Martin Holtkamp

Predictors and prognosis of refractory status epilepticus treated in a neurological intensive care unit

Objective: To assess risk factors and prognosis in patients with refractory status epilepticus (RSE). Methods: We retrospectively analysed all episodes of status epilepticus (SE) treated between 1993 and 2002 on the neurological intensive care unit (NICU) of the Charité-Universitätsmedizin Berlin. The predictive and prognostic features of RSE were compared with non-RSE (NRSE). All patients with “de novo” SE were followed up to identify the possible development of post-SE symptomatic epilepsy. Results: A total of 83 episodes fulfilled our criteria of SE. Of these 43% were refractory to first line anticonvulsants. The mean age of patients with SE was 53.3 (SD 19) years, with only two patients younger than 18 years. Encephalitis was significantly more often the primary cause in RSE (p<0.05), whereas low levels of antiepileptic drugs were significantly more often associated with NRSE (p<0.001). Hyponatraemia within the first 24 hours after onset of status activity was significantly more often associated with RSE (p<0.05). In RSE, compared with NRSE, significantly longer duration of seizure activity (p<0.001), more frequent recurrence of epileptic activity within the first 24 hours after the end of seizure activity (p<0.001), longer stay in the NICU and in hospital (p<0.001 and p<0.01, respectively), and more frequent development of symptomatic epilepsy (p<0.05) were seen. Conclusions: SE treated in the NICU is frequently refractory to first line anticonvulsant drugs. Encephalitis is a predictor for RSE, which is associated with markedly poor outcome, in particular, the development of post-SE symptomatic epilepsy. Thus prevention of this most severe form of SE should be the primary target of treatment of SE.

Hemicraniectomy in elderly patients with space occupying media infarction: improved survival but poor functional outcome

OBJECTIVE To assess the survival rate and functional outcome in elderly patients with space occupying supratentorial infarction who underwent hemicraniectomy compared with those who received medical treatment alone. METHODS All patients older than 55 years with space occupying middle cerebral artery (MCA) infarction treated in our clinic between January 1998 and July 1999 were included in this retrospective analysis. Patients were eligible for decompressive surgery if they were younger than 75 and had no severe comorbidity. Hemicraniectomy was performed regardless of the affected hemisphere. All patients were followed up for assessment of functional outcome; data were assessed according to the Barthel index and modified Rankin scale and cover a period of 3 to 9 months after infarction. RESULTS Twelve out of 24 patients underwent hemicraniectomy. Eight patients who were operated on survived; only one patient died of transtentorial herniation, three other deaths were due to medical complications. None of the survivors had a Barthel score above 60 or a Rankin score below 4. Nine out of 12 medically treated patients died of transtentorial herniation, one patient died of medical complications. The two surviving patients had a Barthel score below 60 and a Rankin score of 4. CONCLUSIONS Craniectomy in elderly patients with space occupying MCA infarction improves survival rates compared with medical treatment alone. However, functional outcome and level of independence are poor. Craniectomy in elderly patients should not be performed unless a prospective randomised trial proves beneficial.

Non-convulsive status epilepticus in adults: clinical forms and treatment

Non-convulsive status epilepticus (NCSE) is one of the great diagnostic and therapeutic challenges of modern neurology. Because the clinical features of this disorder may be very discrete and sometimes hard to differentiate from normal behaviour, NCSE is usually overlooked and consequently not treated properly. It is important to be familiar with the clinical subtypes such as absence, simple and complex partial, and subtle status epilepticus because each requires tailored management. In order to improve overall care of patients with NCSE, strict diagnostic criteria are needed that should be based on clinical alterations and ictal electroencephalographic changes. NCSE should be terminated rapidly to prevent patients from serious injuries, particularly if consciousness is impaired.

The management of refractory generalised convulsive and complex partial status epilepticus in three European countries: a survey among epileptologists and critical care neurologists

Objective: To survey the current clinical treatment of refractory status epilepticus and to identify steps in its management which may need further investigation. Methods: Epileptologists and critical care neurologists were surveyed using a standardised postal questionnaire. Results: Sixty three of 91 participants (69%) returned the questionnaires. Two thirds of the respondents applied another non-anaesthetising anticonvulsant after failure of first line drugs. General anaesthesia for ongoing complex partial status epilepticus (CPSE) was part of the therapeutic regimen of 75% of the interviewees. A non-barbiturate as general anaesthetic of first choice was used by 42%. Up to 70% titrated the anaesthetic to achieve a burst suppression pattern in the electroencephalogram, indicating deep sedation, and 94% reduce anaesthesia within 48 hours. Conclusions: The management of refractory status epilepticus is heterogeneous in many aspects, even among clinicians who are most familiar with this severe condition. Randomised trials are needed to compare the efficacy, side effects, optimal duration, and depth of general anaesthesia.

Anticonvulsant properties of hypothermia in experimental status epilepticus.

Status epilepticus in patients often does not respond to first-line anticonvulsants, and subsequent treatment escalation with continuous intravenous anesthetics may be associated with significant side-effects. Therefore, alternative treatment regimens are urgently needed. Hypothermia has been shown to reduce excitatory transmission and may thus serve as an interesting adjunct in the management of status epilepticus. In the current experiments, three treatment groups were compared. Animals with self-sustaining status epilepticus were treated with external cooling for 3 h, with low-dose diazepam, or with a combination of both. The effect of these regimens on epileptic activity was compared with untreated controls. Animals that underwent cooling were rewarmed, and all animals were monitored for 5 h to assess occurrence and severity of motor seizures and frequency and amplitude of spontaneous epileptic discharges. Cooling alone significantly reduced number and severity of motor seizures but did not alter epileptic discharges. Cooling in addition to low-dose diazepam significantly diminished amplitudes and frequencies of epileptic discharges, while diazepam alone had only a minor reducing effect on discharge amplitudes. However, at later stages of status epilepticus, diazepam significantly reduced motor seizures. Following rewarming, the discharge frequency tended to increase again, suggesting partial reversibility. The current experiments show that in status epilepticus hypothermia exhibits anticonvulsant effects which are most pronounced if co-administered with low-dose diazepam. The results still require confirmation in other animal models and also clinical studies are urgently needed. However, our data indicate that cooling could well become a future adjunct in the treatment of status epilepticus in patients.

Ketamine successfully terminates malignant status epilepticus

A 22-year-old woman with mitochondriopathy and pre-existing epilepsy developed status epilepticus (SE) not responding to benzodiazepines, phenytoin, thiopental, and propofol. SE was terminated within days after supplemental administration of continuous ketamine infusion to midazolam. The case suggests strong anticonvulsant properties of ketamine even after failure of GABAergic anesthetics, likely due to increased NMDA receptor expression with ongoing seizure activity. Thus, ketamine should be incorporated into therapeutic regimens for difficult-to-treat SE.

Prognosis of juvenile myoclonic epilepsy 45 years after onset: Seizure outcome and predictors

Objectives: Juvenile myoclonic epilepsy (JME) is the most common idiopathic generalized epilepsy subsyndrome, contributing to approximately 3% to 11% of adolescent and adult cases of epilepsy. However, little is known about the long-term medical evolution of this clinical entity. The aim of this study was to analyze long-term outcome in a clinically well-defined series of patients with JME for seizure evolution and predictors of seizure outcome. Methods: In this retrospective cohort study, we analyzed seizure outcome in 66 patients who had JME, were treated at the Department of Neurology, Charité–Universitätsmedizin Berlin, and were initially diagnosed by a single senior epileptologist. Results: After a mean follow-up time of 44.6 years (20–69 years), 59.1% of patients remained free of seizures for at least 5 years before the last contact. Among the seizure-free patients, 28 (71.8%) were still taking antiepileptic drugs and 11 (28.2%) were off medication for at least the last 5 years. We identified manifestation of additional absence seizures at onset of JME as an independent predictor of an unfavorable outcome regarding seizure freedom. Conclusions: A significant proportion of patients with JME were seizure-free and off antiepileptic drug therapy in the later course of their disorder. Patients with JME and additional absence seizures might represent a different JME subtype with a worse outcome.

Incidence and predictors of post‐stroke epilepsy

Stroke is the leading cause of seizures and epilepsy in the elderly. The aim of this study was to assess the incidence of post‐stroke epilepsy (PSE) based on the revised epilepsy definition of the International League Against Epilepsy (ILAE) in a population‐based study and to describe possible predictors.

Nonconvulsive status epilepticus: a diagnostic and therapeutic challenge in the intensive care setting.

Nonconvulsive status epilepticus (NCSE) comprises a group of syndromes that display a great diversity regarding response to anticonvulsants ranging from virtually self-limiting variants to entirely refractory forms. Therefore, treatment on intensive care units (ICUs) is required only for a selection of cases. The aetiology and clinical form of NCSE are strong predictors for the overall prognosis. Absence status epilepticus is commonly seen in patients with idiopathic generalized epilepsy and is rapidly terminated by low-dose of benzodiazepines. The management of complex partial status epilepticus is straightforward in patients with pre-existing epilepsy, but poses major problems if occurring in the context of acute brain lesions. Subtle status epilepticus represents the late stage of undertreated previous overt generalized convulsive status epilepticus and always requires aggressive ICU treatment. Within the intensive care setting, the diagnostic challenge may be seen in the difficulty in delineating nonepileptic conditions such as posthypoxic, metabolic or septic encephalopathies from NCSE. Although all important forms are considered, the focus of this review lies on clinical presentations and electroencephalogram features of comatose patients treated on ICUs and possible diagnostic pitfalls.

Low Sensitivity of Serum Procalcitonin in Bacterial Meningitis in Adults

Several studies have suggested high predictive values of serum procalcitonin (PCT) for the discrimination of bacterial and viral meningitis in children and adults. Here, we report PCT serum concentrations in 12 adults suffering from bacterial meningitis. PCT on admission was normal ( < or = 500 pg/ml) in 3 and between 500 and 1,000 pg/ml in 2 patients without evidence of concurrent bacterial infections. Conversely, in 5 patients with PCT concentrations between 2,268 and 38,246 pg/ml other infections were present. PCT concentrations were higher with typical meningitis agents (pneumococci and meningococci 12,679 +/- 13,092 pg/ml vs. other bacteria 4048 +/- 9187 pg/ml, p = 0.041) whilst in nosocomial bacterial meningitis after neurosurgery (n = 3) serum PCT remained normal. We believe that PCT is of limited diagnostic value in adults suffering from bacterial meningitis, especially in cases due to unusual agents or of nosocomial origin. Elevated PCT in bacterial meningitis may indicate the presence of bacterial inflammation outside the central nervous system.