Non-convulsive status epilepticus: mimics and chameleons.

Non-convulsive status epilepticus (NCSE) is an enigmatic condition with protean manifestations. It often goes unrecognised, leading to delays in its diagnosis and treatment. The principal reason for such delay is the failure to consider and request an electroencephalogram (EEG), although occasional presentations have no scalp or surface electroencephalographic correlate. In certain settings with limited EEG availability, particularly out-of-hours, clinicians should consider treating without an EEG. Patients need a careful risk-benefit analysis to assess the risks of neuronal damage and harm versus the risks of adverse effects from various intensities of therapeutic intervention. Specialists in EEG, intensive care or epilepsy are invaluable in the management of patients with possible NCSE.

Clinical utility of EEG in diagnosing and monitoring epilepsy in adults.

Electroencephalography (EEG) remains an essential diagnostic tool for people with epilepsy (PWE). The International Federation of Clinical Neurophysiology produces new guidelines as an educational service for clinicians to address gaps in knowledge in clinical neurophysiology. The current guideline was prepared in response to gaps present in epilepsy-related neurophysiological assessment and is not intended to replace sound clinical judgement in the care of PWE. Furthermore, addressing specific pathophysiological conditions of the brain that produce epilepsy is of primary importance though is beyond the scope of this guideline. Instead, our goal is to summarize the scientific evidence for the utility of EEG when diagnosing and monitoring PWE.

Hidden in plain sight: Non-convulsive status epilepticus-Recognition and management.

Non-convulsive status epilepticus (NCSE) is an electroclinical state associated with an altered level of consciousness but lacking convulsive motor activity. It can present in a multitude of ways, but classification based on the clinical presentation and electroencephalographic appearances assists in determining prognosis and planning treatment. The aggressiveness of treatment should be based on the likely prognosis and the underlying cause of the NCSE.

Early predictors of refractory status epilepticus: an international two-center study.

BACKGROUND AND PURPOSE: Status epilepticus (SE) refractory to first- and second-line antiepileptic drugs carries high mortality. Little is known on early prediction of refractory SE (RSE)­an essential tool for planning appropriate therapy. Our aim was to identify and validate independent early RSE predictors in adults. METHODS: Clinical and laboratory data on consecutive intensive care unit patients with SE from two academic care centers (a derivation data set from a Swiss center and a validation data set from a US center) were assessed. Multivariable analysis was performed with the derivation set to identify RSE predictors at SE onset. Their external validity was evaluated with an independent validation set. Measures of calibration and discrimination were assessed. RESULTS: In all, 302 patients were analyzed (138 with and 164 without RSE), 171 in the derivation data set and 131 in the validation data set. Acute SE etiology, coma/stupor and serum albumin <35 g/l at SE onset were independent predictors for RSE in the derivation data set [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.01-4.07; OR 4.83, 95% CI 2.42-9.68; OR 2.45, 95% CI 1.16-5.16]. The prediction model showed good measures of calibration (Hosmer-Lemesow goodness-of-fit test P = 0.99) and discrimination (area under the receiver operating characteristic curve 0.8) on the derivation data set­results that were similar in the validation data set (Hosmer-Lemeshow P = 0.24; area under the receiver operating characteristic curve 0.73). CONCLUSIONS: This study confirms the independent prognostic value of readily available parameters for early RSE prediction. Prospective studies are needed to identify additional robust predictors, which could be added to the proposed model for further optimization towards a reliable prediction scoring system.

Electroencephalographic sleep elements and outcome in acute encephalopathic patients: a 4-year cohort study.

BACKGROUND AND PURPOSE: Acute encephalopathy in hospitalized patients is common and associated with high mortality. Preservation of physiological sleep has been associated with favorable outcomes in acute brain injury. It is hypothesized that electroencephalographic presence of sleep elements is associated with good outcome in encephalopathic adults. METHODS: This observational study was performed at an academic tertiary medical care center. Clinical data, electroencephalogram (EEG) characteristics and outcome of critically ill patients with acute encephalopathy were assessed. EEGs were interpreted regarding the presence of sleep elements (K-complexes, vertex sharp-waves and sleep spindles). Associations between sleep elements and outcome (graded by the Glasgow Outcome Scale, GOS) were analyzed. RESULTS: One hundred and forty-two consecutive patients with a median age of 64.5 years (range 18-98) and mean Glasgow Coma Scale 10.4 (± 3.8) were included. Leading etiologies were infections (47.2%), intracranial hemorrhages (14.1%) and ischaemic strokes (10.6%). All EEGs demonstrated encephalopathy patterns and 38% had ≥ 1 sleep element (27.5% K-complexes, 31.7% vertex sharp-waves and 33.8% sleep spindles). Patients without sleep elements were older (P = 0.010) and septic shock was more common (P = 0.014). Amongst sleep elements, K-complexes were significantly associated with good outcome, even after adjusting for possible confounders (odds ratio for GOS 5 = 2.79, 95% confidence interval 1.16-6.69) and without significant effect modification across subgroups. CONCLUSIONS: Whilst EEG sleep elements were detected more frequently in patients with favorable outcome, only K-complexes were significantly and independently associated with good outcome in intensive care unit patients with acute encephalopathy, findings that need to be confirmed in larger prospective studies.

Uncovering clinical and radiological associations of triphasic waves in acute encephalopathy: a case-control study.

BACKGROUND AND PURPOSE: Triphasic waves (TWs) are archetypal waveforms seen on electroencephalography (EEG) in some forms of encephalopathy. Their particular underlying pathological substrates are largely unexplored. This case-control study was designed to identify and quantify specific clinical and neuroradiological associations underlying TWs and to determine if TWs predicate outcome. METHODS: From 2004 to 2012, adult encephalopathic patients with TWs (cases) were matched 1:1 with encephalopathic patients without TWs (controls) by Glasgow Coma Scale (GCS) and the frequency range of EEG background activity. Clinical characteristics, neuroimaging and outcomes were assessed. RESULTS: The mean age of 190 patients (95 with and 95 without TWs) was 66.6 years (±15.6). In multivariable analyses, patients with TWs had significantly higher odds for liver insufficiency [odds ratio (OR) = 8.10, 95% confidence interval (CI) 1.98-33.08], alcohol abuse (OR = 3.65, 95% CI 1.25-10.63), subcortical brain atrophy (OR = 2.82, 95% CI 1.39-5.71) and respiratory tract infections (OR = 1.28, 95% CI 1.01-4.71). With each additional independent predictor, the odds increased for the occurrence of TWs (1 predictor, OR = 2.40, 95% CI 1.16-5.13; ≥2 predictors, OR = 9.20, 95% CI 3.27-25.62). Mortality was 15% and tended to be higher in patients with TWs (19% with vs. 11% without TWs). CONCLUSIONS: Alcohol abuse, liver insufficiency, infections and subcortical brain atrophy were independently associated with TWs in patients matched for clinical and EEG features of encephalopathy. These associations strengthen the hypothesis that TWs evolve from an interplay of pathological neurostructural, metabolic and toxic conditions. When matched for EEG background activity and GCS, TWs were not associated with death.

Slow pseudoperiodic lateralized epileptiform discharges in nonconvulsive status epilepticus in a patient with cerebral palsy and a large central meningioma.

The presence of cerebral palsy and that of slow growing brain tumors are risk factors for convulsive and nonconvulsive status epilepticus. Nonconvulsive status epilepticus (NCSE) needs electroencephalographic (EEG) monitoring to be confirmed as it may be clinically subtle. Furthermore, it may present with a variety of ictal EEG morphologies. We report a case of a patient with cerebral palsy and a large central meningioma. Electroencephalogram showed a slow pattern of periodic lateralized epileptiform discharges (PLEDs) (a pattern considered as being situated in the ictal-interictal continuum) on an alpha background. The patient was treated for NCSE successfully with benzodiazepines followed by up-titration of his antiepileptic drug doses.

Psychogenic amnesia and self-identity: a multimodal functional investigation.

BACKGROUND: Patients with psychogenic amnesia generally suffer from episodic memory deficits associated with an impairment of self-identity. While the first is generally attributed to limbic dysfunction, the latter might be related to posterior parietal cortex. METHODS AND RESULTS: In a patient with acute repetitive psychogenic amnesia, three different functional investigations (fMRI, electrical-neuroimaging, PET) during both resting-state and a behavioural paradigm testing 'time-travel' showed left posterior parietal activation, unlike in 12 control subjects. CONCLUSION: Impairment of self-identity and episodic memory in psychogenic amnesia may be associated with functional alterations of left posterior parietal cortex.

Antiepileptic drugs modify power of high EEG frequencies and their neural generators.

BACKGROUND: The clinical and molecular effects of antiepileptic drugs (AEDs) have been extensively investigated. Much less is known about their effects on human electrophysiology. METHODS: Topographic analysis in the frequency domain has been used to analyze 104 electroencephalogram (EEG) epochs of 52 patients presenting with first-ever generalized seizure, with normal MRI and EEG. Patients were treated with valproate, arbamazepine, or lamotrigine in monotherapy (each group n = 13). Thirteen patients without medication served as a control group. RESULTS: Carbamazepine and lamotrigine, both sodium-channel modulators, altered brain topography in the gamma range in the same frequency bands (50-60 Hz). Valproate, which has multiple actions on sodium and calcium channels as well as GABA turnover, modified brain topography in the low gamma range (30-40 Hz). No such changes were found in the control group. For all AEDs, the neural generators were shifted more anteriorly in medial temporal through to inferior frontal regions. CONCLUSION: Decreased gamma-power and anterior shift of neural generators after AED introduction reflect AED influence on human electrophysiology.

Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society.

OBJECTIVE: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid use, prenatal vitamin K use, risk of hemorrhagic disease of the newborn, clinical implications of placental and breast milk transfer of antiepileptic drugs (AEDs), risks of breastfeeding, and change in AED levels during pregnancy. METHODS: A 20-member committee evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and October 2007. RESULTS: Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in amounts that may be clinically important. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentration of lamotrigine, phenytoin, and to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative. RECOMMENDATIONS: Supplementing women with epilepsy with at least 0.4 mg of folic acid before they become pregnant may be considered (Level C). Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered (Level B) and monitoring of levetiracetam and oxcarbazepine (as monohydroxy derivative) levels may be considered (Level C). A paucity of evidence limited the strength of many recommendations.

Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): obstetrical complications and change in seizure frequency: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society.

OBJECTIVE: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including the risk of pregnancy complications or other medical problems during pregnancy in WWE compared to other women, change in seizure frequency, the risk of status epilepticus, and the rate of remaining seizure-free during pregnancy. METHODS: A 20-member committee including general neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and February 2008. RESULTS: For WWE taking antiepileptic drugs, there is probably no substantially increased risk (greater than two times expected) of cesarean delivery or late pregnancy bleeding, and probably no moderately increased risk (greater than 1.5 times expected) of premature contractions or premature labor and delivery. There is possibly a substantially increased risk of premature contractions and premature labor and delivery during pregnancy for WWE who smoke. Seizure freedom for at least 9 months prior to pregnancy is probably associated with a high likelihood (84%-92%) of remaining seizure-free during pregnancy. RECOMMENDATIONS: Women with epilepsy (WWE) should be counseled that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high rate (84%-92%) of remaining seizure-free during pregnancy (Level B). However, WWE who smoke should be counseled that they possibly have a substantially increased risk of premature contractions and premature labor and delivery during pregnancy (Level C).

Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): teratogenesis and perinatal outcomes: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society.

OBJECTIVE: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy. METHODS: Systematic review of relevant articles published between January 1985 and June 2007. RESULTS: It is highly probable that intrauterine first-trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine and possible compared to phenytoin or lamotrigine. Compared to untreated WWE, it is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the development of MCMs. It is probable that antiepileptic drug (AED) polytherapy as compared to monotherapy regimens contributes to the development of MCMs and to reduced cognitive outcomes. For monotherapy, intrauterine exposure to VPA probably reduces cognitive outcomes. Further, monotherapy exposure to phenytoin or phenobarbital possibly reduces cognitive outcomes. Neonates of WWE taking AEDs probably have an increased risk of being small for gestational age and possibly have an increased risk of a 1-minute Apgar score of <7. RECOMMENDATIONS: If possible, avoidance of valproate (VPA) and antiepileptic drug (AED) polytherapy during the first trimester of pregnancy should be considered to decrease the risk of major congenital malformations (Level B). If possible, avoidance of VPA and AED polytherapy throughout pregnancy should be considered to prevent reduced cognitive outcomes (Level B). If possible, avoidance of phenytoin and phenobarbital during pregnancy may be considered to prevent reduced cognitive outcomes (Level C). Pregnancy risk stratification should reflect that the offspring of women with epilepsy taking AEDs are probably at increased risk for being small for gestational age (Level B) and possibly at increased risk of 1-minute Apgar scores of <7 (Level C).

Pregnancy registries in epilepsy: a consensus statement on health outcomes.

Most pregnant women with epilepsy require antiepileptic drug (AED) therapy. Present guidelines recommend optimizing treatment prior to conception, choosing the most effective AED for seizure type and syndrome, using monotherapy and lowest effective dose, and supplementing with folate. The Epilepsy Therapy Project established the international Health Outcomes in Pregnancy and Epilepsy (HOPE) forum to learn more about the impact of AEDs on the developing fetus, particularly the role of pregnancy registries in studying AED teratogenicity. The primary outcome of interest in these registries is the occurrence of major congenital malformations, with some data collected on minor malformations. Cognitive and behavioral outcomes are often beyond the timeframe for follow-up of these registries and require independent study. The HOPE consensus report describes the current state of knowledge and the limitations to interpretations of information from the various sources. Data regarding specific risks for both older and newer AEDs need to be analyzed carefully, considering study designs and confounding factors. There is a critical need for investigations to delineate the underlying mechanisms and explain the variance seen in outcomes across AEDs and within a single AED.

Neurologic prognosis and withdrawal of life support after resuscitation from cardiac arrest.

OBJECTIVE: To study the impact of neurologic prognostication on the decision to withdraw life-sustaining therapies (LST) in comatose patients resuscitated after cardiac arrest. METHODS: The authors prospectively studied a consecutive series of post-resuscitation comatose patients referred for neurologic prognostication at a single center for 4 years. For most patients, neurologic prognostication was not sought due to early death or rapid return to consciousness. Prognostication was based on Glasgow Coma Score (GCS) and Brainstem Reflex Score (BRS), with EEG and cortical evoked potentials (CEP), which were graded as benign, uncertain, and malignant. The outcomes were as follows: survivors (Group S), brain or cardiac death (Group D), and death from withdrawal of life sustaining therapy (Group W). In Group W, the time interval to withdrawal of LST was analyzed by EEG and CEP grades. RESULTS: Of 58 patients studied, 10 were in Group S, 8 in Group D, and 40 in Group W. Initial median GCS and BRS was similar for all groups with significant improvement noted in Group S, but not in Group D or Group W. In Group W, CEP grade correlated with the median duration of continued therapy before a decision to withdraw LST: 7 days for benign CEP, 2 days for uncertain CEP, and 1 day for malignant CEP, p = 0.0004. CONCLUSION: In patients with poor neurologic recovery early after resuscitation from cardiac arrest, physicians appear to use the cortical evoked potential grade to estimate prognosis. Cortical evoked potential grade correlated with the waiting time until life sustaining therapies were withdrawn after no improvement in neurologic examination was seen.

The etiology and diagnosis of status epilepticus.

Status epilepticus (SE) is a common, serious, potentially life-threatening, neurologic emergency characterized by prolonged seizure activity. Generalized convulsive status epilepticus (GCSE) is the most widely recognized form of SE. Direct consequences of convulsive movements from SE can result in injury to the body and brain. Nonconvulsive status epilepticus (NCSE) is underrecognized, with controversy surrounding the consequences and treatment. High mortality rates with GCSE have been noted in the past. New treatments for SE are emerging with new parenteral drug formulations as well as new agents for refractory SE, offering an opportunity to improve outcome. Special drug delivery systems, drug combinations, and neuroprotective agents that prevent the subsequent development of epilepsy may soon emerge as future options for treating SE.

The neurologic consequences of eclampsia.

BACKGROUND: Toxemia of pregnancy (preeclampsia/eclampsia) is a syndrome characterized by pregnancy-induced hypertension, edema, and proteinuria, although it is often associated with more generalized multisystem abnormalities that affect the nervous system, the liver, kidneys, and coagulation. For the most part, preeclampsia/eclampsia is a reversible process that almost always improves after delivery of the baby. Despite recent advances in diagnosis and management, eclampsia remains the second most common cause of maternal death in the United States. Because of the often severe repercussions on the nervous system, neurologists can make important contributions to the management of patients with eclampsia. Although preeclampsia is largely under the purview of obstetrics, neurologists can provide input to the management of intracranial vascular problems, seizures, and raised intracranial pressure. Input on the severity and nature of neurologic problems will enable the obstetrician to determine whether to expedite or to delay child birth. REVIEW SUMMARY: There is an increasing body of evidence on the associated endothelial dysfunction, breakdown of the blood-brain barrier, and failure of cerebrovascular autoregulation with vasospasm, ischemia, and cerebral edema. Therapy is directed at controlling blood pressure, giving magnesium sulfate to treat the preeclamptic/eclamptic process itself, and instituting antiseizure medicines (e.g., diazepam or phenytoin) when uncontrolled seizures or status epilepticus supervene. CONCLUSION: Cerebrovascular accidents occur more frequently in young women during pregnancy and the puerperium, and there is an unmet need for basic and clinical research directed at the pathophysiology of the eclamptic process so as to provide more directed therapy.

Clinical correlates and prognosis in early spindle coma.

OBJECTIVE: To determine the prognostic significance of spindle coma (SC) according to etiology and EEG reactivity. METHODS: We reviewed 15 patients with SC due to various causes within 8 days of coma to determine the prognostic significance of this EEG pattern. RESULTS: The outcome among survivors was favorable: among 13 survivors, 9 were independent in all activities of daily living (ADLs) at 6 months; 3 were dependent in all ADLs; and one remained in coma. EEG reactivity to noxious stimuli best predicted outcome: All patients (whatever the coma etiology) with EEG reactivity survived; conversely, not all patients without EEG reactivity died. CONCLUSION: In our patients, EEG reactivity independent of etiology predicted survival, neurological examination did not predict outcome. Most SC survivors had a meaningful recovery achieving all ADLs. From the literature, the cause of SC was predictive of outcome: encephalopathy, seizures and trauma had the best prognosis while hypoxia, CRA and structural lesions carried the worst. Literature review revealed that 23% of patients [56/242] died or remained in a persistent vegetative state (PVS). Best outcomes occurred when SC was due to drugs, encephalopathy or seizures: (0/14 died or were in a PVS). With trauma 15% [25/169] died or were in a PVS). Intermediate outcomes occurred with hypoxia and cardio-respiratory arrest (CRA): 33% [7/21] died or were in a PVS. The gravest outcomes occurred with brain-stem and cerebral infarctions, and tumors: 73% [22/30] died or were in a PVS.