Sleep-wake characteristics in a mouse model of severe traumatic brain injury: Relation to posttraumatic epilepsy.

Study objectives: Traumatic brain injury (TBI) results in sequelae that include posttraumatic epilepsy (PTE) and sleep-wake disturbances. Here, we sought to determine whether sleep characteristics could predict development of PTE in a model of severe TBI. Methods: Following controlled cortical impact (CCI) or sham injury (craniotomy only), CD-1 mice were implanted with epidural electroencephalography (EEG) and nuchal electromyography (EMG) electrodes. Acute (1st week) and chronic (months 1, 2, or 3) 1-week-long video-EEG recordings were performed after the injury to examine epileptiform activity. High-amplitude interictal events were extracted from EEG using an automated method. After scoring sleep-wake patterns, sleep spindles and EEG delta power were derived from nonrapid eye movement (NREM) sleep epochs. Brain CTs (computerized tomography) were performed in sham and CCI cohorts to quantify the brain lesions. We then employed a no craniotomy (NC) control to perform 1-week-long EEG recordings at week 1 and month 1 after surgery. Results: Posttraumatic seizures were seen in the CCI group only, whereas interictal epileptiform activity was seen in CCI or sham. Sleep-wake disruptions consisted of shorter wake or NREM bout lengths and shorter duration or lower power for spindles in CCI and sham. NREM EEG delta power increased in CCI and sham groups compared with NC though the CCI group with posttraumatic seizures had lower power at a chronic time point compared with those without. Follow-up brain CTs showed a small lesion in the sham injury group suggesting a milder form of TBI that may account for their interictal activity and sleep changes. Significance: In our TBI model, tracking changes in NREM delta power distinguishes between CCI acutely and animals that will eventually develop PTE, but further work is necessary to identify sleep biomarkers of PTE. Employing NC controls together with sham controls should be considered in future TBI studies.

Quantitative spatio-temporal characterization of epileptic spikes using high density EEG: Differences between NREM sleep and REM sleep.

In this study, we applied high-density EEG recordings (HD-EEG) to quantitatively characterize the fine-grained spatiotemporal distribution of inter-ictal epileptiform discharges (IEDs) across different sleep stages. We quantified differences in spatial extent and duration of IEDs at the scalp and cortical levels using HD-EEG source-localization, during non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep, in six medication-refractory focal epilepsy patients during epilepsy monitoring unit admission. Statistical analyses were performed at single subject level and group level across different sleep stages for duration and distribution of IEDs. Tests were corrected for multiple comparisons across all channels and time points. Compared to NREM sleep, IEDs during REM sleep were of significantly shorter duration and spatially more restricted. Compared to NREM sleep, IEDs location in REM sleep also showed a higher concordance with electrographic ictal onset zone from scalp EEG recording. This study supports the localizing value of REM IEDs over NREM IEDs and suggests that HD-EEG may be of clinical utility in epilepsy surgery work-up.

Slit Ventricle Syndrome Leads to 10-Year History of Repetitive Transient Central Herniation Masquerading as Seizures: Hydrocephalus Case Report.

BACKGROUND: Slit-ventricle syndrome (SVS) is a recognized complication of ventricular shunt malfunction, resulting in cyclical symptoms without ventricular dilatation. We present a case of SVS with transient, repetitive, and progressive signs of brainstem herniation evidenced by pupillary dilatation, posturing, and unresponsiveness, with diffuse voltage attenuation on electroencephalogram (EEG). CASE DESCRIPTION: A 32-year-old female presented with a history of hydrocephalus and ventriculoperitoneal shunt placement at 9 months of age. She began experiencing significant headaches in college, later accompanied by stereotypical 5- to 25-minute episodes of unresponsiveness, posturing and pupillary dilatation, and failing anticonvulsant therapy. No neurosurgical evaluation was sought because of small ventricles on brain imaging. Episodes became progressively more frequent over a 10-year period, eventually occurring daily. On presentation, 5 clinical events were captured on EEG over 12 hours of monitoring. With each episode, she became unresponsive and hypertensive, with fixed, dilated pupils and flexor posturing. Between events, she was awake and alert, without confusion or postictal state. She had papilledema and limited extraocular movements, with normal pupils and vital signs. Computed tomography scanning showed small ventricles. A shunt tap revealed no flow. With each episode onset, an EEG revealed an abrupt background rhythm slowing to 2-3 Hz delta range without epileptiform discharges. Between events, EEGs displayed normal waveform activity. Emergent ventriculoperitoneal shunt revision resulted in no further episodes in a 4-year follow-up period. CONCLUSIONS: SVS can lead to severe intermittent brainstem herniation syndrome in the setting of shunt malfunction. Seizure diagnosis should be reserved for cases with proven functional shunt and EEG confirmation of epileptiform activity.

Histone deacetylase inhibitors restore normal hippocampal synaptic plasticity and seizure threshold in a mouse model of Tuberous Sclerosis Complex.

Abnormal synaptic plasticity has been implicated in several neurological disorders including epilepsy, dementia and Autism Spectrum Disorder (ASD). Tuberous Sclerosis Complex (TSC) is an autosomal dominant genetic disorder that manifests with seizures, autism, and cognitive deficits. The abnormal intracellular signaling underlying TSC has been the focus of many studies. However, nothing is known about the role of histone modifications in contributing to the neurological manifestations in TSC. Dynamic regulation of chromatin structure via post translational modification of histone tails has been implicated in learning, memory and synaptic plasticity. Histone acetylation and associated gene activation plays a key role in plasticity and so we asked whether histone acetylation might be dysregulated in TSC. In this study, we report a general reduction in hippocampal histone H3 acetylation levels in a mouse model of TSC2. Pharmacological inhibition of Histone Deacetylase (HDAC) activity restores histone H3 acetylation levels and ameliorates the aberrant plasticity in TSC2+/- mice. We describe a novel seizure phenotype in TSC2+/- mice that is also normalized with HDAC inhibitors (HDACis). The results from this study suggest an unanticipated role for chromatin modification in TSC and may inform novel therapeutic strategies for TSC patients.

Plasma exchange in cryptogenic new onset refractory status epilepticus.

OBJECTIVE: New onset refractory status epilepticus (NORSE) is a recently described entity and has been difficult to treat because the etiology is often cryptogenic. Our aim in each case was to stop status epilepticus while simultaneously searching for the etiology. METHODS: We describe three patients who presented with NORSE, who were refractory to multiple anticonvulsants and general anesthetics for at least 5 days. All patients had an extensive evaluation including MRI brain, CSF studies, radiologic scans for malignancy and serological autoimmune and infectious investigations. RESULTS: Each patient responded dramatically to the use of plasma exchange therapy with cessation of status epilepticus by the fourth day of treatment. Although an etiology was sought after, no appropriate cause for NORSE could be found. CONCLUSION: We propose early use of plasma exchange therapy (Class IV evidence) in hopes to prevent the complications of status epilepticus and prolonged hospitalization.

Seizure outcome and complications following hypothalamic hamartoma treatment in adults: endoscopic, open, and Gamma Knife procedures.

OBJECT: This study aimed at identifying outcomes with respect to seizures, morbidity, and mortality in adult patients undergoing resective or Gamma Knife surgery (GKS) to treat intractable epilepsy associated with hypothalamic hamartoma (HH). METHODS: Adult patients undergoing surgical treatment for HH-related epilepsy were prospectively monitored at a single center for complications and seizure outcome by using a proprietary database. Preintervention and postintervention data for patients 18 years of age and older, and with at least 1 year of follow-up, were analyzed, with specific attention to seizure control, complications, hormonal status, and death. RESULTS: Forty adult patients were found in the database (21 were women). The median HH volume was 0.54 cm(3). In 70% of patients, it was located inside the third ventricle, attached unilaterally and vertically to the hypothalamus (Delalande Type II). Most patients (26) underwent an endoscopic resection, 10 patients had a transcallosal or other type of open (pterional or orbitozygomatic) resection, and 4 patients chose GKS. Twenty-nine percent became seizure free in the long term, and overall a majority of patients (55%) reported at least > 90% seizure improvement. Only 3 patients were ultimately able to discontinue anticonvulsants, whereas most patients were taking an average of 2 antiepileptic drugs pre- and postoperatively. The only factor significantly correlated with seizure-free outcome was the absence of mental retardation. The HH volume, HH type, and amount of resection or disconnection were not correlated to seizure freedom. A total of 4 patients (10%) died, 2 immediately after surgery and 2 later. All of them had undergone a resection, as opposed to GKS, and still had seizures. Postoperatively, persistent neurological deficits were seen in 1 patient; 34% of patients had mild hormonal problems; and 59% experienced weight gain of at least 6.8 kg (average gain 12.7 kg). CONCLUSIONS: Surgical or GKS procedures in adults with HH provided seizure freedom in one-third of patients. The only significant favorable prognostic factor was the absence of mental retardation. The overall mortality rate was high, at 10%. Other important morbidities were persistent hormonal disturbances and weight gain.

Modifications to the subtemporal selective amygdalohippocampectomy using a minimal-access technique: seizure and neuropsychological outcomes.

OBJECT: The authors introduce a minimal-access subtemporal approach for selective resection of the amygdala and hippocampus in patients with temporal lobe epilepsy and describe seizure and neuropsychological outcomes. METHODS: Between October 2003 and April 2007, 41 consecutive patients with intractable unilateral nonlesional temporal lobe epilepsy underwent image-guided subtemporal amygdalohippocampectomy. Baseline characteristics, preoperative evaluations, and seizure outcomes were assessed. Eighteen patients underwent pre- and postoperative neuropsychological testing for cognitive functioning, executive functioning, verbal and visual memory, and mood. RESULTS: Important aspects of the subtemporal approach include a low temporal keyhole craniotomy, use of image guidance, preservation of the tentorium, incision in the fusiform gyrus, and subpial, en bloc resection of the hippocampus. There were no deaths and no cases of significant postoperative morbidity. At 1 year, 29 of 36 patients (81%) were without seizures or auras. At 2 years, 17 of 23 (74%) patients were seizure- and aura-free. Detailed neuropsychological testing of language, memory, cognitive functioning, and executive functioning suggested that most patients exhibited either stability or improvement in their scores, regardless of language lateralization. CONCLUSIONS: A minimal-access subtemporal approach for amygdalohippocampectomy is an effective treatment for temporal lobe epilepsy yielding encouraging preliminary seizure and neuropsychological outcomes.

Practice parameters for the use of autotitrating continuous positive airway pressure devices for titrating pressures and treating adult patients with obstructive sleep apnea syndrome: an update for 2007. An American Academy of Sleep Medicine report.

These practice parameters are an update of the previously published recommendations regarding the use of autotitrating positive airway pressure (APAP) devices for titrating pressures and treating adult patients with obstructive sleep apnea syndrome. Continuous positive airway pressure (CPAP) at an effective setting verified by attended polysomnography is a standard treatment for obstructive sleep apnea (OSA). APAP devices change the treatment pressure based on feedback from various patient measures such as airflow, pressure fluctuations, or measures of airway resistance. These devices may aid in the pressure titration process, address possible changes in pressure requirements throughout a given night and from night to night, aid in treatment of OSA when attended CPAP titration has not or cannot be accomplished, or improve patient comfort. A task force of the Standards of Practice Committee of the American Academy of Sleep Medicine has reviewed the literature published since the 2002 practice parameter on the use of APAP. Current recommendations follow: (1) APAP devices are not recommended to diagnose OSA; (2) patients with congestive heart failure, patients with significant lung disease such as chronic obstructive pulmonary disease; patients expected to have nocturnal arterial oxyhemoglobin desaturation due to conditions other than OSA (e.g., obesity hypoventilation syndrome); patients who do not snore (either naturally or as a result of palate surgery); and patients who have central sleep apnea syndromes are not currently candidates for APAP titration or treatment; (3) APAP devices are not currently recommended for split-night titration; (4) certain APAP devices may be used during attended titration with polysomnography to identify a single pressure for use with standard CPAP for treatment of moderate to severe OSA; (5) certain APAP devices may be initiated and used in the self-adjusting mode for unattended treatment of patients with moderate to severe OSA without significant comorbidities (CHF, COPD, central sleep apnea syndromes, or hypoventilation syndromes); (6) certain APAP devices may be used in an unattended way to determine a fixed CPAP treatment pressure for patients with moderate to severe OSA without significant comorbidities (CHF, COPD, central sleep apnea syndromes, or hypoventilation syndromes); (7) patients being treated with fixed CPAP on the basis of APAP titration or being treated with APAP must have close clinical follow-up to determine treatment effectiveness and safety; and (8) a reevaluation and, if necessary, a standard attended CPAP titration should be performed if symptoms do not resolve or the APAP treatment otherwise appears to lack efficacy.

Epilepsy surgery outcome among US veterans.

We retrospectively studied the outcome of anterior temporal lobectomy (ATL) among a population of veterans and evaluated outcome related to comorbidities. Veterans who underwent ATL between 1990 and 2001 at the Veterans Administration Hospital in Madison, Wisconsin, were included. Data related to postoperative seizure outcome, quality of life outcome, and employment outcome were collected. Factors associated with favorable outcome and outcome related to comorbidities were evaluated. Twenty-seven patients were entered into the study. The mean age at onset of seizures was 25 years (+/-10.2). History of a non-substance abuse psychiatric diagnosis, and substance abuse was present in 26% (7/27) and 30% (9/27), respectively, prior to surgery. While 66.6% (18/27) had a good outcome (Engel's Class I), no difference in the frequency of good outcome was seen among the patients with a history of substance abuse, other psychiatric diagnosis (71%), or no psychiatric diagnosis (67%). There was a significant correlation between seizure outcome and quality of life score (r(s)=0.67, p<0.001) and postoperative employment gains (r(s)=0.48, p=0.01). Outcomes among veterans that underwent ATL can be satisfactory even in the context of the late mean age of epilepsy onset and the psychiatric diagnoses that were present in this sample.