EAN consensus statement for management of patients with neurological diseases during the COVID-19 pandemic.

BACKGROUND AND PURPOSE: The recent SARS-CoV-2 pandemic has posed multiple challenges to the practice of clinical neurology including recognition of emerging neurological complications and management of coexistent neurological diseases. In a fast-evolving pandemic, evidence-based studies are lacking in many areas. This paper presents European Academy of Neurology (EAN) expert consensus statements to guide neurologists caring for patients with COVID-19. METHODS: A refined Delphi methodology was applied. In round 1, statements were provided by EAN scientific panels (SPs). In round 2, these statements were circulated to SP members not involved in writing them, asking for agreement/disagreement. Items with agreement >70% were retained for round 3, in which SP co-chairs rated importance on a five-point Likert scale. Results were graded by importance and reported as consensus statements. RESULTS: In round one, 70 statements were provided by 23 SPs. In round two, 259/1061 SP member responses were received. Fifty-nine statements obtained >70% agreement and were retained. In round three, responses were received from 55 co-chairs of 29 SPs. Whilst general recommendations related to prevention of COVID-19 transmission had high levels of agreement and importance, opinion was more varied concerning statements related to therapy. CONCLUSION: This is the first structured consensus statement on good clinical practice in patients with neurological disease during the COVID-19 pandemic that provides immediate guidance for neurologists. In this fast-evolving pandemic, a rapid response using refined Delphi methodology is possible, but guidance may be subject to change as further evidence emerges.

Alcohol withdrawal syndrome: mechanisms, manifestations, and management.

The alcohol withdrawal syndrome is a well-known condition occurring after intentional or unintentional abrupt cessation of heavy/constant drinking in patients suffering from alcohol use disorders (AUDs). AUDs are common in neurological departments with patients admitted for coma, epileptic seizures, dementia, polyneuropathy, and gait disturbances. Nonetheless, diagnosis and treatment are often delayed until dramatic symptoms occur. The purpose of this review is to increase the awareness of the early clinical manifestations of AWS and the appropriate identification and management of this important condition in a neurological setting.

Practical recommendations for the process of proposing, planning and writing a neurological management guideline by EAN task forces.

The European Academy of Neurology (EAN), founded in 2014 after the merging of the two previously active European Neurological Societies, considers the production of neurological guidelines a major obligation, as this is a major tool to improve clinical practice in neurology. This paper updates practical suggestions to develop guidelines about the treatment and diagnosis of neurological diseases within the framework of the EAN. Its aim is to make uniform, traceable and explicit the path from the decision to write an EAN guideline to its publication. We explain the protocol structure, handling of conflicts of interest, format, timeline and process of revision and acceptance. It provides the view of the Scientific Committee and the Board of the EAN. We hope to make easier a larger involvement of the EAN scientific community in producing guidelines.

Transorbital sonography in acute optic neuritis: a case-control study.

BACKGROUND AND PURPOSE: Acute unilateral optic neuritis is associated with a thickening of the retrobulbar portion of the optic nerve as revealed by transorbital sonography, but no comparison has been made between nerve sheath diameter and optic nerve diameter in patients with acute optic neuritis versus healthy controls. We evaluated optic nerve sheath diameter and optic nerve diameter in patients with acute optic neuritis and healthy controls and compared optic nerve sheath diameter and optic nerve diameter with visual-evoked potentials in patients. MATERIALS AND METHODS: A case-control study was performed in 2 centers. Twenty-one consecutive patients with onset of visual loss during the prior 10 days and established acute noncompressive unilateral optic neuritis were compared with 21 healthy controls, matched for sex and age (±5 years). Two experienced vascular sonographers performed the study by using B-mode transorbital sonography. Visual-evoked potentials were performed on the same day as the transorbital sonography and were evaluated by an expert neurophysiologist. Sonographers and the neurophysiologist were blinded to the status of the patient or control and to clinical information, including the side of the affected eye. RESULTS: The median optic nerve sheath diameter was thicker on the affected side (6.3 mm; interquartile range, 5.9-7.2 mm) compared with the nonaffected side (5.5 mm; interquartile range, 5.1-6.2 mm; P < .0001) and controls (5.2 mm; interquartile range, 4.8-5.5 mm; P < .0001). The median optic nerve diameter was 3.0 mm (range, 2.8-3.1 mm) on the affected side and 2.9 mm (range, 2.8-3.1 mm) on the nonaffected side (P = not significant.). Both sides were thicker than those in controls (2.7 mm; interquartile range, 2.5-2.8 mm; P = .001 and .009). No correlation was found between optic nerve sheath diameter and optic nerve diameter and amplitude and latency of visual-evoked potentials in patients with optic neuritis. CONCLUSIONS: Transorbital sonography is a promising tool to support the clinical diagnosis of acute optic neuritis. Further studies are needed to define its specific role in the diagnosis and follow-up of optic neuritis.

Guidance for the preparation of neurological management guidelines by EFNS scientific task forces - revised recommendations 2012.

This paper is meant to provide guidance to anyone wishing to write a neurological guideline for diagnosis or treatment, and is directed at the Scientist Panels and task forces of the European Federation of Neurological Societies (EFNS). It substitutes the previous guidance paper from 2004. It contains several new aspects: the guidance is now based on a change of the grading system for evidence and for the resulting recommendations, and has adopted The Grading of Recommendations, Assessment, Development and Evaluation system (GRADE). The process of grading the quality of evidence and strength of recommendations can now be improved and made more transparent. The task forces embarking on the development of a guideline must now make clearer and more transparent choices about outcomes considered most relevant when searching the literature and evaluating their findings. Thus, the outcomes chosen will be more critical, more patient-oriented and easier to translate into simple recommendations. This paper also provides updated practical recommendations for planning a guideline task force within the framework of the EFNS. Finally, this paper hopes to find the approval also by the relevant bodies of our future organization, the European Academy of Neurology.

Predictors of attack severity and duration in multiple sclerosis: a prospective study.

OBJECTIVE: To evaluate predictors of severity and duration of early Multiple Sclerosis (MS) attacks. METHODS: We analyzed 248 attacks in 95 patients in a prospective study. Severity: the difference between the EDSS score at the day of maximum worsening and the EDSS score before the onset of the attack. DURATION: the time between the date of onset of the first symptom and the date of maximum improvement of the last symptom. RESULTS: The number of involved Functional Systems (FS), FS type (brainstem and pyramidal), and total attack duration were linked to severity. Number of FS involved, FS type (sphincteric and sensory), and severity of the attack were related to duration. Neither severity nor duration were correlated to other predictors: gender, age and season at attack onset, speed of onset, infections in the preceding month, age at first attack, season of birth and first attack, CSF examination, first brain MRI, recovery from the first attack. In the multivariate analysis, the Odds Ratio (OR) and Confidence Intervals (CI) for severe attacks was 3.6, 1.7-7.7 for involvement of pyramidal FS, 2.6, 1.2-6.0 for brainstem and 2.5, 1.2-5.3 for long attack duration. Sphincteric (4.4; 1.7-11.0) and sensory FS (1.8; 1.0-3.2) were the only variables explaining duration. The probability of a second moderate/severe or long attack was not influenced by severity or duration of the first. CONCLUSION: FS are predictive of severity and duration of early MS attacks. Severity and duration of the first attack do not predict severity and duration of the second.

EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy.

BACKGROUND: Although Wernicke encephalopathy (WE) is a preventable and treatable disease it still often remains undiagnosed during life. OBJECTIVES: To create practical guidelines for diagnosis, management and prevention of the disease. METHODS: We searched MEDLINE, EMBASE, LILACS, Cochrane Library. CONCLUSIONS AND RECOMMENDATIONS: 1 The clinical diagnosis of WE should take into account the different presentations of clinical signs between alcoholics and non alcoholics (Recommendation Level C); although prevalence is higher in alcoholics, WE should be suspected in all clinical conditions which could lead to thiamine deficiency (good practice point - GPP). 2 The clinical diagnosis of WE in alcoholics requires two of the following four signs; (i) dietary deficiencies (ii) eye signs, (iii) cerebellar dysfunction, and (iv) either an altered mental state or mild memory impairment (Level B). 3 Total thiamine in blood sample should be measured immediately before its administration (GPP). 4 MRI should be used to support the diagnosis of acute WE both in alcoholics and non alcoholics (Level B). 5 Thiamine is indicated for the treatment of suspected or manifest WE. It should be given, before any carbohydrate, 200 mg thrice daily, preferably intravenously (Level C). 6 The overall safety of thiamine is very good (Level B). 7 After bariatric surgery we recommend follow-up of thiamine status for at least 6 months (Level B) and parenteral thiamine supplementation (GPP). 8 Parenteral thiamine should be given to all at-risk subjects admitted to the Emergency Room (GPP). 9 Patients dying from symptoms suggesting WE should have an autopsy (GPP).

HLA-class I markers and multiple sclerosis susceptibility in the Italian population.

Previous studies reported an association with multiple sclerosis (MS) of distinct HLA-class I markers, namely HLA-A*02, HLA-Cw*05 and MOG-142L. In this work, we tested the association with MS of A*02 and Cw*05 in 1273 Italian MS patients and 1075 matched controls, which were previously analyzed for MOG-142, and explored the relationship among these three markers in modulating MS risk. HLA-A*02 conferred a statistically robust MS protection (odds ratio, OR=0.61; 95% confidence intervals, CI=0.51-0.72, P<10(-9)), which was independent of DRB1*15 and of any other DRB1* allele and remained similar after accounting for the other two analyzed class I markers. Conversely, the protective effect we previously observed for MOG-142L was secondary to its linkage disequilibrium with A*02. Cw*05 was not associated considering the whole sample, but its presence significantly enhanced the protection in the HLA-A*02-positive group, independently of DRB1: the OR conferred by A*02 in Cw*05-positive individuals (0.22, 95% CI=0.13-0.38) was significantly lower than in Cw*05-negative individuals (0.69, 95% CI=0.58-0.83) with a significant (P=4.94 x 10(-5)) multiplicative interaction between the two markers. In the absence of A*02, Cw*05 behaved as a risk factor, particularly in combination with DRB1*03 (OR=3.89, P=0.0006), indicating that Cw*05 might be a marker of protective or risk haplotypes, respectively.

Factors predicting incomplete recovery from relapses in multiple sclerosis: a prospective study.

OBJECTIVE: To prospectively evaluate predictors of incomplete recovery after the first attacks in a cohort of patients with clinically isolated syndrome or relapsing-remitting multiple sclerosis. METHODS: Seventy-two consecutive patients recruited from January 2001 to December 2003, evaluated every six months or at any relapse up to 31 July 2005. Relapse intervals were calculated from the date of onset, nadir, onset of improvement and maximum improvement. Predictive factors analysed were relapse-related (age at relapse onset, season and severity of the relapse, type of symptoms, speed of onset, plateau and total duration, number of affected Functional systems, preceding infections) and individual-related (gender, age at first attack, season of birth and first attack, characteristics of first brain MRI and cerebrospinal fluid oligoclonal bands, Link Index, IgG). RESULTS: We counted 209 attacks: 44 (21%) left mild sequelae, and 27 (13%) severe. The highest probability of sequelae was associated with sphincteric symptoms (9/20; 45%), followed by sensitive (38/113; 34%), motor (20/84; 24%), visual (13/61; 21%), cerebellar (4/24; 17%), brainstem (5/44; 11%) and others (0/6) ( P 0.005). Four variables were still relevant to predict sequelae after multivariate analysis: mild, moderate or severe relapses versus very mild (Odds ratio = 17.2, 95% confidence limits = 2.2-136.4), intermediate or long relapses versus short (3.2, 1.5-6.9), age >or= 30 at relapse onset (2.9, 1.5-5.7) and bi-polysymptomatic versus monosymptomatic (2.2, 1.1-4.3). CONCLUSIONS: Factors predicting incomplete recovery are more closely linked to the characteristics of the single relapse (extension and duration of tissue damage) than to the patient's genetic and environmental background.

Inter-coder agreement for ICD-9-CM coding of stroke.

The objective was to evaluate agreement among neurologists for coding stroke, using the International Classification of Diseases 9th Revision - Clinical Modification (ICD-9-CM). Clinical records of 53 consecutive patients (27 stroke or TIA and 26 other diseases) discharged from our general neurology department were coded by four neurology residents, four general neurologists and four neurologists trained in ICD-coding (experts). Inter-coder agreement was evaluated by the kappa statistic. The overall kappa value for coding 430-438 was 0.77 (95% confidence interval 0.70-0.84) for primary (PDx) and 0.82 (0.77-0.88) for PDx+secondary diagnoses (SDx). It was 0.73-0.86 for the residents, 0.78-0.90 for the neurologists and 0.67-0.88 for the experts. The overall kappa values (PDx, SDx) for specific codes were 0.83-0.88 for 431-intracerebral haemorrhage (residents: 0.75-0.89; neurologists: 0.91-0.96; experts: 0.78-0.88) and 0.48-0.51 for 434-occlusion of cerebral arteries) (residents: 0.26-0.26; neurologists: 0.61-0.66; experts: 0.60-0.65). Agreement was substantial for the whole code group 430-438 and higher for code 431 than 434. Reliability was generally improved when both PDx and SDx were considered. Specific training did not increase inter-coders' agreement.

EFNS guideline on the diagnosis and management of alcohol-related seizures: report of an EFNS task force.

Despite being a considerable problem in neurological practice and responsible for one-third of seizure-related admissions, there is little consensus as to the optimal investigation and management of alcohol-related seizures. The final literature search was undertaken in September 2004. Consensus recommendations are given graded according to the EFNS guidance regulations. To support the history taking, use of a structured questionnaire is recommended. When the drinking history is inconclusive, elevated values of carbohydrate-deficient transferrin and/or gammaglutamyl transferase can support a clinical suspicion. A first epileptic seizure should prompt neuroimaging (CT or MRI). Before starting any carbohydrate containing fluids or food, patients presenting with suspected alcohol overuse should be given prophylactic thiamine parenterally. After an alcohol withdrawal seizure (AWS), the patient should be observed in hospital for at least 24 h and the severity of withdrawal symptoms needs to be followed. For patients with no history of withdrawal seizures and mild to moderate withdrawal symptoms, routine seizure preventive treatment is not necessary. Generally, benzodiazepines are efficacious and safe for primary and secondary seizure prevention; diazepam or, if available, lorazepam, is recommended. The efficacy of other drugs is insufficiently documented. Concerning long-term recommendations for non-alcohol dependent patients with partial epilepsy and controlled seizures, small amounts of alcohol may be safe. Alcohol-related seizures require particular attention both in the diagnostic work-up and treatment. Benzodiazepines should be chosen for the treatment and prevention of recurrent AWS.

Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity.

BACKGROUND: There is no consensus method for determining progression of disability in patients with multiple sclerosis (MS) when each patient has had only a single assessment in the course of the disease. METHODS: Using data from two large longitudinal databases, the authors tested whether cross-sectional disability assessments are representative of disease severity as a whole. An algorithm, the Multiple Sclerosis Severity Score (MSSS), which relates scores on the Expanded Disability Status Scale (EDSS) to the distribution of disability in patients with comparable disease durations, was devised and then applied to a collection of 9,892 patients from 11 countries to create the Global MSSS. In order to compare different methods of detecting such effects the authors simulated the effects of a genetic factor on disability. RESULTS: Cross-sectional EDSS measurements made after the first year were representative of overall disease severity. The MSSS was more powerful than the other methods the authors tested for detecting different rates of disease progression. CONCLUSION: The Multiple Sclerosis Severity Score (MSSS) is a powerful method for comparing disease progression using single assessment data. The Global MSSS can be used as a reference table for future disability comparisons. While useful for comparing groups of patients, disease fluctuation precludes its use as a predictor of future disability in an individual.

Cerebral venous thrombosis: a retrospective multicentre study of 48 patients.

The objective was to describe the clinical features and management of cerebral venous thrombosis (CVT) in non-selected centres. An observational study in 11 neurological departments in NW Italy was carried out from 1995 through 1999 on 38 female and 10 male patients. Mean age: 44.8 years, SD=14.3. Onset: acute in 21 patients (44%), subacute in 17 (35%) and chronic in 10 (21%). Most frequent onset: with focal deficits and/or seizures, followed by impaired consciousness or confusion, isolated headache, isolated intracranial hypertension and cavernous syndrome. No risk factor was found in 8 patients (17%). The superior sagittal sinus was involved in 27 patients (56%) and the transverse sinus in 29 (60%). Anticoagulants were used in 45 patients (94%). Rankin Scale score at discharge: 0 (27 patients), 1 (four), 2 (five), 3 (five), 4 (none), 5 (one) and six were dead. Thirteen patients had deep CVT: age, risk factors, neurological signs and outcome differed from cortical CVT (35 patients), although not significantly. Clinical features, risk factors and outcome of CVT patients from non-selected centres are similar to those from specialised centres.

Accuracy of the ICD-9 codes for identifying TIA and stroke in an Italian automated database.

The object of this study was to evaluate the sensitivity and positive predictive value (PPV) of International Classification of Diseases, 9th revision (ICD-9) codes 430-438 in the Sistema Informativo Sanitario Regionale (SISR), an Italian health care automated database. We compared the SISR with a manual search of all cases of transient ischaemic attack (TIA) and stroke discharged from the Novara Hospital, NW Italy. Results were as follows: SISR list: 1017 patients; manual list 1005. Linked: 896; false negatives: 109; false positives: 121. Sensitivity of codes 430-438: 77% at the primary position only and 89% at either the primary or secondary position; PPV: 93% and 88%. Sensitivity and PPV for specific codes vs. each subcategory (sensitivity at the primary position only/any position; PPV at the primary position only/any position): for 430, subarachnoid haemorrhage (33/35%; 46/43%); for 431, cerebral haemorrhage (57/59%; 77/75%); for 434, cerebral infarction (35/37%; 90/87%); for 436, stroke of unknown type (29/29%; 19/16%); and for 435, TIA (75/82%; 80/78%). The SISR database has a high PPV; sensitivity is high for TIA, but low for specific stroke ICD codes.

Genomic P elements and P-M characteristics of eastern Australian populations of Drosophila melanogaster.

As part of our effort to monitor changes in the clinical pattern of P element-associated traits in eastern Australian Drosophila melanogaster, we investigated the genomic P elements of 293 isofemale lines collected in the period 1991-1994 from 45 localities. P elements were present in many copies in all genomes examined, with full-size P and KP element size classes accounting for the large majority. SR elements were not present in at least 92% of the lines tested. South of about 26 degrees south Latitude (degree SLat), the ratio of KP to full-size P elements (KP/P ratio) increased, correlating weakly with the P-M phenotypes of the populations, from moderately P populations (26-29 degrees SLat) to M populations (37-38 degrees SLat). North of 26 degrees SLat, in weak P populations, the KP/P ratio was higher than between 26 and 29 degrees Slat. The KP/P ratio appears to be higher in the northern populations than it was when previous studies were done. Overall, a high KP/P ratio among lines correlated roughly with a lack of P activity, but it also correlated with reduced repressor function. In a sample of 30 lines, a maternal effect of repressor function did not show a pattern with latitude, nor with KP/P ratio, nor with presence or absence of P activity.