Fibrocartilaginous embolism: a rare cause leading to spinal cord infarction?

PURPOSE: Fibrocartilaginous nucleus pulposus components herniation and embolism rarely causes acute ischaemic events involving the spinal cord. Few reports have suggested this as a mechanism leading to anterior spinal artery syndrome. The purpose of this study was to evaluate the topography and pattern of this rare myelopathy by MRI. METHODS: A retrospective observational case series of patients, admitted to our Institute between 2008 and 2021, with a diagnosis of fibrocartilaginous embolism based on typical clinical and radiological features. RESULTS: Five patients were identified (2 men and 3 women; range 13-38 years). No one had pre-existing vascular risk factors. All referred potential precipitating event in the 24 h prior to symptom onset. MRI findings showed increased signal intensity of the spinal cord on T2-weighted images in all cases and degenerative disc changes opposite to it in four of them. The outcome was poor: three showed only partial sensitivity and motor improvement (mRs 4, 3, and 2, respectively); one completely recovered except for isolated hand paresis (mRs 1); and one remained severely neurologically affected (mRs 5). CONCLUSIONS: Fibrocartilaginous embolism must be a differential diagnosis in case of otherwise unexplained spinal cord infarction in adult and paediatric low risk population. Neuroradiological findings such as abnormal spinal cord signal intensity and degenerative disc changes can aid in early diagnosis of this rare myelopathy. The prevalent myelopathy location was thoracic. All signal alterations were detected in the anterior region of the spinal cord in the territories of the anterior spinal artery.

Multidrug resistance proteins expression in glioma patients with epilepsy.

Epilepsy occurs in glioma, especially in low-grade glioma (LGG), but also in glioblastoma (GBM). In about 20 % of patients pharmacological treatment with anti-epileptic drugs (AEDs) fails. Refractory epilepsy is a multifactorial phenomenon not yet completely understood. The multidrug resistance phenotype was initially associated to P-glycoprotein (Pgp), an ATP-dependent transporter belonging to the same superfamily of multidrug resistance-associated proteins (MRPs). Glutathione-S-transferase-π (GST-π) is also involved in refractory epilepsy. In the present work we investigated the expression of Pgp, MRP1, MRP3 and GST-π in surgical specimens obtained from 35 patients with glioma and epilepsy. We observed MRP1 expression in tumor and endothelial cells (EC), MRP3 and Pgp expression mainly in ECs and GST-π predominantly in tumor cells (TC). MRP1 and MRP3 were more expressed in high grade glioma (HGG) than in LGG. In 6 cases we could compare tumor and periphery detecting the same MRP1 and Pgp expression, while MRP3 was mainly expressed in the tumor. We observed a trend of a better outcome in seizure control associated with a lower expression of MRP1 and MRP3. MRP3 was statistically more expressed in TCs of HGG than LGG (p = 0.0401) and more expressed in tumor than in periphery, in agreement with recent works that identify MRP3 as a potential target in GBM. Moreover, MRP3 was investigated in association with refractory epilepsy for the first time in our study and it was less expressed in patients with complete response to AEDs (p = 0.0550). Our preliminary data show an association between multidrug resistance transporters and refractory epilepsy in glioma.

The burden of brain tumor: a single-institution study on psychological patterns in caregivers.

Quality of life and well-being in caregivers are usually partly neglected since all attention is focused on patients and the way they react to the illness. Carers also usually neglect their own needs, especially when the illness of the patient is as complex as a brain tumor. The aim of this study is to investigate how caregivers deal with a diagnosis of brain tumor in their relatives and how they manage their quality of life and psychosocial well-being. One hundred primary caregivers of patients with brain tumors were interviewed and were asked to fill in self-administered questionnaires detecting multidimensional levels of quality of life, anxiety, depression, and psychosocial reaction to the patient's illness. Data were related with some functional and psychosocial information collected about the patient's disease. Caregivers try to react to the illness of their relatives by mobilizing their physical reaction and growing their self-esteem, but they live with a clinically significant impairment of their quality of life, and experience a deep level of anxiety and depression. The caregivers' burden appears mainly in their ability to provide care and in financial strain. The length of disease and the functional status of patients significantly influence caregivers' psychosocial well-being. Despite the appearance they want to show their affected relatives, caregivers suffer from deep limitation in their quality of life. The relevance of caregivers' burden suggests the importance of psychological support to improve reaction to the illness.

Recurrent brain tumour: the impact of illness on patient's life.

PURPOSE: Despite advances in therapies that offer improved survival rates, clinical course of brain tumours leads to a progressive functional deterioration in patients with modifications in their psychological reaction to the disease. Patients with brain tumours are rarely assessed for quality of life and psychological variables, and even fewer studies have assessed patients who have experienced a recurrence of brain tumours. Therefore, the aim of the present study is to investigate the patients with recurrent brain tumours and their reaction to the illness. METHOD: We enrolled 81 patients with recurrent CNS tumours. Karnofsky Performance Status scale (KPS) was used to evaluate functional status of patients; the multidimensional aspect of quality of life was assessed through "Functional Assessment of Cancer Therapy-Brain" (FACT-Br), "Hospital Anxiety and Depression Scale" and "Psychological Distress Inventory". These were all used as tests of psychological well-being. RESULTS: Distress and almost all mean FACT-Br subscale scores seemed to be significantly lower in patients, in comparison with normative data. Surprisingly, the emotional well-being mean score was significantly higher in our recurrence sample than in patients with brain tumours at first diagnosis. Anxiety seemed not to be influenced by a relapse diagnosis; instead, depression was higher and differed significantly from normative data. Low correlation between KPS and FACT-Br total and some sub-scores was found. CONCLUSIONS: Apparent dissociation between patients' judgment on their quality of life (bad except for emotional) and their reported distress (low) is the most intriguing finding, suggesting highly preserved coping strategies in the emotional sphere, despite intact judgment and disease awareness.

Therapeutic Approaches in Adult Primary Spinal Cord Astrocytoma: A Systematic Review.

THE ISSUE: Gliomas are primary tumors arising from supporting cells of the central nervous system (CNS), usually in the brain. The 2021 World Health Organization (WHO) classifies gliomas as adult-type diffuse gliomas or circumscribed astrocytic gliomas depending on their histology and molecular features. Spinal astrocytic gliomas are very rare, and nowadays no standard of therapy is available. Treatment options are limited: surgery is often not radical, and adjuvant therapies include mostly radiotherapy (RT) or systemic chemotherapy (CHT). There is lack of knowledge about the efficacy and safety of therapies and their multidisciplinary approaches. THE AIM OF THE REVIEW: A systematic review of the literature from January 2000 to June 2021 was performed, including both clinical trials and observational studies on histological adult primary spinal cord astrocytomas (SCA), with a minimum follow-up of 6 months and reporting the overall survival, progression-free survival or clinical neurological outcome after any therapeutic approach (surgery, RT or CHT). What are the main findings? A total of 1197 citations were identified by the Medline search and additional records; based on our inclusion criteria, 18 studies were included with a total of 285 adult patients. We documented the lack of any clinical trial. What are the conclusions? The available literature data are limited to series/retrospective studies, including heterogeneous patients, i.e., astrocytoma as well as ependymoma or pediatric/adult age, with scanty data on the outcomes of interest. No clinical trials have been run. Due to the rarity of this disease, multicentric clinical trials with molecular investigations are mandatory to better manage such a rare disease.

Bevacizumab at recurrence in high-grade glioma.

Bevacizumab has been introduced in the management of high-grade gliomas after preliminary studies that showed an acceptable safety and a marked increase in clinico-radiological responses in comparison with second-line chemotherapy. The objective is to synthetically review the present use of bevacizumab--alone or in combination--in the context of recurrent high-grade glioma and highlight the future developments. The methodology of this study is to analyse and discuss relevant literature studies using bevacizumab in recurrent high-grade glioma. Bevacizumab may be used as single-agent therapy in recurrent high-grade glioma, with good clinico-radiological responses having little effect on survival. The open questions and developments include new MRI criteria for evaluation of response to anti-angiogenic agents, the identification of putative factors predicting response/failure of bevacizumab and the introduction of bevacizumab in first-line management of high-grade glioma.

The Role and the Effect of Magnesium in Mental Disorders: A Systematic Review.

INTRODUCTION: Magnesium is an essential cation involved in many functions within the central nervous system, including transmission and intracellular signal transduction. Several studies have shown its usefulness in neurological and psychiatric diseases. Furthermore, it seems that magnesium levels are lowered in the course of several mental disorders, especially depression. OBJECTIVES: In this study, we wish to evaluate the presence of a relationship between the levels of magnesium and the presence of psychiatric pathology as well as the effectiveness of magnesium as a therapeutic supplementation. METHODS: A systematic search of scientific records concerning magnesium in psychiatric disorders published from 2010 up to March 2020 was performed. We collected a total of 32 articles: 18 on Depressive Disorders (DD), four on Anxiety Disorders (AD), four on Attention Deficit Hyperactivity Disorder (ADHD), three on Autism Spectrum Disorder (ASD), one on Obsessive-Compulsive Disorder (OCD), one on Schizophrenia (SCZ) and one on Eating Disorders (ED). RESULTS: Twelve studies highlighted mainly positive results in depressive symptoms. Seven showed a significant correlation between reduced plasma magnesium values and depression measured with psychometric scales. Two papers reported improved depressive symptoms after magnesium intake, two in association with antidepressants, compared to controls. No significant association between magnesium serum levels and panic or Generalized Anxiety Disorder (GAD) patients, in two distinct papers, was found. In two other papers, a reduced Hamilton Anxiety Rating Scale (HAM-A) score in depressed patients correlated with higher levels of magnesium and beneficial levels of magnesium in stressed patients was found. Two papers reported low levels of magnesium in association with ADHD. Only one of three papers showed lower levels of magnesium in ASD. ED and SCZ reported a variation in magnesium levels in some aspects of the disease. CONCLUSION: The results are not univocal, both in terms of the plasma levels and of therapeutic effects. However, from the available evidence, it emerged that supplementation with magnesium could be beneficial. Therefore, it is necessary to design ad hoc clinical trials to evaluate the efficacy of magnesium alone or together with other drugs (antidepressants) in order to establish the correct use of this cation with potential therapeutic effects.

The Effect of DHA Supplementation on Cognition in Patients with Bipolar Disorder: An Exploratory Randomized Control Trial.

Bipolar disorder (BD) is a severe mental disorder with a wide range of cognitive deficits, both in the euthymic and acute phase of the disease. Interestingly, in recent years, there has been a growing interest in investigating the impact of ω-3 polyunsaturated fatty acids on cognition in BD. In this context, the aim of this study is to evaluate the effect of docosahexaenoic acid (C22:6 ω-3, DHA) supplementation on cognitive performances in euthymic BD patients. This is an exploratory, single-centre, double-blind randomized controlled trial evaluating 12 weeks DHA supplementation (1250 mg daily) vs. a placebo (corn oil) in 31 euthymic BD patients compared to 15 healthy controls (HCs) on cognitive functions, assessed by the Brief Assessment of Cognition in Affective Disorder (BAC-A). Plasma levels of DHA were measured. After 12 weeks of treatment, no significant group differences were observed in all neuropsychological tests between the four groups, except for the emotion inhibition test, where HCs with DHA had higher scores compared to either BD with DHA (z = 3.9, p = 0.003) or BD with placebo (t = 3.7, p = 0.005). Although our results showed that DHA could be effective for ameliorating cognition in healthy subjects, future studies are still needed to clarify the impact of DHA on cognition in BD.

Systemic sagopilone (ZK-EPO) treatment of patients with recurrent malignant gliomas.

It has been demonstrated that sagopilone (ZK-EPO) has antitumor activity in human orthotopic glioma models in vitro and in vivo. The objective of this study was to evaluate the safety and efficacy of ZK-EPO in patients with pretreated, recurrent malignant gliomas. Fifteen patients with recurrent malignant gliomas who had received prior surgery, radiotherapy, and >or=2 lines of alkylating chemotherapy were recruited. ZK-EPO (16 mg/m(2)) was administered iv for 3 h every 21 days. The primary end point was six months progression-free survival (PFS-6); secondary end points were safety, toxicity, response rate, and median time to progression (TTP). Magnetic resonance imaging (MRI) evaluations were performed every two cycles and toxicity was evaluated at each cycle using common terminology criteria for adverse events (CTCAE 3.0). A median of four cycles was administered. The median TTP was 13 weeks. PFS-6 was achieved in five patients (33%), three with glioblastoma multiforme and two with anaplastic astrocytoma. The most common treatment-related adverse event was neuropathy, which occurred in 6/15 patients. ZK-EPO had an acceptable safety profile and clinically relevant activity in patients with pretreated, recurrent malignant gliomas.

The Role of Docosahexaenoic Acid (DHA) on Cognitive Functions in Psychiatric Disorders.

Cognitive impairment is strongly associated with functional outcomes in psychiatric patients. Involvement of n-3 long chain polyunsaturated fatty acid (n-3 LC-PUFA), in particular docosahexaenoic acid (DHA), in brain functions is largely documented. DHA is incorporated into membrane phospholipids as structural component, especially in the central nervous system where it also has important functional effects. The aim of this review is to investigate the relationship between DHA and cognitive function in relation to mental disorders. Results from few randomized controlled trials (RCTs) on the effects of DHA (alone or in combination) in psychotic, mood and neurodevelopmental disorders, respectively, suggest that no conclusive remarks can be drawn.

The Risk of Thrombocytopenia During Valproic Acid Therapy: A Critical Summary of Available Clinical Data.

Valproate is an effective anti-epileptic and mood stabilizer drug, but its prescription may be complicated by the development of thrombocytopenia. The purpose of the present manuscript is to provide a critical overview about the risk of thrombocytopenia during treatment with valproate. A search of the main database sources has been conducted to identify relevant papers about the topic. In the studies with a larger sample size (> 150 subjects), thrombocytopenia occurred in 12-18% of subjects receiving treatment with valproate. Advanced age, female gender, and high doses were found to be risk factors for the development of thrombocytopenia during treatment with valproate. Future research is needed to clarify the clinical impact of the occurrence of thrombocytopenia during valproate treatment (e.g., the risk of life-threatening events such as stroke or the development of thrombocytopenia during short- versus long-term administration, or oral versus intravenous formulations).

Adult leukoencephalopathies with prominent infratentorial involvement can be caused by Erdheim-Chester disease.

BACKGROUND: Leukoencephalopathies with prominent involvement of cerebellum and brainstem, henceforward called prominent infratentorial leukoencephalopathies (PILs), encompass a variety of inherited and acquired white matter diseases. Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis likely under-diagnosed as cause of adult PIL. METHODS: We reviewed the clinical and laboratory information of ten consecutive sporadic adult patients with PIL of unknown origin, who were investigated for ECD. RESULTS: There were seven males and three females; mean age at clinical onset was 49.6 years (range 38-59); cerebellar ataxia with or without other neurological symptoms was the only or the main clinical manifestation; diabetes insipidus was present in three individuals. Eight patients had white matter focal supratentorial abnormalities, in addition to the infratentorial white matter changes. Six out of eight patients had spinal cord lesions. Thoraco-abdominal CT showed periaortic sheathing in two patients, whole-body FDG-PET revealed increased glucose uptake in the long bones of the legs in five patients, brain FDG-PET showed overt infratentorial hypermetabolism in one patient. In eight patients, ECD was confirmed by bone scintigraphy, pathological data, or both. Two ECD patients treated with vemurafenib showed a marked improvement of neurological symptoms and brain MRI abnormalities at 1 year follow-up. CONCLUSIONS: Symptoms of PIL can be the only clinical manifestation of ECD. Adult patients with PIL of unknown origin should undergo investigations aimed at unveiling ECD, including bone scintigraphy and whole-body FDG-PET. The early diagnosis allows starting disease-modifying therapies of an otherwise life-threatening disease.

Neuropsychiatric Burden in Huntington's Disease.

Huntington's disease is a disorder that results in motor, cognitive, and psychiatric problems. The symptoms often take different forms and the presence of disturbances of the psychic sphere reduces patients' autonomy and quality of life, also impacting patients' social life. It is estimated that a prevalence between 33% and 76% of the main psychiatric syndromes may arise in different phases of the disease, often in atypical form, even 20 years before the onset of chorea and dementia. We present a narrative review of the literature describing the main psychopathological patterns that may be found in Huntington's disease, searching for a related article in the main database sources (Medline, ISI Web of Knowledge, Scopus, and Medscape). Psychiatric conditions were classified into two main categories: affective and nonaffective disorders/symptoms; and anxiety and neuropsychiatric features such as apathy and irritability. Though the literature is extensive, it is not always convergent, probably due to the high heterogeneity of methods used. We summarize main papers for pathology and sample size, in order to present a synoptic vision of the argument. Since the association between Huntington's disease and psychiatric symptoms was demonstrated, we argue that the prevalent and more invalidating psychiatric components should be recognized as early as possible during the disease course in order to best address psychopharmacological therapy, improve quality of life, and also reduce burden on caregivers.

Helping patients to reduce tobacco consumption in oncology: a narrative review.

The present overview focuses on evidence of smoking cessation approaches in oncology settings with the aim to provide health personnel a critical perspective on how to help their patients. This narrative review is structured in two main sections: the first one describes the psycho-cognitive variables involved in the decision to continue smoking after a cancer diagnosis and during the treatment; the second section relates methods and tools may be recommended, being evidence-based, to support smoking cessation in oncology settings. Active smoking increases not only susceptibility to common cancers in the general population, but also increases disease severity and comorbidities in cancer patients. Nowadays, scientific evidence has identified many strategies to give up smoking, but a lack of knowledge exists for treatment of nicotine dependence in the cancer population. Health personnel is often ambiguous when approaching the problem, while their contribution is essential in guiding patients towards healthier choices. We argue that smoking treatments for cancer patients deserve more attention and that clinical features, individual characteristics and needs of the patient should be assessed in order to increase the attempts success rate. Health personnel that daily work and interact with cancer patients and their caregivers have a fundamental role in the promotion of the health changing. For this reason, it is important that they have adequate knowledge and resources in order to support cancer patients to stop tobacco cigarette smoking and promoting and healthier lifestyle.

Reversible Valproate Induced Pisa Syndrome and Parkinsonism in a Neuro-Oncology Patient with Depression and Epilepsy.

Neurological and psychiatric conditions frequently overlap in neuro-oncology. This overlapping negatively affects patients' quality of life and decreases the ability of providers to manage specific symptoms by therapy modulation, especially when psychopharmacotherapy needs to be prescribed. We describe here a patient with recurrent brain tumor, symptomatic epilepsy and depression who developed Pisa syndrome and parkinsonism after several months of valproic acid use. An accurate recognition of symptoms and treatment side effect allowed an appropriate clinical approach so as to rapidly improve both movement disorder and depression without increasing the risk of developing seizure. This has improved the autonomy and quality of life in a patient with poor prognosis.

Experiencing brain cancer: what physicians should know about patients.

UNLABELLED: During the last 20 years, numerous studies have highlighted the need to consider Quality of Life (QoL) issues in the treatment of brain cancer. However, gaps in scientific knowledge are still present as we have poor data surrounding the whole experience in patients and regarding their needs. The present study was aimed at evaluating QoL in brain cancer patients and correlated aspects. In particular, we aimed to assess QoL, mood state, and emotional issues in order to describe the patients' experience to find out the critical aspects involved. METHODS: We obtained data from 85 patients during chemotherapy treatment at the National Neurological Institute 'C. Besta' of Milan, Italy. We used standardised questionnaires to assess different aspects of patients' QoL. In particular, the functional assessment of cancer therapy-brain (FACT-Br) and the Hamilton scale were used. We also performed a semi-structured ad hoc interview in order to collect -narrative data about patients' experience. RESULTS: Our data depict a difficult adjustment process to the illness, even though positive elements emerged. Indeed, patients reported a satisfying self-perceived QoL, although specific concerns are still present. Further, even if many patients report depressive symptoms, only a minority have a severe condition. CONCLUSION: Brain cancer may heavily affect patients' QoL and well being. However, some element of the context may improve the -adjustment to the disease. In particular, we found that most patients found psychosocial resources to cope with cancer and that spiritual well being also seems to play a key role. These issues deserve further studies in order to obtain significant clinical recommendations.

The densitometric physical fractionator for counting neuronal populations: application to a mouse model of familial amyotrophic lateral sclerosis.

The method of the 'densitometric physical fractionator' presented here realizes an accurate and reproducible stereological quantification, not requiring a motorized or controlled z-axis, of cell populations. It includes a special software for the calibration of the optics alignment of the microscope and a semi-automatic procedure that integrates specific densitometric functions for image analysis, to identify the reference volume and the particle profiles. This improves the identification of the cells significantly, reduces variability in the subjective choice of the particles by the operators, and allows a consistent saving of time during the analysis. The method is proved to be unbiased and the accuracy and reproducibility of the results has been validated through intra- and inter-operator analyses. Furthermore, it has been applied to calculate the loss of spinal motor neurons during pathology progression in transgenic mice for superoxide-dismutase Cu/Zn dependent (SOD1) mutants, a model of amyotrophic lateral sclerosis (ALS).

Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL): a new report of an Italian woman and review of the literature.

We report the clinical case of a 43year old Italian woman and her family with Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL), also known as Nasu-Hakola disease. PLOSL is a unique disease clinically characterized by a progressive presenile frontal-lobe dementia and multiple cystic bone lesions, typically leading to fractures of the limbs in the third decade of life. This rare recessively inherited disease is caused by mutations in one of two genes encoding different subunits of a receptor signalling complex, TYROBP and TREM2. In the present case fractures after microtrauma were not diagnosed, despite a radiological demonstration of the characteristic bone lesions in PLOSL. Further investigation led to the same diagnosis in her brother, with similar clinical presentation and the same mutation. Therefore a diagnosis of PLOSL should be considered in cases of presenile frontal-lobe dementia, even if the hallmark of pathological fractures is absent.

Clinical and radiological features of brain neurotoxicity caused by antitumor and immunosuppressant treatments.

Antitumor and immunosuppressant treatment-related neurotoxicity can determine nonspecific clinical syndromes. Exclusion of other possible causes, among which tumor progression, appearance of paraneoplastic disease, renal or hepatic failure, diabetes or hypertension, is relevant. We report clinical and neuroradiological features in five patients with neurotoxic syndromes due to chemotherapy/radiotherapy or immunosuppression in the context of neoplastic disease/organ transplantation. Acute neurological syndrome developed in three patients after methotrexate (MTX), cyclosporine A, and L-asparaginase therapy, respectively. MRI showed posterior reversible encephalopathy in two cases and venous thrombosis with intraparenchymal hematoma in the third patient. Late onset clinical syndrome occurred in the last two patients, treated with MTX or radiation therapy for breast cancer metastasis and pituitary adenoma. Neuroimaging showed brain diffuse abnormalities. Patients affected by tumors suffer from increased risk for treatment-related toxicities. Appearance or worsening of neurological signs and symptoms challenge the clinician to discriminate between CNS involvement by the tumor, toxicity of drugs, parane-oplastic disease and infections. MRI has a key role in differential diagnosis. Close interaction between the neurologist, the oncologist and the neuroradiologist leads to the optimal management of patients.