Highlights • Numerous studies have shown that repetitive transcranial magnetic stimulation (rTMS) produced significant clinical effects in patients with various neurological and psychiatric ...disorders. • This review presents guidelines on the therapeutic use of rTMS issued by a group of European experts. • Level A or B evidence supports an efficacy of rTMS protocols in depression, pain, motor stroke and schizophrenia.
Antiphospholipid syndrome (APS) is an autoimmune antibody-mediated condition characterized by thrombotic events and/or pregnancy morbidity in association with persistent positivity to ...antiphospholipid antibodies (aPL). The nervous system is frequently affected, as intracranial vessels are the most frequent site of arterial pathology. Over the course of years, many other neurological conditions not included in the diagnostic criteria, have been associated with APS. The pathogenic mechanisms behind the syndrome are complex and not fully elucidated. aPL enhance thrombosis, interfering with different pathways. Nevertheless, ischemic injury is not always sufficient to explain clinical features of the syndrome and immune-mediated damage has been advocated. This may be particularly relevant in the context of neurological complications. The reason why only a subgroup of patients develop non-criteria nervous system disorders and what determines the clinical phenotype are questions that remain open. The double nature, thrombotic and immunologic, of APS is also reflected by therapeutic strategies. In this review we summarize known neurological manifestations of APS, revisiting pathogenesis and current treatment options.
Parkinson's disease (PD) is characterized by loss of dopaminergic neurons and intraneuronal accumulation of alpha-synuclein, both in the basal ganglia and in peripheral sites, such as the gut. ...Peripheral immune activation and reactive oxygen species (ROS) production are important pathogenetic features of PD. In this context, the present study focused on the assessment of
effects of probiotic bacterial strains in PBMCs isolated from PD patients vs. healthy controls.
40 PD patients and 40 matched controls have been enrolled. Peripheral blood mononuclear cells (PBMCs) were isolated and co-cultured with a selection of probiotics microorganisms belonging to the
and
genus.
release of the major pro- (Tumor Necrosis Factor-alpha and Interleukin-17A and 6) and anti-inflammatory (Interleukin 4 and 10) cytokines by PBMCs, as well as the production of ROS was investigated. Furthermore, we assessed the ability of probiotics to influence membrane integrity, antagonize the growth of potential pathogen bacteria, such as
and
and encode tyrosine decarboxylase genes (
).
All probiotic strains were able to inhibit inflammatory cytokines and ROS production in both patients and controls. The most striking results were obtained in PD subjects with
LS01 and
which significantly reduced pro-inflammatory and increased the anti-inflammatory cytokines (
< 0.05). Furthermore, most strains determined restoration of membrane integrity and inhibition of
and
. Finally, we also showed that all the strains do not carry
gene, which is known to decrease levodopa bioavailability in PD patients under treatment.
Probiotics exert promising
results in decreasing pro-inflammatory cytokines, oxidative stress and potentially pathogenic bacterial overgrowth.
longitudinal data are mandatory to support the use of bacteriotherapy in PD.
A connection between amyotrophic lateral sclerosis (ALS) and altered gut microbiota composition has previously been reported in animal models. This work is the first prospective longitudinal study ...addressing the microbiota composition in ALS patients and the impact of a probiotic supplementation on the gut microbiota and disease progression.
Fifty patients and 50 matched controls were enrolled. The microbial profile of stool samples from patients and controls was analyzed via PCR-Denaturing Gradient Gel Electrophoresis, and the main microbial groups quantified via qPCR. The whole microbiota was then analyzed via next generation sequencing after amplification of the V3-V4 region of 16S rDNA. Patients were then randomized to receive probiotic treatment or placebo and followed up for 6 months with ALSFRS-R, BMI, and FVC%.
The results demonstrate that the gut microbiota of ALS patients is characterized by some differences with respect to controls, regardless of the disability degree. Moreover, the gut microbiota composition changes during the course of the disease as demonstrated by the significant decrease in the number of observed operational taxonomic unit during the follow-up. Interestingly, an unbalance between potentially protective microbial groups, such as Bacteroidetes, and other with potential neurotoxic or pro-inflammatory activity, such as Cyanobacteria, has been shown. The 6-month probiotic treatment influenced the gut microbial composition; however, it did not bring the biodiversity of intestinal microbiota of patients closer to that of control subjects and no influence on the progression of the disease measured by ALSFRS-R was demonstrated.
Our study poses the bases for larger clinical studies to characterize the microbiota changes as a novel ALS biomarker and to test new microbial strategy to ameliorate the health status of the gut.
CE 107/14, approved by the Ethics Committee of the "Maggiore della Carità" University Hospital, Italy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cognitive impairment (CI) is a frequent and disabling symptom in Multiple Sclerosis (MS). Axonal damage may contribute to CI development from early stages. Nevertheless, no biomarkers are at the ...moment available to track CI in MS patients. We aimed to explore the correlation of cerebrospinal fluid (CSF) axonal biomarkers, in particular: light-chain neurofilaments (NFL), Tau, and Beta-amyloid protein (Abeta) in MS patients with CI at the diagnosis. 62 newly diagnosed MS patients were enrolled, and cognition was evaluated using the Brief International Cognitive Assessment for MS (BICAMS) battery. CSF NFL, Abeta, and Tau levels were determined with commercial ELISA. Patients with CI (45.1%) did not differ for demographic, clinical, and MRI characteristics (except for lower educational level), but they displayed greater neurodegeneration, exhibiting higher mean CSF Tau protein (162.1 ± 52.96 pg/ml versus 132.2 ± 63.86 pg/ml
p
:0.03). No differences were observed for Abeta and NFL. The number of impaired tests and Tau were significantly correlated (
r
:0.32
p
:0.01). Tau was higher in particular in patients with slowed information processing speed (IPS) (
p
:0.006) and a linear regression analysis accounting for EDSS, MRI, and MS subtype confirmed Tau as a weak predictor of IPS and cognitive impairment. In conclusion, CI has an important burden on the quality of life of MS patients and should be looked for even at diagnosis. Axonal damage biomarkers, and in particular Tau, seem to reflect cognition impairment in the early stages.
A 35-year-old Caucasian woman presented an abrupt onset of bilateral impaired vision, and arrived to our attention two weeks later. She had a previous episode of mild dizziness. She underwent a ...fluorescein angiography showing branch retinal artery occlusions and a brain magnetic resonance imaging (MRI) revealing several supraand infratentorial FLAIR-hyperintense white matter lesions, two with contrast enhancement. Thrombophilic, autoimmune and infective (including Human Immunodeficiency Virus, Borrelia burgdorferi, Hepatitis B Virus, Hepatitis C Virus, Herpes Simplex Virus 1-2, Varicella Zoster Virus) screening was negative. Cerebrospinal fluid analysis showed intrathecal IgG synthesis. We suspected a Primary Central Nervous System Vasculitis, and intravenous steroids were started. Three months later a second brain MRI showed seven new lesions without contrast enhancement, and she revealed a cognitive impairment and bilateral hearing loss. Reviewing the clinical history and MRI, she fulfilled diagnostic criteria for Susac syndrome. She had two cycles of cyclophosphamide, and recovered in 6 months and then remained stable with metotrexate.
Parkinson's disease (PD) is a common neurodegenerative disease characterized by loss of dopaminergic neurons in the
of the midbrain
. PD pathophysiology is complex, multifactorial, and not fully ...understood yet. Nonetheless, recent data show that immune system hyperactivation with concomitant production of pro-inflammatory cytokines, both in the central nervous system (CNS) and the periphery, is a signature of idiopathic PD. About 5% of PD patients present an early onset with a determined genetic cause, with either autosomal dominant or recessive inheritance. The involvement of immunity in the genetic forms of PD has been a matter of interest in several recent studies. In this review, we will summarize the main findings of this new and promising field of research.
Aquaporin-4 antibody (AQP4-IgG) neuromyelitis optica spectrum disorders (NMOSD) are rare idiopathic autoimmune diseases, presenting with optic neuritis (ON), longitudinally extensive transverse ...myelitis (LETM), and brainstem syndromes and a prevalence range between 0.5 and 4/100,000. Only 3% to 25% of NMOSD have been described as a paraneoplastic (PN) syndrome (PNNMOSD). Both idiopathic NMOSD (INMOSD) and PNNMOSD cases mostly affect females, but PNNMOSD usually presents with a spinal cord or brainstem involvement in elderly patients. Few cases of both malignancies (for the majority breast or lung cancer) and benign tumors (monoclonal gammopathy) were previously reported. Currently, there is no consensus on treatment approach for PNNMOSD (only surgical removal or surgery combined with chronic immunosuppression). Here, we present a series of three newly diagnosed PNNMOSD cases, who differ from each other for demographic and clinical features, tumor association, long-term treatment, and outcome. We propose that a PN etiology should be considered always whenever a new diagnosis of NMOSD is made, not only in patients over 50 years old or in spinal cord/brainstem lesions presentations. Our findings add to existing evidence and raise awareness on PNNMOSD. We enhance the importance for the clinicians of recognizing tumor symptoms and signs whenever a NMOSD is newly diagnosed.
Background
Ultrasonography of the optic nerve sheath diameter (ONSD) is used for the non-invasive assessment of increased intracranial pressure (ICP). ONSD values are usually obtained by averaging ...the measurements of the two eyes, but asymmetric ONSD dilation is possible, leading to potentially inaccurate ICP estimation when using binocular averaging. In addition, few data are available about the asymmetry of the ONSD and the use of the maximum ONSD value between eyes for raised ICP detection. The aim of the study was to evaluate the interocular ONSD asymmetry in healthy subjects and patients with intracranial hypertension (IH) by ultrasonography and to investigate whether the maximum ONSD could be as useful as the binocular assessment.
Methods
Forty healthy subjects and 40 patients with IH (20 with idiopathic intracranial hypertension and 20 with intracerebral hemorrhage) who underwent transorbital sonography were retrospectively enrolled. The prevalence and degree of ONSD asymmetry were compared among groups; ONSD median binocular and maximum values were compared.
Results
Forty-two out of 80 subjects (52.5%) showed significant ONSD asymmetry, without significant differences in prevalence among groups (
p
= 0.28). The median asymmetry was higher in patients than in healthy subjects (0.45 mm vs 0.23 mm;
p
= 0.007), without significant differences between the two pathologies (
p
= 0.58). Both binocular and maximum ONSD measurements were significantly higher in patients with IH than in controls (
p
< 0.001).
Conclusions
Interocular ONSD asymmetry occurs both in healthy subjects and, more consistently, in patients with IH. Both binocular and maximum ONSD may be useful markers for increased ICP detection.
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