•Transcription factors and cytokines evaluation at first episode of Multiple sclerosis and Neuro-behçet disease.•IL-10 in CSF as a discriminative marker between Multiple sclerosis and Neuro-Behçet ...disease.•In initial blood, increased Tbet expression in NB patients only and elevated IFN-γ expression in MS or NB.•Enhanced CSF samples inflammation assessed by ROR-γt, IL-17a and IFN-γ in patients compared to controls.
Multiple Sclerosis (MS) and Neuro-Behçet’s Disease (NBD) are two recurrent disorders affecting the central nervous system (CNS) by causing inflammation and irreversible damage. Inaugural clinical symptoms for both diseases might be very similar and definitive diagnosis could be delayed. The present study aimed to find out possible differences at early stages in the transcription factors/cytokines expression profiles in blood and cerebrospinal fluid (CSF) of MS and NBD patients which could be useful discriminative markers. Cytokines and transcription factors related to Th1, Th2, Th17 and T regulatory populations were studied by quantitative RT-PCR simultaneously in PBMCs and CSF, from 40 patients presenting a first episode of clinical features related to CNS inflammation and 22 controls with non inflammatory neurological diseases enrolled mainly for severe headache. The follow up of 12 months did allow a definitive diagnosis of remitting relapsing MS (RRMS) in 21 patients and of NBD in the other 19 among those with CNS inflammation compared to controls. In initial blood samples, T-bet was significantly increased in NBD patients only while IFN-γ was elevated in patients who evolved into RRMS or NBD. IL-17a, GATA-3 and IL-4 were significantly lower in RRMS patients than in the NBD group. In initial CSF samples, ROR-γt, IL-17a and IFN-γ were significantly elevated in patients compared to controls. The most striking finding was the significant increase of CSF IL-10 that we did observe in NBD patients only. Thus, we propose CSF IL-10 as a predictive marker to help clinicians discriminating between these two neurological disorders.
Background Concomitant diagnosis of neuromyelitis optica spectrum disease and pulmonary tuberculosis has rarely been reported. Case report We report a case involving a young Tunisian male patient who ...developed dry cough followed, 2 months later, by weakness in the lower limbs. The findings of central nervous system imaging and anti-aquaporin-4 antibody positivity were compatible with the diagnosis of neuromyelitis optica spectrum disease. Constellation of the clinical and the typical radiological pulmonary findings in our patient, coming from an endemic region, allowed the diagnosis of pulmonary tuberculosis, although sputum smear examination for acid-fast bacilli and cultures was negative. The patient received anti-tuberculous polytherapy associated with immunomodulation, consisting of methylprednisolone and intravenous immunoglobulins. Pulmonary infection symptoms initially improved but with no motor recovery. The patient suddenly died at home 4 months after the onset of the first symptoms. Current data regarding the clinical presentation of this underreported concomitant or associated condition, the possible pathophysiological mechanisms, and the therapeutic options were reviewed. Conclusions This case underscores the necessity to understand the exact mechanism of these coincident entities and to clarify the best immunomodulatory choice since immunosuppression targeting neuromyelitis optica spectrum disease can lead to dissemination of pulmonary tuberculosis. Keywords: Neuromyelitis optica, Pulmonary tuberculosis, Optic neuritis, Acute transverse myelitis
Inflammatory demyelinating disorders of the central nervous system are debilitating conditions of the young adult, here we focus on multiple sclerosis (MS) and neuro-Behçet disease (NBD). MS is an ...autoimmune disorder of the central nervous system. NBD, a neurological manifestation of an idiopathic chronic relapsing multisystem inflammatory disease, the behçet disease. The diagnosis of MS and NBD relies on clinical symptoms, magnetic resonance imaging and laboratory tests. At first onset, clinical and imaging similarities between the two disorders may occur, making differential diagnosis challenging and delaying appropriate management. Aiming to identify additional discriminating biomarker patterns, we measured and compared gene expression of a broad panel of selected genes in blood and cerebrospinal fluid (CSF) cells of patients suffering from NBD, MS and non inflammatory neurological disorders (NIND). To reach this aim, bivariate and multivariate analysis were applied. The Principal Analysis Component (PCA) highlighted distinct profiles between NBD, MS, and controls. Transcription factors foxp3 in the blood along with IL-4, IL-10, and IL-17 expressions were the parameters that are the main contributor to the segregation between MS and NBD clustering. Moreover, parameters related to cellular activation and inflammatory cytokines within the CSF clearly differentiate between the two inflammatory diseases and the controls. We proceeded to ROC analysis in order to identify the most distinctive parameters between both inflammatory neurological disorders. The latter analysis suggested that IL-17, CD73 in the blood as well as IL-1β and IL-10 in the CSF were the most discriminating parameters between MS and NBD. We conclude that combined multi-dimensional analysis in blood and CSF suggests distinct mechanisms governing the pathophysiology of these two neuro-inflammatory disorders.
When the central nervous system (CNS) is the primary affected site in an initial attack of Behçet’s disease (BD), the differential diagnosis is particularly challenging. Some cases remain ...unclassified or qualified as probable neuro-Behçet’s disease (NBD). Several cytokines are involved in the immunopathogenesis of this disease; however, studies establishing the differential cytokine pattern between probable and definite NBD are scarce. Twenty-eight parenchymal NBD patients, diagnosed according to the International Consensus Recommendation (ICR) criteria and classified into definite (D-NBD; n = 17) and probable (P-NBD; n = 11), were sampled at their first neurological symptoms, and compared with healthy control subjects (n = 20). Oligoclonal bands (OCB) of IgG were detected by isoelectric focusing on agarose, and immunoblotting of matched serum and cerebrospinal fluid (CSF) sample pairs. T cell cytokines (INF-γ, IL-4, IL-17, and IL-10) and transcription factors related to Th1, Th2, Th17, and T regulatory populations (respectively T-bet, GATA-3, ROR-γt, and Foxp3) were studied by quantitative RT-PCR in peripheral blood mononuclear cells (PBMCs) and CSF cells. Inflammatory cytokines such as IL-6, TNF-α, and IL-1β were also analyzed. CSF OCB pattern 2 was present in only 1 out of 28 neuro-Behçet’s patients who belonged to the P-NBD group. Two D-NBD patients had OCB in CSF showing pattern 4. In the D-NBD CSF samples, IL-17 and IL-10 expressions were significantly elevated compared to P-NBD. Moreover, D-NBD patients had increased levels of T-bet/GATA-3 and ROR-γt/Foxp3 ratios compared to P-NBD. Furthermore, a significant increase of CSF IL-6 in D-NBD, compared to P-NBD and the controls, was found. In addition to the increased IL-6 level, the data obtained suggest the existence in D-NBD patients of a significantly disrupted balance between Th17 effector and T regulatory cells, as reflected by the enhanced ROR-γt/Foxp3 ratio. This could be considered as an additional criterion for definite neuro-Behçet’s disease.
Remitting-RelapsingMultiple Sclerosis (RRMS) and Neuro-Behçet Disease (NBD) are two chronic neuroinflammatory disorders leading to neurological damage. Herein, we investigated in these patients the ...IL-10-producing cells during the early stages of these disorders. Cellular and molecular investigations were carried out on treatment naive patients suffering from RRMS and NBD recruited at the first episode of clinical relapse. Our findings demonstrate that CSF-B cells from NBD patients, but not RRMS, are the major source of intrathecal IL-10 as compared to T-CD4 cells. Moreover, we showed a lower expression of TGF-β and IL35, in the CSF cells of NBD patients as compared to the control group. Specific in vitro CpG stimulation of peripheral blood B cells from NBD patients resulted in a concomitant early mRNA expression of IL6 and IL10 but was limited to IL10 for RRMS patients. Furthermore, mRNA expression of IL-6 and IL-10 receptors was assessed and intriguingly IL6ST receptor subunit was significantly lower in NBD CSF, but not RRMS while IL10RB was increased in both. Deciphering the role of increased IL-10-producing B cells and IL10RB despite relapsing disease as well as the discordant expression of IL6 and IL6ST may pave the way for a better understanding of the pathophysiology of these neuro-inflammatory disorders.
Disorganization of the neurofilament network is a prominent feature of
several neurodegenerative disorders including amyotrophic lateral sclerosis
(ALS), infantile spinal muscular atrophy and axonal ...Charcot-Marie-Tooth disease. Giant axonal neuropathy (GAN, MIM 256850), a severe, autosomal
recessive sensorimotor neuropathy affecting both the peripheral nerves and
the central nervous system, is characterized by neurofilament accumulation,
leading to segmental distension of the axons. GAN corresponds
to a generalized disorganization of the cytoskeletal intermediate filaments
(IFs), to which neurofilaments belong, as abnormal aggregation of multiple
tissue-specific IFs has been reported: vimentin in endothelial cells, Schwann
cells and cultured skin fibroblasts, and glial fibrillary acidic protein (GFAP)
in astrocytes. Keratin IFs also seem to be alterated,
as most patients present characteristic curly or kinky hairs.
We report here identification of the gene GAN, which encodes a novel,
ubiquitously expressed protein we have named gigaxonin. We found one frameshift,
four nonsense and nine missense mutations in GAN of GAN patients. Gigaxonin
is composed of an amino-terminal BTB (for Broad-Complex, Tramtrack and Bric
a brac) domain followed by a six kelch repeats, which are predicted to adopt
a β-propeller shape. Distantly related proteins sharing
a similar domain organization have various functions associated with the cytoskeleton,
predicting that gigaxonin is a novel and distinct cytoskeletal protein that
may represent a general pathological target for other neurodegenerative disorders
with alterations in the neurofilament network.
In this study, we investigate the impact of apolipoprotein E epsilon 4 (APOE
ɛ
4) as a major risk factor of Alzheimer’s disease (AD), based on the clinical presentation of the disease in our ...population on the one hand, and comparison of the results with the findings from the literature on the other hand. Our study covered a population of 144 patients versus 90 healthy controls matched with each other in terms of age, gender, age of onset, etc. All patients underwent neurological examination, comprehensive neuropsychological assessment and brain magnetic resonance imaging. Controls were selected based on the neurological examination and the Arabic version of the mini-mental state examination (MMSE). Patients were classified as probable typical amnestic AD and atypical nonamnestic AD if the patient had logopenic variant primary aphasia, posterior cortical atrophy, behavioural or dysexecutive variants, corticobasal syndrome, nonfluent and semantic variants of primary progressive aphasia associated to biological diagnosis for AB42, Tau and Ptau biomarks in the cerebrospinal fluid. Genotyping was performed using the polymerace chain reaction restriction fragment length polymorphism (PCR-RFLP) method. The study of the allelic frequency of APOE in cases and controls show that APOE ɛ4 is associated with an increased risk for AD (
P
= 0.002). We observed that the distribution of APOE
ɛ
4 within the AD group differs depending on the phenotype. Nonamnestic AD was more common in patients not carrying APOE
ɛ
4 (APOE ɛ4 (−)) compared to carriers of homozygous or heterozygous APOE
ɛ
4 (APOE
ɛ
4 (+)) (
P
= 0.038). In addition to its known effect as a major risk factor, we found that patients with AD are APOE ɛ4 negative, they show cognitive decline in nonmemory domains (language, behaviour, attention, executive and visuospatial functions).
Background. The Sjögren Syndrome (SS) can include various manifestations of central nervous system impairment. Extrapyramidal signs are known to be very rare and unusually discovered on early onset ...in this pathology. Observation. A 46-year-old woman with a history of progressive Parkinsonism for 6 years and a normal brain magnetic resonance imaging was partially improved with levodopa therapy. The later discovery of a sicca syndrome led to performing of further investigations, which revealed the presence of anti-SSA antibodies and a sialoadenitis of grade 4 according to Chisholm’s classification on labial salivary gland biopsy. The diagnosis of primary SS was established and the adjunction of corticotherapy has remarkably improved Parkinson’s signs without use of other immunosuppressive agents. Conclusion. Based on these findings, we discuss the hypothesis of either a causal link between SS and Parkinsonism or a fortuitous association of two distinct pathologies with or without a shared immunopathogenesis.
The triggering effect of herpes simplex virus infection on the development of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is now well established. However, there are very few reports that ...has linked a varicella zoster virus (VZV) reactivation with anti-NMDAR encephalitis. In this report, we describe a case of a 57-year-old man presented with atypical clinical presentation of anti-NMDAR encephalitis with gait ataxia, complete ophtalmoplegia, and abolished reflexes followed by drowsiness and confusion. Initial diagnosis of Bickerstaff’s brainstem encephalitis was suspected. Few days later, the patient developed herpes zoster in a localized right T1-T2 dermatome. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) for VZV was negative. CSF anti-NMDA antibodies were proved positive. A diagnosis of anti-NMDAR encephalitis with concomitant VZV skin reactivation was retained. Favorable outcome with combined antiviral treatment and immunomodulatory therapy was observed. Concomitant VZV reactivation with autoimmune encephalitis is possible. Prognosis and therapeutic options in this rare condition remain to be clarified.
It is widely recognized that Alzheimer's disease (AD) is the main cause of dementia in the elderly. AD is typically characterized by the extraneuronal plaque made up essentially of the amyloid β ...peptide and intraneuronal tangles of hyperphosphorylated microtubule-associated Tau protein. This study investigates the possible interaction between AD and the deletion/insertion polymorphism in intron 9 of the Tau gene haplotype and APOE state in a Tunisian AD cases population (n = 85) and control (n = 91). The H2/H2 genotype was higher in the AD group as compared to the controls (22.4% vs. 7.8%). The frequency of H2 allele is higher in the patients group, and the difference of allele frequency is statistically significant between the two groups (χ2 = 12.220, p < 0.05). H2 allele is correlated with the female gender within the patient group (χ2 = 7.649, p = 0.006) Tau H2 haplotype can be identified as a risk factor of AD in the studied Tunisian population and was associated to female gender. There is no significant correlation between the frequency of Tau gene ins/del polymorphism and cognitive profile distribution in the patient group (p > 0.05).
PDF
