Association Between Dose Escalation of Anesthetics and Outcomes in Patients With Refractory Status Epilepticus.

BACKGROUND AND OBJECTIVES: To investigate the association between dose escalation of continuously administered IV anesthetics and its duration with short-term outcomes in adult patients treated for refractory status epilepticus (RSE). METHODS: Clinical and electroencephalographic data of patients with RSE without hypoxic-ischemic encephalopathy who were treated with anesthetics at a Swiss academic medical center from 2011 to 2019 were assessed. The frequency of anesthetic dose escalation (i.e., dose increase) and its associations with in-hospital death or return to premorbid neurologic function were primary endpoints. Multivariable logistic regression analysis was performed to identify associations with endpoints. RESULTS: Among 111 patients with RSE, doses of anesthetics were escalated in 57%. Despite patients with dose escalation having a higher morbidity (lower Glasgow Coma Scale [GCS] score at status epilepticus [SE] onset, more presumably fatal etiologies, longer duration of SE and intensive care, more infections, and arterial hypotension) as compared with patients without, the primary endpoints did not differ between these groups in univariable analyses. Multivariable analyses revealed decreased odds for death with dose escalation (odds ratio 0.09, 95% CI 0.01-0.86), independent of initial GCS score, presumably fatal etiology, SE severity score, SE duration, and nonconvulsive SE with coma, with similar functional outcome among survivors compared with patients without dose escalation. DISCUSSION: Our study reveals that anesthetic dose escalation in adult patients with RSE is associated with decreased odds for death without increasing the proportion of surviving patients with worse neurofunctional state than before RSE. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that anesthetic dose escalation decreases the odds of death in patients with RSE.

Injuring neurons induces neuronal differentiation in a population of hippocampal precursor cells in culture.

A novel population of hippocampal precursor cells (HPCs) that can be induced to differentiate into astrocytes and oligodendrocytes can be derived from hippocampal cultures grown in serum-free media. The HPCs are PDGF-responsive, do not proliferate with bFGF, and grow as sheets of cells rather than gathering into neurospheres. The HPCs share many markers (A2B5, GD3, poly-sialylated neuronal common adhesion molecule (PSA-NCAM), and NG2) with oligodendrocyte precursor cells (OPCs). The HPCs do not express markers for mature neurons, astrocytes, or oligodendrocytes. Like OPCs, the HPCs differentiate into glial fibrillary acidic protein (GFAP)+ astrocytes and GalC+ oligodendrocytes with the addition of bone morphogenetic protein-4 (BMP-4) and triiodothyronine (T3), respectively. They do not differentiate into neurons with the addition or withdrawal of basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF), or retinoic acid (RA). These HPCs can be stimulated to differentiate into neuron-like cells by the induction of neuronal injury or cell death in nearby cultured neurons or by conditioned medium from injured neuronal cultures. Under these conditions, HPCs grow larger, develop more extensive dendritic processes, become microtubule-associated protein-2-immunoreactive, express large voltage-dependent sodium currents, and form synaptic connections. The conversion of endogenous pluripotent precursor cells into neurons in response to local brain injury may be an important component of central nervous system homeostasis.

Rituximab stabilizes multifocal motor neuropathy increasingly less responsive to IVIg.

The authors report a patient with anti-GM(1) antibody-negative multifocal motor neuropathy (MMN) who was increasingly less responsive to IV immunoglobulins (IVIgs). Five yearly courses of the monoclonal anti-CD20 antibody rituximab were well tolerated and extended the interval of IVIg administration from 7 to 12 days (corresponding to 42% reduction of IVIg) during this period. Rituximab may be a benefit for patients with MMN.

Brain tumor and seizures: pathophysiology and its implications for treatment revisited.

Seizures affect approximately 50% of patients with primary and metastatic brain tumors. Partial seizures have the highest incidence, followed by secondarily generalized, depending on histologic subtype, location, and tumor extent. The underlying pathophysiologic mechanisms of tumor-associated seizures are poorly understood and include theories of altered peritumoral amino acids, regional metabolism, pH, neuronal or glial enzyme and protein expression, as well as immunologic activity. An involvement of changed distribution and function of N-methyl-d-aspartate subclass of glutamate receptors also has been suggested. The often unpredictable responses to seizures after surgical tumor removal add substantial evidence that multiple factors are involved. The therapy of tumor-related seizures is far from perfect. Several factors contribute to these treatment difficulties, such as tumor growth and drug interactions; however, one of the main reasons for poor seizure control may result from the insufficient or even absent influence of the currently available antiepileptic drugs (AEDs) on most of the pathophysiologic mechanisms of tumor-related seizures. Studies are needed to elucidate more clearly the pathophysiologic mechanisms of tumor-related seizures and to identify and develop the optimal AEDs.

Diagnosis and Treatment of Nonconvulsive Status Epilepticus in an Intensive Care Unit Setting.

Nonconvulsive status epilepticus (NCSE) in adults is a heterogeneous epileptic emergency and includes absence status (AS), complex-partial status epilepticus (CPSE), and the status epilepticus of epileptic encephalopathy (SEEE). The latter seems to be strikingly frequent among patients in intensive care units (ICU). Diagnosis of NCSE is difficult, but has to be made quickly. It relies on clinical signs and a confirmation electroencephalography (EEG). According to the different etiologies and outcomes of AS, CPSE, and SEEE, treatment has to be individually adapted, but needs to follow some basic principles--treatment should take place in the ICU and be monitored by continuous EEG. With a few exceptions, the first drug is an intravenous benzodiazepine, mainly lorazepam. Intravenous fosphenytoin or phenytoin or valproate may follow next. If some forms of NCSE are resistant to first- and second-line treatments, single or combinations of anesthetics and enteral antiepileptic drugs (AEDs) may be added. This opinion is not evidence-based, and randomized controlled prospective trials to evaluate optimal treatment of NCSE are of first priority.