Ivan Osorio

Intrinsic time-scale decomposition: time-frequency-energy analysis and real-time filtering of non-stationary signals

We introduce a new algorithm, the intrinsic time-scale decomposition (ITD), for efficient and precise time–frequency–energy (TFE) analysis of signals. The ITD method overcomes many of the limitations of both classical (e.g. Fourier transform or wavelet transform based) and more recent (empirical mode decomposition based) approaches to TFE analysis of signals that are nonlinear and/or non-stationary in nature. The ITD method decomposes a signal into (i) a sum of proper rotation components, for which instantaneous frequency and amplitude are well defined, and (ii) a monotonic trend. The decomposition preserves precise temporal information regarding signal critical points and riding waves, with a temporal resolution equal to the time-scale of extrema occurrence in the input signal. We also demonstrate how the ITD enables application of single-wave analysis and how this, in turn, leads to a powerful new class of real-time signal filters, which extract and utilize the inherent instantaneous amplitude and frequency/phase information in combination with other relevant morphological features.

Treatment of Refractory Generalized Tonic‐Clonic Status Epilepticus with Pentobarbital Anesthesia After High‐Dose Phenytoin

Summary: We report the results of treatment of refractory generalized tonic‐clonic status epilepticus in 17 adults. Of 13 patients who received high‐dose phenytoin (PHT, mean dose 23.8 mg/kg), seizure control was sustained in five patients. In 12 cases, anesthetic doses of pentobarbital rapidly suppressed convulsions, but sustained control required prolonged treatment. Breakthrough seizures were, in most cases, explained by inadequate serum pentobarbital concentrations, although we could not establish a therapeutic range of serum concentrations. EEG monitoring is necessary to assess the therapeutic response but is not a reliable index of depth of anesthesia. Some cases developed pharmacodynamic tolerance to pentobarbital. The most serious treatment complications were cardiorespiratory, but the most common and disabling side effects, although reversible, were neurologic. Fifteen patients were discharged from the hospital in stable condition; two patients died, but not as a direct consequence of treatment. Our results suggest a very good outcome of pentobarbital anesthesia for patients in refractory status epilepticus who are a reasonable medical risk and who receive optimal medical management.

The characteristics and mechanisms of visual disturbance associated with anticonvulsant therapy

Eight epileptic patients receiving anticonvulsants had recurrent visual disturbances in the form of diplopia and oscillopsia in the horizontal or vertical planes. The symptoms could be ascribed to impaired vergence mechanisms, vertical nystagmus, or abnormalities of the vestibulo-ocular reflex. Other eye movements, such as pursuit and gaze-holding, were also affected, but did not lead to complaints. Episodes of visual disturbance were often preceded by prodromes of ocular or systemic discomfort, after which oscillopsia or diplopia evolve rapidly. The symptomatology was stereotyped but unique for each patient and may reflect idiosyncratic susceptibility to the ocular motor side effects of anticonvulsants. Six of the 8 patients were taking carbamazepine and phenytoin in combination, which have similar effects on the ocular motor system.

Cerebral venous thrombosis in paroxysmal nocturnal hemoglobinuria Report of two cases

We report the clinical, radiologic, and postmortem findings in two patients with paroxysmal nocturnal hemoglobinuria (PNH) who developed cerebral venous thromboses (CVTs). In contrast with those in most published cases, our patients did not have focal neurologic signs. Antemortem diagnosis of CVT had been made by MR cerebral venograms. We conclude that (1) PNH should be considered in any patient with stroke associated with iron deficiency anemia, hemolysis, hemoglobinuria, or hemosiderinuria; (2) PNH should be in the differential diagnosis of CVT; (3) the latter could present without focal neurologic signs; and (4) MR cerebral venography may be a reliable diagnostic alternative to cerebral angiography when CVT is suspected.

Overnight Versus Progressive Conversion of Multiple Daily-Dose Divalproex to Once-Daily Divalproex Extended Release: Which Strategy Is Better Tolerated by Adults With Intellectual Disabilities?

Divalproex (DVP) delayed release and DVP extended release (DVP ER) are approved by the Food and Drug Administration for bipolar disorder, epilepsy, and migraine prophylaxis. Divalproex ER is given once daily, improving compliance and reducing adverse events. Overnight switch to DVP ER is advised in the package insert but could produce more adverse events in this susceptible population. In this pilot study, we compared tolerability of overnight versus gradual switching to DVP ER in 16 adults with intellectual and developmental disabilities receiving DVP, in 9 for epilepsy and in all 16 for comorbid bipolar disorder. The study design was open with parallel groups. Sixteen subjects with intellectual and developmental disabilities were randomized to overnight or gradual conversion for 4 to 6 days. A blinded rater completed the Multidimensional Observation Scale for Elderly Subjects on days +1, +4, and +8 after the switch began. We found no major differences between the 2 groups at each time point. Neither group of subjects, except for 1 subject in the overnight group, manifested sedation, seizures, worsening of tremor, or gastrointestinal adverse events. One subject in the overnight group manifested acute diarrhea and vomiting, followed by a very brief tonic leg seizure 6 days later. Larger studies are warranted.

Comments on requirements for valid and meaningful assessment of therapies for epilepsy and a note of clarification about "open-" vs. "closed-loop" modalities.

The Michael Prize was initiated in 1975 to stimulate and support research in epileptology. Beginning this year, the Michael Forum and Prizes are supported by UCB. The prize is meant to recognize scientists in the early stages of their research career because it is awarded to those below the age of 45 years. It has become one of the most highly regarded international awards in epilepsy research. The prize has gone to individuals and groups in Austria, Brazil, Britain, Canada, Germany, Hungary, Israel, Italy, Poland, Switzerland and the USA. The past winners include many current leaders in the field of epilepsy. A complete list can be obtained from the web site of the Michael Foundation, http://www.stiftung-michael.de/e inhalt.html. The Michael Forum represents the biannual meeting of the Michael Prize winners, both present and those of past years, to discuss recent developments in epileptology in a two-day, open discussion symposium. This year’s meeting was held in Potsdam, just outside of Berlin, and the following short report summarizes the talks on clinical aspects, imaging, and basic science.

Realtime Detection, Quantification, Warning, and Control of Epileptic Seizures—The Foundations of a New Epileptology

The aim of abating seizures in a spatio-temporally selective manner is not a modern one. As early as 150 AD, Pelops from Alexandria, the teacher of Galen, was reported to have aborted what would likely be referred to today as ‘a simple partial seizure with sensory-motor manifestations’ by tying a ligature around the affected limb at the time of the appearance of the first paroxysmal manifestation. Brown-Sequard, Jackson, and, later, Gowers, who coined the term ‘counter-irritation’ to denote a strategy to abate seizures, reintroduced the notion of contingent therapy in the 19th century, an objective that since then and until recently was ignored. After nearly two millennia, the seminal tasks of automated seizure detection and contingent warning and delivery of therapy endowed with realtime feedback capabilities are finally not only feasible but also possibly safe and efficacious. This substantive advance, which at this juncture is in an ‘embryonic’ developmental stage, attempts to address the lack of efficacy of systemically administered pharmacological agents in a large group of patients with epilepsy, together with the relatively high incidence of serious idiosyncratic or intolerable dose-dependent adverse effects, including exacerbation of seizures, and to decrease the risk of injury and the psychosocial burden resulting from their unpredictability. The medical, psychosocial, and economic benefits that will be derived from achieving these objectives are salutary and self-evident to patients, their care-givers, and healthcare providers.