Probable Sudden Unexpected Death in Dogs With Epilepsy (pSUDED)

Sudden unexpected death in human epileptic patients (SUDEP) is defined as death related to recurrent unprovoked seizures, death occurring unexpectedly, and suddenly in a patient with reasonable state of health, without an obvious medical cause of death, trauma, asphyxia, or intractable status epilepticus, and in post mortem examination no obvious reason for death can be found. “Probable SUDEP” (pSUDEP) is defined as SUDEP not confirmed pathologically. The adapted abbreviation for dogs is used in the following: “pSUDED” (probable sudden unexpected death in dogs with epilepsy). The aim of the present monocentric retrospective study using an online questionnaire was to evaluate the occurrence of pSUDED. Data of canine patients presented with seizures between 01/1998 and 05/2018 were retrospectively analyzed and classified according to their etiology (n = 1,503). Owners were contacted by telephone to participate in answering a validated questionnaire. A total of 509 owners were reached, and 373 owners completed the questionnaire. In addition to signalement (e.g., breed), special attention was paid to the frequency and presentation of seizures and seizures in the context of death. Fifty-one percent (191/373) of the dogs were dead at the endpoint of the study. A large proportion of the dogs was euthanized (149/191) because of seizure severity or health problems unrelated to seizures. Idiopathic epilepsy (IE) was diagnosed in 19/34 dogs which died unexpectedly. Of these seven animals had to be excluded for further investigation of pSUDED because of status epilepticus or aspiration pneumonia as a result of the seizures. In 12 dogs with IE the last seizure event occurred between 6 h and ~3 months before death. pSUDED was suspected in these dogs and an occurrence rate of 4.5–10% was calculated. pSUDED appears in a similar occurrence rate as human SUDEP and should be considered as a possible complication in epileptic dogs. The results of this study suggest that dogs with IE but especially those with brachycephalic syndrome and cluster seizures have an increased risk to die of pSUDED. Owners of dogs with seizures should be educated about the risk of sudden death in dogs with epilepsy.

Non-epileptic seizure caused by selective serotonin reuptake inhibitors (SSRI) - case report

Context: Seizures are the most frequent clinical emergency neurological manifestation, corresponding to 1-5% of the visits, except for trauma. Several conditions have the potential to reduce the seizure threshold, and the use of antidepressant drugs as selective serotonin reuptake inhibitors is one of those reported. The seizure triggering risk related to SSRIs use is low, being 0.1%, perceptibly lower than that of tricyclic antidepressants, with a 1% rate. Case report: Male patient, previously healthy, 23-year-old, was seen at the Emergency Room in Rio Branco after a generalized seizure lasting 3 minutes. Complementary exams, including computed tomography, were all normal. Magnetic resonance imaging of the skull without atypical findings and electroencephalogram showed dysrhythmia by waves and discrete spicules. Patient reported using escitalopram (esc) 20mg for 3 months after 10mg progression dose, in use for 1 year, without clinical improvement. Due to the seizure event, medication management was switched for sertraline 50mg intake. After 2 months, the patient had a new generalized seizure, preceded by prolonged depersonalization. Complementary exams were normal, 10mg of esc was reestablished and the patient ceased with the seizures. Conclusions: The diagnostic hypothesis: patient’s seizure threshold is low, and seizures are triggered by SSRI higher doses adverse effect. Due to case rarity and SSRI efficacy and tolerance, it is suggested to encourage the discussion about administration safety of these drugs.

Complex Febrile Seizures: An Update

Febrile seizures are the most common seizures in childhood. Febrile seizures are divided into two groups: simple and complex. Simple febrile seizures (SFS) are generalized, short, and occur only once in 24 hours. Complex febrile seizures are prolonged, focal, or repeat more than once in 24 hours. Around 35% of children experience complex features as part of their initial seizure event. These children have more chances of complex recurrences than children with SFS. While the guidelines for SFS remain clear, there are no clear guidelines for the evaluation of children with complex febrile seizures. The conflicting results about electroencephalography (EEG) utilization preclude drawing meaningful conclusions. An EEG can be obtained in children with persistent alteration of consciousness after the seizure, and emergent neuroimaging is not required in most cases. Due to low incidence of bacterial meningitis in the post-vaccination era, it is reasonable to perform lumbar puncture (LP) only if there is clinical concern for central nervous system infection. LP should also be considered in children between 6 and 12 months of age with incomplete or unknown vaccination status or who have been previously treated with antibiotics. Further, antipyretics are used to make children more comfortable during the febrile process, but are ineffective in reducing the rate of seizure reoccurrence. Continuous antiepileptic therapy and intermittent oral diazepam are effective in the prevention of subsequent febrile seizures, but they do not reduce the risk of epilepsy and have potential unwanted side effects. In specific circumstances, the benefits of antiseizure medications may outweigh the risks. Treatment may be a consideration in cases of febrile status: patients with electroclinical features suggesting a specific epilepsy syndrome or children with limited access to health care services.

Assessment of Porous Type Gas Bearings: Measurements of Bearing Performance and Rotor Vibrations

Gas bearings are an attractive means of load support for rotating machinery due to their low mechanical power losses and dispensing of expensive lubrication systems. A subset of gas bearing technology, porous type gas bearings utilize a porous material as a means of feeding externally pressurized gas (typically air) to the bearing clearance region. When compared to typical orifice type hydrostatic bearings, porous bearings distribute pressurized gas more uniformly into the film clearance, thus resulting in a higher load capacity for similar flow rates [1]. The majority of the literature on porous type gas bearings focuses on the numerical evaluation of cylindrical bushings, yet experimental data on their performance is scant. As a follow up to Ref. [2], the paper presents an analysis of measurements of flow, drag torque and rotordynamic response of a large (100 mm OD, ∼275 N) rotor supported on two tilting pad (five-pad) porous journal bearings (specific load∼19 kPa). Measurements of air mass flow into the bearings, with and without the rotor in place, show that the film clearance offers little restriction. The mass flow rate is proportional to the supply pressure and lead to an estimated permeability coefficient. In operation with various levels of supply pressure and with the rotor spinning to 8 krpm (133 Hz, surface speed ∼42 m/s), several rotordynamic response tests (masses up to 6.9 gram) show the rotor amplitude of synchronous response is proportional to the mass imbalance; hence demonstrating the system is linear. Finally, rotor speed coast down tests from 8 krpm show that the bearings offer little drag friction; and increasing the supply pressure gives to lesser drag. The measurements verify the pair of gas bearings support effectively the rigid rotor with little expense in mass flow rate delivered to them. Most importantly, while operating at 10 krpm with a large added imbalance, the system survived a seizure event with little damage to the rotor and bearings, both restored to a near pristine condition after a simple cleaning procedure.

ODM-201 and the CNS: A clinical perspective.

275^ Background: ODM-201 is a potent, new generation androgen receptor inhibitor with activity in preclinical in vivo and in vitro studies. ODM-201 shows negligible penetration into the rat brain at pharmacological doses. In the phase I/II study with 134 patients with progressive castration-resistant prostate cancer (CRPC) (the ARADES study) patients with a history, or risk, of a seizure were not excluded. We reviewed the ARADES safety database to assess potential seizure or seizure-related adverse events (AEs). Methods: The following AE terminology was reviewed: seizure, syncope, presyncope, loss of consciousness, depressed level of consciousness, encephalopathy, and transient ischemic attack, hallucinations, vasovagal syndrome, falls and fall-related injuries, nonpathologic fractures, urinary or fecal incontinence, tonic-clonic activity, abnormal EEGs. We further reviewed medical histories and use of anti-seizure medications, as well as medications that could lower the seizure threshold and identified any seizure or seizure like condition as an AE. Results: Twenty one percent of the patients had concomitant medications indicated for epilepsy or other seizure-related disorders. Twelve patients had one or more of the above listed AE. None of the patients experienced seizures or related disorders while receiving ODM-201; one seizure event was reported to occur 27 days after stopping treatment. There were five fall events, one syncope, one presyncope, and four urinary incontinence cases - all interpreted by the investigators as not related to ODM-201 treatment and not leading to treatment discontinuation. Careful evaluation of these cases suggested that these events were unlikely to be related to seizure. Conclusions: ODM-201 has negligible brain entrance in nonclinical models. Treatment with ODM-201 was not linked with CNS-related events in patients in this trial. These preliminary findings suggest minimal CNS safety concerns. Clinical trial information: NTC01317641, NTC01429064.

Detection of Epileptic Seizure Event and Onset Using EEG

This study proposes a method of automatic detection of epileptic seizure event and onset using wavelet based features and certain statistical features without wavelet decomposition. Normal and epileptic EEG signals were classified using linear classifier. For seizure event detection, Bonn University EEG database has been used. Three types of EEG signals (EEG signal recorded from healthy volunteer with eye open, epilepsy patients in the epileptogenic zone during a seizure-free interval, and epilepsy patients during epileptic seizures) were classified. Important features such as energy, entropy, standard deviation, maximum, minimum, and mean at different subbands were computed and classification was done using linear classifier. The performance of classifier was determined in terms of specificity, sensitivity, and accuracy. The overall accuracy was 84.2%. In the case of seizure onset detection, the database used is CHB-MIT scalp EEG database. Along with wavelet based features, interquartile range (IQR) and mean absolute deviation (MAD) without wavelet decomposition were extracted. Latency was used to study the performance of seizure onset detection. Classifier gave a sensitivity of 98.5% with an average latency of 1.76 seconds.

Sudden unexpected, unexplained death in epilepsy autopsied patients

Sudden unexpected, unexplained death in epilepsy (SUDEP) has been reported to be responsible for 2 to 17% of all deaths in patients with epilepsy. This study was conducted to determine the circumstances of SUDEP and the autopsy findings in these patients. Fifty-three individuals whose cause of death was related to epilepsy were identified and in 30 cases relatives or friends were interviewed about the circumstances of death and other information which allowed to classify the patients as SUDEP or not. The death certificates were also reviewed. We found 20 cases of SUDEP. Most of them were found dead lying on the bed with no evidence of seizure event, and most of them had pulmonary and/or cerebral edema as the cause of death. The incidence and the risk of SUDEP can only be fully ascertained if all sudden deaths had postmortem examination. Consensus in certifying SUDEP cases would allow better accuracy in national mortality rate.