Status epilepticus (SE) treatment strategies vary substantially from one institution to another due to the lack of data to support one treatment over another. To provide guidance for the acute treatment of SE in critically ill patients, the Neurocritical Care Society organized a writing committee to evaluate the literature and develop an evidence-based and expert consensus practice guideline. Literature searches were conducted using PubMed and studies meeting the criteria established by the writing committee were evaluated. Recommendations were developed based on the literature using standardized assessment methods from the American Heart Association and Grading of Recommendations Assessment, Develop- ment, and Evaluation systems, as well as expert opinion when sufficient data were lacking.

/pdf/guidelines-for-the-evaluation-and-management-of-status-3h3cqurhgk.pdf

Guidelines for the Evaluation and Management of Status Epilepticus

A set of related medical disorders that lack a proper classification system and diagnostic criteria is like a society without laws. The result is incoherence at best, chaos at worst. For this reason, the International Classification of Headache Disorders (ICHD) is arguably the single most important breakthrough in headache medicine over the last 50 years. The ICHD identifies and categorizes more than a hundred different kinds of headache in a logical, hierarchal system. Even more important, it has provided explicit diagnostic criteria for all of the headache disorders listed. The ICHD quickly became universally accepted, and criticism of the classification has been minor relative to that directed at other disease classification systems. Over the 20 years following publication of the first edition of the ICHD, headache research has rapidly accelerated despite sparse allocation of resources to that effort. In summary, the ICHD has attained widespread acceptance at the international level and has substantially facilitated both clinical research and clinical care in the field of headache medicine.

International Classification of Headache Disorders

The representation of pain in the cerebral cortex is less well understood than that of any other sensory system. However, with the use of magnetic resonance imaging and positron emission tomography in humans, it has now been demonstrated that painful heat causes significant activation of the contralateral anterior cingulate, secondary somatosensory, and primary somatosensory cortices. This contrasts with the predominant activation of primary somatosensory cortex caused by vibrotactile stimuli in similar experiments. Furthermore, the unilateral cingulate activation indicates that this forebrain area, thought to regulate emotions, contains an unexpectedly specific representation of pain.

https://science.sciencemag.org/content/sci/251/4999/1355.full.pdf

Multiple representations of pain in human cerebral cortex

https://biblio.ugent.be/publication/8650534/file/8672654.pdf

Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014–2018)

Pain is a diverse sensory and emotional experience that likely involves activation of numerous regions of the brain. Yet, many of these areas are also implicated in the processing of nonpainful somatosensory information. In order to better characterize the processing of pain within the human brain, activation produced by noxious stimuli was compared with that produced by robust innocuous stimuli. Painful heat (47-48 degrees C), nonpainful vibratory (110 Hz), and neutral control (34 degrees C) stimuli were applied to the left forearm of right-handed male subjects. Activation of regions within the diencephalon and telencephalon was evaluated by measuring regional cerebral blood flow using positron emission tomography (15O-water-bolus method). Painful stimulation produced contralateral activation in primary and secondary somatosensory cortices (SI and SII), anterior cingulate cortex, anterior insula, the supplemental motor area of the frontal cortex, and thalamus. Vibrotactile stimulation produced activation in contralateral SI, and bilaterally in SII and posterior insular cortices. A direct comparison of pain and vibrotactile stimulation revealed that both stimuli produced activation in similar regions of SI and SII, regions long thought to be involved in basic somatosensory processing. In contrast, painful stimuli were significantly more effective in activating the anterior insula, a region heavily linked with both somatosensory and limbic systems. Such connections may provide one route through which nociceptive input may be integrated with memory in order to allow a full appreciation of the meaning and dangers of painful stimuli. These data reveal that pain-related activation, although predominantly contralateral in distribution, is more widely dispersed across both cortical and thalamic regions than that produced during innocuous vibrotactile stimulation. This distributed cerebral activation reflects the complex nature of pain, involving discriminative, affective, autonomic, and motoric components. Furthermore, the high degree of interconnectivity among activated regions may account for the difficulty of eliminating pathological pain with discrete CNS lesions.

https://www.jneurosci.org/content/jneuro/14/7/4095.full.pdf

Distributed processing of pain and vibration by the human brain.

Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction that occurs secondary to infection in the body without overt CNS infection. SAE is frequently encountered in critically ill patients in intensive care units, and in up to 70% of patients with severe systemic infection. The severity of SAE can range from mild delirium to deep coma. Seizures and myoclonus are infrequent and cranial nerves are almost always spared, but most severe cases have an associated critical illness neuromyopathy. Development of SAE probably involves a number of mechanisms that are not mutually exclusive and vary from patient to patient. Substantial neurological and psychological morbidities often occur in survivors. Mortality is almost always due to multiorgan failure rather than neurological complications, and is almost 70% in patients with severe SAE. Further research into the pathophysiology, management and prevention of SAE is needed. This Review discusses the epidemiology and clinical presentation of SAE. Recent evidence for SAE pathophysiology is outlined and a diagnostic approach to patients with this syndrome is presented. Lastly, prognosis and management of SAE is discussed.

/pdf/sepsis-associated-encephalopathy-12t50uhbmq.pdf

Sepsis-associated encephalopathy

Background Refractory status epilepticus (RSE) is defined as continued seizures after 2 or 3 antiepileptic drugs have failed. Several intravenous agents have been used for RSE; however, problems occur with their toxicity and/or effectiveness. Objective To report our experience with inhalational anesthesia (IA) in patients who were refractory to other antiepileptic drugs. Design, Setting, and Participants Retrospective review during a 4-year period of patients with RSE treated with isoflurane and/or desflurane. Main Outcome Measure Efficacy of IA on therapy in terminating RSE. Results Seven patients (4 male) aged 17 to 71 years received 7 to 15 (mean, 10) antiepileptic drugs in addition to IAs. The IAs were initiated after 1 to 103 (mean, 19) days of RSE and were used for a mean ± SD 11 ± 8.9 days. All patients received isoflurane, and 1 patient in addition received desflurane anesthesia 21 days after the onset of RSE for a total of 19 days. Regardless of seizure type, isoflurane and desflurane consistently stopped epileptic discharges with adequate, sustained electroencephalographic burst suppression within minutes of initiating IA therapy. Four patients had good outcomes, 3 died (1 of acute hemorrhagic leukoencephalitis, 1 of bowel infarction, and 1 of toxic encephalopathy, who remained in a persistent vegetative state until death 5.5 months after the onset of seizures). Complications during IA therapy included hypotension (7/7), atelectasis (7/7), infections (5/7), paralytic ileus (3/7), and deep venous thrombosis (2/7). No patient developed renal or hepatic dysfunction. Conclusions Isoflurane and desflurane adequately suppressed RSE in all cases. Complications were common, but mortality and long-term morbidity were related to the underlying disease and duration of RSE. Prolonged use of isoflurane and desflurane is well tolerated.

https://jamanetwork.com/journals/jamaneurology/articlepdf/786375/NOC30344.pdf

Treatment of Refractory Status Epilepticus With Inhalational Anesthetic Agents Isoflurane and Desflurane

Systemic sepsis commonly produces brain dysfunction, sepsis-associated encephalopathy, which can vary from a transient, reversible encephalopathy to irreversible brain damage. The encephalopathy in the acute phase clinically resembles many metabolic encephalopathies: a diffuse disturbance in cerebral function with sparing of the brain stem. The severity of the encephalopathy, as reflected in progressive EEG abnormalities, often precedes then parallels dysfunction in other organs. Recent research has revealed a number of potentially important, non-mutually exclusive, mechanisms that have therapeutic implications.

Progress in clinical neurosciences: sepsis-associated encephalopathy: evolving concepts.

EEG morphology of partial epileptic seizures

Out of 858 epileptic patients, 24 had painful seizures. Three distinct groups emerged: (1) those with unilateral pain in the face, arm, leg or trunk (Unilateral Group)--10 cases; (2) a Cephalic Group with pain restricted to the head--11 cases; and (3) an Abdominal Group with central abdominal pain--3 cases. Unilateral pain consistently implicated ictal involvement of the contralateral rolandic region at the time of pain. In most cases it was probably due to involvement of the primary somatosensory cortex (SI). Cephalic pain did not localize the site of seizure origin. In most cases it probably arose by a vascular mechanism. Abdominal ictal pain reflected temporal lobe epileptic activity in our cases. The mechanism of its production is uncertain, but it is unlikely to be due to a peripheral (for example gastrointestinal) mechanism.

G. Bryan Young

Papers

Sepsis-associated encephalopathy

Treatment of Refractory Status Epilepticus With Inhalational Anesthetic Agents Isoflurane and Desflurane

Progress in clinical neurosciences: sepsis-associated encephalopathy: evolving concepts.

EEG morphology of partial epileptic seizures

Painful epileptic seizures