Knowledge of physiological aging in healthy human brain is increasingly important for neuroscientific research and clinical diagnosis. To investigate neuronal decline in normal aging brain eighty-one healthy subjects aged between 20 to 70 years were studied with MRI and whole-brain 1H-MR spectroscopic imaging. Concentrations of brain metabolites N-acetyl-aspartate (NAA), choline (Cho), total creatine (tCr), myo-inositol (mI), and glutamine+glutamate (Glx) in ratios to internal water, and the fractional volumes of brain tissue were estimated simultaneously in eight cerebral lobes and in cerebellum. Results demonstrated that an age-related decrease in gray matter volume was the largest contribution to changes in brain volume. Both lobar NAA and the fractional volume of gray matter (FVGM) decreased with age in all cerebral lobes, indicating that the decreased NAA was predominantly associated with decreased gray matter volume and neuronal density or metabolic activity. In cerebral white matter Cho, tCr, and mI increased with age in association with increased fractional volume, showing altered cellular membrane turn-over, energy metabolism, and glial activity in human aging white matter. In cerebellum tCr increased while brain tissue volume decreased with age, showing difference to cerebral aging. The observed age-related metabolic and microstructural variations suggest that physiological neuronal decline in aging human brain is associated with a reduction of gray matter volume and neuronal density, in combination with cellular aging in white matter indicated by microstructural alterations and altered energy metabolism in the cerebellum.

Background: Therapeutic plasma exchange (TPE) in steroid-unresponsive relapses of patients with multiple sclerosis (MS) is an established therapy with response rates of up to 70%. Immunoadsorption (IA) specifically removes immunoglobulins from the patient’s plasma. It is hypothesized that IA therapy might be better tolerated than and as effective as TPE in the treatment of MS relapses. Experiences with IA therapy of steroid-unresponsive MS relapses are limited. Methods: We report our experiences with IA therapy in a series of 10 patients with steroid-unresponsive MS relapses. Results: A marked to moderate clinical response with clear gain of function was observed in 66% of our patients. IA therapy was well tolerated. Conclusions: IA therapy is an effective and well-tolerated therapeutic option for steroid-unresponsive MS relapses.

Background and purpose Whole brain 1H-MR spectroscopic imaging (wbMRSI) was used in combination with quantitative MRI (qMRI) to study the effects of normal aging on healthy human brain metabolites and microstructure. Materials and Methods Sixty healthy volunteers aged 21 to 70 years were studied. Brain maps of the metabolites NAA, Cr, and Cho, and the tissue irreversible and reversible transverse relaxation times, T2 and T2′, were derived from the datasets. The relative metabolite concentrations [NAA], [tCr] and [Cho] as well as the values of relaxation times were measured with ROIs placed within frontal and parietal WM, centrum semiovale (CSO), splenium of the corpus callosum (SCC), hand motor area (HK), occipital GM, putamen, thalamus, pons ventral/dorsal (BSv/BSd), cerebellar white matter (CbWM) and posterior lobe (CbGM). Linear regression analysis and Pearson’s correlation tests were used to analyze the data. Results Aging resulted in decreased [NAA] in occipital GM, putamen, SCC, and BSv, and decreased [tCr] in BSd and putamen. [Cho] did not change significantly in selected brain regions. T2 increased in CbWM and decreased in SCC with aging, while the T2′ decreased in the occipital GM, HK, putamen, and increased in the SCC. Correlations were found between [NAA] and T2′ in occipital GM and putamen and between [tCr] and T2′ in the putamen. Conclusion The effects of normal aging on brain metabolites and microstructure are regional dependent. Correlations between both processes are evident in the gray matter. The obtained data could be used as references for future studies on patients.

Age-related accumulative metabolic changes in aging human brain correlated with reduced neuronal metabolic activity and density, reflected by decreased NAA, reduced mitochondrial activity by decreased ATP, and reduced membrane synthesis by decreased PME. These changes are associated with age-related decrease of neuronal volume. Global NAA and ATP might be used as surrogate biomarker for monitoring aging in human brain.

The 2010 McDonald criteria were developed to allow a more rapid diagnosis of relapsing-remitting multiple sclerosis (MS) by only one MRI of the brain. Although cerebrospinal fluid (CSF) is not a mandatory part of the latest criteria, the evidence of an intrathecal humoral immunoreaction in the form of oligoclonal bands (OCB) is crucial in the diagnostic workup. To date, the impact of the 2010 McDonald criteria on the prevalence of OCB has not been investigated. We retrospectively evaluated data of 325 patients with a clinical relapse suggestive of demyelination that were treated in a German university hospital between 2010 and 2015. One hundred thirty-six patients (42%) were diagnosed with MS and 189 patients with CIS when the criteria of 2010 were applied. The criteria of 2005 allowed only 70 patients (22%) to be designated as MS. In contrast, the prevalence of OCB was marginal affected in MS patients with 96% for the criteria of 2010 and 98.5% for the criteria of 2005. In conclusion, OCB are prevalent in most MS patients and reflect the chronic inflammatory nature of the disease. We recommend CSF examination to exclude alternative diagnoses and reevaluation of the diagnosis MS in patients with negative OCB.

Objective: To estimate alterations in neurometabolic profile of patients with early stage Parkinson's disease (PD) by using a short echo-time whole brain magnetic resonance spectroscopic imaging (wbMRSI) as possible biomarker for early diagnosis and monitoring of PD. Methods: 20 PD patients in early stage (H&Y ≤ 2) without evidence of severe other diseases and 20 age and sex matched healthy controls underwent wbMRSI. In each subject brain regional concentrations of metabolites N-acetyl-aspartate (NAA), choline (Cho), total creatine (tCr), glutamine (Gln), glutamate (Glu), and myo-inositol (mIns) were obtained in atlas-defined lobar structures including subcortical basal ganglia structures (the left and right frontal lobes, temporal lobes, parietal lobes, occipital lobes, and the cerebellum) and compared between patients and matched healthy controls. Clinical characteristics of the PD patients were correlated with spectroscopic findings. Results: In comparison to controls the PD patients revealed altered lobar metabolite levels in all brain lobes contralateral to dominantly affected body side, i.e., decreases of temporal NAA, Cho, and tCr, parietal NAA and tCr, and frontal as well as occipital NAA. The frontal NAA correlated negatively with the MDS-UPDRS II ( R = 22120.585, p = 0.008), MDS-UPDRS IV ( R = −0.458, p = 0.048) and total MDS-UPDRS scores ( R = −0.679, p = 0.001). Conclusion: In early PD stages metabolic alterations are evident in all contralateral brain lobes demonstrating that the neurodegenerative process affects not only local areas by dopaminergic denervation, but also the functional network within different brain regions. The wbMRSI-detectable brain metabolic alterations reveal the potential to serve as biomarkers for early PD.

Background: Sjögren's syndrome is a chronic autoimmune-mediated disease that can cause a variety of neurological manifestations. Methods: This study investigated characteristics of clinical and cerebrospinal fluid (CSF) features in patients with neurological diseases associated with Sjögren's syndrome. Eighty-two patients were examined separately according to the presence of Sjögren's syndrome alone or in combination with other autoimmune diseases. Results: In the 47 patients with primary Sjögren's syndrome, peripheral neuropathy (57%) was found most frequently, followed by the involvement of the central nervous system (CNS; 17%), cranial neuropathy (15%), and myalgia (11%). These patients did not display consistent signs of inflammation in the CSF. Slight pleocytosis of 8-107 cells/µL was found in patients with peripheral neuropathy (9%), cranial neuropathy (20%), and CNS involvement (25%). Oligoclonal bands indicating intrathecal IgG synthesis occurred in 26% of patients with peripheral neuropathy, 20% of patients with cranial neuropathy, and 25% of patients with CNS involvement. Conclusions: In patients with Sjögren's syndrome and neurological manifestations, inflammatory CSF changes were rarely found and did not show a characteristic pattern irrespective of peripheral or central genesis of neurological deficits. Analysis of the CSF presents therefore an important diagnostic procedure to exclude other autoimmune and infectious diseases.

While the revised McDonald criteria of 2010 allow for the diagnosis of multiple sclerosis (MS) in an earlier stage, there is still a need to identify the risk factors for conversion to MS in patients with clinically isolated syndrome (CIS). Since the latest McDonald criteria were established, the prognostic role of cerebrospinal fluid (CSF) and visual evoked potentials (VEP) in CIS patients is still poorly defined. We conducted a monocentric investigation including patients with CIS in the time from 2010 to 2015. Follow-ups of 120 patients revealed that 42% converted to MS. CIS patients with positive oligoclonal bands (OCB) were more than twice as likely to convert to MS as OCB negative patients (hazard ratio = 2.6). The probability to develop MS was even higher when a quantitative intrathecal IgG synthesis was detected (hazard ratio = 3.8). In patients with OCB, VEP did not add further information concerning the conversion rate to MS. In patients with optic neuritis and negative OCB, a significantly higher rate converted to MS when VEP were delayed. In conclusion, the detection of an intrathecal IgG synthesis increases the conversion probability to MS. Pathological VEP can help to predict the conversion rate to MS in patients with optic neuritis without an intrathecal IgG synthesis.