References of "Lancet Neurology"
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See detailDiagnostic precision of PET imaging and functional MRI in disorders of consciousness: a clinical validation study
Stender, Johan; Gosseries, Olivia ULg; Bruno, Marie-Aurélie ULg et al

in Lancet Neurology (2014)

Background: Bedside clinical examinations can have high rates of misdiagnosis of unresponsive wakefulness syndrome (vegetative state) or minimally conscious state. The diagnostic and prognostic usefulness ... [more ▼]

Background: Bedside clinical examinations can have high rates of misdiagnosis of unresponsive wakefulness syndrome (vegetative state) or minimally conscious state. The diagnostic and prognostic usefulness of neuroimaging-based approaches has not been established in a clinical setting. We did a validation study of two neuroimaging-based diagnostic methods: PET imaging and functional MRI (fMRI). Methods: For this clinical validation study, we included patients referred to the University Hospital of Liège, Belgium, between January, 2008, and June, 2012, who were diagnosed by our unit with unresponsive wakefulness syndrome, locked-in syndrome, or minimally conscious state with traumatic or non-traumatic causes. We did repeated standardised clinical assessments with the Coma Recovery Scale—Revised (CRS—R), cerebral 18F-fluorodeoxyglucose (FDG) PET, and fMRI during mental activation tasks. We calculated the diagnostic accuracy of both imaging methods with CRS—R diagnosis as reference. We assessed outcome after 12 months with the Glasgow Outcome Scale—Extended. Findings: We included 41 patients with unresponsive wakefulness syndrome, four with locked-in syndrome, and 81 in a minimally conscious state (48=traumatic, 78=non-traumatic; 110=chronic, 16=subacute). 18F-FDG PET had high sensitivity for identification of patients in a minimally conscious state (93%, 95% CI 85—98) and high congruence (85%, 77—90) with behavioural CRS—R scores. The active fMRI method was less sensitive at diagnosis of a minimally conscious state (45%, 30—61) and had lower overall congruence with behavioural scores (63%, 51—73) than PET imaging. 18F-FDG PET correctly predicted outcome in 75 of 102 patients (74%, 64—81), and fMRI in 36 of 65 patients (56%, 43—67). 13 of 42 (32%) of the behaviourally unresponsive patients (ie, diagnosed as unresponsive with CRS—R) showed brain activity compatible with (minimal) consciousness (ie, activity associated with consciousness, but diminished compared with fully conscious individuals) on at least one neuroimaging test; 69% of these (9 of 13) patients subsequently recovered consciousness. Interpretation: Cerebral 18F-FDG PET could be used to complement bedside examinations and predict long-term recovery of patients with unresponsive wakefulness syndrome. Active fMRI might also be useful for differential diagnosis, but seems to be less accurate. Funding: The Belgian National Funds for Scientific Research (FNRS), Fonds Léon Fredericq, the European Commission, the James McDonnell Foundation, the Mind Science Foundation, the French Speaking Community Concerted Research Action, the University of Copenhagen, and the University of Liège. [less ▲]

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See detailAdvances and challenges in neurostimulation for headaches
MAGIS, Delphine ULg; Schoenen, Jean ULg

in Lancet Neurology (2012), 11(8), 708-719

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See detailEfficacy and tolerability of lasmiditan, an oral 5-HT(1F) receptor agonist, for the acute treatment of migraine: a phase 2 randomised, placebo-controlled, parallel-group, dose-ranging study.
Farkkila, Markus; Diener, Hans-Christoph; Geraud, Gilles et al

in Lancet Neurology (2012), 11(5), 405-13

BACKGROUND: Lasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a ... [more ▼]

BACKGROUND: Lasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a proof-of-concept migraine study. We aimed to assess the efficacy and safety of oral lasmiditan for the acute treatment of migraine. METHODS: In this multicentre, double-blind, parallel-group, dose-ranging study in 43 headache centres in five European countries, patients with migraine with and without aura and who were not using prophylaxis were randomly assigned (1:1:1:1:1) to treat one moderate or severe attack at home with 50 mg, 100 mg, 200 mg, or 400 mg lasmiditan, or placebo. Study drug and placebo were supplied in identical numbered tablet packs. The randomisation code was generated by an independent statistician. Patients and investigators were masked to treatment allocation. The primary endpoint was dose response for headache relief (moderate or severe becoming mild or none) at 2 h. The primary analysis was done in the modified intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00883051. FINDINGS: Between July 8 2009, and Feb 18, 2010, 512 patients were randomly assigned to treatment, 391 of whom received treatment. 86 patients received placebo (81 included in primary analysis) and 305 received lasmiditan (50 mg n=79, 100 mg n=81, 200 mg n=69, and 400 mg n=68 included in primary analysis). There was a linear association between headache response rate at 2 h and lasmiditan dose (Cochran-Armitage test p<0.0001). Every lasmiditan treatment dose significantly improved headache response at 2 h compared with placebo (lasmiditan 50 mg: difference 17.9%, 95% CI 3.9-32.1, p=0.022; 100 mg: 38.2%, 24.1-52.4, p<0.0001; 200 mg: 28.8%, 9.6-39.9, p=0.0018; 400 mg: 38.7%, 23.9-53.6, p<0.0001). The proportion of patients with treatment-emergent adverse events increased with increasing doses (53/82 [65%], 59/82 [72%], 61/71 [86%], and 59/70 [84%] for lasmiditan 50, 100, 200, and 400 mg, respectively vs 19/86 [22%] for placebo). Most adverse events were mild or moderate in intensity, with 16 of 82 (20%), 23 of 82 (28%), 28 of 71 (39%), and 31 of 70 (44%) of patients on lasmiditan 50, 100, 200, and 400 mg, respectively reporting a severe adverse event compared with five of 86 (6%) on placebo. The most common adverse events were CNS related and included dizziness, fatigue, vertigo, paraesthesia, and somnolence. INTERPRETATION: Oral lasmiditan seems to be safe and effective in the acute treatment of migraine. Further assessment in larger placebo-controlled and triptan-controlled trials are needed to assess the potential role of lasmiditan in acute migraine therapy. FUNDING: CoLucid Pharmaceuticals. [less ▲]

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See detailHeadache: spreading from molecules to patients
Schoenen, Jean ULg; Coppola, G.

in Lancet Neurology (2010), 9

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See detailTension-Type Headache: Current Research and Clinical Management
Fumal, Arnaud ULg; Schoenen, Jean ULg

in Lancet Neurology (2008), 7(1), 70-83

Tension-type headache (TTH) is the most common form of headache, and chronic tension-type headache (CTTH) is one of the most neglected and difficult types of headache to treat. The pathogenesis of TTH is ... [more ▼]

Tension-type headache (TTH) is the most common form of headache, and chronic tension-type headache (CTTH) is one of the most neglected and difficult types of headache to treat. The pathogenesis of TTH is multifactorial and varies between forms and individuals. Peripheral mechanisms (myofascial nociception) and central mechanisms (sensitisation and inadequate endogenous pain control) are intermingled: the former predominate in infrequent and frequent TTH, whereas the latter predominate in CTTH. Acute therapy is effective for episodes of TTH, whereas preventive treatment--which is indicated for frequent and chronic TTH--is, on average, not effective. For most patients with CTTH, the combination of drug therapies and non-drug therapies (such as relaxation and stress management techniques or physical therapies) is recommended. There is clearly an urgent need to improve the management of patients who are disabled by headache. This Review summarises the present knowledge on TTH and discusses some of its more problematic features. [less ▲]

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See detailPerception of pain in the minimally conscious state with PET activation: an observational study.
Boly, Mélanie ULg; Faymonville, Marie-Elisabeth ULg; Schnakers, Caroline et al

in Lancet Neurology (2008), 7(11), 1013-20

BACKGROUND: Patients in a minimally conscious state (MCS) show restricted self or environment awareness but are unable to communicate consistently and reliably. Therefore, better understanding of cerebral ... [more ▼]

BACKGROUND: Patients in a minimally conscious state (MCS) show restricted self or environment awareness but are unable to communicate consistently and reliably. Therefore, better understanding of cerebral noxious processing in these patients is of clinical, therapeutic, and ethical relevance. METHODS: We studied brain activation induced by bilateral electrical stimulation of the median nerve in five patients in MCS (aged 18-74 years) compared with 15 controls (19-64 years) and 15 patients (19-75 years) in a persistent vegetative state (PVS) with (15)O-radiolabelled water PET. By way of psychophysiological interaction analysis, we also investigated the functional connectivity of the primary somatosensory cortex (S1) in patients and controls. Patients in MCS were scanned 57 (SD 33) days after admission, and patients in PVS 36 (9) days after admission. Stimulation intensities were 8.6 (SD 6.7) mA in patients in MCS, 7.4 (5.9) mA in controls, and 14.2 (8.7) mA in patients in PVS. Significant results were thresholded at p values of less than 0.05 and corrected for multiple comparisons. FINDINGS: In patients in MCS and in controls, noxious stimulation activated the thalamus, S1, and the secondary somatosensory or insular, frontoparietal, and anterior cingulate cortices (known as the pain matrix). No area was less activated in the patients in MCS than in the controls. All areas of the cortical pain matrix showed greater activation in patients in MCS than in those in PVS. Finally, in contrast with patients in PVS, those in MCS had preserved functional connectivity between S1 and a widespread cortical network that includes the frontoparietal associative cortices. INTERPRETATION: Cerebral correlates of pain processing are found in a similar network in controls and patients in MCS but are much more widespread than in patients in PVS. These findings might be objective evidence of a potential pain perception capacity in patients in MCS, which supports the idea that these patients need analgesic treatment. [less ▲]

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See detailCessation versus continuation of 6-month migraine preventive therapy with topiramate (PROMPT): a randomised, double-blind, placebo-controlled trial
Diener, Hans-Christoph; Agosti, Reto; Allais, Gianni et al

in Lancet Neurology (2007), 6(12), 1054-1062

Background Use of preventive therapy for migraine is often recommended for only 6-9 months, but no randomised, placebo-controlled trials have investigated migraine frequency after the end of prophylaxis ... [more ▼]

Background Use of preventive therapy for migraine is often recommended for only 6-9 months, but no randomised, placebo-controlled trials have investigated migraine frequency after the end of prophylaxis. We assessed the effects of discontinuation of topiramate after a treatment period of 6 months. Methods 818 patients who have migraines were enrolled from 88 clinics in 21 countries. After a 4-8-week lead-in period, patients received topiramate in a 26-week open-label phase. Daily dose was increased from 25 mg to 100 mg in steps of 25 mg every week; the dose could be adjusted further in the range 50-200 mg/day, but was stable for the final 4 weeks. Patients were randomly assigned to continue this dose or switch to placebo for a 26-week double-blind phase. The primary endpoint was the difference in number of days with migraine during the last 4 weeks of the double-blind phase compared with the last 4 weeks of the open-label phase. Analysis was by intention to treat. This trial is registered with EudraCT, number 2005-000321-29. Findings 559 patients (68.3%) completed the open-label phase; 514 entered the double-blind phase and were assigned to topiramate (n=255) or placebo (n=259). The mean increase in number of migraine days was greater in the placebo group (1.19 days in 4 weeks, 95% CI 0.71 to 1.66; p < 0.0001) than in the topiramate group (0.10, -0.36 to 0.56; p=0.5756; mean difference between groups -1.09, -1.75 to -0.43). Patients in the placebo group had a greater number of days on acute medication than did those in the topiramate group (mean difference between groups -0.95, -1.49 to -0.41; p=0.0007). Quality of life, as assessed by the MIDAS questionnaire, fell in the placebo group but remained stable in the topiramate group. Patients were more satisfied with the efficacy of topiramate than with that of placebo, whereas satisfaction with tolerability was similar in both treatment groups. Interpretation Sustained benefit was reported after discontinuation of topiramate, although number of migraine days did increase. These findings suggest that patients should be treated for 6 months, with the option to continue to 12 months in some patients. [less ▲]

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See detailOccipital nerve stimulation for drug-resistant chronic cluster headache: a prospective pilot study
Magis, Delphine ULg; Allena, Marta; Bolla, Monica et al

in Lancet Neurology (2007), 6(4), 314-321

Background Drug-resistant chronic duster headache (drCCH) is a devastating disorder for which various destructive procedures have been tried unsuccessfully. Occipital nerve stimulation (ONS) is a new ... [more ▼]

Background Drug-resistant chronic duster headache (drCCH) is a devastating disorder for which various destructive procedures have been tried unsuccessfully. Occipital nerve stimulation (ONS) is a new, safe strategy for intractable headaches. We undertook a prospective pilot trial of ONS in drCCH to assess clinical efficacy and pain perception. Methods Eight patients with drCCH had a suboccipital neurostimulator implanted on the side of the headache and were asked to record details of frequency, intensity, and symptomatic treatment for their attacks in a diary before and after Continuous ONS. To detect changes in cephalic and extracephalic pain processing we measured electrical and pressure pain thresholds and the nociceptive blink reflex. Findings Two patients were pain free after a follow-up of 16 and 22 months; one of them still had occasional autonomic attacks. Three patients had around a 90% reduction in attack frequency. Two patients, one of whom had had the implant for only 3 months, had improvement of around 40%. Mean follow-up was 15.1 months (SD 9.5, range 3-22). Intensity of attacks tends to decrease earlier than frequency during ONS and, on average, is improved by 50% in remaining attacks. All but one patient were able to substantially reduce their preventive drug treatment. Interruption of ONS by switching off the stimulator or because of an empty battery was followed within days by recurrence and increase of attacks in all improved patients. ONS did not significantly modify pain thresholds. The amplitude of the nociceptive blink reflex increased with longer durations of ONS. There were no serious adverse events. Interpretation ONS could be an efficient treatment for drCCH and could be safer than deep hypothalamic stimulation. The delay of 2 months or more between implantation and significant clinical improvement suggests that the procedure ads via slow neuromodulatory processes at the level of upper brain stem or diencephalic centres. [less ▲]

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See detailQuantifying consciousness
Laureys, Steven ULg; Piret, Sonia ULg; Ledoux, Didier ULg

in Lancet Neurology (2005), 4(12), 789-790

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See detailBrain function in coma, vegetative state, and related disorders
Laureys, Steven ULg; Owen, Adrian M; Schiff, Nicholas D

in Lancet Neurology (2004), 3(9), 537-546

We review the nosological criteria and functional neuroanatomical basis for brain death, coma, vegetative state, minimally conscious state, and the locked-in state. Functional neuroimaging is providing ... [more ▼]

We review the nosological criteria and functional neuroanatomical basis for brain death, coma, vegetative state, minimally conscious state, and the locked-in state. Functional neuroimaging is providing new insights into cerebral activity in patients with severe brain damage. Measurements of cerebral metabolism and brain activations in response to sensory stimuli with PET, fMRI, and electrophysiological methods can provide information on the presence, degree, and location of any residual brain function. However, use of these techniques in people with severe brain damage is methodologically complex and needs careful quantitative analysis and interpretation. In addition, ethical frameworks to guide research in these patients must be further developed. At present, clinical examinations identify nosological distinctions needed for accurate diagnosis and prognosis. Neuroimaging techniques remain important tools for clinical research that will extend our understanding of the underlying mechanisms of these disorders. [less ▲]

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See detailHeadache with focal neurological signs or symptoms: a complicated differential diagnosis
Schoenen, Jean ULg; Sandor, P. S.

in Lancet Neurology (2004), 3(4), 237-245

Headache syndromes can be associated with focal neurological symptoms or signs. Good knowledge of primary headaches, a detailed history and a thorough clinical examination are prerequisites for their ... [more ▼]

Headache syndromes can be associated with focal neurological symptoms or signs. Good knowledge of primary headaches, a detailed history and a thorough clinical examination are prerequisites for their differential diagnosis. The neurological symptoms produced by the migraine aura are the most characteristic and recognisable. However, structural lesions, such as vascular malformations, can produce similar symptoms to migraine with aura, which highlights that paraclinical investigations are necessary in most patients with headache and focal neurological symptoms. In this review, we provide an overview of the differential diagnosis of the most common headache disorders with focal neurological symptoms or signs to refresh the practising neurologist's differential diagnostic knowledge for the clinical situation and to aid the teaching of neurology residents. [less ▲]

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See detailGlobal democratic consensus on neuropathological disease criteria.
Achim, Cristian; Auer, Roland; Bergeron, Catherine et al

in Lancet Neurology (2002), 1(6), 340

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