Michal Dufek

Intracerebral event-related potentials to subthreshold target stimuli.

OBJECTIVES Event-related potentials (ERPs) elicited by subthreshold visual stimuli were recorded directly from human frontal and temporal lobe structures to study unconscious perception. METHODS Thirteen intractable epileptic patients undergoing depth electrode recordings prior to their surgical treatment participated in the study. An original method of modified visual oddball paradigm with supraliminal and subliminal stimuli was applied, and the averaged responses to both kinds of stimuli were subsequently compared. RESULTS The results clearly prove that, at least from an electrophysiological viewpoint, the mechanism of unaware processing of visual stimuli in the human brain does not differ substantially from the aware processing. Finding the subliminal P3 waveform in a number of cortical structures (hippocampus and parahippocampal gyrus bilaterally, and left-sided mesiofrontal, orbitofrontal and lateral temporal cortex) indicates their involvement in unconscious processing, in spite of the fact that typical large-scale neurocognitive networks are not completely activated. The absence of activation consistently observed bilaterally in dorsolateral prefrontal cortices, in connection with right-sided cortical frontal lobe structures and right-sided lateral temporal neocortex in unconscious perception, supports the importance of these structures for the awareness of visual stimuli. The proof of the significantly faster unaware information processing represents another distinctive feature of implicit visual perception. CONCLUSIONS Based on the presented findings and comparisons with the results of previous ERP, functional magnetic resonance imaging, positron emission tomography, and clinical neuropsychological studies, a crucial role of the large-scale neural system for conscious experience of perception is suggested, which is distributed extensively among the dorsal posterior association areas and the prefrontal cortex, with the dominant part being that of the right hemisphere.

Serum inflammatory biomarkers in Parkinson's disease.

Numerous recent findings indicate the involvement of a neuroinflammatory reaction in the neurodegeneration in idiopathic Parkinsons disease (PD). We examined 29 consecutive patients with PD, ages 54-84 years, most of whom were moderately impaired (median UPDRS 19; Hoehn-Yahr 3; MMSE 28). A series of serum biomarkers were investigated, and their levels were correlated with the degree of the motor and cognitive impairment. There were no abnormalities of IL-6, acute phase proteins (C-reactive protein, serum amyloid A, alpha 1-antitrypsin, orosomucoid, ceruloplasmin, alpha 2-macroglobulin, transferrin, prealbumin) and factors of the complement system (C1q, C1-INH, C3, C4). A decrease in Mannan-binding lectin (MBL) levels was observed in six patients; an elevation of tumor necrosis factor-alpha (TNF-alpha) was found in 12 patients. No statistically significant correlation was found between the patients clinical state (neuropsychologic and motor, as expressed by UPDRS III, Hoehn-Yahr, and MMSE) and the immunomarker changes. Our results indicate that the inflammatory process may be reflected in the serum; nevertheless, further research is needed to elucidate the possible clinical implications.

The role of frontal and temporal lobes in visual discrimination task — depth ERP studies

Visual event-related potentials were simultaneously recorded from different anatomical structures within frontal and temporal lobes in 12 epileptic patients. A simple discrimination task was performed to complement previous studies on the localization of P3 generators in the human brain. The role of multiple cortical structures in the generation of both P3a and P3b components was confirmed. Activities contemporary to a visual P3b were recorded in the hippocampus, amygdala and temporal pole. Anterior cingulate and orbitofrontal cortices-generated activities more closely related in time to the surface P3a. Earlier events related to visual discrimination took place in more lateral sites of the frontal lobe, but their contribution to the scalp P3 remains uncertain. Subsequently, mutual temporal relations among single generators were analyzed. The results suggested a processing-level hierarchy within the neural network for directed attention with a key role played by the dorsolateral prefrontal cortex.

Effect of BG-12 on contrast-enhanced lesions in patients with relapsing--remitting multiple sclerosis: subgroup analyses from the phase 2b study.

Background: In a phase 2b study in patients with relapsing–remitting MS (RRMS), BG-12 240 mg three times daily significantly reduced the number of new gadolinium-enhanced (Gd+) lesions from weeks 12 to 24 (primary end point) by 69% compared with placebo. Objective: In this analysis, the effect of BG-12 240 mg three times daily on the number of Gd+ lesions from weeks 12 to 24 was evaluated in subgroups based on baseline disease characteristics and demographics. Methods: Two hundred and fifty-seven patients were randomized equally to receive BG-12 (120 mg once daily or three times daily or 240 mg three times daily) or placebo. Results: BG-12 240 mg three times daily significantly reduced the number of new Gd+ lesions compared with placebo in the following subgroups: Expanded Disability Status Scale (EDSS) score ≤ 2.5 (74%), EDSS score > 2.5 (63%), no Gd+ lesions (80%), ≥ 1 Gd+ lesion (55%), age < 40 years (49%), age ≥ 40 years (89%), female patients (81%), disease duration ≤ 6 years (81%) and disease duration > 6 years (54%) (all comparisons p < 0.05). Conclusion: BG-12 demonstrated efficacy in patients with RRMS by decreasing new Gd+ lesion development across a range of subgroups defined by baseline disease characteristics or demographics.

Vascular pathology in patients with idiopathic Parkinson's disease.

To study the impact of brain vessel pathology on the clinical status of Parkinsons disease (PD), in 57 consecutive patients the clinical and neuropsychological data were compared with clinical MRI signs of vascular impairment and with the ultrasound brain vessel investigations. There was a significant correlation between clinical and cognitive status and intimomedial thickness, which is an indicator of large vessel impairment. Cognitive status was significantly related to the pulsatility index (an indicator of small vessel impairment). This study provides evidence that subclinical vascular pathology could influence the clinical status by contributing to motor and cognitive dysfunction in PD.

Safety of performing CT angiography in stroke patients treated with intravenous thrombolysis

Objective Exposure to contrast agents may cause nephrotoxicity. The safety of performing CT angiography without having knowledge of the baseline creatinine level in stroke patients treated with tissue plasminogen activator (tPA) has not been established. Methods This is an observational cohort study, with a historical control group to evaluate the safety of CT angiography performed before tPA treatment given within 3 h of symptom onset. The CT angiography group represents all patients treated with tPA between September/2003 and November/2007 who had CT angiography. The control group consists of all patients treated with tPA between January 1999 and August 2003 when CT angiography was not performed. The primary outcome was a creatinine increase in 24–72 h compared with baseline; the secondary outcome was a creatinine increase by ≥44 μmol/l in 24–72 h and the incidence of symptomatic intracerebral haemorrhage (sICH). Results Baseline parameters between the CT angiography group (164 patients, age 70±11; 91 male) and the control group (77 patients, age 67±11; 45 male) were similar. In the CT angiography group, the mean creatinine increase was −0.89 mmol/l and in the control group 2.2 mmol/l (p=0.42). A creatinine increase of ≥44 μmol/l occurred in five patients (3%) in the CT angiography group and in three patients (4%) in the control group (p=0.50). Also, in the CT angiography group, eight patients (5%) had sICH as compared with three patients (4%) in the control group (p=0.73). Conclusion Contrast agents given for CT angiography, performed in patients with normal and abnormal creatinine level, neither caused renal injury nor interfered with the safety of tPA treatment.

A pilot study on systemic thrombolysis followed by low molecular weight heparin in ischemic stroke

Low molecular weight heparin (LMWH) administered immediately after intravenous thrombolysis (IT) may reduce the risk of arterial re‐occlusion. Its benefit, however, may not outweigh the risk of intracranial hemorrhage (ICH). We sought preliminary data regarding safety of this combined therapy in an open‐label, non‐randomized study. The patients received either a standard anticoagulation (AC) starting 24 h after IT (the standard AC group) or AC with 2850 IU of nadroparin, given every 12 h immediately after IT (the early AC group). Sixty patients received IT treatment: 25 in the standard AC group [mean age 66, median National Institutes of Health Stroke Scale (NIHSS) 13, 64% men] and 35 in the early AC group (mean age 68, median NIHSS 13, 69% men). Symptomatic ICH occurred in one patient (4%) in the standard AC group and three patients (8.6%) in the early AC group [odds ratio (OR) 1.8; 95%CI 0.2–12.8]. At 3 months, nine patients in the standard AC group (36%) and 16 patients in the early AC group (45.7%) achieved a modified Rankin scale 0 or 1 (OR 1.2; 95%CI 0.5–3.2). Our study suggests that treatment with LMWH could be associated with higher odds of ICH, although it may not necessarily lead to a worse outcome. This justifies larger clinical trials.

Interleukin-6 May Contribute to Mortality in Parkinson’s Disease Patients: A 4-Year Prospective Study

Objectives. The association between abnormal serum immunomarkers and mortality in 53 consecutive Parkinsons disease patients was studied. Materials and Methods. The plasma level of specific inflammatory cytokines was investigated: mannan-binding lectin (MBL), interleukin- (IL-) 6, and tumor necrosis factor-alpha (TNF-α). The baseline serum immunomarkers obtained from patients who died (n = 16) during a four-year follow-up period were compared with the data of patients who survived (n = 37). Results. The baseline level of IL-6 was significantly higher in the deceased patients than in the survivors. Elevated IL-6 levels and age were major independent contributors to disease mortality. Differences between other plasma cytokine level abnormalities were not significant. Conclusion. This study showed that IL-6 elevation may be a marker of increased mortality risk in Parkinsons disease patients. The inflammation may act in association with other factors and comorbidities in progressive neurodegenerative pathology.

Impairment of brain vessels may contribute to mortality in patients with Parkinson's disease.

The effect of brain‐vessel pathology on mortality in 57 consecutive PD patients was studied.

Wegener's granulomatosis: ischemic stroke as the first clinical manifestation (case study).

Sirs: Wegener’s granulomatosis (WG) is a vasculitic syndrome characterised by necrotising granulomas in the ear, nose and throat region, lungs and kidneys [2]. Neurological complications often constitute the most incapacitating features of Wegener’s granulomatosis, and occur in 22 % to 54 % of cases [2, 6, 7]. The involvement of the peripheral nervous system is the most frequent neurological complication of WG [8, 11]. Involvement of the brain and meninges is seen in less than 10 % of patients, and is manifested as intracerebral or subarachnoid haemorrhage, or as cerebral arterial or venous thrombosis [10, 11, 13]. Some of these cerebral vascular complications are secondary to inflammatory vasculitis, but arterial occlusion secondary to direct invasion from nasal or paranasal sites into the skull base and emboli from marantic endocarditis has also been reported [5, 11]. Intracerebral or subarachnoidal haemorrhage is usually a terminal event [2]. Other cerebral involvements include meningitis, encephalitis, and seizure disorder [4, 6, 13]. This paper presents a patient with a cerebral lesion as the initial symptom of WG. Cerebral lesions are very rarely the initial symptoms of WG [1, 3, 10]. A female smoker, aged 52 year, developed clinical symptoms of an ischaemic brainstem stroke on 27 November, 1999. The neurological status was: central vestibular syndrome; palleocerebellar syndrome; left-sided paresis of the abducens nerve; right-sided paresis of the facial nerve; and left-sided hemihypesthesia. MRI revealed a hyperintense signal in the right medulla oblongata (as the result of the ischaemic stroke), and further multiple hyperintensions in the white matter, both subcortically and periventricularly (Fig. 1). Intracranial carotid angiography revealed that the small arterioles were of normal diameter. A high erythrocyte sedimentation rate (105/h), thrombocytosis (652 x10E3/μL, normal range 150–450 x10E3/μL), and an increased CRP (96 mg/L, normal range < 10 mg/L) were observed. Therefore, additional haematological and immunological examinations were performed. C-ANCA (antineutrophil cytoplasmic antibodies) were present (1:320); P-ANCA (antineutrophil perinuclear antibodies) and antinuclear antibodies (ANA)-rheumatoid factor in IgG, IgA, and IgM classes were negative. The patient did not express any typical WG clinical symptoms. Further laboratory findings (including urea, creatinine clearance, urine osmolality, and urine excretion), ultrasonography of the intracranial arteries, peripheral arteries and arteria temporalis, CT of the paranasal sinuses, endoscopy of cavum septi nasi, epipharyngoscopy, lung function tests, transthoracic echocardiography, and skin and subcutaneous tissue biopsies were all negative. Transoesophageal echocardiography was not perLETTER TO THE EDITORS