Non-convulsive status epilepticus during lithium treatment at therapeutic doses

Abstract The purpose of this study is to report the case of a patient with normal lithium serum levels who developed non-convulsive status epilepticus (NCSE). A 52-year-old woman with bipolar disorder type I (DSM-IV) treated with lithium experienced bradypsychism and episodes of confusion and spatial disorientation without signs or symptoms of lithium intoxication. Lithium serum levels were in the normal range. A brain MR scan was negative; the electroencephalogram (EEG) revealed a background 3–4 Hz delta rhythm and diffuse spike discharges. Prompt EEG and clinical response to intravenous diazepam therapy was observed. Based on these findings, a diagnosis of NCSE was made and lithium therapy was withdrawn, resulting in symptom remission and EEG normalization. The treatment was resumed after two months to test the correlation between NCSE and lithium therapy. Resumption of therapeutic range lithium induced the same clinical symptoms and EEG patterns; the therapy was thus definitively discontinued. The present data—signalling the temporal correlation of clinical and EEG changes with drug administration and withdrawal—suggest that even in the therapeutic range lithium treatment may trigger NCSE onset in predisposed subjects.     

Differences in the EEG profiles of early and late responders to antipsychotic treatment in first-episode, drug-naive psychotic patients

The aim of this study was to search for differences in the EEG of first-episode, drug-naive patients having a schizophrenic syndrome which presented different time courses in response to antipsychotic treatment. Thirteen patients who fulfilled DSM-IV diagnosis for schizophrenia or schizophreniform disorder participated in this study. Before beginning antipsychotic treatment, the EEG was recorded. On the same day psychopathological ratings were assessed using the AMDP system, and again after 7 and 28 days of treatment. The resting EEG (19 leads) was subject to spectral analysis involving power values for six frequency bands. The score for the schizophrenic syndrome was used to divide the patients into two groups: those who displayed a clinically meaningful improvement of this syndrome (reduction of more than 30%) after 7 days of treatment (early responders, ER) and those who showed this improvement after 28 days (late responders, LR). Analysis of variance for repeated measures between ER, LR and their matched controls with the 19 EEG leads yielded highly significant differences for the factor group in the alpha2 and beta2 frequency band. No difference was found between the slow-wave frequency bands. Compared to controls the LR group showed significantly higher alpha2 and beta2 power and, in comparison to the ER group, significantly higher alpha2 power. There were no significant differences between the ER and the control group. These findings point to differences in brain physiology between ER and LR. The implications for diagnosis and treatment are discussed.     

Iron states and cognitive abilities in young adults: neuropsychological and neurophysiological assessment

Many investigators found that iron deficiency anemia (IDA) had a great influence on cognitive functions in infants and children. However, studies of such topic in adults are few and controversial. We prospectively assessed the possible influence of IDA and iron supplementation (for 3 months) on cognitive function and intelligence of 28 young adults with IDA. We used group of hematological, cognitive, neurophysiological tests for assessment including: mini-mental state examination (MMSE), Wechsler memory scale-revised (WMS-R), Wechsler adult intelligence scale-revised (WAIS-R), event-related potentials (ERPs), and electroencephalography (EEG). Compared to controls, patients demonstrated lower scores of different cognitive tests (MMSE, WMS-R, and WAIS-R), which showed significant improvement after treatment. Prolongation of ERPs latencies (N200 and P300) and reduction in their amplitudes (P200 and P300) were identified with significant increase in amplitude occurred after treatment. EEG abnormalities were observed in 55% of patients which showed improvement in 35% after treatment. Positive correlation was identified before and after treatment between hemoglobin levels and MMSE (P=0.01, 0.05), total verbal (P=0.04) and performance (P=0.05, 0.04) IQ scores. Negative correlation was identified between before and after treatment between P300 latency and total IQ of WAIS-R (P=0.03, 0.008) and hemoglobin level (P=0.4, 0.01). Positive correlation was found before and after treatment between P300 amplitude and total IQ (P=0.028, 0.01) and serum iron (P=0.01, 0.001). In conclusion, IDA is a significant factor in cognitive performance in adult population, which can be partially reversed by treatment.     

Sulthiame add-on therapy in children with focal epilepsies associated with encephalopathy related to electrical status epilepticus during slow sleep (ESES)

Purpose: In children with symptomatic or idiopathic focal epilepsies, their disease may evolve into an epileptic encephalopathy related to continuous spike and wave during slow sleep (CSWS) or electrical status epilepticus during slow sleep (ESES). ESES syndrome implies serious risks of neuropsychologic impairment, and its treatment has frequently been disappointing. The aim of this study is to present our experience using sulthiame as add‐on treatment in 53 patients with ESES syndrome that was refractory to other antiepileptic drugs (AEDs). Methods: Neurologic examinations, cerebral magnetic resonance imaging (MRI), and repeated prolonged sleep electroencephalography (EEG) studies were performed in all cases. Data about school achievements and or neuropsychological evaluations were obtained repeatedly during the follow‐up of 1.5–16 years. Sulthiame was added in doses ranging between 5 and 30 mg/kg/day. Key Findings: Since add‐on of sulthiame, 10 of 28 patients in the symptomatic group became seizure free: 4 patients with normal EEG studies and 6 with residual spikes. Nine of 28 patients showed a significant reduction in number of seizures and presented spikes but no ESES on EEG. The other nine cases showed neither clinical nor EEG improvement. A striking result was that 3 of 11 children with unilateral polymicrogyria and ESES syndrome became seizure free, and in another six a significant improvement in frequency of seizures and in EEG abnormalities seemed to be related to the add‐on of sulthiame. Twenty‐one of the 25 patients in the idiopathic group became seizure free and without ESES in <3 months after add on of sulthiame. In two of the patients the changes were seen in a few days. Significance: We understand that sulthiame may be effective as add‐on treatment in children with ESES syndrome.     

Possible relationship between electroencephalogram finding and lithium response in bipolar disorder

The relationship between electroencephalogram (EEG) finding and lithium response was retrospectively examined in 58 patients with bipolar disorder. All necessary information was obtained from the clinical charts. The patients were categorized into two groups (responder or nonresponder) with regard to the lithium response and into three groups (normal, borderline, or abnormal) concerning the EEG finding. The information both on EEG and lithium response could be obtained from 27 patients. Only five cases were classified as lithium responders. None of these five responders had abnormal EEG finding, while all of five patients with abnormal EEG finding were categorized into nonresponder. No statistically significant interaction was detected between EEG finding and lithium response. This retrospective study suggests that epileptiform EEG abnormality is worth studying further as a possible predictor of lithium resistance in bipolar disorder.     

Response to stimulant drug treatment in hyperactive children: Prediction from EEG and neurological findings

A study of neurological examinations, EEG findings, and behavioral responses to methylphenidate treatment in 57 hyperactive boys, 5 to 10 years of age, is reported and discussed. The results indicated that subjects with minor neurological abnormalities in 4 or more categories responded with significantly more improvement (p<.01) to methylphenidate treatment than subjects without abnormalities. Subjects with abnormal EEGs had significantly more improvement (p<.001) than those with normal EEGs. A significant correlation was found between the degree of evidence of brain dysfunction (obtained from EEG and neurological examinations) and the probability of response to methylphenidate treatment. It is suggested that both the neurological and the EEG examinations play a significant role in the assessment of hyperactive children.This study was supported in part by NIMH Grant MH17039, a grant from the Andrew Norman Foundation, a grant from the Julius R. Wolf Foundation, and a grant from CIBA Pharmaceutical Company.     

Is the EEG helpful in diagnosing and monitoring lithium intoxication? A case report and review of the literature

Lithium is potentially toxic to the central nervous system. Clinical lithium neurotoxicity may appear at any time during therapy and may go unrecognized. Failure to appreciate this fact leads to delays in diagnosis and treatment, placing the patient at risk of permanent neurological damage or death. In spite of a largely clinical diagnosis of lithium intoxication, the EEG provides an objective criterion of intoxication. We report a case of lithium intoxication with neurotoxic symptoms associated with marked EEG changes despite moderate lithium serum levels. In contrast to the interindividually varying EEG changes under uncomplicated lithium therapy, pathological EEG findings are the rule in the case of intoxication. Several reports evince a closer relationship between neurotoxic symptoms with EEG changes than with serum levels of lithium. This is of clinical interest with respect to intoxication under therapeutic lithium serum levels, since the EEG is the only examination indicating an intoxication. In patients with intoxication, the phenomenon of long-lasting EEG changes after discontinuation of lithium is discussed with respect to neuronal storing of lithium and persisting neurological disturbances.     

The Spectrum from BCECTS to LKS: The Rolandic EEG Trait—Impact on Cognition

Summary:  The laboratory hallmark of BCECTS is the rolandic discharge (RD) in the EEG of patients, occurring in a characteristic topographical, vigilance-related, event-related, and age-related pattern, disappearing during puberty. RDs are present in 2% of healthy children. About 8% of children with RDs have epilepsy. An increased prevalence rate of RDs is found in children with cognitive and behavioral disorders, with headaches and some genetic syndromes. In some patients, the cognitive disorders are transient but in others they are progressive, resulting in stable mental retardation after puberty. A recent study of 36 BCECTS patients addressed the following questions. (1) the possible relationship between the severity of RDs and the neuropsychological deficits; (2) the profile of neuropsychological deficits; (3) changes of cognition related to EEG changes; and (4) effects of therapy. No correlation was found between global IQ and the severity of the RDs. All the children had at least one specific learning disorder (sometimes long-lasting). When the children were treated, a correlation between cognitive and EEG improvement could not be demonstrated. Recently, 21 patients without epilepsy but with attention deficit and hyperactivity and/or learning disorders were studied: an open treatment trial with sulthiame resulted in improved sustained and selective attention. The neurobiology of RDs and their relationship to cognitive dysfunction and epilepsy requires further study.     

EEG changes induced by long-term lithium therapy]

The effect of longstanding therapy using lithium salts compared to other psychotropic drugs in combination with lithium salts or other psychotropic drugs alone, on the human EEG is examined and compared with the literature. We found in our sample of 56 patients under lithium therapy: (1) that lithium salts - like other psychotropic drugs - evoke a significant increase in paroxysmal dysrhythmic activity and EEG abnormalities collectively; (2) that lithium salts cause an increase in rhythmical patterns and abnormalities in vigilance; and that (3) the combination of lithium salts with other psychotropic drugs leads to a significant augmentation of focal abnormalities of the left brain area and epileptic potentials, while EEG recordings without abnormalities are significantly diminished under this therapy. It results from this investigation that the risk for central decompensation in relation to the individual disposition seems to be especially high for the combination therapy.     

Lithium and valproate treatment of pathological gambling: a randomized single-blind study

OBJECTIVE: The aim of the present study was to evaluate the efficacy and safety of lithium and valproate in nonbipolar pathological gamblers. METHOD: Forty-two subjects with DSM-IV-defined pathological gambling entered a 14-week single-blind trial with lithium (N = 23) or valproate (N = 19). A total of 15 subjects on lithium treatment and 16 patients on valproate treatment completed the 14-week protocol. RESULTS: At the end of the 14-week treatment period, both the lithium and the valproate groups showed significant (p <.01) improvement in mean score on the Yale-Brown Obsessive Compulsive Scale modified for pathological gambling. This improvement did not significantly differ between groups. Fourteen (60.9%) of the 23 patients taking lithium and 13 (68.4%) of the 19 patients taking valproate were responders based on a Clinical Global Impressions-Improvement score of much or very much improved. CONCLUSION: Findings from the present study suggest the efficacy of both lithium carbonate and valproate in the treatment of pathological gambling. This is the first controlled trial of the efficacy of mood stabilizers in pathological gambling. A double-blind, placebo-controlled trial is required to confirm these findings.     

Prediction of treatment resistance in obsessive compulsive disorder patients based on EEG complexity as a biomarker

ObjectiveThis study aimed to identify an Electroencephalography (EEG) complexity biomarker that could predict treatment resistance in Obsessive compulsive disorder (OCD) patients. Additionally, the statistical differences between EEG complexity values in treatment-resistant and treatment-responsive patients were determined. Moreover, the existence of correlations between EEG complexity and Yale-Brown Obsessive Compulsive Scale (YBOCS) score were evaluated.MethodsEEG data for 29 treatment-resistant and 28 treatment-responsive OCD patients were retrospectively evaluated. Approximate entropy (ApEn) method was used to extract the EEG complexity from both whole EEG data and filtered EEG data, according to 4 common frequency bands, namely delta, theta, alpha, and beta. The random forests method was used to classify ApEn complexity.ResultsApEn complexity extracted from beta band EEG segments discriminated treatment-responsive and treatment-resistant OCD patients with an accuracy of 89.66% (sensitivity: 89.44%; specificity: 90.64%). Beta band EEG complexity was lower in the treatment-resistant patients and the severity of OCD, as measured by YBOCS score, was inversely correlated with complexity values.ConclusionsThe results indicate that, EEG complexity could be considered a biomarker for predicting treatment response in OCD patients.SignificanceThe prediction of treatment response in OCD patients might help clinicians devise and administer individualized treatment plans.     

Latency and episodes before treatment: response to lithium maintenance in bipolar I and II disorders

Objectives: To test whether longer treatment-delays or more pretreatment illness episodes are followed by diminished response to lithium maintenance.

Methods: In 360 DSM-IV bipolar I (n=220) or II (n=140) patients, effects of latency from illness onset to starting lithium and number of pretreatment episodes were evaluated by survival analysis based on the number of months stable before a first recurrence on lithium. Factors associated with treatment latency were identified by regression modeling. Relationships of time, episode number, and morbidity before treatment to the overall proportion of time ill on lithium were also tested by nonparametric correlation.

Results: Latency to first lifetime lithium maintenance averaged 8.3 years, with 9.3 episodes/subject. Time stable before a first recurrence on lithium averaged 29.6 months and was unrelated to treatment latency (in terciles) or to a high (≥ten), intermediate (four–nine), or low (
Conclusions: Treatment latency and prelithium episode number were unrelated to morbidity during treatment. Although multiple untreated episodes can lead to severe disability, lithium evidently can greatly limit morbidity, even after years of delay and multiple episodes of bipolar illness.
     

奎硫平联合碳酸锂治疗双相抑郁患者的疗效

目的:探讨奎硫平联合碳酸锂治疗双相抑郁患者的疗效和不良反应. 方法:将符合中国精神障碍分类和诊断标准第3版双相情感障碍抑郁发作诊断标准的64例患者随机分为奎硫平合并碳酸锂组(研究组)和氟西汀合并碳酸锂组(对照组).疗程8周.临床评定采用汉密尔顿抑郁量表(HAMD)及汉密尔顿焦虑量表(HAMA),用治疗中出现的症状量表(TESS)评定不良反应. 结果:治疗8周,研究组和对照组有效率分别为84.4％、78.1％,痊愈率分别为53.1％、46.9％,两组疗效差异无统计学意义(分别为t =0.10,P＞0.05;t=0.25,P＞0.05);研究组患者抑郁症状于第2周末明显改善,而焦虑症状于第1周末即显著好转;治疗8周末两组TESS评分差异无统计学意义(t=0.46,P＞0.05).结论:奎硫平联合碳酸锂治疗双相抑郁疗效明确,使用较为安全,而且起效较快.     

Continuous EEG monitoring during thrombolysis in acute hemispheric stroke patients using the brain symmetry index.

Continuous EEG monitoring could benefit stroke patients as it may detect changes in brain function in a possible reversible state, allowing early intervention. The Brain Symmetry Index (BSI) was introduced previously as a measure to quantify ischemia in acute hemispheric stroke patients, and a positive correlation was found between the BSI and the National Institutes of Health Stroke Scale. Here, we explore the feasibility and potential clinical relevance of continuous EEG monitoring in acute hemispheric stroke, with the BSI as an indicator of the effect of thrombolysis with recombinant tissue plasminogen activator (r-tPA). Patients with acute hemispheric stroke treated with r-tPA were monitored using a bipolar eight channel EEG. The BSI is defined as the mean of the absolute value of the difference in the mean hemispheric amplitude spectrum; values range from 0 (no asymmetry) to 1 (maximal asymmetry). The clinical condition of the patients was assessed with the National Institutes of Health Stroke Scale. In this pilot study 16 patients were included. In all patients, the BSI remained constant or showed improvement during and after treatment with r-tPA. The correlation between the BSI and National Institutes of Health Stroke Scale in this study is significant, and confirms previous results. The correlation between the change in BSI and the change in National Institutes of Health Stroke Scale during treatment with r-tPA is significant, as well. No clinical significant complications occurred during r-tPA treatment. Our results show that continuous EEG monitoring using the BSI is technically feasible and provides real-time information about the effect of thrombolysis in acute hemispheric stroke patients.     

Lithium: clinical study by brain electrical activity mapping. A case report

One of the axes of research in our department is oriented on the study of the action of psychotropic drugs on the Central Nervous System by the means of the non invasive and direct techniques of cerebral imagery. First approach: EEG mapping In depressive states, the modification of nocturnal wakefulness states observed under lithium therapy begins to be well known. However, under lithium monotherapy, few diurnal studies have been performed. EEG mapping, based on a protocol and a strict methodology, could represent an interesting technique to approach the mechanisms of lithium action in psychopathological states concerned by this type of therapy. Second approach: Nuclear Magnetic Resonance (NMR) We studied the manic-depressive states in man before and after chronic administration of lithium salts. This research is performed in fundamental molecular studies, in vitro, and from modification of certain parameters in protonic NMR imagery that can be observed in these pathological states. We are participating in a research program and we preliminarily present: 1. the study by protonic NMR of the in vitro interaction between the lithium ion and water which is free or bound to the total cerebral tissue of rats (acute intravenous treatment by Li+ in different doses and at different times of tissular penetration). 2. the study by lithium NMR of the in vitro kinetics of the erythrocyte's lithium penetration in man, for the plasmatic concentrations (acute intravenous dose) considered as therapeutic in manic-depressive states. These measures performed by spectroscopic NMR are coupled with a classical dosage of lithium made with a flame spectrophotometer.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lithium augmentation fails to reduce symptoms in poorly responsive schizophrenic outpatients.

BACKGROUND: Nearly one third of patients suffering from schizophrenia do not fully respond to antipsychotic medication. Safe, effective, and cost-efficient methods to reduce symptoms are clearly needed; therefore, lithium as an adjunct to fluphenazine decanoate was tested in a placebo-controlled trial in outpatients who were part of the Treatment Strategies of Schizophrenia (TSS) study. METHOD: Forty-one patients with DSM-III schizophrenia or schizoaffective disorder were assigned to either adjunctive lithium or placebo after at least 6 months of fluphenazine decanoate treatment to stabilize symptoms had failed. The trial was designed for 8 weeks of treatment, and patients assigned to placebo could afterward be administered lithium in an 8-week, open-label study. RESULTS: Assessment of the intent-to-treat analysis revealed no significant differences in demographic variables between the lithium and placebo groups. Although both groups showed significant (p = .00135) improvement as measured by total scores on the Brief Psychiatric Rating Scale (BPRS), there were no significant differences in response between the lithium and placebo groups. Patients originally treated with placebo added to neuroleptic did not have significantly greater improvement when receiving open-label adjunctive lithium. CONCLUSION: Although success with lithium augmentation therapy for persistent psychosis has been reported in the past, this study of well-characterized patients showed no benefit for this common strategy, thus indicating that care be used in utilizing lithium augmentation.     

Cortical myoclonus during lithium exposure

BACKGROUND: Myoclonus can occur in association with lithium therapy at toxic and therapeutic dosages, and can be a predominant and disabling adverse effect. Moreover, myoclonus has been reported when lithium has been combined with cyclic antidepressants and with the neuroleptic clozapine. Although clinical case reports exist, no electrophysiologic data are available that provide a source or a neurophysiological mechanism for the myoclonus seen in lithium therapy. OBJECTIVE: To describe the electrophysiologic characteristics and source of the myoclonus associated with lithium therapy. DESIGN AND METHODS: We retrospectively analyzed 5 cases of myoclonus during lithium therapy. We reviewed the clinical features and results of previous electrophysiologic testing. Four patients received lithium monotherapy; and 1, sertraline hydrochloride and nefazodone hydrochloride in addition to lithium. The electrophysiologic data that had been gathered included multichannel surface electromyographic (EMG) recordings with simultaneous electroencephalography (EEG), somatosensory evoked potentials, and elicitation of long-latency EMG reflexes to median and digital nerve stimulation. RESULTS: All 5 patients showed multifocal action myoclonus without reflex activation and only rare occurrence at rest. In each case, back-averaging created a focal EEG transient over the contralateral sensorimotor area preceding the myoclonus EMG discharge. In 2 of the patients receiving lithium monotherapy, the therapy was discontinued and the myoclonus disappeared. CONCLUSIONS: Lithium, by itself, can be associated with prominent clinical myoclonus, short-duration (<50-millisecond) myoclonus EMG discharges and cortical action myoclonus without the presence of epileptiform abnormalities on the routine EEG. This myoclonus is different from the most common form that is well documented to occur with tricyclic antidepressant therapy by clinical and electrophysiologic means.     

Lithium intoxication mimicking clinical and electrographic features of status epilepticus: a case report and review of the literature.

A 58-year-old patient who was somnolent, distractible and confused is presented. She was previously treated with lithium, and a plasma level was mildly elevated at 1.7 mmol/l (normal 0.5-1.5 mmol/l). The EEG was suggestive of electrographic status epilepticus. Following treatment with i.v. lorazepam, neither mental status nor EEG abnormalities improved. She had a full recovery of mental function and markedly improved EEG findings following discontinuation of lithium. The EEG is an effective tool for diagnosing lithium neurotoxicity in patients with normal or mildly elevated lithium plasma levels. However, caution is needed before making an assumption of status epilepticus.     

Myoclonic seizures with lithium

Myoclonus has been infrequently observed in patients receiving lithium therapy, and associated electroencephalographic (EEG) changes have not been well described. We report two women, ages 35 and 48, who, after the initiation of lithium carbonate therapy, had several generalized tonic-clonic seizures followed by myoclonic seizures. In both, myoclonus was associated with repetitive sharp waves on the EEG. Although the epileptogenicity of lithium remains controversial, the occurrence of myoclonic seizures associated with lithium treatment suggests a proconvulsant effect of lithium in susceptible individuals.