Paul Rhomberg

Neural correlates of distance and congruity effects in a numerical Stroop task: an event-related fMRI study

This study aimed at investigating the neural correlates of a number-size congruity task. Using an event-related fMRI design, we presented one-digit number pairs to 17 participants in a number-size interference task that required subjects to focus on one stimulus property (e.g., numerical size) and to ignore the other (physical size). In different blocks, participants were asked to decide which digit of a digit pair was numerically larger (numerical comparison task) or physically larger (physical comparison task). Stimuli were classified into three categories: (a) congruent: physical and numerical comparison leads to the same response; (b) incongruent: physical and numerical comparison leads to different responses; (c) neutral: the stimuli differ only with regard to the task-relevant stimulus property. Behavioral results reflect robust distance effects (quicker reaction times for long distances relative to short ones) and size congruity effects (longer reaction times for incongruent relative to congruent stimuli) in both tasks. Imaging results reveal that-compared to congruent trials-incongruent trials led to a stronger activation in the dorsolateral prefrontal cortex and the anterior cingulate cortex, areas associated with attentional control. The distance effect (neutral condition only) led to a stronger activation in bilateral parietal areas including the intraparietal sulcus (IPS).

Does caffeine modulate verbal working memory processes? An fMRI study.

To assess the effect of caffeine on the functional MRI signal during a 2-back verbal working memory task, we examined blood oxygenation level-dependent regional brain activity in 15 healthy right-handed males. The subjects, all moderate caffeine consumers, underwent two scanning sessions on a 1.5-T MR-Scanner separated by a 24- to 48-h interval. Each participant received either placebo or 100 mg caffeine 20 min prior to the performance of the working memory task in blinded crossover fashion. The study was implemented as a blocked-design. Analysis was performed using SPM2. In both conditions, the characteristic working memory network of frontoparietal cortical activation including the precuneus and the anterior cingulate could be shown. In comparison to placebo, caffeine caused an increased response in the bilateral medial frontopolar cortex (BA 10), extending to the right anterior cingulate cortex (BA 32). These results suggest that caffeine modulates neuronal activity as evidenced by fMRI signal changes in a network of brain areas associated with executive and attentional functions during working memory processes.

Laser acupuncture induced specific cerebral cortical and subcortical activations in humans

As recent studies demonstrated, acupuncture can elicit activity in specific brain areas. This study aims to explore further the central effect using laser acupuncture. We investigated the cerebral effects of laser acupuncture at both acupoints GB43 with functional magnetic resonance imaging (fMRI). As a control condition the laser was mounted at the same acupoints but without application of laser stimulation. The group results showed significant brain activations within the thalamus, nucleus subthalamicus, nucleus ruber, the brainstem, and the Brodmann areas 40 and 22 for the acupuncture condition. No significant brain activations were observed within the placebo condition. The activations we observed were laser acupuncture-specific and predominantly ipsilateral. This supports the assumption that acupuncture is mediated by meridians, since meridians do not cross to the other side. Furthermore, we could show that laser acupuncture allows one to design a pure placebo condition.

Fulminant demyelinating encephalomyelitis Insights from antibody studies and neuropathology

Objectives: Antibodies to myelin oligodendrocyte glycoprotein (MOG) are detectable in inflammatory demyelinating CNS diseases, and MOG antibody–associated diseases seem to have a better prognosis despite occasionally severe presentations. Methods: We report the case of a 71-year-old patient with acute visual and gait disturbance that dramatically worsened to bilateral amaurosis, tetraplegia, and respiratory insufficiency within a few days. Results: MRI showed multiple progressive cerebral and spinal lesions with diffusion restriction (including both optic nerves) and marginal contrast enhancement. Routine blood and CSF measures including oligoclonal bands were normal. At disease onset, MOG immunoglobulin G was detected (serum titer 1:1,280, corresponding CSF titer was 1:20) and remained positive in patient serum. Aquaporin-4 antibodies were absent at disease onset but seroconverted to positive at week 9. In addition, CSF glial fibrillary acid protein and myelin basic protein levels were very high at onset but decreased during disease course. After 4 months, the patient died despite immunomodulatory treatment. Postmortem neuropathologic examination revealed an acute multiple sclerosis (MS) defined by multiple demyelinating lesions with a pronounced destructive component and loss of astrocytes. Lesion pattern of optic chiasm met MS pattern II characterized by antibody and complement-mediated demyelination. Conclusion: The case with the clinical presentation of an acute demyelinating encephalomyelitis with predominant optic and spinal involvement, absent oligoclonal bands, a histopathology of acute MS pattern II and development of aquaporin-4 antibodies extends the spectrum of MOG antibody–associated encephalomyelitis. Although, MOG antibodies are suspected to indicate a favorable prognosis, fulminant disease courses are possible and warrant an aggressive immunotherapy.

Spreading depolarizations in patients with spontaneous intracerebral hemorrhage: Association with perihematomal edema progression.

Pathophysiologic mechanisms of secondary brain injury after intracerebral hemorrhage and in particular mechanisms of perihematomal-edema progression remain incompletely understood. Recently, the role of spreading depolarizations in secondary brain injury was established in ischemic stroke, subarachnoid hemorrhage and traumatic brain injury patients. Its role in intracerebral hemorrhage patients and in particular the association with perihematomal-edema is not known. A total of 27 comatose intracerebral hemorrhage patients in whom hematoma evacuation and subdural electrocorticography was performed were studied prospectively. Hematoma evacuation and subdural strip electrode placement was performed within the first 24 h in 18 patients (67%). Electrocorticography recordings started 3 h after surgery (IQR, 3–5 h) and lasted 157 h (median) per patient and 4876 h in all 27 patients. In 18 patients (67%), a total of 650 spreading depolarizations were observed. Spreading depolarizations were more common in the initial days with a peak incidence on day 2. Median electrocorticography depression time was longer than previously reported (14.7 min, IQR, 9–22 min). Postoperative perihematomal-edema progression (85% of patients) was significantly associated with occurrence of isolated and clustered spreading depolarizations. Monitoring of spreading depolarizations may help to better understand pathophysiologic mechanisms of secondary insults after intracerebral hemorrhage. Whether they may serve as target in the treatment of intracerebral hemorrhage deserves further research.

Progressive multifocal leukoencephalopathy complicating untreated chronic lymphatic leukemia: Case report and review of the literature

A 58-year old female with a four-year history of previously untreated CLL at Binet stage A complained about word finding problems, impaired vision, and gait unsteadiness. Concerning her CLL she was asymptomatic and had never required any specific treatment. Her neurological examination disclosed cognitive alterations, homonyme hemianopia to the right, aphasia, and mild right-sided hemiparesis. Cerebral MRI showed a hyperintense lesion on T2 weighted images without contrast enhancement. CSF examination revealed normal findings, including CSF protein, cell count, cytology and PCR-analysis was negative for the presence of JC virus DNA. On follow-up MRI, performed 2 weeks later, the T2 lesion was further enlarging. Subsequent stereotactic brain biopsy was diagnostic for PML revealing abnormal oligodendrocytes staining positive against antibodies specific for simian vacuolating virus 40. In addition, repeated CSF analyses for JC-Virus DNA in the course of the disease became positive. After confirmation of diagnosis treatment with mirtazapine (30 mg/d) and mefloquine (250 mg/d) was initiated. Rapid clinical progression correlated to further worsening on MRI. Therefore this treatment was terminated after 16 days and the regime was changed to a five-day courses of cytarabine (2 mg/kg/d) combined with intrathecal administration of liposomal cytarabine (50 mg). Due to further clinical progression with global aphasia, blindness and severe right-sided hemiparesia, medication was stopped. The Patient died three and a half months after onset of symptoms.

Enteral nutrition increases interstitial brain glucose levels in poor-grade subarachnoid hemorrhage patients:

Low brain tissue glucose levels after acute brain injury are associated with poor outcome. Whether enteral nutrition (EN) reliably increases cerebral glucose levels remains unclear. In this retrospective analysis of prospectively collected observational data, we investigate the effect of EN on brain metabolism in 17 poor-grade subarachnoid hemorrhage (SAH) patients undergoing cerebral microdialysis (CMD) monitoring. CMD-values were obtained hourly. A nutritional intervention was defined as the clinical routine administration of EN without supplemental parenteral nutrition. Sixty-three interventions were analyzed. The mean amount of EN per intervention was 472.4 ± 10.7 kcal. CMD-glucose levels significantly increased from 1.59 ± 0.13 mmol/l at baseline to a maximum of 2.03 ± 0.2 mmol/l after 5 h (p < 0.001), independently of insulin-treatment, baseline serum glucose, baseline brain metabolic distress (CMD-lactate-to-pyruvate-ratio (LPR) > 40) and the microdialysis probe location. The increase in CMD-glucose was directly dependent on the magnitude of increase of serum glucose levels (p = 0.007). No change in CMD-lactate, CMD-pyruvate, CMD-LPR, or CMD-glutamate (p > 0.4) was observed. Routine EN also increased CMD-glucose even if baseline concentrations were critically low ( < 0.7 mmol/l, neuroglucopenia; p < 0.001). These results may have treatment implications regarding glucose management of poor-grade aneurysmal SAH patients.

Brain temperature but not core temperature increases during spreading depolarizations in patients with spontaneous intracerebral hemorrhage

Spreading depolarizations (SDs) are highly active metabolic events, commonly occur in patients with intracerebral hemorrhage (ICH) and may be triggered by fever. We investigated the dynamics of brain-temperature (Tbrain) and core-temperature (Tcore) relative to the occurrence of SDs. Twenty consecutive comatose ICH patients with multimodal electrocorticograpy (ECoG) and Tbrain monitoring of the perihematomal area were prospectively enrolled. Clusters of SDs were defined as ≥2 SDs/h. Generalized estimating equations were used for statistical calculations. Data are presented as median and interquartile range. During 3097 h (173 h [81–223]/patient) of ECoG monitoring, 342 SDs were analyzed of which 51 (15%) occurred in clusters. Baseline Tcore and Tbrain was 37.3℃ (36.9–37.8) and 37.4℃ (36.7–37.9), respectively. Tbrain but not Tcore significantly increased 25 min preceding the onset of SDs by 0.2℃ (0.1–0.2; p < 0.001) and returned to baseline 35 min following SDs. During clusters, Tbrain increased to a higher level (+0.4℃ [0.1–0.4]; p = 0.006) when compared to single SDs. A higher probability (OR = 36.9; CI = 36.8–37.1; p < 0.001) of developing SDs was observed during episodes of Tbrain ≥ 38.0℃ (23% probability), than during Tbrain ≤ 36.6℃ (9% probability). Spreading depolarizations – and in particular clusters of SDs – may increase brain temperature following ICH.

Early thrombosis prophylaxis with enoxaparin is not associated with hematoma expansion in patients with spontaneous intracerebral hemorrhage

Early pharmacological deep vein thrombosis (DVT) prophylaxis is recommended by guidelines, but rarely started within 48 h. We aimed to analyze the effect of early (within 48 h) versus late (>48 h) DVT prophylaxis on hematoma expansion (HE) and outcome in patients with spontaneous intracerebral hemorrhage (ICH).