The detection of neural autoantibodies in patients with antiepileptic-drug-resistant epilepsy predicts response to immunotherapy.

BACKGROUND AND PURPOSE: The detection of antibodies binding neural antigens in patients with epilepsy has led to the definition of 'autoimmune epilepsy'. Patients with neural antibodies not responding to antiepileptic drugs (AEDs) may benefit from immunotherapy. Aim of this study was to evaluate the frequency of autoantibodies specific to neural antigens in patients with epilepsy and their response to immunotherapy. METHODS: Eighty-one patients and 75 age- and sex-matched healthy subjects (HS) were enrolled in the study. Two groups of patients were included: 39 patients with epilepsy and other neurological symptoms and/or autoimmune diseases responsive to AEDs (group 1) and 42 patients with AED-resistant epilepsy (group 2). Patients' serum and cerebrospinal fluid were evaluated for the presence of autoantibodies directed to neural antigens by indirect immunofluorescence on frozen sections of mouse brain, cell-based assays and a radioimmunoassay. Patients with AED-resistant epilepsy and neural autoantibodies were treated with immunotherapy and the main outcome measure was the reduction in seizure frequency. RESULTS: Neural autoantibodies were detected in 22% of patients (18/81), mostly from the AED-resistant epilepsy group (P = 0.003), but not in HS. Indirect immunofluorescence on mouse brain revealed antibodies binding to unclassified antigens in 10 patients. Twelve patients received immunotherapy and nine (75%) achieved >50% reduction in seizure frequency. CONCLUSIONS: A significant proportion of patients with AED-resistant epilepsy harbor neural-specific autoantibodies. The detection of these antibodies, especially of those binding to synaptic antigens, may predict a favorable response to immunotherapy, thus overcoming AED resistance.

Inflammation and iron metabolism in adult patients with epilepsy: does a link exist?

PURPOSE: Inflammation has been shown to play a key role in epilepsy, and may also affect both the iron status and metabolism. Consequently, a relationship between iron metabolism and neuronal excitability and seizures could be expected. METHODS: We aimed at characterizing in 37 adult patients affected by focal epilepsy during the interictal period serum inflammatory cytokines, such as interleukin 6 (IL-6), IL-6 soluble receptor (IL6-sR), interleukin 1 (IL-1), IL-1 receptor-antagonist (IL-1RA), tumor necrosis factor-α (TNF-α), and markers of iron status and metabolism: hemoglobin concentration (Hgb), mean corpuscular volume (MCV), hematocrit (Hct) red blood cell (RBC) count, serum iron and copper concentrations, ceruloplasmin (iCp), the ceruloplasmin enzymatic activity (eCp), the specific ceruloplasmin activity (eCp/iCp), total ferroxidase activity, transferrin (Tf), serum ferritin (SF), Tf saturation (Sat-Tf), and ratio of ceruloplasmin to transferrin (Cp/Tf). We investigated the correlations between these biological markers as well their relationship with patients' clinical features. A group of 43 healthy subjects had the same serologic measurements to serve as controls. RESULTS: Our findings showed in the group of patients with epilepsy an increase of IL-6 (p=0.026) and a decrease of TNF-α (p=0.002) with respect to healthy subjects. For the first time, we also detected significant changes in iron metabolism as an increase of Cp/Tf (p=0.011) and a decrease of Tf (p=0.031), possibly driven by cytokine modifications and consistent with inflammation as acute phase and antioxidant activity markers. Accordingly, TNF-α positively correlated with Tf (p=0.005). Finally, a significant positive correlation between seizures frequency and eCp (p=0.046) and inversely with Hgb (p=0.038) and Hct (p=0.041), and an inverse correlation between TNF-α and the duration of epilepsy (p=0.021) was detected. CONCLUSIONS: Our findings demonstrate a relevant relationship between epilepsy and systemic inflammation, with a consistent link between seizures, inflammatory cytokines (IL-6 and TNF-α) and iron regulation and metabolism, as acute phase and antioxidant markers.

An unusual cause of dementia: essential diagnostic elements of corticobasal degeneration-a case report and review of the literature.

Corticobasal degeneration (CBD) is an uncommon, sporadic, neurodegenerative disorder of mid- to late-adult life. We describe a further example of the pathologic heterogeneity of this condition. A 71-year-old woman initially presented dysarthria, clumsiness, progressive asymmetric bradykinesia, and rigidity in left arm. Rigidity gradually involved ipsilateral leg; postural instability with falls, blepharospasm, and dysphagia subsequently developed. She has been previously diagnosed as unresponsive Parkinson's Disease. At our clinical examination, she presented left upper-arm-fixed-dystonia, spasticity in left lower limb and pyramidal signs (Babinski and Hoffmann). Brain MRI showed asymmetric cortical atrophy in the right frontotemporal cortex. Neuropsychological examination showed an impairment in visuospatial functioning, frontal-executive dysfunction, and hemineglect. This case demonstrates that association of asymmetrical focal cortical and subcortical features remains the clinical hallmark of this condition. There are no absolute markers for the clinical diagnosis that is complicated by the variability of presentation involving also cognitive symptoms that are reviewed in the paper. Despite the difficulty of diagnosing CBD, somatosensory evoked potentials, motor evoked potentials, long latency reflexes, and correlations between results on electroencephalography (EEG) and electromyography (EMG) provide further support for a CBD diagnosis. These techniques are also used to identify neurophysiological correlates of the neurological signs of the disease.