Neuronal and Neuroaxonal Damage Cerebrospinal Fluid Biomarkers in Autoimmune Encephalitis Associated or Not with the Presence of Tumor.

The aim of this study was to evaluate the association of neuronal damage biomarkers (neurofilament light chain (NFL) and total tau protein (T-tau)) in the CSF of patients with autoimmune encephalitis (AE) with the presence of an underlying malignancy and to determine correlations with patient characteristics. The study comprised 21 patients with encephalitis associated with antibodies against intracellular (n = 11) and surface/synaptic antigens (extracellular, n = 10) and non-inflammatory disease controls (n = 10). Patients with AE associated with intracellular antigens had increased CSF-NFL (p = 0.003) but not T-tau levels compared to controls. When adjusted for age, CSF-NFL but not CSF-T-tau was higher in patients with encephalitis associated with intracellular antigens as compared to those with encephalitis associated with extracellular antigens (p = 0.032). Total tau and NFL levels were not significantly altered in patients with encephalitis associated with extracellular antigens compared to controls. NFL in the total cohort correlated with neurological signs of cerebellar dysfunction, peripheral neuropathy, presence of CV2 positivity, presence of an underlying tumor and a more detrimental clinical outcome. AE patients with abnormal MRI findings displayed higher NFL levels compared to those without, albeit with no statistical significance (p = 0.07). Using receiver operating characteristic curve analysis, CSF-NFL levels with a cut-off value of 969 pg/mL had a sensitivity and specificity of 100% and 76.19%, respectively, regarding the detection of underlying malignancies. Our findings suggest that neuronal integrity is preserved in autoimmune encephalitis associated with extracellular antigens and without the presence of tumor. However, highly increased NFL is observed in AE associated with intracellular antigens and presence of an underlying tumor. CSF-NFL could potentially be used as a diagnostic biomarker of underlying malignancies in the clinical setting of AE.

Craniofacial and Neurological Phenotype in a Case of Oculodentodigital Syndrome.

INTRODUCTION: Oculodentodigital syndrome (ODDS) is a rare genetic disorder caused by mutations in the gap junction GJA1 gene encoding connexin-43 (chromosome 6q22). A typical ODDS case is presented. MATERIAL AND METHODS: A 40-year-old male patient was examined neurologically and genetically. He had a history of recent parieto-occipital leukodystrophy, some episodes of temporary hearing loss, and characteristic facial features of ODDS. Sequencing of the GJA1 gene was performed in patient's total genomic DNA sample isolated from peripheral blood cells. RESULTS: A novel heterozygous missense mutation (443G>A) was identified in the GJA1 gene, resulting in coding for a different amino acid (Arg148Gln). CONCLUSION: The molecular genetic analysis confirmed the diagnosis of ODDS. The novel mutation, located within a calmodulin binding region of connexin-43, probably affects proper channel function.

Diffuse glioma manifesting as normal pressure hydrocephalus: A potential pitfall in diagnosis-a case report.

•Hydrocephalus is rarely reported in patients with diffuse glioma.•We describe a patient with a low-grade glioma presenting a complex phenotype initially masquerading as hydrocephalus of unknown etiology.•The exact pathophysiological mechanism underlying hydrocephalus in the setting of diffuse glioma remains to be elucidated.•Caution is advised regarding hydrocephalus of unknown etiology, reevaluation is necessary.

Anti-NMDA receptor encephalitis presenting as isolated aphasia in an adult.

Anti-NMDA receptor (NMDA-r) encephalitis is a relatively rare cause of autoimmune encephalitis with divergent clinical presentations. We report a case of an adult patient with anti-NMDA-r encephalitis presenting with isolated, abrupt-onset aphasia. Her condition remained unaltered over a period of 6 months. The patients' electroencephalogram findings were typical for NMDA-r encephalitis; however, her magnetic resonance imaging and cerebrospinal fluid analysis were normal. She responded well to immunotherapy, and aphasia eventually resolved. The natural course of the present case contradicts the rapidly progressive nature of typical NMDA-r encephalitis. Furthermore, it broadens the clinical spectrum of anti-NMDA-r encephalitis, to incorporate isolated, nonprogressive aphasia.

Recognition of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) in Two Oligosymptomatic Sisters with Low CADASIL Scale Scores and a Venous Dysplasia: Report of a Novel Greek Family.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) due to mutations of the NOTCH3 gene is the most common cause of inherited cerebral small-vessel disease and one of the genetic causes of migraine with aura. The so-called CADASIL scale has been proposed as a clinical screening tool, and a score of 15 or higher seems useful in identifying patients with high probability of carrying NOTCH3 mutations. We studied a novel Greek family with clinical features compatible with CADASIL. Genetic analysis of NOTCH3 in the 2 living patients revealed the R182C mutation. Both patients had low scores (12 and 14) in the CADASIL scale, probably due to their relatively young age (38 and 37 years, respectively) at which cognitive decline and external capsule involvement have not developed yet. Another unusual feature in the second patient was a venous dysplasia in the parietal lobe. Observations presented here add to the notion that the CADASIL scale, although useful, probably needs a revision, taking into account the patient's age at which the score is calculated.

Vertebral hemangiomas in the thoracic spine of multiple sclerosis patients are connected with fewer demyelinating lesions at the same level. Possible impact on pathophysiology and clinical course.

OBJECTIVES: Mechanisms of angiogenesis regulate multiple sclerosis (MS) lesions' evolution, displaying both neuroprotective and harmful effects. Factors traditionally considered as purely angiogenic, like vascular endothelial growth factor (VEGF), exert complex heterogenous actions on both neural and vascular malformation-derived tissues. Aim of this retrospective study was to examine, for the first time, potential associations between the presence of common vascular malformations, like vertebral hemangiomas (VHs), and several clinico-radiological MS parameters. METHODS: 236 MS patients who were followed in our Outpatient Clinic were recruited in this study. Outcome measures concerned demographics, disease-derived variables, and MS-lesions' distribution in VHs - positive and negative patients. All data were collected retrospectively. Potential correlations were assessed with univariate statistical analyses (p = 0.05), followed by multivariate regression models, for purposes of confounder-effects elimination. RESULTS: VH presence showed significant negative correlations with presence of MS lesions in the thoracic (p = 0.005 for thoracic VHs), but not the cervical cord. Trends towards negative associations of VH presence with subtentorial MS lesions and positive family history for MS were also observed. DISCUSSION: Our observations suggest that VH presence may reduce the risk of thoracic demyelinating lesions in MS patients. They could be explained as part of a multifaceted angiogenic process, concomitantly enhancing neural repair and abnormal hemangioma vascularization.

Oxidative damage to plasma proteins in patients with chronic alcohol dependence: the effect of smoking.

BACKGROUND: Accumulating evidence implicates oxidative stress in ethanol-induced toxicity. Ethanol has been reported to be involved in oxidative damage, mostly in vitro, or in post mortem tissues, while biochemical abnormalities in the blood or serum are scanty or lacking. The aim of the present study was to examine the oxidative status of plasma proteins as markers of oxidative stress in subjects with chronic alcohol dependence (CAD). Since smoking has also been associated with oxidative stress this factor was also considered. PATIENTS AND METHODS: A total of 71 patients with CAD and 61 healthy volunteers of comparable age were included in the study. The protein carbonyl assay was carried out in plasma, as a reliable measure of general oxidative protein damage, in these two groups. RESULTS: Increased plasma protein carbonyls (PCs) were found in patients with CAD as compared with the control group [mean values (nmollmg protein): 4.73+/-1.46 and 3.62+/-0.91 respectively, p<0.000001]. Within the control group, smokers had higher PCs than the non-smokers, however this difference was of marginal significance [mean values (nmol/mg protein): 3.93+/-1.32 and 3.47+/-0.63, respectively]. The CAD group had significantly increased PCs compared with both the smoker and the non-smoker subgroups of the controls (p<0.001 and p<0.0001, respectively). Duration of alcohol consumption, daily alcohol intake, smoke load, folic acid and vitamin B12 levels did not correlate significantly with PC levels. CONCLUSION: The above results support the evidence for systemic oxidative stress in CAD, which must be attributed mainly to alcohol consumption, while smoking may act synergistically.

Interleukin-12 is reduced in cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia.

UNLABELLED: Interleukin-12 is a heterodimeric cytokine produced by activated blood monocytes, macrophages and glial cells. It enhances differentiation and proliferation of T cells and increases production of proinflammatory cytokines, such as Interferon-gamma and Tumor Necrosis Factor-alpha. There is little information about the involvement of IL-12 in the pathophysiology of Alzheimer's disease (AD) and other tauopathies. OBJECTIVES: The objective of our study was to assess the role of IL-12 as a potential marker of immune reactions in patients with AD and frontotemporal dementia (FTD). PATIENTS AND METHODS: We measured by immunoassay cerebrospinal fluid (CSF) IL-12 levels in 19 patients with AD and 7 patients with FTD in comparison with CSF IL-12 levels in 30 patients with non-inflammatory neurological diseases served as neurological control patients (NCTRL). IL-12 levels were correlated with age, age of disease onset, disease duration, MMSE score, and rate of dementia progression. Abeta42 and Total tau (tau(T)) levels in CSF were also measured. RESULTS: Patients with AD had significantly lower CSF IL-12 levels compared with NCTRL patients (p<0.001). Patients with FTD had also lower CSF IL-12 levels compared with NCTRL patients (p<0.05). Age, sex, disease duration and MMSE score did not affect IL-12 levels in any of the groups. In AD a significant positive correlation was noted between IL-12 levels and tau(T) levels (Rs=0.46, p=0.048). CONCLUSIONS: Our findings may suggest a reduced inflammatory reaction during the course of AD and FTD. A neurotrophic role of IL-12 and other proinflammatory cytokines cannot be excluded.