs). At age 3 years, there was severe language deterioration consistent with Landau-Kleffner syndrome (LKS). At that time, an EEG showed almost continual generalized spikes and poly spikes, worse during sleep. Video-EEG showed generalized tonic seizures associated with generalized EEG ictal activity. Magnetic resonance imaging (MRI) showed a cystic and solid lesion of the left hippocampal and parahippocampal gyri without surrounding edema. Subdural strip electrodes under the left temporal and overlying the left frontal lobes demonstrated interictal spikes simultaneously in all recording contacts. Ictal EEG activity occurred in the temporal electrodes 0.2–1 s before appearing in the frontal electrodes. After left temporal lobectomy with subtotal resection of a low-grade astrocytoma, he had an immediate marked decrease in seizures. In 1 month he was seizure-free, and in 6 months had no further seizures and markedly improved language. These findings provide further evidence that left temporal structural epileptogenic lesions may contribute significantly to the pathophysiology of LKS.     

The Landau-Kleffner syndrome: A review

The Landau-Kleffner syndrome or the syndrome of acquired epileptic aphasia was first described in 1957. The disorder is characterised by gradual or rapid loss of language in a previously normal child. All children have abnormal EEG compatible with the diagnosis of epilepsy, however, only 70% have clinical seizures. The present article presents a review of the current knowledge concerning this disorder. Information is provided related to the clinical picture, etiology, pathogenesis, treatment and outcome.

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Zusammenfassung Das Landau-Kleffner-Syndrom oder das Syndrom der erworbenen epileptischen Aphasie wurde erstmals 1957 beschrieben. Die Störung ist charakterisiert durch den allmählichen oder raschen Verlust der Sprache eines zuvor normal entwickelten Kindes. Alle Kinder haben abnorme EEG-Befunde, die mit der Diagnose einer Epilepsie vereinbar sind. Jedoch haben lediglich 70% der Betroffenen klinisch apparente Krampfanfälle. Der vorliegende Artikel faßt den gegenwärtigen Wissensstand zu dieser Störung zusammen. Es werden Informationen zum klinischen Bild, zur Ätiologie, Pathogenese, Behandlung und Verlauf vermittelt.

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Résumé Le syndrome Landau-Kleffner, ou bien le syndrome de l'aphasie épileptique acquise, a été découvert en 1957. Ce dysfonctionnement se charactérise par la perte graduelle ou rapide du langage chez un enfant jusque là normal. Tous les enfants présentent des électro-encéphalogrammes anormaux correspondant à des critères diagnostiques de l'épilepsie, mais 70% d'entre eux seulement ont des attaques cliniques. Cet article présente un survol des connaissances actuelles relatives à ce dysfonctionnement, et se propose de donner des informations quant à son aspect clinique, son étiologie, sa pathogénie, son traitement ainsi que son issue.

     

Aicardi Syndrome: A Longitudinal Clinical and Electroencephalographic Study

Summary: We report clinical and EEC follow-up of 6 children with Aicardi syndrome. Age at seizure onset was <3 months in 5 patients and 4 months in 1 patient. All patients had spasms, and these continued at time of follow-up in 5 patients. Five patients had seizures other than spasms which disappeared during early infancy. Bilateral independent bursts (BIBs) characteristic of Aicardi syndrome were noted in 4 patients. In 1, BIBs showed suppression-burst patterns. BIBs converted to hypsarrhythmia or multifocal spikes with a tendency to BIBs during sleep. BIBs disappeared completely during both waking and sleeping states between the ages of 3 years 1 month and 4 years 9 months. After BIB disappearance, the EEG of 1 patient showed diffuse slow spike-and-wave complexes most of which appeared asynchronously. At onset, 1 patient had early-infantile epileptic encephalopathy with suppression-burst which evolved initially into West syndrome (WS) and then Lennox-Gastaut syndrome (LGS). The other 3 children also had WS.     

Landau-Kleffner综合征的临床特征(附3例报告)

目的探讨Landau-Kleffner综合征(LKS)的临床特征。方法回顾性分析3例LKS患者的临床资料。结果3例临床表现均有获得性失语、癫发作及精神行为异常;脑电图呈局灶性棘波放电,头颅CT及MRI未见异常。经治疗癫发作控制较好,但失语及精神行为异常恢复较慢。结论LKS是以获得性失语和癫发作为临床特征;脑电图可见异常放电。治疗后可部分恢复。     

Landau-Kleffner Syndrome: Consistent Response to Repeated Intravenous γ-Globulin Doses: A Case Report

Summary: Purpose: Although several treatments have been tried for Landau-Kleffner syndrome (LKS) too many patients are refractory to known therapies. We report an 8–year-old girl who failed other therapies but who had a consistent response after treatment with intravenous (i.v.) γ-globulin. Methods: We monitored the girl from the age of 6 years, when she presented with a 6–month history of loss of language with normal hearing, normal brain magnetic resonance imaging (MRI), increased cerebrospinal fluid (CSF) IgG index, and an EEG showing almost continuous, predominantly left-sided spike- and slow-wave complexes. She had no clinical seizures and did not respond to consecutive trials of valproate (VPA), clonazepam (CZP), prednisone, and carbamazepine (CBZ). She received three courses of intravenous (i.v.) γ-globulin; after each course, clinical and electrographic improvement lasted a few months. After each of the initial two eourses, clinical improvement lasted 3–4 months but was followed by recurrence of the spikes on the EEG and by speech deterioration. Results: However, her last remission has been continuous for the past 16 months. Her CSF IgG index became normal after the first i.v. γ-globulin infusion. Conclusions: Based on our experience with this patient and on other investigators' experience, we believe that further research into immunologic mechanisms and therapies of this syndrome are warranted.     

Case of Landau-Kleffner Syndrome Secondary to Inflammatory Demyelinating Disease

Summary: A 6-year old girl developed acquired aphasia with epilepsy and a paroxysmal EEG (Landau-Kleffner syndrome). Isoelectric CSF focusing showed oligoclonal IgG bands. Small lesions were visualized in periventricular left frontal white matter and right parietal lobe centrum semiovale with magnetic resonance imaging (MRI). After a week of ACTH therapy, the EEG paroxysmal activity disappeared; during the next few months, the language disorder improved. Further MRI examination showed a decrease in size and signal of the left frontal lesions, with localized white matter atrophy, dilatation of the subarachnoidal spaces, and disappearance of the right parietal lesion. The clinical and neuroradiologic features and the laboratory data suggest an acute disseminated encephalomyelitis.     

Successful use of intravenous immunoglobulin as initial monotherapy in Landau-Kleffner syndrome

PURPOSE: There is a need for new and more effective therapies for Landau-Kleffner syndrome. In this article we present the first case in which a patient with Landau-Kleffner syndrome was given intravenous immunoglobulin (IVIG) as his first and only therapy and responded to it. METHODS: This previously healthy, left-handed boy presented at 31 months of age with a 3-month history of auditory agnosia, behavioral abnormalities, and progressive, eventually complete loss of speech. Electroencephalography (EEG) showed frequent and, in sleep, continuous right central and temporal spike slow wave discharges. Metabolic workup, magnetic resonance imaging, and auditory evoked potentials were normal. Cerebrospinal fluid IgG index was high (18%). The patient was treated with IVIG, as his initial and only therapy, receiving 500 mg/kg/day over four consecutive days. RESULTS: On the third day of IVIG, the patient started using single words, and on the fourth, two-word sentences. Two weeks later his speech and behavior returned to normal. At the end of 4 days of IVIG therapy, EEG was within normal limits. Two months later, however, he had a severe relapse clinically and by EEG. He promptly responded to another course of IVIG. A subsequent cerebrospinal fluid IgG index showed normalization (6%). Three months later he had essentially normal speech and behavior. CONCLUSIONS: Repeated, immediate, and remarkable clinical and EEG responses of this patient suggest that IVIG was helpful as first-line therapy in the treatment of Landau-Kleffner syndrome. It also supports the hypothesis that immunological mechanisms contributed to his symptoms.     

Psychogenic Seizures in Old Age: A Case Report

Psychogenic seizures are unusual after age 60 years, A 73-year-old woman had onset of psychogenic seizures at age 69 years. Five to six attacks occurred each month, usually at night, characterized by an initial subjective sensation and headache followed by generalized stiffening and shaking. Continuous EEG-closed circuit television (EEG-CCTV) monitoring clearly showed these episodes to be nonepileptic. Discontinuation of antiepileptic drugs (AEDs) did not increase the frequency or severity of attacks. Epileptiform discharges were not recorded during the awake, drowsy, or sleeping states. Psychiatric evaluation identified significant turmoil in the patient's life and a history of childhood sexual and physical abuse. Psychogenic seizures may begin in old age and should be considered in the differential diagnosis of intractable seizures in the elderly. Predominantly nocturnal occurrence should not exclude the diagnosis.     

Ictal Clinical Electroencephalographic Findings of Spasms in West Syndrome

Summary: The electroencephalographic/video recordings of 955 spasms in children with cryptogenic and symptomatic West syndrome (WS) were reviewed to define the relation between a clinical manifestation of a spasm and its EEG pattern, and to examine whether these features reflect the etiology and prognosis of WS. The review confirmed the spasm to be a distinct type of seizure, with a unique clinical and EEG pattern unlike that of all other recognized seizures. Symmetric spasms were present in cryptogenic and symptomatic patients. In contrast, asymmetric spasms, or focal signs recognizable during a spasm, strongly indicated the existence of a cerebral lesion. In both etiological groups, the characteristic ictal EEG pattern of the spasms consisted of a positive-vertex slow wave. The other two patterns apparently correlated to a spasm, were fast activity, here called spindle-like, and decremental activity. The fast activity corresponded to a clinical stare, and the decremental activity, when present, represented a postictal event. Although it was independent from the etiology of the spasms, persisting hypsarrhythmia during a cluster of spasms appeared to be an EEG pattern that correlated with a favorable outcome.     

Predictivity of Plasma Prolactin Levels in Differentiating Epilepsy from Pseudoseizures: A Prospective Study

The predictivity of raised plasma prolactin (PRL) concentrations in differentiating seizure from syncopal attack was prospectively assessed in all patients consecutively admitted to the Clinica Neurologica of Brescia, Italy in a 12-month period who fulfilled the criteria for either a seizure or syncopal attack. Postictal plasma prolactin concentration (P1) was assessed as soon as possible after the event. Three further assessments were performed: P2 was sampled 1 h after P1, P3, and P4 were sampled in the morning for the next 2 days. Patients who had had a seizure showed significantly increased P1 concentrations, when P1 was sampled within 60 min of the attack. In seizure patients assessed >1 h after the event, P1 was not significantly different from either P2, P3, or P4. In patients who had had a syncopal attack, PRL concentration never increased. In patients assessed ≤60 min after the seizure, cutoff criterion of P1 exceeding by + 3 SD the mean calculated on P2, P3, and P4 yielded a positive predictive value of 89% and a negative predictive value of 61%. These findings confirm that plasma prolactin concentration is highly predictive of true epilepsy but barely predictive of pseudoseizures.     

麻痹性痴呆二例的临床特征与诊断

目的分析麻痹性痴呆(GPI)的临床特征及提供早期诊断依据。方法回顾性分析经临床和实验室检查确诊的2例麻痹性痴呆患者的有关临床资料。结果GPI的临床特征(1) 2例患者慢性起病,进行性发展; (2)痴呆是核心症状, 2例患者入院时长谷川痴呆量表评分为4分和17分,均伴夸大妄想、病理性欣快等精神症状; (3) 1例患者的瞳孔左右不等大,光反射迟钝或消失但辐辏反射保持, 2例患者均有构音障碍、肌张力增高及反射异常等; (4) 2例患者血清、脑脊液梅毒抗体反应均为阳性,脑脊液蛋白含量增加、细胞数增多(以淋巴细胞为主); (5)头颅MRI示2例患者均有脑萎缩, 1例患者有脑实质异常信号影,为多发、散在病灶,广泛脑白质纤维变性。结论GPI误诊率高,临床表现、实验室及影像学检查是诊断的重要依据。     

Progressive Myoclonus Epilepsies: Clinical and Genetic Aspects

The progressive myoclonus epilepsies (PMEs) are a group of rare genetic disorders previously shrouded in nosological confusion. Recent advances have clarified the features of these disorders and provided a rational approach to diagnosis. The major causes of PME are now known to be Unverricht—Lundborg disease, myoclonus epilepsy ragged-red fiber (MERRF) syndrome, Lafora disease, neuronal ceroid lipofuscinoses, and sialidoses. Over the past 3 years, a series of molecular genetic findings have further refined the understanding of the PMEs. The specific mutation responsible for many cases of MERRF has been identified, and the genes for Unverricht—Lundborg disease and for juvenile neuronal ceroid lipofuscinosis have been linked to chromosomes 21 and 16, respectively. Although the PMEs are among the rarest of the inherited epilepsies, because of molecular genetic discoveries they may soon be the best understood at the neurobiologic level.     

Intraictal Activation in the Neocortex: A Marker of the Epileptogenic Region

Summary: During the course of a seizure, subdural recordings often show secondary areas which develop in-dependent electrographic sequences that may outlast the primary seizure sequence. We reviewed the subdural data on 8 patients with intraictal secondarily activated foci (ISF). In 6 patients, ISFs were documented to be capable of generating independent seizures; ISF seizures occurred during the initial subdural monitoring period in 3, but became ictal generators only after excision of the primary focus in the other 3. Prominent interictal abnormalities were observed at the ISFs in 5 of 8 patients. The ISF in 1 patient correlated with the structural lesion on magnetic resonance imaging (MRI) scan. We believe that ISFs have significant epileptogenicity and should be re-sected when possible.     

The Diagnostic Yield of a Second EEG After Partial Sleep Deprivation: A Prospective Study in Children with Newly Diagnosed Seizures

Summary: Purpose: To assess the diagnostic yield of a repeated EEG (REPEEG) after partial sleep deprivation (SD) in children and adolescents with one or more seizures who previously had had a standard EEG (STDEEG) without epileptiform abnormalities (EAs). In the literature, 32–75% of such REPEEGs after SD were reported to show EA. Methods: In a prospective, multicentred study, we selected children aged 1 month to 16 years with one or more idiopathic or remote symptomatic newly diagnosed seizures. A REPEEG was recorded in children without EAs in their STDEEG. Results: Of 552 children and adolescents who entered the study, 243 (44%) had a STDEEG without EAs. In 177 (73% of eligible children), REPEEGs were recorded after SD. We found EAs in 61 (34.5%) REPEEGs and new nonepileptiform abnormalities in five (1%). In 552 children in the total cohort, the REPEEG thus added 11% with EAs to the 56% with EAs in the STDEEG. Of REPEEGs, 81% included sleep compared with 20% of STDEEGs. In about half the REPEEGs, EAs occurred during sleep only. One child had tonic-clonic seizures probably related to the SD. Conclusions: One third of REPEEGs yielded new diagnostic information. Partial, age-dependent SD was highly effective in inducing sleep, which is important because in many cases EAs were found only during EEG recording in sleep. The procedure was safe and convenient.     

Rational treatment options with AEDs and ketogenic diet in Landau-Kleffner syndrome: Still waiting after all these years

Antiepileptic drugs (AEDs) remain a first treatment approach in Landau-Kleffner syndrome (LKS) and related syndromes. In the current literature, only class IV evidence is available. Inclusion criteria and outcome parameters are ill-defined. Most commonly, valproate, ethosuximide, and/or benzodiazepines are used. More recent case series show that sulthiame and especially levetiracetam can be considered as effective drugs. Smaller studies also point to the ketogenic diet as a valuable treatment option in LKS.     

艾滋病痴呆综合征临床分析

目的研究中国人群艾滋病(AIDS)痴呆综合征(ADC)的特征。方法对上海交通大学附属第一人民医院和上海市传染病医院收治的诊断为ADC的6例AIDS患者进行临床分析。结果所有患者均在清醒状态下表现为近记忆减退及注意力集中困难,其中3例伴有运动障碍。6例ADC患者中2例伴有空泡性脊髓病。诊断为AIDS后,ADC的平均诊断时间为6 5个月。所有患者均死于呼吸衰竭,平均寿命为41 8岁。结论ADC是AIDS患者最常见的神经系统并发症,常发生在AIDS的进展期。ADC通常伴有空泡性脊髓病,预后极差。