ABSTRACT
Neuroacanthocytosis (NA) syndromes are a group of genetically defined diseases characterized by the association of red blood cell acanthocytosis, progressive degeneration of the basal ganglia and neuromuscular features with characteristic persistent hyperCKemia. The main NA syndromes include autosomal recessive chorea-acanthocytosis (ChAc) and X-linked McLeod syndrome (MLS). A series of Italian patients selected through a multicenter study for these specific neurological phenotypes underwent DNA sequencing of the VPS13A and XK genes to search for causative mutations. Where it has been possible, muscle biopsies were obtained and thoroughly investigated with histochemical assays. A total of nine patients from five different families were diagnosed with ChAC and had mostly biallelic changes in the VPS13A gene (three nonsense, two frameshift, three splicing), while three patients from a single X-linked family were diagnosed with McLeod syndrome and had a deletion in the XK gene. Despite a very low incidence (only one thousand cases of ChAc and a few hundred MLS cases reported worldwide), none of the 8 VPS13A variants identified in our patients is shared by two families, suggesting the high genetic variability of ChAc in the Italian population. In our series, in line with epidemiological data, McLeod syndrome occurs less frequently than ChAc, although it can be easily suspected because of its X-linked mode of inheritance. Finally, histochemical studies strongly suggest that muscle pathology is not simply secondary to the axonal neuropathy, frequently seen in these patients, but primary myopathic alterations can be detected in both NA syndromes.
Subject(s)
Muscle, Skeletal , Mutation , Vesicular Transport Proteins , Adult , Child , Cohort Studies , Erythrocytes/metabolism , Erythrocytes/pathology , Female , Humans , Italy , Male , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Muscular Diseases/genetics , Muscular Diseases/metabolism , Muscular Diseases/pathology , Neuroacanthocytosis/genetics , Neuroacanthocytosis/metabolism , Neuroacanthocytosis/pathology , Vesicular Transport Proteins/genetics , Vesicular Transport Proteins/metabolismABSTRACT
BACKGROUND: Autophagic vacuolar myopathies (AVMs) are an emerging group of heterogeneous myopathies sharing histopathological features on muscle pathology, in which autophagic vacuoles are the pathognomonic morphologic hallmarks. Glycogen storage disease type II (GSDII) caused by lysosomal acid α-glucosidase (GAA) deficiency is the best-characterised AVM. AIMS: This study aimed to investigate the mutational profiling of seven neuromuscular outpatients sharing clinical, myopathological and biochemical findings with AVMs. METHODS: We applied a diagnostic protocol, recently published by our research group for suspected late-onset GSDII (LO-GSDII), including counting PAS-positive lymphocytes on blood smears, dried blood spot (DBS)-GAA, muscle biopsy histological and immunofluorescence studies, GAA activity assay and expression studies on muscle homogenate, GAA sequencing, GAA multiplex ligation-dependent probe amplification (MLPA) and whole exome sequencing (WES). RESULTS: The patients had a limb girdle-like muscular pattern with persistent hyperCKaemia; vacuolated PAS-positive lymphocytes, glycogen accumulation and impaired autophagy at muscle biopsy. Decreased GAA activity was also measured. While GAA sequencing identified no pathogenic mutations, WES approach allowed us to identify for each patient an unexpected mutational pattern in genes cooperating in lysosomal-autophagic machinery, some of which have never been linked to human diseases. CONCLUSIONS: Our data suggest that reduced GAA activity may occur in any condition of impaired autophagy and that WES approach is advisable in all genetically undefined cases of autophagic myopathy. Therefore, deficiency of GAA activity and PAS-positive lymphocytes should be considered as AVM markers together with LC3/p62-positive autophagic vacuoles.
Subject(s)
Autophagy/genetics , Genotype , Lysosomal Storage Diseases/pathology , Muscular Diseases/pathology , Phenotype , Autophagy/physiology , Glycogen Storage Disease Type II/genetics , Glycogen Storage Disease Type II/pathology , Humans , Lysosomal Storage Diseases/genetics , Lysosomes/metabolism , Muscular Diseases/genetics , Mutation/genetics , Exome Sequencing/methods , alpha-Glucosidases/genetics , alpha-Glucosidases/metabolismABSTRACT
INTRODUCTION: ATTRv amyloidosis is worldwide spread with endemic foci in Portugal and Sweden, Japan, Brazil, Maiorca, and Cyprus. A national Registry was developed to characterise the epidemiology and genotype-phenotype correlation of ATTRv amyloidosis in Italy and to allow a better planning of diagnostic and therapeutic services. METHODS: Fifteen Italian referral centres for amyloidosis spread all over the country have contributed to the Registry. RESULTS: Four-hundred-forty-seven subjects were enrolled, 187 asymptomatic carriers and 260 affected patients. Thirty-one different mutations were recorded. The seven most represented genetic variants were significantly different in terms of age at onset, clinical features and geographical distribution. National prevalence is 4.33/million with higher values in Southern Italy. Overall symptoms of polyneuropathy were present at disease onset in about half of the patients, symptoms of cardiomyopathy in a quarter of patients, the rest referring carpal tunnel syndrome, dysautonomia or lumbar spinal stenosis. 52.6% of patients were in FAP stage 1, 20.4% in stage 2 and 13.5% in stage 3, while 13.5% patients had no neuropathy, presenting only cardiological symptoms. CONCLUSIONS: We presented an epidemiological study based on collaboration among referral centres for ATTRv amyloidosis spread in all the Italian territory, using web-based Registry. It provided a detailed map of the regional distribution of the disease. The increased awareness of the disease among general practitioners and medical specialists has contributed to reduce the diagnostic delay and the rate of misdiagnosis. The Registry will allow to collect also future information about clinical and instrumental follow-up.
Subject(s)
Amyloid Neuropathies, Familial/epidemiology , Adult , Aged , Aged, 80 and over , Amyloid Neuropathies, Familial/diagnosis , Amyloid Neuropathies, Familial/genetics , Amyloid Neuropathies, Familial/pathology , Cardiomyopathies/epidemiology , Cardiomyopathies/pathology , Female , Genotype , Humans , Italy/epidemiology , Male , Middle Aged , Mutation , Phenotype , Polyneuropathies/epidemiology , Polyneuropathies/pathology , Prealbumin/genetics , Prevalence , RegistriesABSTRACT
Progranulin gene (GRN) mutations are among the leading causes of frontotemporal lobar degeneration, a group of neurodegenerative diseases characterized by remarkable clinical heterogeneity. In this article, we report the new GRN 708+4A>T splicing mutation, identified in 2 siblings of a family with several members affected by cognitive, behavioral, and motor disorders. Plasma progranulin dosage and GRN expression analysis, together with in silico prediction studies, supported the pathogenicity of the mutation. Both the patients displayed a clinical syndrome in which language impairment was largely predominant. However, motor speech deficits were the major feature in one case, diagnosed as progressive nonfluent aphasia, whereas marked semantic alterations were present in the other, whose clinical phenotype was in favor of a mixed aphasia. The profile of neuroanatomical alterations from imaging studies was in line with the clinical phenotypes. Therefore, also this novel GRN mutation is associated with haploinsufficiency and phenotypic heterogeneity, which are both typical features of progranulinopathies.
Subject(s)
Aphasia, Broca/genetics , Aphasia, Primary Progressive/genetics , Mutation , Phenotype , Progranulins/genetics , Aged , Aphasia, Broca/diagnostic imaging , Aphasia, Primary Progressive/diagnostic imaging , Brain/diagnostic imaging , Haploinsufficiency/genetics , Humans , Positron-Emission Tomography , SiblingsSubject(s)
Attention , Bipolar Disorder/diagnostic imaging , Bipolar Disorder/psychology , Adolescent , Adult , Comorbidity , Diagnostic and Statistical Manual of Mental Disorders , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Psychomotor Performance , Wechsler Scales , Young AdultABSTRACT
BACKGROUND: Extracellular matrix molecular components, previously linked to multisystem syndromes include collagens, fibrillins and laminins. Recently, we described a novel multisystem syndrome caused by the c.9418G>A p.(V3140M) mutation in the laminin alpha-5 (LAMA5) gene, which affects connective tissues of all organs and apparatus in a three generation family. In the same family, we have also reported a myopic trait, which, however, was linked to the Prolyl 4-hydroxylase subunit alpha-2 (P4HA2) gene. Results of investigation on vitreous changes and their pathogenesis are reported in the present study. MATERIALS AND METHODS: Nineteen family individuals underwent complete ophthalmic examination including best-corrected visual acuity (BCVA), fundus examination, fundus photography, intraocular pressure measurement, axial length measurement using ocular biometry, Goldmann visual field examination, standard electroretinogram, SD-OCT. Segregation analysis of LAMA5 and P4HA2 mutations was performed in enrolled members. RESULTS: The vitreous alterations fully segregated with LAMA5 mutation in both young and adult family members. Slight reduction of retinal thickness and peripheral retinal degeneration in only two patients were reported. CONCLUSIONS: In this work we showed that PVD is a common trait of LAMA5 multisystem syndrome, therefore occurring as an age-unrelated trait. We hypothesize that the p.(V3140M) mutation results in a reduction of retinal inner limiting membrane (ILM) stability, leading to a derangement in the macromolecular structure of the vitreous gel, and PVD. Further investigations will be necessary to elucidate the role of wild type and mutated LAMA5 in the pathogenesis of PVD.
Subject(s)
Genes, Dominant , Laminin/genetics , Mutation , Vitreous Detachment/genetics , Vitreous Detachment/pathology , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Pedigree , Prognosis , Visual AcuityABSTRACT
X-linked adrenoleukodystrophy (X-ALD) is a rare inherited metabolic disease affecting the nervous system and the adrenal glands. It is caused by a mutation of the ABCD1 gene, resulting in the impaired degradation of very long-chain fatty acids and their subsequent accumulation in several organs and tissues. X-ALD is notable for its high phenotypical variability, that includes isolated adrenocortical insufficiency, slowly progressive myelopathy with paraparesis, ataxia, and peripheral neuropathy to severe childhood cerebral forms. Here, we describe the case of an X-ALD patient with a p.Gly343Val mutation in ABCD1 gene, who presented in adulthood with a spinal syndrome of mild severity, and later developed a progressive cognitive and behavioral syndrome. Our patient showed a striking correlation between clinical phenotype and neuroimaging, including a brain fluoro-2-deoxy-d-glucose positron emission tomography that displayed an atypical cerebral glucose metabolism.
ABSTRACT
Behçet's disease is a chronic inflammatory disorder manifesting as a vasculitis that affects arteries and veins of any size. Up to 44% of cases may also present with neurological symptoms, thus defining Neuro-Behçet's disease. We describe a case of Neuro-Behçet's disease characterized by progressive behavioral and cognitive deterioration prevailing over other neurological symptoms, without evident systemic involvement.
Subject(s)
Behcet Syndrome/complications , Cognition Disorders/etiology , Leukoencephalopathies/etiology , Vasculitis/etiology , Adult , Behcet Syndrome/diagnosis , Behcet Syndrome/pathology , Behcet Syndrome/physiopathology , Cognition Disorders/diagnosis , Cognition Disorders/pathology , Cognition Disorders/physiopathology , Humans , Leukoencephalopathies/diagnosis , Leukoencephalopathies/pathology , Leukoencephalopathies/physiopathology , Magnetic Resonance Imaging , Vasculitis/diagnosis , Vasculitis/pathology , Vasculitis/physiopathologyABSTRACT
Hereditary spastic paraplegia (HSP) refers to a group of genetically heterogeneous neurodegenerative motor neuron disorders characterized by progressive age-dependent loss of corticospinal motor tract function, lower limb spasticity, and weakness. Recent clinical use of next generation sequencing (NGS) methodologies suggests that they facilitate the diagnostic approach to HSP, but the power of NGS as a first-tier diagnostic procedure is unclear. The larger-than-expected genetic heterogeneity-there are over 80 potential disease-associated genes-and frequent overlap with other clinical conditions affecting the motor system make a molecular diagnosis in HSP cumbersome and time consuming. In a single-center, cross-sectional study, spanning 4 years, 239 subjects with a clinical diagnosis of HSP underwent molecular screening of a large set of genes, using two different customized NGS panels. The latest version of our targeted sequencing panel (SpastiSure3.0) comprises 118 genes known to be associated with HSP. Using an in-house validated bioinformatics pipeline and several in silico tools to predict mutation pathogenicity, we obtained a positive diagnostic yield of 29% (70/239), whereas variants of unknown significance (VUS) were found in 86 patients (36%), and 83 cases remained unsolved. This study is among the largest screenings of consecutive HSP index cases enrolled in real-life clinical-diagnostic settings. Its results corroborate NGS as a modern, first-step procedure for molecular diagnosis of HSP. It also disclosed a significant number of new mutations in ultra-rare genes, expanding the clinical spectrum, and genetic landscape of HSP, at least in Italy.
ABSTRACT
Valosin-containing protein (VCP) mutations are rare causes of autosomal dominant frontotemporal dementias associated with Paget's disease of bone, inclusion body myopathy, and amyotrophic lateral sclerosis. We analyzed the VCP gene in a cohort of 199 patients with frontotemporal dementia and identified 7 heterozygous mutations in unrelated families, including 3 novel mutations segregating with dementia. This expands the VCP mutation spectrum and suggests that although VCP mutations are rare (3.5% in this study), the gene should be analyzed even in absence of the full syndromic complex. Reporting genetic variants with convincing arguments for pathogenicity is important considering the large amount of data generated by next-generation sequencing and the growing difficulties to interpret rare genetic variants identified in isolated cases.
Subject(s)
Frontotemporal Dementia/genetics , Frontotemporal Dementia/physiopathology , Valosin Containing Protein/genetics , Aged , Cohort Studies , Humans , Male , Middle Aged , Mutation, Missense , PedigreeABSTRACT
OBJECTIVES: Bipolar disorder (BD) patients with a comorbid substance use disorder (SUD) are notoriously difficult to treat. Atypical antipsychotics (AAPs) are widely prescribed in BD, but their efficacy in patients with comorbid SUD is still debated. The aim of the present article is to systematically review the literature findings on the efficacy and safety of AAPs in BD patients with comorbid SUD. METHODS: We searched PubMed to identify original studies focused on the treatment of dual diagnosed BD with AAPs. RESULTS: Ten articles met our inclusion/exclusion criteria, involving a total of 969 subjects, 906 affected by BD and 793 with comorbid SUD: 4 were randomized controlled trials, 4 were open label trials and 2 were observational studies, published between 2002 and 2017. The most commonly abused substances were alcohol and cocaine. The AAPs used to treat patients were quetiapine (n = 337), asenapine (n = 119), olanzapine (n = 80), risperidone (n = 62), and aripiprazole (n = 48). In terms of safety, AAPs were usually well tolerated. Atypical antipsychotics were usually efficacious on acute mood symptoms, whereas their impact on substance-related issues was reported only in those studies without a placebo comparison. CONCLUSIONS: According to our results, even though AAPs are widely used and efficacious in treating the clinical symptoms of BD, there are not enough data to suggest their adjunctive benefit on craving and substance consumption.
Subject(s)
Antipsychotic Agents/therapeutic use , Bipolar Disorder/complications , Bipolar Disorder/drug therapy , Substance-Related Disorders/complications , Antipsychotic Agents/adverse effects , Comorbidity , Humans , Observational Studies as Topic , Prospective Studies , Randomized Controlled Trials as Topic , Retrospective Studies , Treatment OutcomeABSTRACT
Mutations in the GAA gene may cause a late onset Pompe disease presenting with proximal weakness without the characteristic muscle pathology, and therefore a test for GAA activity is the first tier analysis in all undiagnosed patients with hyperCKemia and/or limb-girdle muscular weakness. By using MotorPlex, a targeted gene panel for next generation sequencing, we analyzed GAA and other muscle disease-genes in a large cohort of undiagnosed patients with suspected inherited skeletal muscle disorders (n = 504). In this cohort, 275 patients presented with limb-girdle phenotype and/or an isolated hyperCKemia. Mutational analysis identified GAA mutations in ten patients. Further seven affected relatives were identified by segregation studies. All the patients carried the common GAA mutation c.-32-13T >G and a second, previously reported mutation. In the subcohort of 275 patients with proximal muscle weakness and/or hyperCKemia, we identified late-onset Pompe disease in 10 patients. The clinical overlap between Pompe disease and LGMDs or other skeletal muscle disorders suggests that GAA and the genes causing a metabolic myopathy should be analyzed in all the gene panels used for testing neuromuscular patients. However, enzymatic tests are essential for the interpretation and validation of genetic results.
Subject(s)
Glycogen Storage Disease Type II/diagnosis , Muscle Weakness/diagnosis , Mutation , alpha-Glucosidases/genetics , Adult , Aged , DNA Mutational Analysis , Female , Glycogen Storage Disease Type II/genetics , High-Throughput Nucleotide Sequencing/methods , Humans , Male , Middle Aged , Muscle Weakness/geneticsSubject(s)
Flecainide/therapeutic use , Myotonic Disorders/drug therapy , Voltage-Gated Sodium Channel Blockers/therapeutic use , Adolescent , Adult , Electromyography , Female , Humans , Male , Middle Aged , Muscle, Skeletal/physiopathology , Myotonic Disorders/physiopathology , Pedigree , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Fingolimod is a modulator of Central and peripheral sphingosine pathways, which is currently approved for treatment of Multiple Sclerosis (MS). In animal models it reduces inflammation, but it is also able to potentiate glutamatergic transmission and synaptic plasticity. We aimed to explore whether Fingolimod is able to modify the clinical expression of new demyelinating lesions with respect to IFNß-1a in relapsing remitting MS (RRMS) patients suboptimal responders to IFNß-1a. METHODS: 103 patients with RRMS switching for inefficacy from IFNß-1a to Fingolimod and treated for at least 12 months were included. Annualised Relapse Rate (ARR), EDSS and the number of new brain and spinal gadolinium enhancing (Gd +) and T2 lesions were retrospectively assessed in the whole group during each treatment period. The likelihood of co-occurrence of new Gd + lesions and clinical relapses during IFNß-1a and Fingolimod treatment was analysed. RESULTS: The mean duration of treatment with IFNß-1a and Fingolimod was 3.14 (SD 1.6) and 3.22 years (SD 1.1) respectively. Significant reduction of ARR (p < .001), total number of Gd + and T2 lesions (p < .001) was found switching from IFNß-1a to Fingolimod. Gd + lesions occurring during treatment with Fingolimod were more likely to be asymptomatic compared with IFNß-1a (88% vs 30.9%, p = < .025). CONCLUSION: Fingolimod reduces clinical and radiological inflammation in MS. Additionally, it limits the clinical expression of new Gd + lesions, possibly reducing local inflammatory processes and improving brain network plasticity in patients with suboptimal response to IFNß-1a.
Subject(s)
Fingolimod Hydrochloride/therapeutic use , Immunologic Factors/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Adult , Brain/diagnostic imaging , Brain/drug effects , Contrast Media , Disability Evaluation , Drug Substitution , Female , Gadolinium , Humans , Interferon beta-1a/therapeutic use , Magnetic Resonance Imaging , Male , Recurrence , Retrospective Studies , Spinal Cord/diagnostic imaging , Spinal Cord/drug effects , Treatment OutcomeABSTRACT
Aging is a primary risk factor for both neurodegenerative disorders (NDs) and tumors such as adult-onset brain tumors. Since NDs and tumors are severe, disabling, progressive and often incurable conditions, they represent a pressing problem in terms of human suffering and economic costs to the healthcare systems. The current challenge for physicians and researchers is to develop new therapeutic strategies in both areas to improve the patients' quality of life. In addition to genetics and environmental stressors, the increase in cellular oxidative stress as one of the potential common etiologies has been reported for both disorders. Recently, the scientific community has focused on the beneficial effects of dietary antioxidant classes, known as nutraceuticals, such as carotenoids, vitamins, and polyphenols. Among these compounds, polyphenols are considered to be one of the most bioactive agents in neurodegeneration and tumor prevention. Despite the beneficial activity of polyphenols, their poor bioavailability and inefficient delivery systems are the main factors limiting their use in medicine and functional food. The development of polymeric nanoparticle-based delivery systems able to encapsulate and preserve polyphenolic compounds may represent a promising tool to enhance their stability, solubility, and cell membrane permeation. In the present review we provide an overview of the main polyphenolic compounds used for ND and brain tumor prevention and treatment that explores their mechanisms of action, recent clinical findings and principal factors limiting their application in medicine.
Subject(s)
Brain Neoplasms/drug therapy , Neurodegenerative Diseases/drug therapy , Oxidative Stress/drug effects , Polyphenols/therapeutic use , Antioxidants/chemistry , Antioxidants/therapeutic use , Biological Availability , Brain Neoplasms/pathology , Cell Membrane Permeability/drug effects , Humans , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Neurodegenerative Diseases/pathology , Polyphenols/chemistryABSTRACT
Autosomal recessive Pompe disease is a lysosomal disorder caused by mutations of the acid-α-glucosidase (GAA) gene. Deficiency of GAA enzyme leads to glycogen accumulation and autophagy impairment in cardiac and skeletal muscles, but also in lymphocytes. Since an effective therapy is available, a rapid, sensitive, and specific test is crucial to early identify affected subjects. Number of lymphocytes containing PAS-positive vacuoles was evaluated on blood films from 72 consecutive adult patients with hyperckemia and/or muscle weakness, 13 genetically confirmed late-onset-Pompe-disease (LOPD) and 13 of their offspring. GAA activity, measured on dried blood spot (DBS) in all patients inversely correlated with number of PAS-positive lymphocytes. More than 4 PAS-positive lymphocytes were found in 11 out of the 72 patients (6 new diagnosis of LOPD, 3 different glycogen storage myopathies, 1 glucose-6-phosphate dehydrogenase deficiency, 1 caveolinopathy), in all 13 LOPD patients and in the 13 LOPD offspring. These latter resulted to have all a single GAA mutation but low GAA levels. Immunostaining with the autophagy markers LC3 and p62 confirmed the autophagic nature of lymphocytes vacuoles. ROC curve assessment of PAS-positive lymphocytes disclosed 100% of sensitivity and 94% of specificity in recognizing both compound heterozygous and heterozygous GAA carriers. The other myopathies with more than 4 PAS-positive lymphocytes appeared to be all related to impaired autophagy, which seems to be responsible of PAS-positive vacuolated lymphocytes formation. Quantification of PAS-positive lymphocytes in blood films is useful to identify autophagic vacuolar myopathies and should be routinely used as first level test for Pompe disease.
Subject(s)
Glycogen Storage Disease Type II/diagnosis , Glycogen Storage Disease Type II/pathology , Lymphocytes/metabolism , Vacuoles/pathology , alpha-Glucosidases/genetics , Adolescent , Adult , Aged , Autophagy/physiology , Child , Female , Humans , Lysosomes/pathology , Male , Middle Aged , Muscle, Skeletal/pathology , Young AdultABSTRACT
Schizophrenia has been described as a self-disorder, whereas social deficits are key features of the illness. Changes in "resting state" activity of brain networks involved in self-related processing have been consistently reported in schizophrenia, but their meaning for social perception deficits remains poorly understood. Here, we applied a novel approach investigating the relationship between task-evoked neural activity during social perception and functional organization of self-related brain networks during a "resting state". "Resting state" functional MRI was combined with task-related functional MRI using a social perception experiment. Twenty-one healthy control participants (HC) and 21 out-patients with a diagnosis of schizophrenia (SCH) were included. There were no significant differences concerning age, IQ, education and gender between the groups. Results showed reduced "resting state" functional connectivity between ventromedial prefrontal cortex and dorsal posterior cingulate cortex in SCH, compared to HC. During social perception, neural activity in dorsal posterior cingulate cortex and behavioral data indicated impaired congruence coding of social stimuli in SCH. Task-evoked activity during social perception in dorsal posterior cingulate cortex co-varied with dorsal posterior cingulate cortex-ventromedial prefrontal cortex functional connectivity during a "resting state" in HC, but not in SCH. Task-evoked activity also correlated with negative symptoms in SCH. These preliminary findings, showing disrupted prediction of social perception measures by "resting state" functioning of self-related brain networks in schizophrenia, provide important insight in the hypothesized link between self and social deficits. They also shed light on the meaning of "resting state" changes for tasks such as social perception.
Subject(s)
Brain/diagnostic imaging , Neural Pathways/diagnostic imaging , Rest , Schizophrenia , Schizophrenic Psychology , Social Perception , Adult , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Neural Pathways/physiopathology , Oxygen/blood , Schizophrenia/diagnostic imaging , Schizophrenia/pathology , Schizophrenia/physiopathology , Young AdultABSTRACT
We report the case of a young man with sudden onset of diplopia after an upper respiratory tract infection. Based on the first radiological findings acute hemorrhagic leukoencephalitis, a variant of acute disseminated encephalomyelitis, was suspected and treatment with high dose intravenous dexamethasone was started but it was stopped for intolerance. The patient clinically worsened, developing gait instability, ataxia and ophthalmoplegia; brain MRI performed 20 days later showed severe progression of the disease with subependymal dissemination. After brain biopsy of the right temporal lesion the histological diagnosis was glioblastoma. These findings suggest that MRI features of acute hemorrhagic leukoencephalitis may dissimulate the diagnosis of diffuse glioma/glioblastoma. This case underscores the importance of considering diffuse glioma in the differential diagnosis of atypical signs and symptoms of acute hemorrhagic leukoencephalitis and underlines the relevant role of integrating neuroradiologic findings with neuropathology.
ABSTRACT
Neurofibromas are the hallmark lesions in Neurofibromatosis 1 (NF1); these tumors are classified as cutaneous, subcutaneous and plexiform. In contrast to cutaneous and subcutaneous neurofibromas, plexiform neurofibromas can grow quickly and progress to malignancy. Curcumin, a turmeric-derived polyphenol, has been shown to interact with several molecular targets implicated in carcinogenesis. Here, we describe the impact of different dietary patterns, namely Mediterranean diet (MedDiet) compared to the Western diet (WesDiet), both with or without curcumin, on NF1 patients' health. After six months, patients adopting a traditional MedDiet enriched with 1200 mg curcumin per day (MedDietCurcumin) presented a significant reduction in the number and volume of cutaneous neurofibromas; these results were confirmed in subsequent evaluations. Notably, in one patient, a large cranial plexiform neurofibroma exhibited a reduction in volume (28%) confirmed by Magnetic Resonance Imaging. Conversely, neither unenriched MedDiet nor WesDiet enriched with curcumin exhibited any significant positive effect. We hypothesize that the combination of a polyphenol-rich Mediterranean diet and curcumin was responsible for the beneficial effect observed on NF1. This is, to the best of our knowledge, the first experience with curcumin supplementation in NF1 patients. Our report suggests that an integrated nutritional approach may effectively aid in the management of NF1.