General neurology: Current challenges and future implications.

BACKGROUND AND PURPOSE: In the coming decades, the world will face an increasing burden of neurological disorders (ND) and an urgent need to promote brain health. These challenges contrast with an insufficient neurological workforce in most countries, as well as decreasing numbers of general neurologists and neurologists attracted to work in general neurology (GN). This white paper aims to review the current situation of GN and reflect on its future. METHODS: The European Academy of Neurology (EAN) task force (TF) met nine times between November 2021 and June 2023. During the 2023 EAN annual meeting, attendees were asked to answer five questions concerning the future of GN. The document was sent for suggestions and eventually approval to the board and the presidents of the 47 national societies of the EAN. RESULTS: The TF first identified four relevant current and future challenges related to GN: (i) definition, (ii) practice, (iii) education, and (iv) research. The TF then identified seven initiatives to further develop GN at both the academic and community level. Finally, the TF formulated 16 recommendations to promote GN in the future. CONCLUSIONS: GN will remain essential in the coming decades to provide rapid, accessible, and comprehensive management of patients with ND that is affordable and cost-effective. There is also a need for research, education, and other initiatives aiming to facilitate improved working conditions, recognition, and prestige for those pursuing a career in GN.

Reversible paraparesis due to extramedullary hematopoiesis.

Extramedullary hematopoiesis should be considered in the differential diagnosis of spastic paraplegia in a patient with thalassemia. Radiotherapy remains the treatment of choice, and regain of motor power is expected.

Rituximab for people with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is the most common neurological cause of disability in young adults. Off-label rituximab for MS is used in most countries surveyed by the International Federation of MS, including high-income countries where on-label disease-modifying treatments (DMTs) are available.  OBJECTIVES: To assess beneficial and adverse effects of rituximab as 'first choice' and as 'switching' for adults with MS. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registers for completed and ongoing studies on 31 January 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and controlled non-randomised studies of interventions (NRSIs) comparing rituximab with placebo or another DMT for adults with MS. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. We used the Cochrane Collaboration's tool for assessing risk of bias. We rated the certainty of evidence using GRADE for: disability worsening, relapse, serious adverse events (SAEs), health-related quality of life (HRQoL), common infections, cancer, and mortality. We conducted separate analyses for rituximab as 'first choice' or as 'switching', relapsing or progressive MS, comparison versus placebo or another DMT, and RCTs or NRSIs. MAIN RESULTS: We included 15 studies (5 RCTs, 10 NRSIs) with 16,429 participants of whom 13,143 were relapsing MS and 3286 progressive MS. The studies were one to two years long and compared rituximab as 'first choice' with placebo (1 RCT) or other DMTs (1 NRSI), rituximab as 'switching' against placebo (2 RCTs) or other DMTs (2 RCTs, 9 NRSIs). The studies were conducted worldwide; most originated from high-income countries, six from the Swedish MS register. Pharmaceutical companies funded two studies. We identified 14 ongoing studies. Rituximab as 'first choice' for relapsing MS Rituximab versus placebo: no studies met eligibility criteria for this comparison. Rituximab versus other DMTs: one NRSI compared rituximab with interferon beta or glatiramer acetate, dimethyl fumarate, natalizumab, or fingolimod in active relapsing MS at 24 months' follow-up. Rituximab likely results in a large reduction in relapses compared with interferon beta or glatiramer acetate (hazard ratio (HR) 0.14, 95% confidence interval (CI) 0.05 to 0.39; 335 participants; moderate-certainty evidence). Rituximab may reduce relapses compared with dimethyl fumarate (HR 0.29, 95% CI 0.08 to 1.00; 206 participants; low-certainty evidence) and natalizumab (HR 0.24, 95% CI 0.06 to 1.00; 170 participants; low-certainty evidence). It may make little or no difference on relapse compared with fingolimod (HR 0.26, 95% CI 0.04 to 1.69; 137 participants; very low-certainty evidence). The study reported no deaths over 24 months. The study did not measure disability worsening, SAEs, HRQoL, and common infections. Rituximab as 'first choice' for progressive MS One RCT compared rituximab with placebo in primary progressive MS at 24 months' follow-up. Rituximab likely results in little to no difference in the number of participants who have disability worsening compared with placebo (odds ratio (OR) 0.71, 95% CI 0.45 to 1.11; 439 participants; moderate-certainty evidence). Rituximab may result in little to no difference in recurrence of relapses (OR 0.60, 95% CI 0.18 to 1.99; 439 participants; low-certainty evidence), SAEs (OR 1.25, 95% CI 0.71 to 2.20; 439 participants; low-certainty evidence), common infections (OR 1.14, 95% CI 0.75 to 1.73; 439 participants; low-certainty evidence), cancer (OR 0.50, 95% CI 0.07 to 3.59; 439 participants; low-certainty evidence), and mortality (OR 0.25, 95% CI 0.02 to 2.77; 439 participants; low-certainty evidence). The study did not measure HRQoL. Rituximab versus other DMTs: no studies met eligibility criteria for this comparison. Rituximab as 'switching' for relapsing MS  One RCT compared rituximab with placebo in relapsing MS at 12 months' follow-up. Rituximab may decrease recurrence of relapses compared with placebo (OR 0.38, 95% CI 0.16 to 0.93; 104 participants; low-certainty evidence). The data did not confirm or exclude a beneficial or detrimental effect of rituximab relative to placebo on SAEs (OR 0.90, 95% CI 0.28 to 2.92; 104 participants; very low-certainty evidence), common infections (OR 0.91, 95% CI 0.37 to 2.24; 104 participants; very low-certainty evidence), cancer (OR 1.55, 95% CI 0.06 to 39.15; 104 participants; very low-certainty evidence), and mortality (OR 1.55, 95% CI 0.06 to 39.15; 104 participants; very low-certainty evidence). The study did not measure disability worsening and HRQoL.  Five NRSIs compared rituximab with other DMTs in relapsing MS at 24 months' follow-up. The data did not confirm or exclude a beneficial or detrimental effect of rituximab relative to interferon beta or glatiramer acetate on disability worsening (HR 0.86, 95% CI 0.52 to 1.42; 1 NRSI, 853 participants; very low-certainty evidence). Rituximab likely results in a large reduction in relapses compared with interferon beta or glatiramer acetate (HR 0.18, 95% CI 0.07 to 0.49; 1 NRSI, 1383 participants; moderate-certainty evidence); and fingolimod (HR 0.08, 95% CI 0.02 to 0.32; 1 NRSI, 256 participants; moderate-certainty evidence). The data did not confirm or exclude a beneficial or detrimental effect of rituximab relative to natalizumab on relapses (HR 1.0, 95% CI 0.2 to 5.0; 1 NRSI, 153 participants; very low-certainty evidence). Rituximab likely increases slightly common infections compared with interferon beta or glatiramer acetate (OR 1.71, 95% CI 1.11 to 2.62; 1 NRSI, 5477 participants; moderate-certainty evidence); and compared with natalizumab (OR 1.58, 95% CI 1.08 to 2.32; 2 NRSIs, 5001 participants; moderate-certainty evidence). Rituximab may increase slightly common infections compared with fingolimod (OR 1.26, 95% CI 0.90 to 1.77; 3 NRSIs, 5187 participants; low-certainty evidence). It may make little or no difference compared with ocrelizumab (OR 0.02, 95% CI 0.00 to 0.40; 1 NRSI, 472 participants; very low-certainty evidence). The data did not confirm or exclude a beneficial or detrimental effect of rituximab on mortality compared with fingolimod (OR 5.59, 95% CI 0.22 to 139.89; 1 NRSI, 136 participants; very low-certainty evidence) and natalizumab (OR 6.66, 95% CI 0.27 to 166.58; 1 NRSI, 153 participants; very low-certainty evidence). The included studies did not measure SAEs, HRQoL, and cancer. AUTHORS' CONCLUSIONS: For preventing relapses in relapsing MS, rituximab as 'first choice' and as 'switching' may compare favourably with a wide range of approved DMTs. A protective effect of rituximab against disability worsening is uncertain. There is limited information to determine the effect of rituximab for progressive MS.  The evidence is uncertain about the effect of rituximab on SAEs. They are relatively rare in people with MS, thus difficult to study, and they were not well reported in studies. There is an increased risk of common infections with rituximab, but absolute risk is small.  Rituximab is widely used as off-label treatment in people with MS; however, randomised evidence is weak. In the absence of randomised evidence, remaining uncertainties on beneficial and adverse effects of rituximab for MS might be clarified by making real-world data available.

Retraction of: A case report of Morvan syndrome.

[This retracts the article DOI: 10.1093/omcr/omab064.].

A case report of Morvan syndrome.

For legal reasons, the publisher has withdrawn this article from public view. For additional information, please contact the publisher.

Eagle syndrome presenting as a neurological emergency: A case report.

BACKGROUND: Eagle syndrome, due to the elongation of the styloid process as well as the calcification of the stylohyoid ligament, rarely presents itself with a major neurological disorder such as a brain infarct. CASE DESCRIPTION: Authors describe the case report of a previously healthy 64-year-old Caucasian male that complained of inability to control his right upper and lower extremity of an acute nature. Imaging at the emergency department (magnetic resonance of the brain and computerized angiography) showed the presence of elongated styloid process bilaterally with clear predomination at the left side. The brain ischemia (left temporal brain infarct) was due to carotid artery dissection, and the left internal carotid artery was not visualized during the contrast-enhanced angiography. The patient was hospitalized at a neurological facility and thereafter referred to surgery for styloidectomy. CONCLUSION: The present case underscores the need for a prompt diagnosis and an enhanced awareness of this syndrome, especially among emergency department professionals.

Practical needs and considerations for refugees and other forcibly displaced persons with neurological disorders: Recommendations using a modified Delphi approach.

Background: There are >70 million forcibly displaced people worldwide, including refugees, internally displaced persons, and asylum seekers. While the health needs of forcibly displaced people have been characterized in the literature, more still needs to be done globally to translate this knowledge into effective policies and actions, particularly in neurology. Methods: In 2020, a global network of published experts on neurological disease and refugees was convened. Nine physician experts from nine countries (2 low, 1 lower-middle income, 5 upper-middle, 1 high income) with experience treating displaced people originating from 18 countries participated in three survey and two discussion rounds in accordance with the Delphi method. Results: A consensus list of priority interventions for treating neurological conditions in displaced people was created, agnostic to cost considerations, with the ten highest ranking tests or treatments ranked as: computerized tomography scans, magnetic resonance imaging scans, levetiracetam, acetylsalicylic acid, carbamazepine, paracetamol, sodium valproate, basic blood tests, steroids and anti-tuberculous medication. The most important contextual considerations (100% consensus) were all economic and political, including the economic status of the displaced person's country of origin, the host country, and the stage in the asylum seeking process. The annual cost to purchase the ten priority neurological interventions for the entire displaced population was estimated to be 220 million USD for medications and 4.2 billion USD for imaging and tests. Conclusions: A need for neuroimaging and anti-seizure medications for forcibly displaced people was emphasized. These recommendations could guide future research and investment in neurological care for forcibly displaced people.

Limits on testamentary freedom for people with dementia in Albania: Innovative Practice.

The extent to which dementia affects a person's testamentary capacity has been the subject of much litigation with some countries introducing legal tests to assess capacity. In light of substantial societal change in Albania in the last two decades and an epidemic of property litigation, Albanian legal practice is witnessing an increasing number of attempts to posthumously nullify wills. Plaintiffs are mainly relatives of the deceased testator who are unhappy with the quantity or quality of the property they have inherited. Based on plaintiffs' claims, solicitors may request expert neuropsychiatric reviews postmortem, often basing their position on prescription drug use by the testator during his/her last years of life. The authors discuss ethical issues intrinsically related to the difficult role of a potential expert witness in these litigation cases.

Right Hemispheric Leukoencephalopathy as an Incidental Finding Following a Lightning Strike.

BACKGROUND: Lightning injuries may produce a variety of medical conditions, and specific neurological complications have been identified, with the character of immediate aftershock effects or even long-term consequences. AIM: The authors describe the incidental finding following a routine unenhanced brain MRI performed to a young female patient, suffering from a headache. CASE REPORT: Diffuse white matter changes with the character of a leukoencephalopathy were seen, which strictly interested only the right cerebral hemisphere. The parents referred that she suffered from an indoor lightning strike at age of seven months, although she survived with almost no external burns or signs, and recovered uneventfully at that time. A discussion over the effects of electrocution and lightning strike on the human body in general, and over the nervous system, is made. Particular attention must be shown when making the differential diagnosis of leukoencephalopathies with a strictly one-hemisphere extension since several other conditions might resemble each other under the radiological aspect, here including brain viral infections, genetic disorders, and so on. CONCLUSION: The particularity of the long-term aftershock effects of the lightning strike on the central nervous system raise again the necessity of collecting data and duly reporting every electrical accident, lightning events included.

Accuracy of Conventional Diagnostic Methods for Identifying Structural Changes in Patients with Focal Epilepsy.

BACKGROUND: Epilepsy is a neurological disorder characterized by abnormal firing of nerve impulses in the brain. AIM: This study aims to investigate the frequency of appearance of pathological changes in conventional examination methods (electroencephalography-EEG, brain computerized tomography -CT or brain magnetic resonance imaging - MRI) in patients with epilepsy, and relationship between clinical manifestations and localization of changes in CT or MRI. METHODS: In this study we have included 110 patients with focal epilepsy who fulfilled the inclusion criteria out of 557 initially diagnosed patients. Detailed clinical examination together with brain imaging (CT and MRI) and electroencephalography examination was performed. We have evaluated the accuracy of each diagnostic method to localize the epileptic focus. Diagnosis of epilepsy was determined by the ILAE (International League Against Epilepsy) criteria of the year 1989, and classification of epileptic seizures was made according to the ILAE classification 2010. RESULTS: Electroencephalography presented changes in 60.9% of patients; brain CT in 42.1%, and MRI in 78% of the patients. The results of our study showed that clinical manifestations were not always conveyed with pathological changes in conventional examining methods performed. Of the total of 79 patients with changes in imaging (8 with changes in CT and 71 in MRI), 79.7% presented a clinical picture compatible with the region in which morphological changes were found, while in 20.3% of patients the presented morphological changes were not aligned with the clinical picture. CONCLUSION: In patients with epilepsy, conventional examination methods do not always find pathological changes, while clinical manifestations of epilepsy did not always coincide with the location of changes in imaging. Further studies are needed to see if there is clear border between focal and generalized epilepsy.

Epidemiological characteristics and functional disability of multiple sclerosis patients in Kosovo.

BACKGROUND AND OBJECTIVES: Multiple Sclerosis (MS) is a chronic recurrent neurological disease that affects the Central Nervous System. This study aims to determine epidemiological factors that affect the appearance of MS, such as: incidence, prevalence, mortality, case appearance in accordance with the disease phase RRMS, SPMS, PPMS, gender, age, age group, and EDSS. MATERIALS AND METHODS: Deals with analyzing diagnosed and treated patients in the Clinic of Neurology in Prishtina during the period of 2003-2012. The research was conducted through a questionnaire applied in the diagnosed cases of MS. Information on patients was gathered from: history of illness, discharge reports and other relevant documents on MS illness. Clinical and epidemiological-descriptive study methods were used. The acquired results are shown through tables, graphics. Statistical processing was conducted with Microsoft Office Excel. RESULTS: From the total number of doubtful hospitalized cases of demyelinization (644) in the Clinic of Neurology in Prishtina, 412 cases (64%) were diagnosed with MS. For the period of 2003-2012 the prevalence of MS has been 19.6 of patients in 100,000 inhabitants. MS incidence rate was 0.95 of patients in 100,000 inhabitants. MS mortality rate was 0.14 of deceased in 100,000 inhabitants. The ratio female--male is 2.3:1. A larger number of patients fall within the age group of 30-39 years-old. Clinical form trends: RRSM 72.3%, SPSM 22.6%, PPSM 5.1%. The rate of EDSS 78.3% (0-3.5), 14.9% (4-6.5), 6.8% (7-9).

Epidemiological characteristics and functional disability of multiple sclerosis patients in kosovo.

BACKGROUND AND OBJECTIVES: Multiple Sclerosis (MS) is a chronic recurrent neurological disease that affects the Central Nervous System. This study aims to determine epidemiological factors that affect the appearance of MS, such as: incidence, prevalence, mortality, case appearance in accordance with the disease phase RRMS, SPMS, PPMS, gender, age, age group, and EDSS. MATERIALS AND METHODS: Deals with analyzing diagnosed and treated patients in the Clinic of Neurology in Prishtina during the period of 2003-2012. The research was conducted through a questionnaire applied in the diagnosed cases of MS. Information on patients was gathered from: history of illness, discharge reports and other relevant documents on MS illness. Clinical and epidemiological-descriptive study methods were used. The acquired results are shown through tables, graphics. Statistical processing was conducted with Microsoft Office Excel. RESULTS: From the total number of doubtful hospitalized cases of demyelinization (644) in the Clinic of Neurology in Prishtina, 412 cases (64%) were diagnosed with MS. For the period of 2003-2012 the prevalence of MS has been 19.6 of patients in 100,000 inhabitants. MS incidence rate was 0.95 of patients in 100,000 inhabitants. MS mortality rate was 0.14 of deceased in 100,000 inhabitants. The ratio female - male is 2.3:1. A larger number of patients fall within the age group of 30-39 years-old. Clinical form trends: RRSM 72.3%, SPSM 22.6%, PPSM 5.1%. The rate of EDSS 78.3% (0-3.5), 14.9% (4-6.5), 6.8% (7-9).

Clinical variability of the cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy phenotype in two siblings of a large family showing the same mutation.

A 44-year-old Albanian male was consulted and diagnosed with dementia. His magnetic resonance imaging suggested diffuse white matter changes. The suspicion of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) was raised, and a genetic analysis confirmed such a suspicion through uncovering a pathogenic mutation at the level of exon 4 (c.475C>T) of chromosome 19. The patient came from a large family of 13 children, all of whom underwent clinical, genetic, and imaging examination. The pathogenic mutation was found present only in his eldest sister (50 years old), and she presented also very suggestive signs of CADASIL in her respective imaging study, but without any clinically significant counterpart. All other siblings were free from clinical and radiological signs of the disorder. Our opinion was that we were dealing with a mutation showing a very low level of penetrance, with only two siblings affected in a large Albanian family with 13 children.

Factors influencing mini-mental state (MMSE) score in stroke patients.

AIM: To evaluate the usefulness of MMSE score in vascular dementia and the influence of different factors on the MMSE score. SUBJECT AND METHODS: We studied 78 stroke patients followed up at the neurology unit, Specialistic Polyclinic 2, Tirana. A neurological visit is done and the MMSE score is calculated for each of them. We noted the stroke form (ischemic, hemorrhagic), patient's age, education, time from stroke onset, accompanying neurological disorders (parkinsonism, epilepsy), risk factors (arterial hypertension, cardiac diseases, diabetes mellitus, smoking, carotid stenosis). The imaging (CT and/or MRI) of the brain is requested. Independent Samples Test, t-test for Equality of Means, 2 - tailed, is applied for the statistical evaluation. RESULTS: The mean age of the patients in the study is 70.31 years old. There are 37 females (47.43%) and 41 males (52.56%). 12 (15.38%) patients had hemorrhagic and 66 (84.61%) ischemic stroke. The mean time from stroke onset is 4.55 years. 15 (19.2%) patients have parkinsonism, 1 other extra pyramidal disorder, 3 (3.8%) secondary generalized epilepsy. The mean MMSE score for all patients is 23.48. The multi ischemic cerebral lesions were present in the imaging of 12 (15.38%) patients. The generalized cortical atrophy is found in 25 (32%) patients and the temporal atrophy in 14 (17.94%) patients. We analyzed the data of 37 patients [16 (43.24%) females and 21 (56.75%) males], with MMSE score < or = 23. The mean age is 75.39 years old. 6 (16.21%) patients are diagnosed with hemorrhagic stroke. 3 (8.1%) patients have secondary generalized epilepsy, 9 (24.32%) are suffering of parkinsonism and the mean time from stroke onset is 4.31 years. The imaging study revealed multi ischemic cerebral lesions in 9 (24.3%) patients. We found accompanying temporal atrophy in 10 (27%) patients, frontal atrophy in 2 (5.4%) patients, and generalized cortical atrophy in 17 (45.9%) patients. CONCLUSION: Dementia after stroke is frequent. The MMSE is still a useful scale to evaluate the VaD and is related to age, gender, education, stroke age, cardiovascular risk factors, stroke type and localization, other neurological disorders as epilepsy and parkinsonism.

Avoiding parental distress when discussing about SUDEP: the Albanian experience.

INTRODUCTION: Pediatric SUDEP (Sudden Unexpected Death in Epilepsy) is an uncommon event, but its unpredictability has rendered the issue very important to be addressed, under all points of view: medical, moral and legal one. The death of a child has been always considered a dramatic event for the Albanian families, and when it overcomes unexpectedly the emotional reactions might even be more exaggerated. DISCUSSION: Debates about truth-telling on the prognosis, or even on the probability of a sudden death related to the main diagnosis (epilepsy) are old and controversial. Risk factors for SUDEP have been formulated and strategies to confront them have been put in place; however medical (pharmacological) compliance seems by large the most important protective factor. CONCLUSION: To our opinion, disclosing the risk of a sudden death to the family on a child suffering from epilepsy is a necessary act; timing and ways of disclosure are details that need to be refined case-by-case, in a situation where a general consensus or guidelines are lacking. A step-by-step approach and a gradual informing are helpful and psychologically acceptable from the parents or other relatives.

Inapplicability of advance directives in a paternalistic setting: the case of a post-communist health system.

BACKGROUND: The Albanian medical system and Albanian health legislation have adopted a paternalistic position with regard to individual decision making. This reflects the practices of a not-so-remote past when state-run facilities and a totalitarian philosophy of medical care were politically imposed. Because of this history, advance directives concerning treatment refusal and do-not-resuscitate decisions are still extremely uncommon in Albania. Medical teams cannot abstain from intervening even when the patient explicitly and repeatedly solicits therapeutic abstinence. The Albanian law on health care has no provisions regarding limits or withdrawal of treatment. This restricts the individual's healthcare choices. DISCUSSION: The question of 'medically futile' interventions and pointless life-prolonging treatment has been discussed by several authors. Dutch physicians call such interventions 'medisch zinloos' (senseless), and the Netherlands, as one of the first states to legislate on end-of-life situations, actually regulates such issues through appropriate laws. In contrast, leaving an 'advance directive' is not a viable option for Albanian ailing individuals of advanced age. Verbal requests are provided during periods of mental competence, but unfortunately such instructions are rarely taken seriously, and none of them has ever been upheld in a legal or other official forum. SUMMARY: End-of-life decisions, treatment refusal and do-not-resuscitate policies are hazardous options in Albania, from the legal point of view. Complying with them involves significant risk on the part of the physician. Culturally, the application of such instructions is influenced from a mixture of religious beliefs, death coping-behaviors and an immense confusion concerning the role of proxies as decision-makers. Nevertheless, Albanian tradition is familiar with the notion of 'amanet', a sort of living will that mainly deals the property and inheritance issues. Such living wills, verbally transmitted, may in certain cases include advance directives regarding end-of-life decisions of the patient including refusal or termination of futile medical treatments. Since these living wills are never formally and legally validated, their application is impossible and treatment refusal remains still non practicable. Tricks to avoid institutional treatment under desperate conditions are used, aiming to provide legal coverage for medical teams and relatives that in extreme situations comply with the advice of withholding senseless treatment.