How reliable is a simplified MSLT nap termination protocol?

OBJECTIVE: According to current practical guidelines, naps of the Mean Sleep Latency Test (MSLT) must be terminated 15 min after sleep onset, which requires ad hoc scoring. For clinical convenience, some sleep clinics use a simplified protocol with fixed nap lengths of 20min. Its diagnostic accuracy remains unknown. METHODS: A subset of MSLT naps of 56 narcolepsy type 1 (NT1), 98 Parkinson's disease (PD), 117 sleep disordered breathing (SDB), 22 insufficient sleep syndrome (ISS) patients, and 24 patients with idiopathic hypersomnia (IH), originally performed according to the simplified protocol, were retrospectively adjusted to standard protocol (nap termination 15min after sleep onset or after 20min when no sleep occurs). This was feasible in 60% of MSLT naps; in this subset, we compared sensitivity and specificity of both MSLT protocols for identification of patients with and without NT1. RESULTS: Sensitivity of classical MSLT criteria for NT1, i.e. mean sleep latency ≤8.0min and ≥2 sleep onset rapid eye movement periods (SOREMPs), did not differ between protocols (95%). Specificity, however, was slightly lower (88.1% vs. 89.7%) in the simplified nap termination protocol, with 3 SDB patients and 1 ISS patient having false-positive MSLT findings in the simplified but not in the standard protocol. CONCLUSIONS: The use of a simplified MSLT protocol with fixed nap duration had no impact on MSLT sensitivity for NT1, but the longer sleep periods in the simplified protocol increased the likelihood of REM sleep occurrence particularly in non-NT1 conditions, resulting in a slightly lower MSLT specificity compared to the standard protocol.

Deep brain stimulation of the anterior nucleus of the thalamus increases slow wave activity in non-rapid eye movement sleep.

OBJECTIVE: Previous studies suggest that intermittent deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) affects physiological sleep architecture. Here, we investigated the impact of continuous ANT DBS on sleep in epilepsy patients in a multicenter crossover study in 10 patients. METHODS: We assessed sleep stage distribution, delta power, delta energy, and total sleep time in standardized 10/20 polysomnographic investigations before and 12 months after DBS lead implantation. RESULTS: In contrast to previous studies, we found no disruption of sleep architecture or alterations of sleep stage distribution under active ANT DBS (p = .76). On the contrary, we observed more consolidated and deeper slow wave sleep (SWS) under continuous high-frequency DBS as compared to baseline sleep prior to DBS lead implantation. In particular, biomarkers of deep sleep (delta power and delta energy) showed a significant increase post-DBS as compared to baseline (36.67 ± 13.68 µV2 /Hz and 799.86 ± 407.56 µV2 *s, p < .001). Furthermore, the observed increase in delta power was related to the location of the active stimulation contact within the ANT; we found higher delta power and higher delta energy in patients with active stimulation in more superior contacts as compared to inferior ANT stimulation. We also observed significantly fewer nocturnal electroencephalographic discharges in DBS ON condition. In conclusion, our findings suggest that continuous ANT DBS in the most cranial part of the target region leads to more consolidated SWS. SIGNIFICANCE: From a clinical perspective, these findings suggest that patients with sleep disruption under cyclic ANT DBS could benefit from an adaptation of stimulation parameters to more superior contacts and continuous mode stimulation.

Sensitivity of long-term EEG monitoring as a second diagnostic step in the initial diagnosis of epilepsy.

In this retrospective study, we aimed to evaluate the sensitivity and negative predictive value of long-term EEG (L-EEG) in patients being assessed for epilepsy, who had already undergone non-specific standard EEG(s) (S-EEG). Secondary endpoints of this study were: (1) the correlation of non-specific changes on EEG with epileptiform patterns on L-EEG; and (2) the correlation of clinical parameters such as subjective frequency of seizures or epileptogenic lesions on cerebral imaging with epileptiform changes on L-EEG. We retrospectively analysed clinical and electrophysiological data of 75 patients, assessed for epilepsy at the University Hospital Zurich, who had undergone an L-EEG for at least 48 hours, between 2010 and 2015. All patients had already undergone S-EEG(s) before L-EEG, which showed no epileptic changes. Furthermore, the association with clinical parameters, such as frequency of presumptive seizures, abnormalities on standard-EEG, AED intake and cerebral imaging with the final diagnosis, was analysed. Out of 75 patients, 14 (19%) patients were finally diagnosed with epilepsy. In eight of these patients, L-EEGs showed typical ictal/interictal patterns, with a sensitivity of 57% and negative predictive value of 91%. Neither the subjective frequency of seizures nor potentially epileptogenic lesions on cerebral imaging were associated with a positive epilepsy diagnosis. In this preselected cohort of patients, who had already undergone a non-diagnostic S-EEG, the sensitivity of L-EEG remained considerable. Nonetheless, our study also revealed a significant false-negative rate. Based on the high negative predictive value in this study, L-EEG appears to be most useful at excluding epilepsy. Nevertheless, thorough evaluation of seizure history and clinical findings remain crucial for a reliable diagnosis.

Predictive value of EEG in postanoxic encephalopathy: A quantitative model-based approach.

INTRODUCTION: The majority of comatose patients after cardiac arrest do not regain consciousness due to severe postanoxic encephalopathy. Early and accurate outcome prediction is therefore essential in determining further therapeutic interventions. The electroencephalogram is a standardized and commonly available tool used to estimate prognosis in postanoxic patients. The identification of pathological EEG patterns with poor prognosis relies however primarily on visual EEG scoring by experts. We introduced a model-based approach of EEG analysis (state space model) that allows for an objective and quantitative description of spectral EEG variability. METHODS: We retrospectively analyzed standard EEG recordings in 83 comatose patients after cardiac arrest between 2005 and 2013 in the intensive care unit of the University Hospital Zürich. Neurological outcome was assessed one month after cardiac arrest using the Cerebral Performance Category. For a dynamic and quantitative EEG analysis, we implemented a model-based approach (state space analysis) to quantify EEG background variability independent from visual scoring of EEG epochs. Spectral variability was compared between groups and correlated with clinical outcome parameters and visual EEG patterns. RESULTS: Quantitative assessment of spectral EEG variability (state space velocity) revealed significant differences between patients with poor and good outcome after cardiac arrest: Lower mean velocity in temporal electrodes (T4 and T5) was significantly associated with poor prognostic outcome (p<0.005) and correlated with independently identified visual EEG patterns such as generalized periodic discharges (p<0.02). Receiver operating characteristic (ROC) analysis confirmed the predictive value of lower state space velocity for poor clinical outcome after cardiac arrest (AUC 80.8, 70% sensitivity, 15% false positive rate). CONCLUSION: Model-based quantitative EEG analysis (state space analysis) provides a novel, complementary marker for prognosis in postanoxic encephalopathy.

Persistent generalized periodic discharges: A specific marker of fatal outcome in cerebral hypoxia.

OBJECTIVES: Electroencephalography (EEG) is one of the methods used in predicting the outcome after cerebral hypoxia. In this study we aim to evaluate the significance of generalized periodic discharges (GPD) as a prognostic marker. METHODS: We retrospectively analyzed the medical histories of patients, who underwent an EEG after cardiac arrest during the time period from 2005 to 2013 at the University Hospital Zurich. All EEGs were re-interpreted using the 2012 American Clinical Neurophysiology Society (ACNS) classification for intensive care unit (ICU) EEGs. RESULTS: Out of 131 patients, in which an EEG was recorded after cardiopulmonary resuscitation, 119 were included in our study. The average interval between cardiac arrest and EEG-recording was 3.8±3.0days (range: 0-14days). Persistent GPDs (i.e. GPDs more than 24h after the event) were found in thirty-two (26.9%) of the patients initial EEGs. The appearance of persistent GPDs preceded fatal outcome in 100% of all cases (vs. 69.0% in the non-GPD-group, p<0.0001). CONCLUSION: Among other encephalopathic markers in EEG persistent GPDs are a highly specific prognostic marker of fatal outcome in patients with hypoxic encephalopathy. SIGNIFICANCE: Using standardized EEG interpretation, this study identified persistent GPDs as a specific prognostic marker in post cardiac arrest syndrome.

EEG after sleep deprivation is a sensitive tool in the first diagnosis of idiopathic generalized but not focal epilepsy.

OBJECTIVES: Electroencephalography (EEG) is an essential tool in the diagnosis of epilepsy. EEG after sleep deprivation might increase the likelihood of finding specific epileptiform abnormalities. However conflicting data exist concerning the sensitivity and specificity of this method. We aimed to evaluate the role of EEG after sleep deprivation in the first diagnosis of epilepsy. METHODS: We analyzed retrospectively the medical histories of patients who underwent at least one unspecific standard EEG and a subsequent EEG after sleep deprivation during the time period from 2001 to 2014 at the University Hospital Zurich because of suspected epilepsy. RESULTS: Out of 237 patients who fulfilled all inclusion criteria, 69 were finally diagnosed with epilepsy. Seventeen of them showed interictal epileptiform patterns in EEGs after sleep deprivation, giving this method an overall sensitivity of 25%. Sensitivity of EEG after sleep deprivation was superior in patients with primary generalized epilepsies compared to patients with focal epilepsies (64% vs. 17%, p=0.0011). Overall EEG after sleep deprivation was not more sensitive than a subsequent repeated standard EEG in a subgroup of 55 patients (22% vs. 9%; p=0.065). CONCLUSION: After an unspecific standard EEG, EEG after sleep deprivation is a useful tool to increase diagnostic sensitivity in patients with idiopathic generalized epilepsy but not in those with focal epilepsy. SIGNIFICANCE: This study provides further evidence about the usefulness of EEG after sleep deprivation as an additional diagnostic tool in epilepsy.

Funicular myelosis in a butcher: it was the cream cans.

Background. Funicular myelosis is a known consequence of exposure to nitrous oxide. Nevertheless, there are only a few clinical trials assessing its long-term effects and there is no literature about the role of nutritional vitamin B12 supplementation in the context of nitrous oxide abuse. Case Descriptions. We diagnosed funicular myelosis in a young butcher, who consumed high amounts of meat regularly. Since the diagnostic process did not reveal any metabolic causes, reinterrogation of the patient uncovered recreational abuse of nitrous oxide out of whipped cream can gas cartridges. After stopping abuse and supplementation of vitamin B12, the patient recovered almost completely. Conclusions. In our case, even high nutritional vitamin B12 uptake could not compensate the noxious effects of nitrous oxide. Since there are emerging reports of increasing misuse, this should be considered in the diagnostic and therapeutic care of patients with nitrous oxide abuse. Furthermore, our case emphasizes that patients with vitamin B12 deficiency should be assessed for nitrous oxide abuse.

Polarized distribution of AMPA, but not GABAA , receptors in radial glia-like cells of the adult dentate gyrus.

Glial fibrillary acidic protein (GFAP)-positive astrocytes with radial processes [radial glia (RG)-like cells] in the postnatal dentate gyrus share many of the characteristics of embryonic radial glia and appear to act as precursor cells for adult dentate neurogenesis, a process important for pattern separation and hippocampus-dependent learning. Although much work has delineated the mechanisms underlying activity-neurogenesis coupling via gamma-amino butyric acid (GABA)ergic neurotransmission on GFAP-negative transient-amplifying cells and neuroblasts, little is known regarding the effects of neurotransmitters on RG-like cells. Conflicting evidence exists for both GABA and glutamate receptors on these cells. Here, using GFAP reporter mice, we show that the somatic membrane of RG-like cells carries GABAA receptors and glutamate transporters but not ionotropic glutamate receptors, whereas 2-amino-3-(hydroxyl-5-methylisoxazole-4-yl) propionic acid (AMPA) and GABAA receptors are expressed on the processes of these cells. Almost all RG-like cells expressed the GluA2 subunit, which restricts the Ca(2+) permeability of AMPA receptors. The glial GABAA receptors mainly comprised α2/α4, ß1, and γ1/γ3. The selective presence of AMPA receptors on the radial processes may be important for sensing and responding to local activity-driven glutamate release and supports the concept that RG-like astrocytes are composed of functional and structural domains.