A.N. Yuceyar

Antibodies to DNA repair proteins in headache with neurological deficits and cerebrospinal fluid lymphocytosis (HaNDL) patients

Abstract Autoimmune mechanisms have been implicated in the pathogenesis of headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL). Pooled sera of five HaNDL patients and 30 controls (10 multiple sclerosis patients, 10 migraine patients, 10 healthy controls) were screened by protein macroarray. All sera were also individually subjected to immunoprecipitation with neuroblastoma cells and the bound antigens were identified by mass spectrometry. Antibodies to three DNA repair proteins (mitogen-activated protein kinase-4, DNA-dependent protein kinase catalytic subunit, DNA excision repair protein ERCC-6) were identified by both macroarray and immunoprecipitation methods in 3/5 HaNDL sera, but in none of the controls. The presence of DNA repair protein antibodies indicates DNA damage and provides further support for the inflammatory etiology of HaNDL.

Vestibular impairment in chronic inflammatory demyelinating polyneuropathy

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a common, treatable, autoimmune peripheral neuropathy considered to produce imbalance by weakness and proprioceptive impairment rather than vestibular impairment. We measured semicircular canal vestibular function in 21 CIDP patients (15M/6F) by the video head impulse test and postural stability with a battery comprising the modified Clinical Test of Sensory Integration and Balance, the Berg Balance Scale, the Dynamic Gait Index, the Fall Efficiency Scale, and the International Cooperative Ataxia Rating Scale. Of the 21 patients, 16 had vestibular impairment, ranging from mild—affecting just a single semicircular canal, to severe—affecting all 6 canals. Although the severity of the vestibular impairment did not correlate either with the severity of the postural imbalance or of the peripheral neuropathy, our data show that vestibular impairment is an additional challenge to balance that some CIDP patients will face.

Juvenile myasthenia gravis: Comparison of pre and postpubertal cases

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. GBM is characterized by cellular heterogeneity, rapid proliferation, angiogenesis and extensive invasion. Glioma tumor cells actively recruit to the tumor site microglia as well as peripheral macrophages, named Tumor Associate Macrophages (TAMs). TAMs have been shown to be deeply involved in tumor microenvironment by their ability to induce immunosuppression, angiogenesis and invasion. Macrophages that infiltrate cancer tissues can be classified inM1 (proinflammatory) and M2 (anti-inflammatory) according to their “activation” state. M1 macrophages produce type I proinflammatory cytokines, participate in antigen presentation and have an anti-tumorigenic role. Conversely, M2 macrophages produce type II cytokines, promote antiinflammatory responses and have pro-tumorigenic functions. Recent antitumor strategies are aiming to target TAMs with different approaches: inhibiting their recruitment, suppressing their survival, enhancing M1 like and blocking M2 activities. We focused our attention on M1 polarized macrophages and how they could influence glioma cells. We attempted to explore whether soluble factors secreted by M1 polarized microglia/macrophages could impact the cell fate of U251 glioma cells. Our preliminary experiments showed that M1 conditioned medium (M1CM) inhibits tumor cell proliferation aswell as promotes apoptosis. Extracellular vesicles have emerged as important mediators of intercellular communication in cancer. Among them, exosomes are defined as vesicles characterized by a size of 30–100 nm in diameter and microvesicles from 50 nm to 1000 nm, both recognized as important mediators of cell-to-cell communication. Currently studies in other type of cancers indicate that nanovesicles present in the CMplay a role in the modulation of tumor microenvironment. In line with these observations, we found that treatment of U251 cells with exosomes derived from M1 polarized microglia/macrophages decreases glioma cell proliferation. Interestingly, both M1 exosomes and microvesicles were more effective thanM1 total conditionedmedium.Wehypothesize that exosome re-polarization toward an M1 phenotype might oppose glioma progression. These findings shed new light on the complex communication networks in theGBMmicroenvironment and open new future therapeutic strategies.

Optic Neuritis: Visual Outcome and Risk Factors for the Development of Multiple Sclerosis in Western Turkey

Optic neuritis (ON) is highly associated with multiple sclerosis (MS) and conversion rate has been reported to be around 50% over a period of 15 years. We revised the risk factors for developing MS after an attack of ON, in western Turkey. One hundred and twenty-four patients with acute unilateral ON, who were on follow-up for at least 5 years (range 62 to180 months, mean 85 months) were enrolled in the study. Gender, age at onset, seasonal occurrence, severity of visual loss, presence of pain, optic disc appearance, treatment, degree of recovery, presence or absence of lesions on magnetic resonance imaging (MRI) during the initial ON attack and recurrence were considered. Of the 124 patients, 89 (71.8%) were women, 35 (28.2%) were men, with a mean age of 28.7 ± 8.6 years at the time of the initial ON attack. During follow-up, 70 patients (56.5%) developed MS within 17.14 months, ranging from 1 to 125 months. Female gender (p = 0.021), experiencing the attack before 40 years of age (p = 0.02), normal-appearing optic discs (p = 0.005), presence of MRI lesions (p < 0.001), and recurring ON attacks (p = 0.014) were significantly associated with a high risk of developing MS. The period for development of MS was significantly shorter in patients with MRI lesions (p < 0.001). Optic neuritis patients with brain MRI findings showing the morphological evidence of disseminated disease can be considered to have MS at the time of the initial ON attack, and disease-modifying treatments can be initiated.