Summary
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.
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.
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.
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.
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.
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.
Purpose: To assess the effect of vagus nerve stimulation (VNS) on interictal epileptiform activity in the human hippocampus. Clinical studies have established the efficacy of vagus nerve stimulation ...in patients with epilepsy (VNS Study Group, 1995), although the electrophysiologic effects of VNS on the human hippocampus and mesial temporal lobe structures remain unknown.
Methods: We report a case study in which a patient with an implanted VNS underwent intracranial electrode recording before temporal lobectomy for intractable complex partial seizures. Epileptiform spikes and sharp waves were recorded from a depth electrode placed in the patient's left hippocampus. Spike frequencies and sharp‐wave frequencies before and during VNS were compared using both a 5‐ and a 30‐Hz stimulus. Different stimulation rates were tested on different days, and all analyses were performed using a Student's t test.
Results: We found no significant differences in spike frequency between baseline periods and stimulation at 5 and 30 Hz. In contrast, stimulation at 30 Hz produced a significant decrease in the occurrence of epileptiform sharp waves compared with the baseline, whereas stimulation at 5 Hz was associated with a significant increase in the occurrence of epileptiform sharp waves.
Conclusions: VNS produces a measurable electrophysiologic effect on epileptiform activity in the human hippocampus. Although a clinical response to VNS did not occur in our patient before surgery, 30‐Hz VNS suppressed interictal epileptiform sharp waves that were similar in appearance to those seen during the patient's actual seizures. In contrast, 5‐Hz stimulation appeared to increase the appearance of interictal sharp waves.
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.
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.
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, ‘posthypoxic’ TSWA offers us some valuable insights for classifying and managing nonconvulsive status epilepticus.
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