Stephan Rüegg

Background: Refractory status epilepticus (RSE) is the most severe manifestation of status epilepticus (SE), often requiring intensive care and therapeutic coma. It is associated with prolonged intensive care unit (ICU) and hospital stays, as well as increased morbidity and mortality. Treatment involves both intravenous anaesthetics and antiepileptic drugs (AEDs) that can be administrated intravenously, by nasogastric tube or by percutaneous endoscopic gastrostomy. Experience with some of the newer AEDs for the treatment of RSE is restricted and higher-class evidence regarding tolerability and efficacy is lacking. Topiramate is a potent broad-spectrum AED with several modes of action, including blockade of the ionotropic glutamatergic AMPA receptor, which is likely to be an important mechanism for the treatment of SE. While there is no commercially available intravenous formulation, topiramate can be administered enterally, which may make it suitable for the treatment of RSE. Objective: The objective of this study was to evaluate the tolerability, safety profile and efficacy of adjunctive and enterally administered topiramate in patients with RSE. Methods: A medical chart review was performed of all consecutive patients treated for RSE between August 2004 and December 2011 at the ICU of the University Hospital Basel (Basel, Switzerland). Results: 113 (43%) of all consecutive 268 patients with SE developed RSE. Of those, 35 (31%) were treated with topiramate. Median age was 60.5 years. Topiramate was used as an add-on treatment after 1–6 (median 4) prior administered AEDs had failed. It was introduced after a median of 2 (range 2–23) days for a duration of 1–24 (median 3) days. The response rate after topiramate administration as the third AED was 86% (6/7 patients), and remained stable at 67% after administration as the fourth, fifth, sixth or seventh AED when the groups of successfully and probably successfully treated patients were pooled. Overall, RSE was terminated in 71% of patients within 72 hours after first administration of topiramate, in 9% of patients, within 24 hours (none in the 800 mg/day group; 9% in the 400–799 mg/day group; and 11% in the Conclusion: Treatment with enterally administered topiramate was feasible, well tolerated and had a good safety profile in patients with RSE in this observational, single-centre, cohort study. Refractory SE was terminated in the majority of patients within 3 days after initiation of topiramate. Prospective studies are warranted to further evaluate topiramate for the treatment of RSE.

Introduction: The Glasgow Coma Scale (GCS) is the most widely used scoring system for comatose patients in intensive care. Limitations of the GCS include the impossibility to assess the verbal score in intubated or aphasic patients, and an inconsistent inter-rater reliability. The FOUR (Full Outline of UnResponsiveness) score, a new coma scale not reliant on verbal response, was recently proposed. The aim of the present study was to compare the inter-rater reliability of the GCS and the FOUR score among unselected patients in general critical care. A further aim was to compare the inter-rater reliability of neurologists with that of intensive care unit (ICU) staff. Methods: In this prospective observational study, scoring of GCS and FOUR score was performed by neurologists and ICU staff on 267 consecutive patients admitted to intensive care. Results: In a total of 437 pair wise ratings the exact inter-rater agreement for the GCS was 71%, and for the FOUR score 82% (P = 0.0016); the inter-rater agreement within a range of ± 1 score point for the GCS was 90%, and for the FOUR score 92% (P = ns.). The exact inter-rater agreement among neurologists was superior to that among ICU staff for the FOUR score (87% vs. 79%, P = 0.04) but not for the GCS (73% vs. 73%). Neurologists and ICU staff did not significantly differ in the inter-rater agreement within a range of ± 1 score point for both GCS (88% vs. 93%) and the FOUR score (91% vs. 88%). Conclusions: The FOUR score performed better than the GCS for exact inter-rater agreement, but not for the clinically more relevant agreement within the range of ± 1 score point. Though neurologists outperformed ICU staff with regard to exact inter-rater agreement, the inter-rater agreement of ICU staff within the clinically more relevant range of ± 1 score point equalled that of the neurologists. The small advantage in inter-rater reliability of the FOUR score is most likely insufficient to replace the GCS, a score with a long tradition in intensive care.

Das komplexe regionale Schmerzsyndrom (CRPS) ist gekennzeichnet durch einen charakteristischen stadienhaften Ablauf mit den Hauptsymptomen Schmerzen, trophischen und entzündlichen Veränderungen sowie Funktionseinschränkung bis -verlust. Während das letzte mit intensiver Physio- und Ergotherapie behandelt werden muss, können die ersten drei Symptome medikamentös beeinflusst werden: Hauptpfeiler der medikamentösen Therapie der neuropathischen Schmerzen sind Antidepressiva, Antiepileptika und Opioide, während die eigentlichen akuten nozizeptiven Schmerzen und die akute Entzündung auf nicht-steroidale Analgetika und Steroide ansprechen. Zusätzlich wirken auch Calcitonin und die Osteoklasten hemmenden Biphosphonate schmerzlindernd und knochenerhaltend. Der Einsatz von Sympathikolytika außerhalb von lokoregionalen Anästhesieverfahren (welche an anderer Stelle besprochen werden) ist umstritten. Allgemein gibt es im Gebiet der medikamentösen Schmerzbehandlung spezifisch des komplexen regionalen Schmerzsyndroms nur sehr geringe Evidenz; die meisten Erkenntnisse werden aus der Behandlung anderer chronischer neuropathischer Schmerzsyndrome (wie diabetische Polyneuropathie oder post-Zoster-Schmerzen) übernommen oder beruhen auf pathophysiologischen Überlegungen. The main symptoms of excruciating pain, trophic and inflammatory changes, as well as functional impairment of limbs are the hallmark of the complex regional pain syndrome (CRPS). While functional impairments have to be treated by physical and occupational therapy, the former three symptoms are amendable to drug treatment: antidepressants, antiepileptic drugs and opioids are the most important drug classes for alleviating neuropathic pain whereas acute nociceptive pain may be positively influenced by non-steroidal anti-inflammatory drugs and steroids. In addition, calcitonin and the biphosphonates inhibit osteoclasts and therefore loss of bone mass and may thus also reduce pain. The use of sympatholytic agents beyond locoregional anesthesia techniques (which are covered elsewhere in this issue) is not unequivocal. In general, the evidence level for treatment strategies specifically for the complex regional pain syndrome is very poor; most recommendations and algorithms rely on results derived from studies testing drugs against other conditions where chronic (neuropathic) pain is prevalent, like diabetic polyneuropathy or postherpetic neuralgia, or medications are used on the basis of pathomechanistic considerations.

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant muscle disorder, usually of late onset. OPMD is among the few triplet repeat diseases/ polyalanine (poly(A)) expansion diseases for which the function of the mutated gene is quite well established. The disease is characterised by slowly progressive bilateral ptosis, dysphagia and proximal limb weakness, appearing after the age of 40 years. Prevalence and incidence of OPMD are low, but the disease occurs all over the world. The pedigrees of two Swiss kindred have been previously reported in Switzerland. In the last 2 years, accumulation of newly diagnosed cases in North-West Switzerland have been observed, which suggests that OPMD may be more prevalent than previously thought. Primary care providers, opthalmologists and neurologists that are alert for the almost specific combination of clinical signs, together with the availability of reliable genetic testing may help to recognise currently undiagnosed patients. They can advance knowledge and the characterisation of the OPMD population in Switzerland. Since the number of disorders linked to poly(A) expansions is growing rapidly, the study of OPMD may contribute to the understanding of a large group of other developmental and degenerative diseases. On the basis of a patient with "classical" OPMD, this review summarises the clinical, therapeutic, epidemiological, pathomechanistic and genetic aspects of OPMD, provides practical information about the differential diagnosis of OPMD, and presents a survey of different investigational methods.

The authors report a patient with anti-GM₁ 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.

A 63-year-old woman had experienced increasing musculoskeletal pain of the trunk starting 20 years previously. She became unable to relax her muscles and had attacks of generalized stiffness and respiratory arrest, which were triggered by emotion, especially startle. Neurologic evaluations …

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.