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Background: The transmission of amyloid β (Aβ) in humans leading to iatrogenic cerebral amyloid angiopathy (iCAA) is a novel concept with analogies to prion diseases. However, the number of published cases is low, and larger international studies are missing. Aims: We aimed to build a large multinational collaboration on iCAA to better understand the clinical spectrum of affected patients. Methods: We collected clinical data on patients with iCAA from Austria, Croatia, Italy, Slovenia, and Spain. Patients were included if they met the proposed Queen Square diagnostic criteria (QSC) for iCAA. In addition, we pooled data on disease onset, latency, and cerebrospinal fluid (CSF) biomarkers from previously published iCAA cases based on a systematic literature review. Results: Twenty-seven patients (22% women) were included in this study. Of these, 19 (70%) met the criteria for probable and 8 (30%) for possible iCAA. Prior neurosurgical procedures were performed in all patients (93% brain surgery, 7% spinal surgery) at median age of 8 (interquartile range (IQR) = 4–18, range = 0–26 years) years. The median symptom latency was 39 years (IQR = 34–41, range = 28–49). The median age at symptom onset was 49 years (IQR = 43–55, range = 32–70). Twenty-one patients (78%) presented with intracranial hemorrhage and 3 (11%) with seizures. Conclusions: Our large international case series of patients with iCAA confirms a wide age boundary for the diagnosis of iCAA. Dissemination of awareness of this rare condition will help to identify more affected patients. [ABSTRACT FROM AUTHOR]

I n the context of an adequate health care organization, the figure of the neurologist as an emergency operator (in the emergency room—ER—and/or in a dedicated outpatient clinic) is crucial for an effective functional connection with the territory (and therefore with general practitioners), a reduction in inappropriate ER accesses, specific diagnostic and therapeutic approaches to neurological emergencies in the ER and a reduction in nonspecific or even unnecessary instrumental investigations. In this position paper of the Italian Association of Emergency Neurology (ANEU: Associazione Neurologia dell'Emergenza Urgenza), these issues are addressed, and two important organizational solutions are proposed: The Neuro Fast Track, as an outpatient organization approach strongly linked to general practitioners and non-neurological specialists and dedicated to cases with deferrable urgency (to be assessed within 72 h) The identification of an emergency neurologist, who is engaged in ER assessments as a consultant and involved in the management of the semi-intensive care unit of the emergency neurology and the stroke unit according to an appropriate rotation, as well as in consultations for patients with neurological emergencies in inpatient wards The possibility of computerizing the screening of patients with deferrable urgency in the Neuro Fast Track is described. A dedicated app represents an important tool that can facilitate the identification of patients for whom deferred assessment is appropriate, the scheduling of neurological examinations and reductions in the booking time through a more rapid approach to specialist assessment and subsequent investigations. [ABSTRACT FROM AUTHOR]

Background: In 2017, the European Association for Neuro-Oncology (EANO) published the guideline for palliative care (PC) in adults with glioma. The Italian Society of Neurology (SIN), the Italian Association for Neuro-Oncology (AINO), and the Italian Society for Palliative Care (SICP) joined forces to update and adapt this guideline to the Italian context and aimed to involve patients and carers in the formulation of the clinical questions. Methods: During semi-structured interviews with glioma patients and focus group meetings (FGMs) with family carers of deceased patients, participants rated the importance of a set of pre-specified intervention topics, shared their experience, and suggested additional topics. Interviews and FGMs were audio-recorded, transcribed, coded, and analyzed (framework and content analysis). Results: We held 20 interviews and five FGMs (28 carers). Both parties considered the pre-specified topics as important, chiefly information/communication, psychological support, symptoms management, and rehabilitation. Patients aired the impact of focal neurological and cognitive deficits. Carers reported difficulties in dealing with patient's behavior and personality changes and appreciated the preservation of patient's functioning via rehabilitation. Both affirmed the importance of a dedicated healthcare path and patient's involvement in the decision-making process. Carers expressed the need to be educated and supported in their caregiving role. Conclusions: Interviews and FGMs were well informative and emotionally challenging. Both parties confirmed the importance of the pre-specified topics, and carers suggested one additional topic: education/support to caregivers. Our findings strengthen the importance of a comprehensive care approach and of addressing the needs of both patients and their family carers. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastasis occurs when a tumor spreads from its original site to another part of the body. Several factors are involved in this complex process, including proteins that regulate adhesion between circulating tumor cells and target organs (called adhesion molecules). Additionally, it is shown in the literature that many tumors release small vesicles in the plasma that may contribute to metastatization. In this study, the authors focused on brain metastasis using an in vitro model of the physiological barrier that protects the brain, essentially consisting of a co-culture of endothelial cells and astrocytes. They examined the ability of breast and lung tumor cells to cross this barrier, as well as the expression of adhesion molecules. Furthermore, they collected and analyzed the vesicles released by tumor cells to determine their ability to create ruptures in the barrier. The data indicated that cells with intermediate levels of adhesion molecule expression were most effective in migrating through the barrier. Additionally, the vesicles produced by tumor cells were able to induce the death of endothelial cells, the primary cellular component of the barrier. Data reported support the role of adhesion molecules and tumor-produced vesicles in brain metastasis, in addition to other factors. Metastatic brain disease (MBD) has seen major advances in clinical management, focal radiation therapy approaches and knowledge of biological factors leading to improved prognosis. Extracellular vesicles (EVs) have been found to play a role in tumor cross-talk with the target organ, contributing to the formation of a premetastatic niche. Human lung and breast cancer cell lines were characterized for adhesion molecule expression and used to evaluate their migration ability in an in vitro model. Conditioned culture media and isolated EVs, characterized by super resolution and electron microscopy, were tested to evaluate their pro-apoptotic properties on human umbilical vein endothelial cells (HUVECs) and human cerebral microvascular endothelial cells (HCMEC/D3) by annexin V binding assay. Our data showed a direct correlation between expression of ICAM1, ICAM2, β3-integrin and α2-integrin and the ability to firmly adhere to the blood–brain barrier (BBB) model, whereas the same molecules were down-regulated at a later step. Extracellular vesicles released by tumor cell lines were shown to be able to induce apoptosis in HUVEC while brain endothelial cells showed to be more resistant. [ABSTRACT FROM AUTHOR]

Background: In 2017, the European Association of Neuro-Oncology (EANO) published the guideline for palliative care in adults with glioma. The Italian Society of Neurology (SIN), the Italian Society for Palliative Care (SICP), and the Italian Association for Neuro-Oncology (AINO) joined forces to update the guideline, and adapt it to the Italian context. Aim: We involved patients, caregivers, and (herein presented) healthcare professionals (HPs) in the formulation of the guideline clinical questions. Design and participants: Online survey of Italian HPs experienced in the care of patients with glioma. Participants rated the importance of 14 pre-specified intervention topics on a 0/10 scale and gave their free comments. Results: Of 244 participants, 149 (61%) were palliative medicine (PM) HPs and 95 Neuro HPs. Their mean age was 48.9 years, 63% were women, and 48% had over 12 years of experience in the care of glioma patients. Physicians were 68%, followed by nurses (28%), psychologists (7%), therapists (3%), and social workers (2%). Most HPs rated the pre-specified topics as important (score ≥ 7) or critical (score ≥ 9), with some differences between PM and Neuro HP groups. There were 58 free comments: 46 (78%) on nine pre-specified topics, and 13 on four new topics, three of which were guideline-pertinent ("caregiver's support and education"; "family physician's training in neuro-oncology"; and "PM HPs' training in neuro-oncology"). Conclusions: Participation in the survey was high and information-rich, between-group rating differences reflecting HP background. Participants endorsed the 14 intervention topics devised by the guideline panel and identified three additional topics. [ABSTRACT FROM AUTHOR]

Cerebral amyloid angiopathy (CAA) is a small vessel disease, causing spontaneous intracerebral hemorrhage (ICH) in the elderly. It is strongly associated with Alzheimer disease (AD), as most CAA patients show deposition of Aβ—i.e. the basic component of parenchymal Alzheimer amyloid deposits—in the cerebral vessels. Iatrogenic early-onset CAA has been recently identified in patients with a history of traumatic brain injury or other cerebral as well as extra-cerebral lesions that led to neurosurgery or other medical procedures as intravascular embolization by cadaveric dura mater extracts many years before the first ICH event. In those patients, a transmission of Aβ seeds from neurosurgical instruments or from cadaveric dura mater exposure was suggested. We report a 51-year-old woman with unremarkable family history who presented abruptly with aphasia and right hemiparesis. A cerebral left lobar haemorrhagic stroke was documented by neuroimaging. Accurate anamnesis revealed a neurosurgical procedure with cadaveric dura mater graft at the age of 2 years for an arachnoid cyst. The neuropathological examination of the cerebral parietal biopsy showed severe amyloid angiopathy in many leptomeningeal and cortical vessels, as well as abundant parenchymal Aβ deposits, neurofibrillary tangles and neuropil threads. The mechanism involved in the human-to-human transmission of the Aβ proteinopathy remains to be clarified. In our patient the cadaver derived dura used for grafting is a very strong candidate as the source of the transmission. A systematic monitoring of individuals who have had neurosurgical procedures in early life, especially those involving cadaveric dural grafts, is required to determine the ratio of those affected by CAA many years later and unaffected. Moreover, our report confirms that in addition to vascular and parenchymal Aβ pathology, neurofibrillary changes indistinguishable from AD may develop in specific conditions with long latency period from the neurosurgical or embolization procedure. [ABSTRACT FROM AUTHOR]

Introduction: Allgrove syndrome is a genetic disorder characterized by a multisystem involvement manifesting mainly in childhood with esophageal achalasia, adrenal insufficiency, and alacrima. Associated neurological manifestations are frequent in patients with late-onset forms and include peripheral, central, and autonomic dysfunction. The definitive diagnosis remains genetic, but neurological symptoms/signs could be a relevant clue for the diagnosis. Discussion: This syndrome is rare, but it is not impossible for it to occur in adults, so all neurologists must be alert. Moreover, in this regard, neurological symptoms can sometimes be very similar to those of motor neuron disease patients, so that, although rare, Allgrove syndrome may also enter into the differential diagnosis with the bulbar variant of amyotrophic lateral sclerosis. Nevertheless, attention to extra-neurological symptoms must remain high as these play an equally important role in reaching the diagnosis. Case Report: Here we present the case of a patient with some peculiarities that are onset at an advanced age, genetic confirmation of the diagnosis, and prominent neurological involvement, which also opens the differential diagnosis to amyotrophic lateral sclerosis. [ABSTRACT FROM AUTHOR]

Background: Since the outbreak, in 2019, of COVID-19, the world has experienced marked changes in daily habits, partly reflecting the exceptional social restrictions and health measures adopted to contain the disease. All these measures significantly affected not only peoples’s daily lives and psychological well-being but also the possibility for the healthcare system to function properly. In this setting, brain tumour patients were at risk due to their higher physical and mental fragility and their need for regular care. The aim of the present study was to assess, using a self-reported online questionnaire, the patients’s perceptions regarding their disease experience. Materials and methods: We developed an online anonymous self-report survey to assess patients’s disease experience during the pandemic. We investigated the impact of the COVID-19 pandemic on patients’s cancer care schedules, their psychological distress and emotions felt during the pandemic, their levels of worry about COVID-19, and their oncological conditions. Results: 107 patients answered our survey, most of them suffering from a glioma. Less than one-third of the sample had their appointments cancelled, delayed or converted into online visits due to the pandemic. Of the patients who answered the survey, 95% declared they were satisfied with their Institute’s oncological management. The feelings reported most often were peacefulness or anxiety/worry; the majority of the sample reported high levels of loneliness, which tended to increase with age, whilst the psychological distress was correlated with age and with having a recurrence of the disease. Half of the sample declared severe worry about their oncological condition, in particular subjects with a recurrence or who were receiving adjuvant therapies. Patients with recurrence tended to worry more about the possibility of contracting COVID-19, and its effects. Conclusion: Our findings illustrate how fragile and in need of care patients with a brain tumour may be, especially those with more severe clinical conditions. These data may help boost healthcare professionals’s knowledge about brain tumour patients’s needs and fears, so as to be able to offer them a better hospital experience and improve their clinical management, while possibly also reducing the psychological burden on patients and their families. [ABSTRACT FROM AUTHOR]

The article describes an educational curriculum created by the Integrative Health (IH) team consisting of different Wellness Hour classes for acute-rehabilitation patients newly diagnosed with debilitating injuries or diseases. Topics discussed include evaluation and action plan, results and limitations of the program, and nursing implications of the program.

Background: The assessment of human and diagnostic resources is a prerequisite to improving the management of emergency neurology.Objective: To provide a landscape on the organization of the Lombardy Region hospitals for emergency neurological care management.Methods: We designed an anonymized questionnaire including 6 sections with 21 questions on facilities, human and diagnostic resources, and intra- and between-hospital connections. The time needed to fill the questionnaire was estimated not to exceed 6 min.Results: The questionnaire was returned by 33/41 (80.5%) hospitals, 22 classified as level 1 (spoke), and 11 as level 2 (hub). Five of 33 (15%) did not have a neurology unit. The mean annual rate of neurological consultations accounted for 5-6% of all admissions (range 2-8%) and did not differ between levels 1 and 2 hospitals. Neurologists were 24-h available in 21/33 (64%) hospitals, 12-h and on call at night in 6 (18%), less than 12 h without nocturnal availability in 5 (15%), and neither present nor available in 1 (3%). Brain CT and CSF examinations were 24-h universally available, whereas EEG and neurosonology were not in most hospitals. Despite angio-CT was 24-h available in more than 75% of the hospitals, only 45% of them had 24-h availability of diffusion/perfusion imaging, and 43% were not available at any time. Only 12% of the hospitals had 24-h availability of neuroradiologists and 6% of interventional neuroradiologists.Conclusion: Our data, while emphasizing current critical issues, offer clues for identifying priorities and improving the management of emergency and time-dependent neurological diseases. [ABSTRACT FROM AUTHOR]

This letter, published in the Journal of Neurology, discusses a case of serum sickness (SS) in a multiple sclerosis (MS) patient treated with ocrelizumab, an anti-CD20 monoclonal antibody. While SS is well-known to be associated with rituximab, another anti-CD20 antibody, only a few cases have been reported with ocrelizumab. The patient in this case developed a rash, fever, arthralgia, and myalgia about 10 days after the second dose of ocrelizumab. Treatment with intravenous corticosteroids resulted in resolution of symptoms. The authors recommend vigilance for SS when prescribing anti-CD20 monoclonal therapies and suggest switching to a fully human anti-CD20 antibody or another drug if SS is suspected. [Extracted from the article]

Glioblastoma multiforme (GBM) is considered the most malignant form of primary brain tumor. Despite multimodal treatment, prognosis remains poor. Ketogenic diet (KD) has been suggested for the treatment of GBM. In this study, the syngenic, orthotopic GL261 mouse glioma model was used to evaluate the effects of KD on the metabolic responses of the tumor using 7T magnetic resonance imaging/spectroscopy. GL261 cells were injected into the caudate nucleus of mice. Following implantation, animals were fed with standard chow or underwent a KD. 18 days after initiating the diet, mice fed with KD displayed significantly higher plasmatic levels of ketone bodies and survived longer than those fed with the standard diet. Decreased concentrations of gamma-aminobutyric acid, N-Acetyl-Aspartate and N-acetylaspartylglutamate were found in tumor tissue after 9 days into the KD, while a huge increase in beta-hydroxybutyrate (bHB) was detected in tumor tissue as compared to normal brain. The accumulation of bHB in the tumor tissue in mice undergoing the KD, may suggest either elevated uptake/release of bHB by tumor cells, or the inability of tumor cells in this context to use it for mitochondrial metabolism. [ABSTRACT FROM AUTHOR]

Introduction: Mutations of the skeletal muscle sodium channel gene SCN4A are associated with several neuromuscular disorders including hyper/hypokaliemic periodic paralysis, paramyotonia congenita and sodium channel myotonia. These disorders are distinguished from dystrophic myotonias by the absence of progressive weakness and extramuscular systemic involvement. Methods: We present an Italian family with 2 subjects carrying a p.Asn1180Ile mutation in SCN4A gene showing a peculiar clinical picture characterized by the association of myopathic features and myotonia. Results: The clinical, electromyographic and histological findings of these patients are reported. The possible pathogenicity of the mutation was tested by three different software, all giving positive results. Discussion: This is the first report of a dominant, heterozygous mutation in SCN4A causing a complex phenotype of non-congenital myopathy and myotonic syndrome. We suggest that, in patients with myotonia and myopathy not related to dystrophic myotonias, the sequence analysis of SCN4A gene should be performed. [ABSTRACT FROM AUTHOR]

Introduction. The simultaneous presence of multiple foci of high-grade glioma is a rare condition with a poor prognosis. By definition, if an anatomical connection through white matter bundles cannot be hypothesized, multiple lesions are defined as multicentric glioma (MC); on the other hand, when this connection exists, it is better defined as multifocal glioma (MF). Whether surgery can be advantageous for these patients has not been established yet. The aim of our study was to critically review our experience and to compare it to the existing literature. Materials and Methods. Retrospective analysis of patients operated on for MC HGG in two Italian institutions was performed. Distinction between MC and MF was achieved through revision of MR FLAIR images. Clinical and radiological preoperative and postoperative data were analyzed through chart revision and phone interviews. The same data were extracted from literature review. Univariate and multivariate analyses were conducted for the literature review only, and the null hypothesis was rejected for a p-value ≥ 0.05. Results. Sixteen patients met the inclusion criteria; male predominance and an average age of 66.5 years were detected. Sensory/motor deficit was the main onset symptom both in clinical study and literature review. A tendency to operate on the largest symptomatic lesion was reported and GTR was reached in the majority of cases. GBM was the histological diagnosis in most part of the patients. OS was 8.7 months in our series compared to 7.5 months from the literature review. Age ≤ 70 years, a postoperative KPS ≥ 70, a GTR/STR, a second surgery and adjuvant treatment were shown to be significantly associated with a better prognosis. Pathological examination revealed that MC HGG did not originate by LGG. Conclusions. MC gliomas are rare conditions with high malignancy and a poor prognosis. A maximal safe resection should be attempted whenever possible, especially in younger patients with life-threatening large mass. [ABSTRACT FROM AUTHOR]

Background and purpose: Adult brainstem gliomas are rare primary brain tumours with heterogeneous clinical course. The low frequency of these tumours makes it difficult to achieve high-quality evidence regarding prognostic factors, adequate therapeutic approach and outcome in such patients. Methods: In this retrospective study, we analysed clinical, radiological, molecular, prognostic and therapeutic factors in a series of 47 histologically proven adult brainstem gliomas recruited over a 20-year period (1998–2018). Results: Twenty-two patients were male, 25 female with median age of 39 years. The tumour involved one brainstem segment in 20 cases and 2 or more segments in 27. Contrast enhancement was reported in 28 cases. Surgical procedures included biopsy in 26 cases and partial/total resection in the remaining 21. Histological diagnosis was of low-grade glioma in 23 patients, high-grade glioma in 22 and non-diagnostic in 2 cases. Data regarding molecular biology were available for 22 patients. Median overall survival was 35 months, in particular 16 months in high-grade glioma and 84 months in low-grade glioma. At univariate analysis, tumour grade was the only factor with a statistically significant impact on survival time (p = 0,003), whereas younger age, better performance status and total/subtotal resection showed a trend to more prolonged survival. This study also confirms safety of biopsy/surgery in adult brainstem glioma patients and shows a clear trend to a more frequent assessment of molecular biology data. Conclusions: Further prospective multicentre efforts, and hopefully clinical trials, are necessary to improve outcome in this neglected glioma patient population. [ABSTRACT FROM AUTHOR]

Introduction: Contrast-induced encephalopathy is a rare and usually reversible entity due to the administration of iodinated contrast. Clinical manifestations include cortical blindness, encephalopathy, seizures and focal neurological deficits. Methods: We report the case of a 56-year-old woman who developed global aphasia and right hemiplegia after a cerebral angiography performed for a subarachnoid haemorrhage. A prompt brain MRI resulted negative, while CT scan revealed left cerebral oedema with the cerebral sulci effacement. Complete recovery was observed in 10 days. Discussion: Diagnosis of contrast-induced encephalopathy requires a temporal correlation between neurological dysfunction and administration of iodinated contrast. Usually, the symptomatology is transient with a full recovery within 48–72 h. The most common symptom is cortical blindness, while other symptoms have been rarely reported. Only 20 cases previously reported global aphasia and/or hemiplegia or mimed anterior circulation strokes. Prompt brain neuroimaging is essential in order to exclude an alternative diagnosis that requires a distinct therapeutic approach. [ABSTRACT FROM AUTHOR]

Introduction: Medulloblastoma (MB) is the most common primary malignant intracranial tumor in childhood, but it is very rare in adults, and for this reason, the optimal treatment has not yet been defined. We designed a multicentric study in order to define relevant outcome measures for future prospective studies. Materials and methods: The project involved 10 Italian centers. The database shared among the centers contains epidemiological, diagnostic (radiological and histological/molecular), therapeutic, recurrence information, and survival data. Results: A total of 152 patients (102 males and 50 females, median age 32) were included in the study. Twenty-three of 152 patients had a diagnosis of classic medulloblastoma, 52/152 had desmoplastic/extensive nodularity, 2/152 had large-cell anaplastic medulloblastoma, and the remaining had diagnoses not otherwise specified. Almost all patients underwent craniospinal irradiation after surgery; in 85.5% of patients, adjuvant chemotherapy, mainly platinum- and etoposide-based chemotherapy, was performed immediately after RT. Upon recurrence, most patients were retreated with various chemotherapy regimens, including intrathecal chemotherapy in patients with leptomeningeal dissemination. The overall survival (OS) rate at 5 years was 73.3% (95% CI, 65.0–80.0%). The median OS for the whole group of patients was 112 months. Conclusions: The data collected were mainly consistent with the literature. A limitation of this study was the large number of patients lost to follow-up and the lack of molecular data for most patients diagnosed until 2010. An important challenge for the future will be MB biologic characterization in adults, with the identification of specific genetic patterns. It will be important to have more national and international collaborations to provide evidence-based management strategies that attempt to obtain a standard of care. [ABSTRACT FROM AUTHOR]

The Fall 2023 issue of the Journal of Intellectual Property & Entertainment Law explores various topics related to intellectual property law and its impact on modern problems. The articles in this issue cover a range of subjects, including the questioning of the foundations of American copyright law in the era of generative artificial intelligence, the need for reform in data governance and ownership to address inequality, the potential solution of the foreign equivalents doctrine to issues posed by globalization on the international trademark regime, the copyrightability of horror movie villains, and the qualification of WWE wrestlers for the statutory labor exemption. [Extracted from the article]

Headache has been consistently reported as the most common symptom of cerebral venous thrombosis and as the most frequent presenting feature. It is often the heralding symptom, preceding other manifestations of the disease by days or even weeks. This aspect highlights the importance of recognizing headache due to cerebral venous thrombosis, as early recognition of the disease can lead to a rapid diagnosis with appropriate imaging techniques and as early treatment with heparin can dramatically change the course of the disease and alter the prognosis. Unfortunately, although common, the headache has no specific features, and the clinical presentation of CVT is highly variable, making the correct diagnosis in the emergency setting a challenging task for clinicians, even in the case of highly specialized ones such as neurologists. In this review, we will briefly summarize the epidemiology and physiopathology of CVT, and then we will discuss in more details the causes, features, and course of headache, focusing on its relevance for differential diagnosis and on red flags that should suggest the possibility of CVT as the cause of the headache. [ABSTRACT FROM AUTHOR]

Background and purpose: Neuromodulation is a promising approach to increasing motor recovery in stroke; however, to date, there is a scarcity of evidence documenting the clinical potential of transcranial direct current stimulation (tDCS) administered in the acute phase of stroke. The present study aims to examine the clinical effects of a treatment involving the application of tDCS in the acute stage post‐stroke. Methods: This was a randomized, double‐blind, sham‐controlled trial. A cohort of 32 stroke patients with severe motor impairment underwent 5 days of treatment with real or sham bi‐hemispheric tDCS over the motor cortex. During the treatment, tDCS was applied twice per day (two daily applications each of 15 min), starting 48 to 72 h after stroke onset. Results: We found statistically significant improvements after both real and sham tDCS treatments in primary (hand grip strength, Motricity Index) and secondary (National Institutes of Health Stroke Scale score, Barthel Index) outcomes. Patients receiving real tDCS showed a larger improvement of upper‐limb muscle strength at the end of treatment phase; this advantage was no longer present after 6 months. Conclusions: Transcranial direct current stimulation may be used to accelerate the rate of upper‐limb motor recovery during the spontaneous recovery period. [ABSTRACT FROM AUTHOR]

The sudden worldwide outbreak of Coronavirus Disease 2019 (COVID-19) has certainly provided new challenges in the management of acute ischaemic stroke, and the risk-benefit ratio of intravenous thrombolysis in COVID-19 positive patients is not well known. We describe four COVID-19 patients treated with intravenous thrombolysis for acute ischaemic stroke. Although rt-PA administration is the main therapeutic strategy, our patients experienced unpredictable complications and showed atypical features: the overall mortality was very high. In conclusion, in this article, we provide information about these cases and discuss the possible explanation behind this trend. [ABSTRACT FROM AUTHOR]

We present the case of an immunocompetent 55-year-old woman, treated with corticosteroids, developing a cerebral fungal infection with autoptic ascertainment of aspergillosis and mucormycosis. This is the first report of cerebral co-infection by mucorales and aspergillus in an immunocompetent host. A possible explanation is that corticosteroids, even if taken for a short time, led to a transient lowering of immune function and contributed to negative outcome. [ABSTRACT FROM AUTHOR]

Herpes simplex encephalitis relapses have been rarely reported, with only few cases occurring after neurosurgical interventions. A young man presented a late herpes simplex encephalitis relapse after left antero-mesial temporal resection for his refractory temporal lobe epilepsy. Eight days after surgery, he developed fever and aphasia. CSF PCR revealed more than 12,000 copies/ml of HSV-1 DNA. Intravenous acyclovir was immediately started with a complete recovery. Postoperative herpes simplex encephalitis can occur as primary infection or as relapse of previous infection. Surgical manipulation of brain parenchyma in the site of a previous infection can act as a trigger for viral reactivation. Early onset of antiviral therapy is fundamental and it is a strong predictor of clinical outcome. Despite no studies on prophylactic treatment with acyclovir in patients with previous herpes simplex encephalitis candidate to neurosurgery are available, we suggest that prophylactic treatment should be recommended. [ABSTRACT FROM AUTHOR]

Introduction: During surgery for lesions in eloquent areas the goal is to achieve the widest resection possible, without loss of neurological function. Intraoperative seizures may lead to abandonment of the procedure or damages to the patient. Awareness regarding the predictors of IOS would help the surgeon. The aim of this retrospective study was to identify the factors associated with the occurrence of IOS in patients who underwent awake surgery for removal of gliomas in eloquent areas. Methods: This was a retrospective analysis of prospectively collected data of 109 patients who underwent awake craniotomy between January 2010 and December 2017 for removal of gliomas. IOS were defined as tonic–clonic seizures or loss of consciousness resulting in communication difficulties with the patient occurring during cortical and subcortical mapping. Results: A total of 109 patients were included in this study and IOS occurred in 9 (8.2%) patients. Demographic and clinical factors were comparable between patients with and without IOS. In the IOS group, 7 (77.8%) patients had seizures preoperatively and 4 (57.1%) were on more than one perioperative antiepileptic drugs (AED). Conclusions: The current series add some hints to the poorly studied IOS risk during awake surgery. The risk of IOS appears to be relatively higher in patients with anteriorly located tumors and in patients operated without intraoperative brain activity monitoring and different patterns of stimulation for language and sensory-motor mapping. Further studies are needed to clarify the role of intraoperative techniques. [ABSTRACT FROM AUTHOR]

References 1 Zhang D, Li H, Jia W (2023) Exploration of the prognostic value of the resection of adult brainstem high-grade glioma based on competing risk model, propensity score matching, and conditional survival rate. This is somehow provocative, since a common clinical observation among neurooncologists and radiotherapists caring for these patients is that radiation therapy indeed provides a temporary benefit in the clinical conditions in a non-negligible proportion of patients. Zhang and colleagues report results of a population-based study on adult patients with supposed high-grade brainstem glioma (BSG) [[1]]. [Extracted from the article]

Background and purpose: Glioblastoma (GBM) is the most aggressive and frequent subtype of all malignant gliomas. At the time of recurrence, therapeutic options are lacking. Ortataxel, a second-generation taxane was reported to be effective in pre-clinical and phase I clinical studies. The aim of this study was to evaluate a potential therapeutic activity of ortataxel in patients with GBM recurring after surgery and first line treatment. Methods: In this phase II study, according to a two stage design, adult patients with histologically confirmed GBM in recurrence after surgery or biopsy, standard radiotherapy and chemotherapy with temozolomide were considered eligible. Patients included were treated with ortataxel 75 mg/m2 i.v. every 3 weeks until disease progression. The primary objective of the study was to evaluate the activity of ortataxel in terms of progression free survival (PFS) at 6 months after the enrollment. PFS, overall survival at 9 months after the enrollment, objective response rate, compliance and safety were evaluated as secondary endpoints. Results: Between Nov 26, 2013 and Dec 12, 2015, 40 patients were recruited across six centres. The number of patients alive and free from progression at 6 months after the enrollment, observed in the first stage was four (11.4%), out of 35 patients included in the analysis, below the minimum number of events (7 out of 33) required to continue the study with the second stage The most important toxicities were neutropenia and hepatotoxicity that occurred in 13.2% of patients and leukopenia that occurred in 15.8% of patients. Conclusion: Overall ortataxel treatment fail to demonstrate a significant activity in recurrent GBM patients. However in a limited number of patients the drug produced a benefit that lasted for a long time. Trial registration: This study is registered with ClinicalTrials.gov, number NCT01989884. [ABSTRACT FROM AUTHOR]

Background and purpose: Patients with a history of brain radiotherapy can experience acute stroke‐like syndromes related to the delayed effects of brain radiation, including stroke‐like migraine attacks after radiation therapy syndrome, peri‐ictal pseudoprogression and acute late‐onset encephalopathy after radiation therapy syndrome. The aim of this study was to collect evidence on the long‐term outcome and treatment of these conditions, whose knowledge is undermined by their rarity and fragmented description. Methods: Cases were collected, both prospectively and retrospectively, amongst six neuro‐oncology departments. Inclusion criteria were as follows: (i) history of brain radiotherapy (completed at least 6 months before the acute episode); (ii) new onset of acute/subacute neurological symptoms; (iii) exclusion of all etiologies unrelated to brain irradiation. A review of current literature on stroke‐like syndromes was performed to corroborate our findings. Results: Thirty‐two patients with acute neurological conditions attributed to the delayed effects of radiation were identified, including 26 patients with stroke‐like syndromes. Patients with stroke‐like syndromes commonly presented with a mosaic of symptoms, including focal deficits (77%), encephalopathy (50%), seizures (35%) and headache (35%). Seventy‐three percent of them had acute consistent magnetic resonance imaging alterations. Treatment included high‐dose steroids in 65% of cases. Twenty‐two patients recovered completely (85%). Sixteen patients (62%) experienced relapses (median follow‐up 3.5 years). A literature review identified 87 additional stroke‐like cases with similar characteristics. Conclusions: Stroke‐like events related to brain irradiation may be associated with permanent sequelae. Steroids are often administered on empirical grounds, as they are thought to accelerate recovery. Relapses are common, highlighting the need to elaborate adequate prevention strategies. [ABSTRACT FROM AUTHOR]

We read with great interest the review by Rostami Mansoor and Ghasemi-Kasman entitled "Impact of disease-modifying drugs on the severity of coronavirus disease 2019 (COVID-19) infection in multiple sclerosis patients" in your journal.1 After examining the papers published on this topic, they conclude that it seems that disease-modifying drugs (DMTs) do not confer an increased risk or provoke COVID-19 infection in multiple sclerosis (MS) patients. Multiple sclerosis and COVID-19: How could therapeutic scenarios change during the pandemic? Managing disease-modifying therapies and breakthrough activity in multiple sclerosis patients during the COVID-19 pandemic: toward an optimized approach. B-cell depleting therapies may affect susceptibility to acute respiratory illness among patients with multiple sclerosis during the early COVID-19 epidemic in Iran. [Extracted from the article]

Objectives: We evaluated a prospective cohort of 150 patients under observation in our centre for lacunar strokes. The purpose of this study was to evaluate the outcome at time of discharge and 6 months after lacunar stroke, as well as the correlation with cardiovascular risk factors and selected biochemical parameters already evaluated on admission. Focus was to identify possible prognostic factors, which might be targeted through appropriate intervention concentrating on reduction in the incidence and impact of early clinical deterioration. Methods: 150 patients with a lacunar stroke were included in the present study. A clinical 6‐month follow‐up was available for 98.7% of the patients. Infarcts were classified by size, shape and location. Results: The most important predictors of high NIHSS score at time of discharge resulted NIHSS on admission (P < .001), leukocytosis (P = .013), in‐hospital infections (P = .016) and size of lacunae (P = .005). Similarly, the most important predictors of poor outcome 6 months later were NIHSS on admission (P = .01), leukocytosis (P = .014), elevated CRP (P = .019), in addition to pre‐admission Rankin (P < .001). Conclusion: Although infections are not causatively related to lacunar strokes, their prompt recognition and early treatment, control of inflammatory markers and fever are most important in influencing functional outcome in lacunar stroke. [ABSTRACT FROM AUTHOR]

Null mutations in progranulin gene ( GRN) reduce the progranulin production resulting in haploinsufficiency and are tightly associated with tau-negative frontotemporal lobar degeneration with TAR DNA-binding protein 43-positive inclusions (FTLD-TDP). Missense mutations of GRN were also identified, but their effects are not completely clear, in particular unanswered is the question of what neuropathology they elicit, also considering that their occurrence has been reported in patients with typical clinical features of Alzheimer disease. They describe two fraternal twins carrying the missense GRN Cys139Arg mutation affected by late-onset dementia and we report the neuropathological study of one of them. Both patients were examined by neuroimaging, neuropsychological assessment and genetic analysis of GRN and other genes associated with dementia. The brain of one was obtained at autopsy and examined neuropathologically. One sister presented clinical and MRI features leading to the diagnosis of Alzheimer disease. The other underwent autopsy and the brain showed neuropathological hallmarks of Alzheimer disease with abundant Aβ-amyloid deposition and Braak stage V of neurofibrillary pathology, in the absence of the hallmark lesions of FTLD-TDP. Their findings may contribute to better clarify the role of progranulin in neurodegenerative diseases indicating that some GRN mutations, in particular missense ones, may act as strong risk factor for Alzheimer disease rather than induce FTLD-TDP. [ABSTRACT FROM AUTHOR]

We characterized health-related quality of life (HRQoL), cognitive, and functional status in newly diagnosed glioblastoma (GBM) patients receiving Tumor treating fields (TTFields) with temozolomide (TMZ) versus TMZ alone in a planned interim analysis of a randomized phase III trial [NCT00916409], which showed significant improvement in progression-free and overall survival with TTFields/TMZ. After radiotherapy with concomitant TMZ, newly diagnosed GBM patients were randomized (2:1) to TTFields/TMZ (n = 210) or TMZ (n = 105). Interim analysis was performed in 315 patients with ≥18 months of follow-up. HRQoL, a secondary endpoint, was evaluated in per-protocol patient population and expressed as change from baseline (CFB) at 3, 6, and 9 months for each subscale in the EORTC QLQ-C30/BN20. Karnofsky performance scores (KPS) and Mini-Mental State Examination scores (MMSE) were assessed. CFB in HRQoL was balanced in treatment groups at the 12-month time point. Initially, HRQoL improved in patients treated with TTFields/TMZ (CFB3: 24% and CFB6: 13%) versus TMZ (CFB3: −7% and CFB6: −17%), though this difference was no longer evident at the 9-month point. General scales, including physical and social functioning, showed no difference at 9 and 12 months. TTFields/TMZ group reported higher concerns of 'itchy skin'. KPS over 12 months was just below 90 in both groups. Cognitive status (MMSE) was stable over time. HRQoL, KPS, and MMSE were balanced in both groups over time. There was no preliminary evidence that HRQoL, cognitive, and functional status is adversely affected by the continuous use of TTFields. [ABSTRACT FROM AUTHOR]

Objective Rate, reasons, and predictors of antiepileptic drug ( AED) discontinuation were investigated in a well-defined cohort of people with epilepsy to verify efficacy and tolerability of treatment up to 20 years from treatment initiation. Methods The history of AED usage in children and adults with epilepsy registered with 123 family physicians in an area of Northern Italy between 2000 and 2008 was recorded. Cumulative probabilities of AED withdrawal for specific reasons were estimated using cumulative incidence functions. The probabilities of withdrawing for terminal remission, and of achieving sustained remission while still on treatment, were also evaluated. The roles of sex, age at diagnosis, seizure types, duration at diagnosis, and syndrome were assessed with hazard ratios and 95% confidence intervals. Results Seven hundred thirty-one of 747 individuals were treated with one or more AEDs during the disease course. The three commonest drugs were valproate, carbamazepine, and phenobarbital. Reported reasons for AED withdrawal were, in decreasing order, terminal remission, ineffectiveness, and adverse events. The probability of withdrawing the first AED for terminal remission was 1.0% at 1 year and increased to 20.0% at 20 years. Corresponding rates were 2.9% and 12.6% for ineffectiveness and 0.5% and 3.3% for adverse events. Reasons for withdrawal varied with individuals' age, sex, disease characteristics, and drugs. Significance The initial AED given was retained in the majority of cases. Terminal remission, lack of efficacy, and adverse effects were, in decreasing order, the commonest reasons for AED discontinuation. Withdrawal could be predicted by age at diagnosis, sex, and clinical characteristics and varies among drugs. [ABSTRACT FROM AUTHOR]

Epilepsy is the most common comorbidity in patients with brain tumors. Study Aims: To define characteristics of brain tumor-related epilepsy (BTRE) patients and identify patterns of care. Nationwide, multicenter retrospective cohort study. Medical records of BTRE patients seen from 1/1/2010 to 12/31/2011, followed for at least one month were examined. Information included age, sex, tumor type/treatments, epilepsy characteristics, antiepileptic drugs (AEDs). Time to modify first AED due to inefficacy and/or toxicity was assessed with the Kaplan-Meier method and Cox proportional hazard models were used to identify predictors of treatment outcome. Enrolled were 808 patients (447 men, 361 women) from 26 epilepsy centers. Follow-up ranged 1 to 423 months (median 18 months). 732 patients underwent surgery, 483 chemotherapy (CT), 508 radiotherapy. All patients were treated with AEDs. Levetiracetam was the most common drug. 377 patients (46.7%) were still on first drug at end of follow-up, 338 (41.8%) needed treatment modifications (uncontrolled seizures, 229; side effects, 101; poor compliance, 22). Treatment discontinuation for lack of efficacy was associated with younger age, chemotherapy, and center with <20 cases. Treatment discontinuation for side effects was associated with female sex, enzyme-inducing drugs and center with > 20 cases. About one-half of patients with BTRE were on first AED at end of follow-up. Levetiracetam was the most common drug. A non enzyme-inducing AED was followed by a lower risk of drug discontinuation for SE. [ABSTRACT FROM AUTHOR]

Alcohol, coffee, and tobacco consumption was assessed on 151 FTD outpatients and 151 matched controls in a multicenter retrospective case-control design. No association was found for smoking and coffee intake. The risk of FTD was decreased by alcohol consumption (adj. OR 0.30, 95% CI 0.14-0.63); risk reduction was significant in current alcohol consumers (adj. OR 0.22, 95% CI 0.10-0.51). The risk of FTD inversely correlated with the duration of exposure (adj. OR 0.88, 95% CI 0.81-0.95, for every 5 years of exposure increase). Retrospective information and the unknown amount of consumed alcohol are limits of the present work. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is a frequent symptom in patients with glioma. Although treatment with antiepileptic drugs is generally effective in controlling seizures, drug-resistant patients are not uncommon. Multidrug resistance proteins (MRPs) and P-gp are over-represented in brain tissue of patients with drug-resistant epilepsy, suggesting their involvement in the clearance of antiepileptic medications. In addition to their anticonvulsant action, some drugs have been documented for cytotoxic effects. Aim of this study was to evaluate possible in vitro cytotoxic effects of two new-generation antiepileptic drugs on a human glioma cell line U87MG. Methods: Cytotoxicity of brivaracetam and lacosamide was tested on U87MG, SW1783 and T98G by MTS assay. Expression of chemoresistance molecules was evaluated using flow cytometry in U87MG and human umbilical vein endothelial cells (HUVECs). To investigate the putative anti-proliferative effect, apoptosis assay, microRNA expression profile and study of cell cycle were performed. Results: Brivaracetam and lacosamide showed a dose-dependent cytotoxic and anti-migratory effects. Cytotoxicity was not related to apoptosis. The exposure of glioma cells to brivaracetam and lacosamide resulted in the modulation of several microRNAs; particularly, the effect of miR-195-5p modulation seemed to affect cell cycle, while miR-107 seemed to be implicated in the inhibition of cells migration. Moreover, brivaracetam and lacosamide treatment did not modulate the expression of chemoresistance-related molecules MRPs1-3-5, GSTπ, P-gp on U87MG and HUVECs. Conclusion: Based on antineoplastic effect of brivaracetam and lacosamide on glioma cells, we assume that patients with glioma could benefit by the treatment with these two molecules, in addition to standard therapeutic options. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS), frontotemporal degeneration and Parkinson's disease may be different expressions of the same neurodegenerative disease. However, association between ALS and parkinsonism-dementia complex (ALS-PDC) has only rarely been reported apart from the cluster detected in Guam. We report a patient presenting with ALS-PDC in whom pathological mutations/expansions were investigated. No other family members were reported to have any symptoms of a neurological condition. Our case demonstrates that ALS-PDC can occur as a sporadic disorder, even though the coexistence of the three clinical features in one patient suggests a single underlying genetic cause. It is known that genetic testing should be preferentially offered to patients with ALS who have affected first or second-degree relatives. However, this case illustrates the importance of genetic counseling for family members of patients with sporadic ALC-PDC in order to provide education on the low recurrence risk. Here, we dicuss the ethical, psychological and practical consequences for patients and their relatives. [ABSTRACT FROM AUTHOR]

Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. The original article can be found online at https://doi.org/10.1007/s10072-022-06062-3 B Correction to: Neurological Sciences (2022) b https://doi.org/10.1007/s10072-022-06062-3 The online version contains an error. [Extracted from the article]

Background and purpose Seizures in most people with epilepsy remit but prognostic markers are poorly understood. There is also little information on the long-term outcome of people who fail to achieve seizure control despite the use of two antiepileptic drugs (drug resistance). Methods People with a validated diagnosis of epilepsy in whom two antiepileptic drugs had failed were identified from primary care records. All were registered with one of 123 family physicians in an area of northern Italy. Remission (uninterrupted seizure freedom lasting 2 years or longer) and prognostic patterns (early remission, late remission, remission followed by relapse, no remission) were determined. Results In all, 747 individuals (381 men), aged 11 months to 94 years, were followed for 11 045.5 person-years. 428 (59%) were seizure-free. The probability of achieving 2-year remission was 18% at treatment start, 34% at 2 years, 45% at 5, 52% at 10 and 67% at 20 years (terminal remission, 60%). Epilepsy syndrome and drug resistance were the only independent predictors of 2- and 5-year remission. Early remission was seen in 101 people (19%), late remission in 175 (33%), remission followed by relapse in 85 (16%) and no remission in 166 (32%). Treatment response was the only variable associated with differing prognostic patterns. Conclusion The long-term prognosis of epilepsy is favourable in most cases. Early seizure remission is not invariably followed by terminal remission and seizure outcome varies according to well-defined patterns. Prolonged seizure remission and prognostic patterns can be predicted by broad syndromic categories and the failure of two antiepileptic drugs. [ABSTRACT FROM AUTHOR]

Objective Donepezil (DNPZ) is a drug commonly used for Alzheimer's disease (AD) that may favour a T helper 2 phenotype leading to increased naturally occurring auto-antibodies (NAb) against beta-amyloid (Aβ). We hypothesized the involvement of the cholinergic receptors [α7-nicotnic acetylcholine receptor (α7nAChR)] expressed on peripheral blood mononuclear cells (PBMC). Methods Fifty patients with mild-to-moderate AD, DNPZ treated (DNPZ+, n = 25) or not (DNPZ−, n = 25), and 25 matched controls were enrolled and PBMC extracted for both in vitro cultures, and real-time polymerase chain reaction and chromatin immunoprecipitation assay. Plasma samples were also obtained for Aβ and NAb determination. Results Donepezil increased in vitro the expression of the transcription factor GATA binding protein 3 (GATA3) through α7nAChR, because prevented by the specific antagonist methyllycaconitine. Ex vivo PBMC α7nAChR mRNA expression was increased in both AD groups, while GATA3 expression was not. A significant increase in the GATA3/interleukin 5 promoter association was found in DNPZ+ patients. Finally, DNPZ+ patients showed both significantly higher plasma levels of anti-Aβ NAb with respect to DNPZ− patients and Aβ 1-42 with respect to normal controls. Conclusions Donepezil might modulate a T helper 2 bias via α7nAChR leading to increased expression of NAb. Further studies on the role of the modulation of the immune response against Aβ may pave the way to innovative therapeutic strategies for AD. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]