Brief Potentially Ictal Rhythmic Discharges (BIRDs), initially described in neonates, have been shown to correlate with increased risk of seizures in both critically ill and non-critically ill ...adults. In critically ill patients, BIRDs are associated with acute brain injury and worse functional outcomes. In non-critically ill adults, BIRDs are seen in patients with epilepsy with a greater likelihood of having drug resistance. The location of BIRDs seems to better predict the seizure onset zone compared to other interictal epileptiform discharges. The definition of BIRDs includes Paroxysmal Fast Activity (PFA), and they have similar clinical significance regardless of the exact cut-off frequencies. Their potential as a biomarker for seizure activity and seizure onset zone has been suggested. In patients with status epilepticus, BIRDs also resolve or decrease when seizures resolve. Thus, if BIRDs are observed on scalp EEG, more extended EEG monitoring is recommended to estimate their seizure burden and to guide treatment. With the recent addition of BIRDs in the critical care EEG terminology, with future investigations, we may soon be able to reach a consensus about the definition of electrographic seizures and better understand their neurophysiology and clinical significance.
IMPORTANCE Brief potentially ictal rhythmic discharges, termed B(I)RDs, have been described mainly in neonates, and their significance in adults remains unclear. OBJECTIVE To describe the incidence ...of B(I)RDs in critically ill patients and investigate their association with seizures and outcome. DESIGN, SETTING, AND PARTICIPANTS We reviewed the records of prospectively identified patients with B(I)RDs and patients serving as controls matched for age (±5 years) and primary diagnosis. MAIN OUTCOMES AND MEASURES The prevalence of seizures during continuous electroencephalography and functional outcome, as measured by the Glasgow Outcome Scale, were determined. RESULTS We identified B(I)RDs in 20 patients (2%). The pattern most often consisted of very brief (1-3 seconds) runs of sharply contoured theta activity without obvious evolution. All patients with B(I)RDs had cerebral injury, and in cases with a single focal lesion (11 55%), B(I)RDs were localized in the same region in all but 2 cases (18%). Patients with B(I)RDs were more likely to have seizures during continuous electroencephalography than were patients without B(I)RDs (15 of 20 75% vs 10 of 40 25%; P < .001), and 9 patients with B(I)RDs (60%) had only subclinical seizures. Brief potentially ictal rhythmic discharges were identified before seizures in all but 1 case (93%) and ceased in all 12 cases (80%) in which seizures were controlled. Patients with B(I)RDs tended to have a worse outcome than controls (16 80% vs 25 63%); however, this finding was not statistically significant. CONCLUSIONS AND RELEVANCE Brief potentially ictal rhythmic discharges in critically ill patients are associated with a high prevalence (75%) of electrographic seizures and might serve as an early predictor of seizures during subsequent monitoring. A larger prospective study is needed to better understand their clinical and prognostic significance.
Palinacousis is an auditory illusion of sound persisting or repeating after the cessation of an auditory stimulation. Up until now, approximately 32 cases have been reported. The purpose of this ...study is to describe an additional seven cases of palinacousis and review our understanding of audition and palinacousis.
Patients seen in the epilepsy clinic or admitted to the Epilepsy Monitoring Unit (EMU) at The Mount Sinai Hospital who experienced palinacousis were included. In all these patients, an EEG and MRI were performed at some point during their clinical course.
In one case, palinacousis occurred with stimulation of the superior temporal gyrus during brain mapping after a spoken word as well as after the thought of a word. Two people experienced palinacousis during a seizure captured on video EEG. The remaining four cases had palinacousis in the peri- or post-ictal period.
We propose that palinacousis may be coming from the superior temporal gyrus secondary to seizure activity, either onset or spread, or dysfunction of the area in a postictal state. The existence of palinacousis in these pathologic states can help us to understand how we process auditory information.
For drug resistant epilepsy patients who are either not candidates for resective surgery or have already failed resective surgery, neuromodulation is a promising option. Neuromodulatory approaches ...include responsive neurostimulation (RNS), deep brain stimulation (DBS), and vagal nerve stimulation (VNS). Thalamocortical circuits are involved in both generalized and focal onset seizures. This paper explores the use of RNS in the centromedian nucleus of the thalamus (CMN) and in the anterior thalamic nucleus (ANT) of patients with drug resistant epilepsy.
This is a retrospective multicenter study from seven different epilepsy centers in the United States. Patients that had unilateral or bilateral thalamic RNS leads implanted in the CMN or ANT for at least 6 months were included. Primary objectives were to describe the implant location and determine changes in the frequency of disabling seizures at 6 months, 1 year, 2 years, and > 2 years. Secondary objectives included documenting seizure free periods, anti-seizure medication regimen changes, stimulation side effects, and serious adverse events. In addition, the global clinical impression scale was completed.
Twelve patients had at least one lead placed in the CMN, and 13 had at least one lead placed in the ANT. The median baseline seizure frequency was 15 per month. Overall, the median seizure reduction was 33% at 6 months, 55% at 1 year, 65% at 2 years, and 74% at >2 years. Seizure free intervals of at least 3 months occurred in nine patients. Most patients (60%, 15/25) did not have a change in anti-seizure medications post RNS placement. Two serious adverse events were recorded, one related to RNS implantation. Lastly, overall functioning seemed to improve with 88% showing improvement on the global clinical impression scale.
Meaningful seizure reduction was observed in patients who suffer from drug resistant epilepsy with unilateral or bilateral RNS in either the ANT or CMN of the thalamus. Most patients remained on their pre-operative anti-seizure medication regimen. The device was well tolerated with few side effects. There were rare serious adverse events. Most patients showed an improvement in global clinical impression scores.
Brief potentially ictal rhythmic discharges (B(I)RDs) have been described in neonates and critically ill adults, and their association with seizures has been demonstrated. Their significance in ...noncritically ill adults remains unclear. We aimed to investigate their prevalence, electrographic characteristics, and clinical significance.
We identified adult patients with B(I)RDs who received long-term EEG recordings either in the epilepsy monitoring unit or in the ambulatory setting. Patients with acute findings on imaging or status epilepticus were excluded. B(I)RDs were defined as very brief (<10 seconds) runs of focal or generalized sharply contoured rhythmic activity greater than 4 Hz, with or without evolution, that were not consistent with any known normal or benign pattern. The clinical history, EEG, and imaging results were retrieved. Each patient with B(I)RDs was matched by age and etiology to a control group with epileptiform discharges but without B(I)RDs in a 1:2 ratio.
We identified B(I)RDs in 15 patients of 1,230 EEGs (1.2%). The pattern typically consisted of 0.5 to 4 second runs of sharply contoured alpha activity without evolution. All patients with B(I)RDs had epilepsy, and, when compared with controls with epilepsy but without BIRDs, were more likely to be medically refractory (10 of 15 67% vs. 5 of 30 17%; P < 0.01). All seizure onsets colocalized to the B(I)RDs, and most were morphologically similar.
In noncritically ill patients, B(I)RDs are associated with refractory epilepsy and their location is correlated with the seizure onset area.
Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are commonly prescribed for stress ulcer prophylaxis (SUP) in critically ill patients. Several studies have suggested that ...the use of PPIs is a potential risk factor for Clostridium difficile infection (CDI). We compared the incidences of CDI in the PPI group and H2RA group for SUP in critically ill patients.
From August 2005 to July 2012, the incidences of CDI were retrospectively analyzed in patients who were admitted directly to intensive care units and stayed for more than 3 days. SUP-related CDI was defined as a CDI diagnosed during the SUP period. Patient clinical data were analyzed to identify potential risk factors for SUP-related CDI.
Of the 1,005 patients enrolled (444 patients received PPI and 561 received H2RA), 38 (3.8%) were diagnosed with SUP-related CDI. The incidence of SUP-related CDI was considerably higher in patients who received PPI than in those who received H2RA (6.7% vs 1.8%). PPI use for SUP (odds ratio OR, 3.3; confidence interval CI, 1.5 to 7.1; p=0.003) and diabetes mellitus (OR, 2.3; CI, 1.2 to 4.7; p=0.019) were independent risk factors for SUP-related CDI.
PPI therapy is associated with a higher risk of SUP-related CDI than H2RA therapy in critically ill patients.
Although meningioma is the most common primary tumor of the central nervous system, the mechanism of progression from benign to atypical or anaplastic grade remains elusive. The present case reports ...the genomic evaluation of two synchronous meningiomas with different histological grades (benign and atypical) in the same patient. Under the assumption that the atypical tumor may have progressed from the benign tumor, the clonal origin of the lesions was investigated to identify genomic events responsible for the oncogenic process of evolution to higher grades in meningioma. A 59 year-old female patient was diagnosed with two synchronous meningiomas with different histological grades, benign and atypical. Whole-exome sequencing (WES) and RNA sequencing (RNA-seq) analysis of both tumors were done. WES analysis showed that each meningioma harbored distinct mutation profiles, and RNA-seq analysis revealed distinct gene expression profiles between the two tumors. The only apparent common genetic abnormality found in both tumors was the loss of heterozygosity of chromosome 22, raising the possibility that this event is the initial step in tumor formation, after which distinct subsequent mutations lead to the evolvement of two separate tumors of different grades. The result provides additional evidence on previous reports suggesting separate, independent mechanism of progression into higher grades in meningioma.
Drug-resistant epilepsy is a potentially life-threatening condition affecting one-third of people living with epilepsy. Despite existing evidence of improved outcomes in patients who received ...surgical treatment compared to continued medical treatment, epilepsy surgery remains underused in patients with drug-resistant epilepsy. This article discusses the gap between evidence and practice and common misconceptions about epilepsy surgery and reviews the current diagnostic and therapeutic surgical options.
Three randomized controlled trials comparing the medical versus surgical treatment for patients with drug-resistant epilepsy have shown the superiority of surgery in controlling seizures and improving patients' quality of life. In addition to resective surgery, neuromodulation through devices such as responsive neurostimulation and vagal nerve stimulation have also shown efficacy in seizure control that increases over time. Diagnostic and therapeutic surgical tools are tailored to the needs of each patient.
Appropriate patients with drug-resistant epilepsy benefit more from epilepsy surgery than from continuing medical treatment. These patients should be referred to comprehensive epilepsy centers where a thorough presurgical workup and surgical options can be provided. The gap between evidence and practice can be bridged by education, community outreach, and providers' earnest efforts to improve the quality of life of patients with epilepsy.
Opioid drugs produce their pharmacological effects by activating inhibitory guanine nucleotide-binding regulatory protein-linked μ, δ, and κ opioid receptors. One major effector for these receptors ...is adenylyl cyclase, which is inhibited upon receptor activation. However, little is known about which of the ten known forms of adenylyl cyclase are involved in mediating opioid actions. Here we show that all of the major behavioral effects of morphine, including locomotor activation, analgesia, tolerance, reward, and physical dependence and withdrawal symptoms, are attenuated in mice lacking adenylyl cyclase type 5 (AC5), a form of adenylyl cyclase that is highly enriched in striatum. Furthermore, the behavioral effects of selective μ or δ opioid receptor agonists are lost in$AC5_{-/-}$mice, whereas the behavioral effects of selective κ opioid receptor agonists are unaffected. These behavioral data are consistent with the observation that the ability of a μ or δ opioid receptor agonist to suppress adenylyl cyclase activity was absent in striatum of$AC5_{-/-}$mice. Together, these results establish AC5 as an important component of μ and δ opioid receptor signal transduction mechanisms in vivo and provide further support for the importance of the cAMP pathway as a critical mediator of opioid action.
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