Nonconvulsive Status Epilepticus With Generalized Spike-and-Wave Discharges: Pathophysiological and Nosological Considerations.

Absence status epilepticus (ASE) is the most common type of status epilepticus in patients with idiopathic generalized epilepsy (IGE). Like absence seizure, ASE is characterized by generalized spike-and-wave discharges (GSWDs) on the electroencephalogram (EEG). Once considered specific for IGE, GSWDs have increasingly been observed in other forms of epilepsy, as well as in patients with no prior epilepsy. Here, we report three patients with different types of nonconvulsive status epilepticus (NCSE) in which the EEG correlate was GSWDs: a 44-year-old woman with juvenile absence epilepsy who manifested ASE, a 73-year-old woman with anoxic brain injury complicated by NCSE with well-formed GSWDs (as seen in IGE and de novo ASE), and a 41-year-old woman with frontal lobe epilepsy who developed focal NCSE with impaired consciousness. Evidently, patients with generalized epilepsy, focal epilepsy, and no prior epilepsy can all manifest NCSE with similar electroclinical characteristics, i.e., GSWDs and impaired consciousness. This observation adds to the existing evidence that seizures, whether classified as focal or generalized, often involve focal and generalized elements in their pathophysiology. To fully understand seizure pathophysiology, we must steer away from the focal-versus-generalized paradigm that has dominated the nosology of seizures and epilepsy for a very long time.

Minimum Technical Requirements for Performing Ambulatory EEG.

SUMMARY: Ambulatory EEG (AEEG) devices offer portable, multichannel, digital EEG recording with or without video in the patient's natural environment. The technology applied for AEEG recording is like the technology for routine EEG and inpatient long-term video-EEG monitoring but designed to be compact and wearable. Computer-based AEEG technology is well-suited to digital recording, signal processing, and visual display. However, acquiring interpretable EEG outside of the hospital setting presents its own technical challenges. Published guidelines have established technical standards for performing routine EEG and inpatient video-EEG monitoring, but technical standards for AEEG are lacking. Therefore, this guideline provides minimal technical standards for the performance of AEEG which are essential to ensure the quality of studies for clinical and research practice. We expect these minimum standards to evolve over time with improved performance and advances in the technology.

Electroclinical Mismatch During EEG Acquisition: What It Might Mean, What We Might Need to Do.

An electroclinical mismatch is present if the electroencephalogram (EEG) shows evidence of moderate to severe diffuse encephalopathy but the patient's mental status is only mildly altered. We describe five cases in which seizure or status epilepticus was suspected due to electroclinical mismatch. In all five cases, EEG was ordered to rule out nonconvulsive status epilepticus as the cause of the altered mental status. EEG initially showed generalized delta activity (GDA), with variable degrees of rhythmicity, with or without superimposed theta activity, with or without sporadic epileptiform discharges. During EEG acquisition, all patients followed commands and answered questions. The mental status change was limited to mild inattention and temporal disorientation. Benzodiazepine challenge was performed by administering lorazepam 2-mg IV. Within 10 minutes of injection, GDA started to break up and subsequently disappeared. EEG showed prominent sleep spindles in three patients and background changes, indicating drowsiness in two patients. The assessment of clinical response to lorazepam was confounded by sleepiness in all patients. Serial EEG recording or continuous EEG monitoring revealed reemergence of GDA, at times appearing more rhythmic than the GDA in the baseline study. All patients received nonsedating antiseizure drugs. GDA completely resolved and mental status normalized two to five days after starting antiseizure medication. In cases of electroclinical mismatch, the absence of clear-cut epileptiform discharges does not exclude the possibility that cortical hyperexcitability is contributing to the encephalopathic process. A positive response to benzodiazepine challenge suggests the presence of cortical hyperexcitability and the need to start, or increase the dosage of, antiseizure drugs.

Ictal Hypersalivation and Salivary Gland Enlargement in a Patient With Acquired Frontal Lobe Epilepsy.

Hypersalivation is a well-known ictal semiology of benign Rolandic epilepsy and other childhood epilepsy syndromes. There are also occasional reports of adults with temporal, parietal, or frontal lobe epilepsy in which hypersalivation is a prominent seizure manifestation. Notably lacking are reports linking salivary gland enlargement to ictal hypersalivation. A 33-year-old man with frontal lobe epilepsy due to a ruptured aneurysm presented with focal seizures and facial swelling. The only seizures he had in the past were generalized tonic-clonic seizures. Eight days prior to admission, he started having focal seizures characterized by pronounced hypersalivation, speech arrest, impaired awareness, and left upper extremity posturing or automatism. Seizure frequency increased from five to 30 per day. Four days prior to admission, his face started to swell up, and his family thought he had mumps. Computed tomography (CT) of the head showed encephalomalacia in the inferomedial cortex of the right frontal lobe, the same lesion seen in his old CT images. Maxillofacial CT revealed enlargement of the parotid and submandibular glands. Although electroencephalography (EEG) showed seizure onset in the right frontal region, the initial ictal discharge on the scalp may represent seizure propagation from a focus near the zone of encephalomalacia. After seizure freedom was achieved with antiepileptic drugs, the patient's salivary glands decreased in size and returned to normal.

Regulation of microRNA Expression in Sleep Disorders in Patients with Epilepsy.

The effects of epilepsy on sleep and the activating effects of sleep on seizures are well documented in the literature. To date, many sleep-related and awake-associated epilepsy syndromes have been described. The relationship between sleep and epilepsy has led to the recognition of polysomnographic testing as an important diagnostic tool in the diagnosis of epilepsy. The authors analyzed the available medical database in search of other markers that assess correlations between epilepsy and sleep. Studies pointing to microRNAs, whose abnormal expression may be common to epilepsy and sleep disorders, are promising. In recent years, the role of microRNAs in the pathogenesis of epilepsy and sleep disorders has been increasingly emphasized. MicroRNAs are a family of single-stranded, non-coding, endogenous regulatory molecules formed from double-stranded precursors. They are typically composed of 21-23 nucleotides, and their main role involves post-transcriptional downregulation of expression of numerous genes. Learning more about the role of microRNAs in the pathogenesis of sleep disorder epilepsy may result in its use as a biomarker in these disorders and application in therapy.

Dexamethasone as Abortive Treatment for Refractory Seizures or Status Epilepticus in the Inpatient Setting.

Refractory seizures or status epilepticus (RS/SE) continues to be a challenge in the inpatient setting. Failure to abort a seizure with antiepileptic drugs (AEDs) may lead to intubation and treatment with general anesthesia exposing patients to complications, extending hospitalization, and increasing the cost of care. Studies have shown a key role of inflammatory mediators in seizure generation and termination. We describe 4 patients with RS/SE that was aborted when dexamethasone was added to conventional AEDs: a 61-year-old female with temporal lobe epilepsy who presented with delirium, nonconvulsive status epilepticus, and oculomyoclonic status; a 56-year-old female with history of traumatic left frontal lobe hemorrhage who developed right face and hand epilepsia partialis continua followed by refractory focal clonic seizures; a 51-year-old male with history of traumatic intracranial hemorrhage who exhibited left-sided epilepsia partialis continua; and a 75-year-old female with history of breast cancer who manifested nonconvulsive status epilepticus and refractory focal clonic seizures. All patients continued experiencing RS/SE despite first- and second-line therapy, and one patient continued to experience RS/SE despite third-line therapy. Failure to abort RS/SE with conventional therapy motivated us to administer intravenous dexamethasone. A 10-mg load was given (except in one patient) followed by 4.0- 5.2 mg q6h. All clinical and electrographic seizures stopped 3-4 days after starting dexamethasone. When dexamethasone was discontinued 1-3 days after seizures stopped, all patients remained seizure-free on 2-3 AEDs. The cessation of RS/SE when dexamethasone was added to conventional antiseizure therapy suggests that inflammatory processes are involved in the pathogenesis of RS/SE.

Focal Epileptiform Discharges Can Mimic Electrode Artifacts When Recorded on the Scalp Near a Skull Defect.

Breach rhythm, the hallmark of skull defect, is a familiar finding in the electroencephalogram (EEG). A hole in the skull can also give rise to unfamiliar EEG findings. We present 3 patients with a skull defect whose scalp EEG showed focal epileptiform discharges that resembled F4 electrode artifacts-a 23-year-old man with a right-sided craniectomy for traumatic brain injury, a 63-year-old woman with a history of bifrontal craniectomy and meningioma resection, and a 77-year-old woman who had a right hemicraniectomy for a life-threatening subdural hematoma. In all 3 patients, the F4 electrode was directly above or near a skull defect, and scalp EEG showed phase-reversing waves in FP2-F4 and F4-C4 with no clear-cut "physiological field" (even when the EEG was displayed at a higher sensitivity). In the first 2 patients, the technologist tried to eliminate the "electrode artifacts" by cleaning the scalp thoroughly, replacing the F4 electrode, and maintaining electrode impedance between 2 and 5 kΩ. These measures failed to eliminate the "electrode artifacts" so the EEG was recorded from four 10-10 electrode sites around F4. Extending the montage made it clear that what appeared as F4 electrode artifacts were actually focal epileptiform discharges. Correlation with other electroclinical and neuroimaging data was enough to resolve this issue in the third patient, obviating the need to extend the montage. When recording and interpreting the EEG of patients with a craniotomy or craniectomy, EEG professionals should be aware that focal epileptiform discharges can masquerade as electrode artifacts.

Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.

OBJECTIVE: Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin. METHODS: Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset. RESULTS: There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6 months or longer and 14% experienced at least one seizure-free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices. SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.

Periodic Lateralized Epileptiform Discharges can Survive Anesthesia and Result in Asymmetric Drug-induced Burst Suppression.

Drug-induced burst suppression (DIBS) is bihemispheric and bisymmetric in adults and older children. However, asymmetric DIBS may occur if a pathological process is affecting one hemisphere only or both hemispheres disproportionately. The usual suspect is a destructive lesion; an irritative or epileptogenic lesion is usually not invoked to explain DIBS asymmetry. We report the case of a 66-year-old woman with new-onset seizures who was found to have a hemorrhagic cavernoma and periodic lateralized epileptiform discharges (PLEDs) in the right temporal region. After levetiracetam and before anesthetic antiepileptic drugs (AEDs) were administered, the electroencephalogram (EEG) showed continuous PLEDs over the right hemisphere with maximum voltage in the posterior temporal region. Focal electrographic seizures also occurred occasionally in the same location. Propofol resulted in bihemispheric, but not in bisymmetric, DIBS. Remnants or fragments of PLEDs that survived anesthesia increased the amplitude and complexity of the bursts in the right hemisphere leading to asymmetric DIBS. Phenytoin, lacosamide, ketamine, midazolam, and topiramate were administered at various times in the course of EEG monitoring, resulting in suppression of seizures but not of PLEDs. Ketamine and midazolam reduced the rate, amplitude, and complexity of PLEDs but only after producing substantial attenuation of all burst components. When all anesthetics were discontinued, the EEG reverted to the original preanesthesia pattern with continuous non-fragmented PLEDs. The fact that PLEDs can survive anesthesia and affect DIBS symmetry is a testament to the robustness of the neurodynamic processes underlying PLEDs.

Long-term treatment with responsive brain stimulation in adults with refractory partial seizures.

OBJECTIVE: The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures. METHODS: All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy. RESULTS: The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years (p < 0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained (p < 0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%). CONCLUSIONS: The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years.

Unihemispheric burst suppression.

Burst suppression (BS) consists of bursts of high-voltage slow and sharp wave activity alternating with periods of background suppression in the electroencephalogram (EEG). When induced by deep anesthesia or encephalopathy, BS is bihemispheric and is often viewed as a non-epileptic phenomenon. In contrast, unihemispheric BS is rare and its clinical significance is poorly understood. We describe here two cases of unihemispheric BS. The first patient is a 56-year-old woman with a left temporoparietal tumor who presented in convulsive status epilepticus. EEG showed left hemispheric BS after clinical seizure termination with lorazepam and propofol. The second patient is a 39-year-old woman with multiple medical problems and a vague history of seizures. After abdominal surgery, she experienced a convulsive seizure prompting treatment with propofol. Her EEG also showed left hemispheric BS. In both cases, increasing the propofol infusion rate resulted in disappearance of unihemispheric BS and clinical improvement. The prevailing view that typical bihemispheric BS is non-epileptic should not be extrapolated automatically to unihemispheric BS. The fact that unihemispheric BS was associated with clinical seizure and resolved with propofol suggests that, in both cases, an epileptic mechanism was responsible for unihemispheric BS.

Sporadic Creutzfeldt-Jakob disease with focal findings: caveats to current diagnostic criteria.

The clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is largely based on the 1998 World Health Organization diagnostic criteria. Unfortunately, rigid compliance with these criteria may result in failure to recognize sporadic CJD (sCJD), especially early in its course when focal findings predominate and traditional red flags are not yet present. A 61-year-old man presented with a 3-week history of epilepsia partialis continua (jerking of the left upper extremity) and a 2-week history of forgetfulness and left hemiparesis; left hemisensory neglect was also detected on admission. Repeated brain magnetic resonance imaging (MRI) showed areas of restricted diffusion in the cerebral cortex, initially on the right but later spreading to the left. Electroence-phalography (EEG) on hospital days 7, 10, and 14 showed right-sided periodic lateralized epileptiform discharges. On day 20, the EEG showed periodic sharp wave complexes leading to a diagnosis of probable sCJD and subsequently to definite sCJD with brain biopsy. Neurological decline was relatively fast with generalized myoclonus and akinetic mutism developing within 7 weeks from the onset of illness. CJD was not immediately recognized because of the patient's focal/lateralized manifestations. Focal/lateralized clinical, EEG, and MRI findings are not uncommon in sCJD and EEG/MRI results may not be diagnostic in the early stages of sCJD. Familiarity with these caveats and with the most current criteria for diagnosing probable sCJD (University of California San Francisco 2007, MRI-CJD Consortium 2009) will enhance the ability to recognize sCJD and implement early safety measures.

Typical Spike-and-Wave Activity in Hypoxic-Ischemic Brain Injury and its Implications for Classifying Nonconvulsive Status Epilepticus.

INTRODUCTION: Typical spike-and-wave activity (TSWA) in the electroencephalogram (EEG) indicates idiopathic generalized epilepsy (IGE). IGE-related nonconvulsive status epilepticus (NCSE) is typically an absence status epilepticus (ASE). ASE and TSWA respond dramatically to benzodiazepines. Patients with no history of seizure/epilepsy may develop ASE "de novo" in the context of an acute brain disorder. However, we are aware of only one previous case of de novo ASE with TSWA in hypoxic-ischemic brain injury. CASE PRESENTATION: A 65-year-old man, with congestive heart failure and history of substance abuse, survived cardiorespiratory arrest after 18 minutes of cardiopulmonary resuscitation. Post-resuscitation, the patient was in coma with intact brainstem function. Toxicology was positive for cocaine and marijuana. Eyelid myoclonus suggested NCSE, which was initially treated with lorazepam and fosphenytoin. EEG monitoring showed sustained TSWA confirming NCSE and demonstrating de novo ASE (the patient and his family never had seizure/epilepsy). The TSWA was resistant to lorazepam, levetiracetam, and low-dose midazolam; it was eliminated only with midazolam at a dose that resulted in burst-suppression (≥1.2 mg/kg/hour). CONCLUSION: This is an unusual case of TSWA and hypoxic-ischemic brain injury in a patient with no history of seizure/epilepsy. The TSWA was relatively resistant to benzodiazepines suggesting that cerebral hypoxia-ischemia spared the thalamocortical apparatus generating TSWA but impaired the cortical/thalamic inhibitory circuits where benzodiazepines act to suppress TSWA. Albeit rare, 'post-hypoxic' TSWA offers us some valuable insights for classifying and managing nonconvulsive status epilepticus.

Botulinum toxin injections for simple partial motor seizures associated with pain.

Intractable epilepsy with painful partial motor seizures is a relatively rare and difficult disorder to treat. We evaluated the usefulness of botulinum toxin to reduce ictal pain. Two patients received two or four botulinum toxin (BTX) injections at one-to-two-month intervals. Patient 1 had painful seizures of the right arm and hand. Patient 2 had painful seizures involving the left foot and leg. Injections were discontinued after improved seizure control following resective surgery. Both patients received significant pain relief from the injections with analgesia lasting at least two months. Seizure severity was reduced, but seizure frequency and duration were unaffected. For these patients, BTX was effective in temporarily relieving pain associated with muscle contraction in simple partial motor seizures. Our findings do not support the hypothesis that modulation of motor end-organ feedback affects focal seizure generation. BTX is a safe and reversible treatment that should be considered as part of adjunctive therapy after failure to achieve control of painful partial motor seizures.

Cardiac metastasis due to pulmonary metastasis from a transitional cell carcinoma.

We report a rare case of symptomatic cardiac metastasis from a transitional cell carcinoma of the renal pelvis diagnosed by echocardiography. A 75-year-old patient with a long history of neoplasm since 1999 and coronary artery disease with CABG in 2003, was admitted to our department. He underwent cardiac surgery using cardiopulmonary bypass with tumor excision. Histologically it was the same type of transitional cell neoplasm which was operated seven years before. We present all medical history, detailed 2D and 3D echocardiography, intraoperative pictures and discuss possible chain of changes from renal pelvis cancer to clinical manifestation of cardiac mass. There is proved a rapid progression of cardiac tumor with clinical manifestation few months after control TEE examination without any evidence of cardiac mass. It is important that this is a very rare case of left heart metastasis from right side of circulatory system through pulmonary stage of cancer progression.

Neurophysiologic basis of EEG.

SUMMARY: This review article introduces the reader to the very basics of electroencephalography (EEG). It tries to explain in simple terms the physiologic principles of EEG generation and organization at the cellular, cortical and subcortical levels. It also introduces the basic EEG terminology (see the key words).

Lateralization of temporal lobe epilepsy and learning disabilities, as defined by disability-related civil rights law.

PURPOSE: Epilepsy research has identified higher rates of learning disorders in patients with temporal lobe epilepsy (TLE). However, most studies have not adequately assessed complex functional adult learning skills, such as reading comprehension and written language. We designed this study to evaluate our predictions that higher rates of reading comprehension, written language, and calculation disabilities would be associated with left TLE versus right TLE. METHODS: Reading comprehension, written language, and calculation skills were assessed by using selected subtests from the Woodcock-Johnson Psycho-Educational Tests of Achievement-Revised in a consecutive series of 31 presurgical patients with TLE. Learning disabilities were defined by one essential criterion consistent with the Americans with Disabilities Act of 1990. Patients had left hemisphere language dominance based on Wada results, left or right TLE based on inpatient EEG monitoring, and negative magnetic resonance imaging (MRI), other than MRI correlates of mesial temporal sclerosis. RESULTS: Higher rates of reading comprehension, written language, and calculation disabilities were associated with left TLE, as compared with right TLE. Nearly 75% of patients with left TLE, whereas fewer than 10% of those with right TLE, had at least one learning disability. CONCLUSIONS: Seizure onset in the language-dominant hemisphere, as compared with the nondominant hemisphere, was associated with higher rates of specific learning disabilities and a history of poor literacy or career development or both. These results support the potential clinical benefits of using lateralization of seizure onset as a predictor of the risk of learning disabilities that, once evaluated, could be accommodated to increase the participation of patients with epilepsy in work and educational settings.

Sleep disorders.

Humans spend approximately one third of their lives asleep. Although the same medical disorders that occur during wakefulness persist into sleep, there are many disorders that occur exclusively during sleep or are manifestations of a disturbance of normal sleep-wake physiology. The most common reason for referral to a sleep laboratory is OSA, whereas the most common sleep disorder is insomnia. Effective treatments now exist for many sleep disorders, such as OSA and RLS, and a major breakthrough in the treatment of narcolepsy seems imminent. Because all disease processes are adversely affected by insufficient sleep, it is essential that the practicing physician understand the causes and treatments of the common sleep disorders.