Cerebrovascular Autoregulation Monitoring in the Management of Adult Severe Traumatic Brain Injury: A Delphi Consensus of Clinicians.

BACKGROUND: Several methods have been proposed to measure cerebrovascular autoregulation (CA) in traumatic brain injury (TBI), but the lack of a gold standard and the absence of prospective clinical data on risks, impact on care and outcomes of implementation of CA-guided management lead to uncertainty. AIM: To formulate statements using a Delphi consensus approach employing a group of expert clinicians, that reflect current knowledge of CA, aspects that can be implemented in TBI management and CA research priorities. METHODS: A group of 25 international academic experts with clinical expertise in the management of adult severe TBI patients participated in this consensus process. Seventy-seven statements and multiple-choice questions were submitted to the group in two online surveys, followed by a face-to-face meeting and a third online survey. Participants received feedback on average scores and the rationale for resubmission or rephrasing of statements. Consensus on a statement was defined as agreement of more than 75% of participants. RESULTS: Consensus amongst participants was achieved on the importance of CA status in adult severe TBI pathophysiology, the dynamic non-binary nature of CA impairment, its association with outcome and the inadvisability of employing universal and absolute cerebral perfusion pressure targets. Consensus could not be reached on the accuracy, reliability and validation of any current CA assessment method. There was also no consensus on how to implement CA information in clinical management protocols, reflecting insufficient clinical evidence. CONCLUSION: The Delphi process resulted in 25 consensus statements addressing the pathophysiology of impaired CA, and its impact on cerebral perfusion pressure targets and outcome. A research agenda was proposed emphasizing the need for better validated CA assessment methods as well as the focused investigation of the application of CA-guided management in clinical care using prospective safety, feasibility and efficacy studies.

Research priorities in neurocritical care.

This summary of the last session of the First Neurocritical Care Research Conference reviews the discussions about research priorities in neurocritical care. The first presentation reviewed current projects funded by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health and potential models to follow including an independent Neurocritical Care Network or the creation of such a network with the goal of collaborating with already existing ones. Experienced neurointensivists then presented their views on the most common and important research questions that need to be answered and investigated in the field. Finally, utility of clinical registries was discussed emphasizing their importance as hypothesis generators. During the group discussion, interests in comparative effectiveness research, the use of physiological endpoints from monitoring and alternate trial design were expressed.

Prevalence of psychologic disorders after surgical treatment of seizures.

To investigate whether surgical treatment of refractory epilepsy is associated with increased risk for serious psychopathology, 25 treated patients were compared with 25 current candidates for surgery matched on demographic and neuroepileptic characteristics. Diagnoses were made by the National Institute of Mental Health Diagnostic Interview Schedule. No differences between groups in lifetime or point prevalence rates were significant. The rate of psychosis in the postoperative group (8%) approximated the lower estimates in previous studies. Thus, surgical treatment of seizures did not increase the risk for psychopathology. However, patients with temporal lobe electroencephalogram foci or tumor as the epileptogenic lesion were more likely to have serious disorders than other patients. Also, anxiety disorders were more prevalent in our patient groups than in the general population.

Disordered swallowing due to a syrinx: correction by shunting.

Disturbed deglutition is common in diseases of the brainstem and lower cranial nerves, but little is known about the mechanisms involved. We studied a 49-year-old man with symptoms of syringomyelia and syringobulbia lasting 7 years. Esophageal motility studies showed inability to initiate swallowing, esophageal hypomotility, and absence of the lower esophageal sphincter. After decompression of the syrinx by shunting, these abnormalities were corrected, and the patient could once again eat without aspiration. Medullary dysfunction caused by the syrinx was probably responsible for the swallowing difficulties.

New anticonvulsant drugs. Focus on flunarizine, fosphenytoin, midazolam and stiripentol.

In the past decade, several new antiepileptic drugs have been tested. Most recently, 5 new antiepileptic drugs have been launched onto European and US markets. These include vigabatrin, oxcarbazepine and lamotrigine in Europe, and felbamate and gabapentin in the US. In addition to these, 3 additional drugs are in the clinical investigational stage: flunarizine, fosphenytoin and stiripentol. A fourth agent is midazolam, which was originally introduced in 1986, but recently has shown effectiveness in the treatment of status epilepticus. Flunarizine is a selective calcium channel blocker that has shown anticonvulsant properties in both animal and human studies. It is a long-acting anticonvulsant that clinical studies have shown to have effects similar to those of phenytoin and carbamazepine in the treatment of partial, complex partial and generalised seizures. Fosphenytoin was developed to eliminate the poor aqueous solubility and irritant properties of intravenous phenytoin. It is rapidly converted to phenytoin after intravenous or intramuscular administration. In clinical studies, this prodrug showed minimal evidence of adverse events and no serious cardiovascular or respiratory adverse reactions. It may have a clear advantage over the present parenteral formulation of phenytoin. Midazolam is a benzodiazepine that is more potent than diazepam as a sedative, muscle relaxant and in its influence on electroencephalographic measures. It has been shown to be an effective treatment for refractory seizures in status epilepticus. Stiripentol has anticonvulsant properties as well as the ability to inhibit the cytochrome P450 system. There are significant metabolic drug interactions between stiripentol and phenytoin, carbamazepine and phenobarbital (phenobarbitone). Stiripentol has been studied in patients with partial seizures, refractory epilepsy and refractory absence seizures with some efficacious results.

Changes in severe accidental tetanus mortality in the ICU during two decades in Brazil.

INTRODUCTION: Tetanus is still a significant health hazard in developing countries, with high associated mortality. OBJECTIVE: Describe the management of patients with severe tetanus in intensive care units (ICUs), in two different periods. SETTING: ICUs of two general hospitals. DESIGN: Concurrent cohort study. METHODS: Follow-up of all patients hospitalized with the diagnosis of severe tetanus in the ICUs from October 1981 to March 2001. We collected data prospectively, regarding the site of injury, clinical features, frequent clinical and infectious complications, concomitant illnesses, and mortality. The patients were divided into two groups according to the treatment protocol used; before 1993 and after 1993. RESULTS: There were 126 patients in group 1 (93 males) with a mean age of 39.0 +/- 18.8 years. There were 110 patients in group 2 (95 males) with a mean age of 48.4+/-17.8 years. Incubation period, onset period, and symptomatic period were higher in group 2 ( P < or = 0.02). The duration of neuromuscular junction blockade, benzodiazepine administration, mechanical ventilation, and ICU stay were longer in group 2, P < 0.001. Infectious complications were more frequent in group 2 ( P < 0.001). The mortality rate in group 1 was 36.5% and in group 2, 18.0% ( P = 0.002). Mortality was directly associated with symptomatic period, acute renal failure cardiac arrest and hypotension, and inversely associated with onset period in the multivariate analyses. CONCLUSIONS: The reduced mortality in severe accidental tetanus patients in group 2 is probably related to advances in ICU management, despite the higher incidence of infectious complications, which are probably related to the longer ICU stay.

Neurologic emergencies.

This article considers the rapid assessment and initial management of several neurologic emergencies--altered consciousness, increased intracranial pressure, stroke, status epilepticus, acute neurogenic respiratory failure, acute autonomic instability, the neuroleptic malignant syndrome, and spinal cord compression.

Recurrent intracranial epithelioid hemangioendothelioma associated with multicentric disease of liver and heart: case report.

Epithelioid hemangioendothelioma is an unusual vascular neoplasm with prominent cytoplasmic vacuolization representing primitive lumen formation. A case is presented of this unique vascular neoplasm in a woman with a seizure disorder who had cardiac, hepatic, and recurrent nervous system lesions. To our knowledge, this is the third known case of intracranial epithelioid hemangioendothelioma. Emphasis is placed on the indolent course of this rare neoplasm, with a recommendation for aggressive surgical treatment and diligent follow-up.

Multiple subpial transection: a new approach to the surgical treatment of focal epilepsy.

A new operative approach has been designed for the relief of medically intractable focal epilepsy. It is intended particularly to be used in those cases where the epileptogenic lesion lies in "unresectable" cortex; that is, those cerebral regions subserving speech, memory, and primary motor and sensory function. The procedure is based upon experimental evidence indicating 1) that epileptogenic discharge requires substantial side-to-side or horizontal interaction of cortical neurons, and 2) that the major functional properties of cortical tissue depend upon the vertical fiber connections of the columnar units. The technique requires severing of tangential intracortical fibers while preserving the vertical fiber connections of both incoming and outgoing nerve pathways and of the penetrating blood vessels which also have a vertical orientation. In this study, the effect of multiple subpial transection was assessed on both function and seizure control. The effect on function was reviewed in 32 cases; only 20 cases were evaluated with respect to seizure control, since a follow-up period of 5 years or more (5 to 22 years) is required before conclusions can be drawn. Multiple subpial transection was applied to the precentral gyrus in 16 cases, the postcentral gyrus in six, Broca's area in five, and Wernicke's area in five. With respect to function, the major finding was that none of the 32 patients has suffered a clinically significant behavioral deficit (although subtle deficits could be detected by careful neurological examination). Complete control of seizures has been obtained in 11 (55%) of the 20 cases evaluated. Nine patients developed recurrent seizures consequent to progressive disease unsuspected before operation (Rasmussen's encephalitis in five, tumor in three, and subacute sclerosing panencephalitis in one). In none of these cases, however, did the recurrent seizures arise in the transected zone. Thus, the results indicate that multiple subpial transection is about as effective as standard excisional therapy, and can be successfully employed when epileptogenic lesions encroach upon cortical territories, the removal of which would be functionally incapacitating.

Convulsive disorders: status epilepticus.

Status epilepticus (SE) remains one of the most serious disorders affecting the central nervous system. Recent progress in understanding the mechanisms of the brain damage produced by SE make even more apparent the need to quickly terminate this condition, prevent its recurrence, and treat its complications. Intracellular calcium concentrations rise, prompting a cascade of excitotoxic consequences. Therapy for SE currently consists of agents which stop seizures (benzodiazepines, phenytoin, barbiturates). This review discusses their use in SE.

Therapy for status epilepticus.

Recent advances in understanding the pathophysiology of status epilepticus (SE) have increased the urgency with which the study of this disorder should be approached. The clinical pharmacology of anticonvulsants useful in treating SE is reviewed and their application in several of the different types of SE is discussed. The potential for future advances is briefly considered.

Prolonged survival following the inadvertent intrathecal administration of vincristine: clinical and electrophysiologic analyses.

A 23-year-old man with a lymphoblastic lymphoma accidentally received 2.0 mg of vincristine intrathecally instead of intravenously. Although he underwent immediate CSF drainage, symptoms of an ascending myeloencephalopathy developed at 48 h. This progressed to coma, initially with a diffusely slow EEG, which evolved into alpha coma. He also developed a left frontal focus of epileptiform activity. He was transferred to our institution 1 month later. His court-appointed guardian refused to allow discontinuation of supportive treatment; therefore, the evolution of the disorder can be followed for 12 months. Although alpha coma remained the predominant pattern, some EEG evolution did occur, with a progressive decrease in amplitude being most prominent. An increase in amplitude in the 10th month was accompanied by the return of some nystagmoid eye movements. The patient's lymphoma then recurred, and further treatment was not attempted. This tragic case, in which transient exposure to a microtubular poison produced severe CNS toxicity, allows some insights into the mechanisms of alpha coma.

Central nervous system involvement in Rickettsial diseases.

The Rickettsia are obligate intracellular parasites that are usually spread to humans by insects and typically produce vasculitides. The prototypic rickettsial disorder in the United States is Rocky Mountain spotted fever (RMSF). The differential diagnosis of RMSF and related disorders includes other conditions that produce vasculitis, most importantly meningococcemia. The rickettsial disorders are usually treated effectively with tetracycline derivatives.

Status epilepticus.

Status epilepticus is defined as a condition characterized by epileptic seizure prolonged or repeated so as to produce a lasting epileptic state. It is estimated that status epilepticus occurs in 50,000 to 60,000 individuals in the United States, with one third to one half of episodes occurring in patients with established epilepsy.

Status epilepticus.

Generalised convulsive status epilepticus is a medical emergency. Knowledge of the pathophysiology of status epilepticus and the pharmacology of the medications used to treat it allow one to devise a rational protocol for management. Anticipation of medical complications facilitates intervention when required. Prognosis depends largely on the underlying causes.

Status epilepticus in children and adults.

Status epilepticus (SE) in children and adults is one of the most common neurology problems confronting the intensivist. Recognition of SE is usually straightforward, but may be complicated by the effects of other diseases or therapies. Emergent treatment is necessary to prevent further brain damage. This article reviews protocols for standard treatments of SE patients and includes recommendations for the management of refractory SE.

Epilepsy.

"Epilepsy" describes a heterogenous group of disorders bound together by their tendency to produce seizures. Recent advances in the basic neurosciences provide new insights into the pathophysiology and treatment of seizures. In the last decade, revisions of the classification schemata have led to improvements in the recognition of seizure types and of different epilepsies and epileptic syndromes. The clinical utility of these definitions is apparent in diagnosis, therapy, prognostication, and genetic counseling. A plan for the diagnostic evaluation of patients with epilepsy is presented. The therapeutic options for seizure treatment are reviewed including the withdrawal of anticonvulsants. Patients who should probably not be treated with anticonvulsants are identified. Psychological and life-style issues in the management of seizure patients are considered. The concept of adequate control is discussed. Surgical management, an increasingly employed therapeutic modality, is described.

Tetanus: pathophysiology, management, and prophylaxis.

As tetanus has become a rare disease in the developed world, physicians have become less comfortable with its diagnosis and management. The extent of adequate antitetanus immunity in the adult population, especially the elderly, is waning, in great measure because primary care physicians have not made prophylaxis a priority in their routine encounters with patients. Furthermore, as the population of immunocompromised hosts grows, an increasing percentage of our patients may not respond to standard active immunization routines. Unless these trends are reversed, we face a substantial increase in the incidence of this dread disorder. Tetanus is also of interest as a relatively simple model of disordered motor control that can instruct us in the management of the many more common causes of neurogenic muscular rigidity. The toxin produced by Clostridium tetani finds increasing use in laboratories investigating brain function as well. Clinical tetanus is divided into four symptomatic types: generalized tetanus, local tetanus, cephalic tetanus, and neonatal tetanus. This monograph discusses the diagnostic aspects of each type of tetanus, its pathophysiology, diagnosis, differential diagnosis, and treatment. Preventing tetanus should be a high priority for all primary care physicians. Active immunization with tetanus toxoid is remarkably effective and safe. Passive immunization with human tetanus immune globulin is indicated in certain circumstances, which are discussed below.