Milestone Papers
Scientific Panels Submissions
Milestone Papers in Neurology
The section of the Milestone Papers in Neurology will highlight those publications that have changed the way we think about, understand, diagnose or treat neurological diseases and conditions.
You can find below a list of Milestone Papers in Neurology, recommended by the EAN Scientific Panels.
EAN Scientific Panels
| Title of Publication of Milestone Paper | The reason why this paper was selected | Link |
| European Resuscitation Council and European Society of Intensive Care Medicine Guidelines 2021: Post-resuscitation care. | Latest guidelines from the European societies of Resuscitation and Intensive Care on the acute management of comatose patients | Link |
| European Academy of Neurology guideline on the diagnosis of coma and other disorders of consciousness | European guidelines on diagnostic methods for patients with disorders of consciousness, elaborated by a workgroup of this Scientific Panel | Link |
| Practice guideline update recommendations summary: Disorders of consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research | Latest guidelines elaborated by a consortium of American Societies on the care of patients with disorders of consciousness | Link |
| Detection of Brain Activation in Unresponsive Patients with Acute Brain Injury | This is the milestone paper because it is dedicated to the new term in the sphere of DoC - covert cognition and how it can be detected with the help of EEG and its analysis by machine learning. | Link |
| Therapies to Restore Consciousness in Patients with Severe Brain Injuries: A Gap Analysis and Future Directions | For the first time knowledge gap analysis in all five therapeutic classes for patients with DoC was performed with a suggestion of a precision medicine approach in order to address these gaps. | Link |
| Risk factors for 2-year mortality in patients with prolonged disorders of consciousness: An international multicentre study | The international multicentre prospective study devoted to the evaluation of 2-year mortality rate and its bedside predictors (feasible multimodal assessmennt) | Link |
| Title of Publication of Milestone Paper | The reason why this paper was selected | Link |
| Comparison of carbamazepine, phenobarbital, phenytoin and primidone in partial and secondarily generalized tonic-clonic seizures. | This is the milestone paper because it represents the first-in-time evidence class I comparative trial of antiseizure medication treatment. Never again such a methodologiocal masterpiece was published. | Link |
| Presurgical evaluation of epilepsy | This is the most comprehensive and still valid review article and thus the best possible introduction into the concept and methodology of presurgical epilepsy diagnostics. | Link |
| Early identification of refractory epilepsy | This is an all-time citation classic. The study prospectively followed the success of antiseizure medications and revealed that refractoriness can be diagnosed much earlier than previously suggested. | Link |
| Title of Publication of Milestone Paper | The reason why this paper was selected | Link |
| Action recognition in the premotor cortex | Perception and action are core components of human behavior. In this work, the authors recorded the electrical activity of monkeys’ premotor cortex neurons. The activation of these neurons had been primarily associated with action performance. Remarkably, the authors found a subset triggered not only when the monkeys performed a specific action, but also when they observed one experimenter performing similar actions. These neurons were called "mirror neurons". Their existence in the human brain was later uncovered. These results greatly advanced our understanding of the unified mechanisms of action-perception and emotion-related behaviors. | Link |
| Navigation-related structural change in the hippocampi of taxi drivers | Authors studied healthy adults working as taxi drivers in London and showed that: a) their posterior hippocampi were larger than matched controls and b) that hippocampi volume increase was related with the years of practice as taxi drivers. A previous work, with functional brain imaging, showed the activation of the posterior hippocampus in mental tasks related to navigation, thus corroborating the participation of the posterior hippocampi in this function. The work is creative, ecological and demonstrates the effect of environmental stimulation on brain structure in human adults. The latter was a breakthrough in conceptual and empirical knowledge at the time. | Link |
| Dorsal and ventral streams: a framework for understanding aspects of the functional anatomy of language | The authors propose a dual loop model of language organization, based on an evolutionary perspective and on the main cortico-subcortical pathways connecting the anterior and posterior language regions. The ventral pathway supports the mapping of sound to meaning making an interface with the semantic system while the dorsal pathway, lateralized to the left hemisphere, maps sound to the articulatory representations, underlying the processing of phonology and syntax. The model is simple, includes the classical language areas and the subcortical fiber tracts connecting them. It explains the pattern of language disorder that can be found following different brain lesions. | Link |
| Awareness impairment in Alzheimer’s disease and frontotemporal dementia: a systematic MRI review | This review aims to define awareness impairment and related disturbances in neurodegenerative diseases, including Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) spectrum of disorders. This systematic review highlights the importance of awareness impairment and related domains in neurodegenerative disorders, especially in AD and FTLD, and it outlines MRI structural and functional correlates in these populations. | Link |
| Title of Publication of Milestone Paper | The reason why this paper was selected | Link |
| Community-acquired bacterial meningitis | It is an important paper on bacterial meningitis. | Link |
| Title of Publication of Milestone Paper | The reason why this paper was selected | Link |
| The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy | Link |
| Title of Publication of Milestone Paper | The reason why this paper was selected | Link |
| Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria | Several antibody-mediated diseases affecting the CNS have been recently recognized as distinct conditions which enter the differential diagnosis with MS. These include aquaporin-4 seropositive neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Histopathologic, clinical, laboratory and imaging features are significantly different among these conditions. Also treatment and prognosis are diverse. This urges the development and application of diagnostic criteria which are specific for these conditions. This consensus paper, from an International Panel of experts, proposes diagnostic criteria for MOGAD in which the presence of MOG-IgG is a core criterion. A validation of these criteria is now required. | Link |
| Title of Publication of Milestone Paper | The reason why this paper was selected | Link |
| Sporadic Late-Onset Nemaline Myopathy: Current Landscape | Sporadic late-onset nemaline myopathy (SLONM) is a rare adult-onset myopathy of which knowledge has been increasing in the recent years. It typically manifests as a subacute progressive proximal and axial weakness but can also presents as chronic progressive weakness mimicking an inherited neuropathy. It is associated with monoclonal gammopathy and HIV infection. Pathologically is characterized by nemaline rods in muscle fibers. It is responsive to immunomodulatory therapies as intravenous immunoglobulin, as well chemotherapy, and hematopoietic stem cell transplant. This article gives an updated overview of the clinical, serological, EMG, imaging and histologic findings as well as current management approaches of SLONM. | Link |
| Title of Publication of Milestone Paper | The reason why this paper was selected | Link |
| Primary stroke prevention worldwide: translating evidence into action | Stroke is the second most common cause of death and third leading cause of disability, creating a rapidly growing public health burden. Despite the available knowledge about primary stroke prevention, current strategies are partially implemented and inadequately effective, while the reasons underlying this important gap are multifactorial and poorly understood. This Health Policy paper based on a multifaceted methodology, provides a critical situational evaluation of current primary prevention strategies and guidelines, economic analysis, identification of facilitators and barriers for implementation, and evidence-based pragmatic solutions for primary stroke prevention, highlighting the emerging value of the involvement of multiple stakeholders (healthcare professionals, policy makers, patients, funders). | Link |
| Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019 | Updated epidemiological evidence (incidence, prevalence, risk factors, mortality, disability) on stroke is of paramount importance for the planning of evidence-based stroke strategies. This proposed paper, based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), presents standardized epidemiological estimates for stroke for 204 countries and territories from 1990 to 2019. Stroke cases and deaths because of stroke were substantially increased especially in low-income countries, although age-standardized rate reductions were observed especially for those >70 years. The fastest-growing risk factor was high body-mass index. Therefore, the urgent need for effective implementation of primary prevention strategies for stroke is highlighted. | Link |
| Title of Publication of Milestone Paper | The reason why this paper was selected | Link |
| Accelerated Brain Volume Loss Caused by Anti-β-Amyloid Drugs: A Systematic Review and Meta-analysis | Immunomodulatory drugs targeting amyloid-beta brain depositions are on the cusp becoming a game-changer for the therapy of early stages of Alzheimer’s disease. At the same time, there is a substantial controversy among specialists and in the public eye about various aspects of treatment, benefits, and adverse effects. Here, Alves et al. provide a systematic review and meta-analytical evidence (8062 < n < 10279) for anti-amyloid beta therapy-induced accelerated hippocampus and whole-brain atrophy. Similarly, ARIA-inducing monoclonal antibodies accelerated brain atrophy, demonstrated by increased ventricular volume. The authors interpret their findings in the context of therapy-related negative impact on brain health. | Link |
| Title of Publication of Milestone Paper | The reason why this paper was selected | Link |
| Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria | MOGAD or MOG Antibody-Associated Disease is a recently recognized disease entity that differs from MS and NMOSD. Presence of anti-MOG antibodies is crucial in the diagnosis. These international consensus criteria will need to be validated in the coming years, may help to identify patients with MOGAD and will be useful in research and clinical trials investigating novel therapeutic approaches. | Link |
| Title of Publication of Milestone Pape | The reason why this paper was selected | LINK |
| Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma | The phase III trial that demonstrated the survival benefit of the addition of temozolomide to radiotherapy in newly diagnosed glioblastomas, establishing the current standard of treatment | Link |
| An integrated genomic analysis of human glioblastoma multiforme | The first identification of recurrent IDH mutations in gliomas | Link |
| Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma | The phase III trial that first demonstrated the utility of IDH inhibition in treatment-naïve IDH mutant low-grade gliomas | Link |
| Title of Publication of Milestone Paper | The reason why this paper was selected | Link |
| 2022 American College of Rheumatology/EULAR classification criteria for giant cell arteritis | The diagnosis of giant cell arteritis (GCA) with ultrasonography is one of the best examples of how this technique adds accuracy to the diagnosis, quickly and non-invasively, allowing a timely treatment intervention. This paper shows that diagnostic criteria of GCA have greater sensitivity then before, mainly due to the input of the ultrasonography. Its hallmark is the halo sign, a homogenous, hypoechoic artery wall thickening; this inflammatory thickening is non-compressible, where we can press it with the probe, as in the temporal arteries. Depending on the clinical setting, a non-compressible halo sign may replace the need for temporal artery biopsy. | Link |
| Title of Publication of Milestone Paper | The reason why this paper was selected | Link |
| The course of the terminal phase in patients with amyotrophic lateral sclerosis. Journal of Neurology 2001; 248: 612-616. | One of the first european pubblications opening to the role of palliative care in neurology | Link |
| Motor neurone disease: a hospice perspective. Br Med J, 1992. 304(6825): 471-3. | The first evidence of involvement of ALS patients in palliative care | Link |
| Oliver DJ, Borasio GD, Caraceni A, de Visser M, Grisold W, Lorenzl S, Veronese S, Voltz R. A consensus review on the development of palliative care for patients with chronic and progressive neurological disease. Eur J Neurol 2016;23: 30-38. | The first joint publication between EACP and EAN, a consensus document on the role of palliative care in neurology | Link |
| Withdrawal of assisted ventilation at the request of a patient with motor neurone disease: guidance for professionals | This is a seminal paper from the Association for Palliative Medicine of Great Britain and Ireland explaining how to proceed with withdrawals of life sustaining treatments | Link |
| The role of palliative care in patients with neurological diseases. Nature Neurology 2013; 9: 292-295. | This is a complete review of the role of palliative care in neurological conditions | Link |
| Neuropalliative care. Priorities to move the field forward. Neurology 2018; 91: 217-226. | It describes the growht of neuropalliative care as a sub medical specialty and how to best integrate it into neurological pathways of care. | Link |
| Pace A, Dirven L, Koekkoek JAF et al. European Association for Neuro-Oncology (EANO) guidelines for palliative care in adults with glioma. The Lancet Oncology 2017; 18: e330-340. | European guidelines on palliative care in brain tumors | Link |
| Veronese S, Gallo G, Valle A, Cugno C, Chio A, Calvo A, Cavalla P, Zibetti M, Rivoiro C, Oliver DJ. Specialist palliative care improves the quality of life in advanced neurodegenerative disorders: Ne-PAL, a pilot randomized controlled study. BMJ Supp Pall Care 2017; 7: 164-172. | One of the first trials showing benefit of palliative care in neurodegenerative conditions | Link |
| Solari A, Giordanoa A, Sastre-Garriga J, Kopke S, Rahn AC, Kleiter I, Aleksovska K, Battaglia MA, Bay J, Copetti M, Drulovic J, Kooij L, Mens J, Meza Murillo ER, Milanov I, Milo R, Pekmezovic T, Vosburgh J, Silber E, Veronese S, Patti F, Voltz R, Oliver D on behalf of the guideline task force. EAN guideline on palliative care of people with severe, progressive multiple sclerosis. European Journal of Neurology 2020; 27: 1510-1529 | EAN guidelines on palliative care in multiple sclerosis | Link |
| Kluger BM, Hudson P, Hanson LC, Bužgová R, Creutzfeldt CJ, Gursahani R, Sumrall M, White C, Oliver DJ, Pantilat SZ, Miyasaki J. Palliative care to support the needs of adults with neurological disease. Lancet Neurol 2023; 22: 619–31. | Recent review of the evidence of the impact of palliative care in neurological conditions and priorities for education and research | Link |