Acta Neurologica Scandinavica. Supplementum

OBJECTIVES: The present paper summarizes and compares data from our studies on subjective and objective sleep quality and pain thresholds in tension-type headache (TTH), migraine, and controls. MATERIAL AND METHODS: In a blinded controlled explorative study, we recorded polysomnography (PSG) and pressure, heat, and cold pain thresholds in 34 controls, 20 TTH, and 53 migraine patients. Sleep quality was assessed by questionnaires, sleep diaries, and PSG. Migraineurs who had their recordings more than 2 days from an attack were classified as interictal while the rest were classified as either preictal or postictal...

OBJECTIVES: There is increasing knowledge about an association between migraine and ischaemic stroke. Cortical spreading depression (CSD) is the probable biological substrate of migrainous aura. To investigate the influence of CSD on the apparent stroke - migraine association, we hypothesized that magnetic resonance (MR) diffusion weighted images of acute ischaemic stroke patients would reveal an association between small cortical infarctions and migraine. METHODS: We included all patients admitted to the Bergen stroke unit between 2006 and 2012 with verified acute ischaemic stroke by MR imaging...

OBJECTIVES: The aim of this study was to compare the short-term clinical outcome of patients with acute cerebral ischemia and mild symptoms receiving rt-PA with that of patients with acute cerebral ischemia and mild symptoms not treated with rt-PA, and to investigate the frequency of symptomatic intracranial hemorrhage (sICH) in these patients. MATERIALS AND METHODS: All patients with confirmed ischemic stroke/TIA and mild symptoms were included. Mild symptoms were defined as NIHSS score≤5 on admission...

Multiple sclerosis (MS) is characterized by chronic inflammation of the central nervous system, and magnetic resonance imaging (MRI) is used as both a diagnostic tool and a parameter in the clinical evaluation. Multiple sclerosis was long regarded as a disease of the white matter (WM) in the brain, which can be visualized by the standard MRI used in daily practice. There is an increasing amount of evidence that grey matter (GM) pathology plays a role from the start of the MS disease and throughout the clinical course...

OBJECTIVES: There is a wide variation in reported prevalence and incidence of myasthenia gravis (MG). In this study, we aimed to evaluate the validity of two nationwide databases by comparing prevalence and incidence rates reported from three recent studies using the two databases as case-finding method. MATERIALS AND METHODS: Two different Norwegian nationwide databases were used: the acetylcholine receptor antibody database (reference cohort) and the Norwegian Prescription Database (NorPD) (study cohort)...

Neurogenetics has developed enormously in recent years, and the genetic basis of human disorders is being unravelled rapidly. Many neurological disorders are Mendelian disorders, caused by mutations in genes involved in normal function of the brain, spinal cord, peripheral nerves or muscles. Due to high costs and time-consuming procedures, genetic tests have normally been performed late in the diagnostic process, when clinical examination and other tests have indicated a specific gene as the likely disease cause...

Dystonia is a heterogeneous movement disorder and has been defined as 'a syndrome of sustained muscle contractions, frequently causing twisted and repetitive movements, or abnormal postures'. The classification of dystonia has developed along with increasing knowledge, and different schemes have been suggested, including age at onset, body distribution, and etiology as the main differentiating factors. A revised definition and a new classification of dystonia have now been proposed by a group of leading dystonia experts and will be referred here...

OBJECTIVES: Sepiapterin reductase deficiency is a rare, but treatable inherited disorder of tetrahydrobiopterin and neurotransmitter metabolism. This disorder is most probably underdiagnosed. To date, only 44 cases have been described in the literature. We present the clinical and genetic investigations in a family with a complex movement disorder. MATERIALS AND METHODS: We examined two affected sisters and three healthy family members. The cerebrospinal fluid was analyzed for neurotransmitter and pterins, and the sepiapterin reductase gene (SPR) was sequenced...

BACKGROUND: The Global Burden of Disease study (GBD) is a large international initiative to collect and systematize data on disease burden expressed in non-economic terms, to allow comparisons across different disease conditions and countries. OBJECTIVES: To use data from the large GBD 2010 database to determine the importance of neurological disorders in Norway, and to compare it with global data on the same disorders. MATERIALS AND METHODS: Relevant data were extracted from the Lancet publication from December 2012, and from the interactive website of the Institute of Health Metrics and Evaluation on GBD...

To evaluate the efficacy of adjunctive, once-daily perampanel against secondarily generalized (SG) seizures in three Phase III trials (studies 304, 305, and 306) and their extension (study 307). The Phase III studies enrolled patients (≥ 12 years) with uncontrolled partial-onset seizures despite treatment with 1-3 concomitant antiepileptic drugs. Patients completing the core Phase III studies were eligible for the extension study. Endpoints included median percent change in SG seizure frequency, 50% responder (proportion of patients achieving a ≥ 50% reduction in SG seizure frequency), 75% response, and seizure-freedom rates...

The Phase II and Phase III clinical development program of perampanel is providing a wealth of data on the safety and tolerability of this alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist as an adjuvant treatment for refractory partial-onset seizures. In Phase II dose-finding studies, perampanel was associated with an acceptable tolerability profile up to the maximum evaluated dose of 12 mg/day. Subsequent multinational, multicenter, randomized, double-blind, placebo-controlled Phase III registration studies further supported the tolerability of perampanel across the dose range 2-12 mg/day, with interim data from ongoing extension studies indicating that safety outcomes may be maintained over several years...

The efficacy of adjunctive perampanel has been investigated in an extensive clinical development program across a broad, multinational population of patients with refractory partial-onset seizures. Further to the results of two Phase II dose-finding studies, perampanel was evaluated in three large Phase III registration studies at the predicted no-effect dose of 2 mg/day and the predicted effective doses of 4, 8, and 12 mg/day. In all three studies, perampanel 4, 8, and 12 mg/day consistently provided significant reductions in the frequency of partial-onset seizures compared with placebo...

Perampanel [2-(2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl)benzonitrile; E2007] is a potent, selective, orally active non-competitive AMPA receptor antagonist developed for the treatment of epilepsy. Perampanel has a 2,3'-bipyridin-6'-one core structure, distinguishing it chemically from other AMPA receptor antagonist classes. Studies in various physiological systems indicate that perampanel selectively inhibits AMPA receptor-mediated synaptic excitation without affecting NMDA receptor responses. Blocking of AMPA receptors occurs at an allosteric site that is distinct from the glutamate recognition site...

Epileptic seizures occur as a result of episodic abnormal synchronous discharges in cerebral neuronal networks. Although a variety of non-conventional mechanisms may play a role in epileptic synchronization, cascading excitation within networks of synaptically connected excitatory glutamatergic neurons is a classical mechanism. As is the case throughout the central nervous system, fast synaptic excitation within and between brain regions relevant to epilepsy is mediated predominantly by AMPA receptors. By inhibiting glutamate-mediated excitation, AMPA receptor antagonists markedly reduce or abolish epileptiform activity in in vitro preparations and confer seizure protection in a broad range of animal seizure models...

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors play a key role in mediating glutamatergic transmission in the cortex. Perampanel (2-[2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl] benzonitrile) is a potent, orally active, highly selective, non-competitive AMPA-type glutamate receptor antagonist, identified via a focused discovery program at Eisai Research Laboratories. Development of perampanel as adjunctive therapy for the treatment of partial-onset seizures was planned in keeping with regulatory guidance and guidelines on antiepileptic drug (AED) development...

No abstract text is available yet for this article.

OBJECTIVE: Mild cognitive impairment (MCI) is a subtle memory disorder not matching criteria for dementia. There is evidence for vascular comorbidity in several types of dementia. We hypothesized that neurovascular workup would detect a high degree of vascular disease in patients with MCI. MATERIALS AND METHODS: In cooperation with our memory clinic, patients with amnestic MCI were referred to our department for neurovascular investigation. The workup encompassed ultrasound examination with carotid duplex including Intima-Media-Thickness (IMT) measurement, and transcranial Doppler (TCD) including one-hour microemboli monitoring, cerebrovascular reactivity measurement and Bubble test...

BACKGROUND: The purpose of this article is to find possible predictors associated with long-term mortality and long-term cardiovascular death after stroke. METHODS: A cohort of 550 patients with acute stroke admitted to a single hospital within 24 h of a stroke were recruited consecutively. Patients were followed for 12 years or until death. Information on death was collected through linkage with the National Population Register of Statistics Norway, an official register containing name, date of birth, address, and date of death, and the National Register of Cause of Death...

In acute ischemic stroke, rapid revascularization of the cerebral 'penumbra volume' is the key to better patient outcome. The largest and most proximal cerebral thrombotic artery occlusions can in most cases only be opened by intra-arterial intervention. The use of intra-arterial revascularization is rapidly expanding throughout Europe and North America, despite the risk for serious complications and the fact that the benefit of this treatment has not yet been proven in large, randomized clinical trials. Oslo University Hospital has performed approximately 60 intra-arterial procedures annually in acute ischemic stroke during the last few years...

OBJECTIVES: The understanding of stroke has changed in the recent years from rehabilitation to an emergency approach. We review existing data from symptom recognition to thrombolysis and identify challenges in the different phases of patient treatment. RESULTS: Implementation of treatment in dedicated stroke units with a multidisciplinary team exclusively treating stroke patients has led to significant reduction of stroke morbidity and mortality. Yet, first the introduction of treatment with intravenous rtPA (IVT) has led to the 'time is brain' concept where stroke is conceived as an emergency...