Multiple sclerosis is a chronic inflammatory and demyelinating disorder of the CNS with an unknown aetiology. Although intrathecal immunoglobulin G (IgG) synthesis is a key feature of the disease, little is still known about the B cell response in the CNS of multiple sclerosis patients. We analysed the phenotype and kinetics of different B cell subsets in patients with multiple sclerosis, infectious disease (IND) and non-inflammatory neurological disease (NIND). B cells were detected in the CSF of multiple sclerosis and IND patients, but were largely absent in NIND patients. In the CSF, the majority of B cells had a phenotype of memory B cells and short-lived plasma blasts (PB); plasma cells were absent from the compartment. The proportion of PB was highest in multiple sclerosis patients and patients with acute CNS infection. While PB disappeared rapidly from the CSF after resolution of infection in IND patients, these cells were present at high numbers throughout the disease course in multiple sclerosis patients. CSF PB numbers in multiple sclerosis patients strongly correlated with intrathecal IgG synthesis and inflammatory parenchymal disease activity as disclosed by MRI. This study identifies short-lived plasma blasts as the main effector B cell population involved in ongoing active inflammation in multiple sclerosis patients.

Multiple sclerosis is a chronic inflammatory and demyelinating disorder of the CNS with an unknown aetiology. Although intrathecal immunoglobulin G (IgG) synthesis is a key feature of the disease, little is still known about the B cell response in the CNS of multiple sclerosis patients. We analysed the phenotype and kinetics of different B cell subsets in patients with multiple sclerosis, infectious disease (IND) and non-inflammatory neurological disease (NIND). B cells were detected in the CSF of multiple sclerosis and IND patients, but were largely absent in NIND patients. In the CSF, the majority of B cells had a phenotype of memory B cells and short-lived plasma blasts (PB); plasma cells were absent from the compartment. The proportion of PB was highest in multiple sclerosis patients and patients with acute CNS infection. While PB disappeared rapidly from the CSF after resolution of infection in IND patients, these cells were present at high numbers throughout the disease course in multiple sclerosis patients. CSF PB numbers in multiple sclerosis patients strongly correlated with intrathecal IgG synthesis and inflammatory parenchymal disease activity as disclosed by MRI. This study identifies short-lived plasma blasts as the main effector B cell population involved in ongoing active inflammation in multiple sclerosis patients.

Our findings demonstrate that the early phase of B burgdorferi meningoradiculitis is characterized by a well-coordinated immune response involving specific cytokine release and plasma cell recruitment, followed by a long-lasting, antigen-specific B-cell response in the central nervous system.

Neuroimaging studies in attention-deficit/hyperactivity disorder (ADHD) have shown abnormalities in several brain areas including the frontostriatal circuitry and were mostly conducted in children and adolescents. We investigated 30 never-medicated adult ADHD patients (16 males) and 30 matched healthy control individuals. Functional magnetic resonance imaging was acquired during a working memory paradigm (n-back). Group activation maps and group differences of activation were calculated using voxel-based analyses. The generic activation pattern was more extended in the control group. In ADHD patients, significantly decreased activation was found in the right inferior parietal cortex. Disturbed parietal brain function may particularly contribute to inattention and working memory impairment in ADHD patients.

Context Glucocorticoid-induced myopathy is a characteristic symptom of endogenous Cushing’s syndrome. Its long-term outcome is largely unknown Objective To evaluate long-term muscle function following remission of endogenous Cushing’s syndrome Study design Observational longitudinal cohort study Setting Tertiary care hospitals and specialized outpatient clinic Patients As part of the prospective multicenter German Cushing’s Registry we assessed muscle strength in patients with overt endogenous Cushing’s syndrome. We studied the patients at the time of diagnosis (n=88), after 6 months (n=69) and thereafter annually following surgical remission over a period of up to four years (1 year: n=55; 2 years: n=34; 3 years: n=29; 4 years: n=22). Muscle function was evaluated by hand grip strength and by chair rising test Results Grip strength was decreased to 83 % of normal controls (100 %) at time of diagnosis. It further decreased to 71 % after 6 months in remission (p≤0.001) and showed no improvement during further follow-up compared to baseline. Chair rising test performance improved initially (8 seconds at baseline vs 7 seconds after 6 months, p=0.004) but remained at this reduced level thereafter (7 seconds after 3 years vs 5 seconds in controls, p=0.038). In multivariate analysis we identified as predictors for long-term muscle dysfunction age, waist-to-hip-ratio and HbA1c at baseline. Furthermore, muscle strength during follow-up was strongly correlated with quality of life Conclusion This study shows that Cushing’s syndrome associated myopathy does not spontaneously resolve during remission. This calls for action to identify effective interventions to improve muscle dysfunction in this setting

Increased multisystem morbidity and mortality in patients with Cushing's syndrome comprise clinical problems and challenges, both at the time of diagnosis and in remission. Relevant comorbidities and clinical problems include hypertension, diabetes, overweight, myopathy and a high risk for acute complications such as infections and venous thrombembolism. Although there are therapy recommendations for most of these comorbidities, there is a lack of large, prospective studies to confirm and optimise them. Mortality is especially high during active disease and within the first year after diagnosis, as a result of cardiovascular events, infections and suicide. All in all, interdisciplinary therapy management is important for reducing morbidity and mortality over the long‐term.

Purpose Recurrence after pituitary surgery in Cushing’s disease (CD) is a common problem ranging from 5% (minimum) to 50% (maximum) after initially successful surgery, respectively. In this review, we give an overview of the current literature regarding prevalence, diagnosis, and therapeutic options of recurrent CD. Methods We systematically screened the literature regarding recurrent and persistent Cushing’s disease using the MESH term Cushing’s disease and recurrence. Of 717 results in PubMed, all manuscripts in English and German published between 1980 and April 2020 were screened. Case reports, comments, publications focusing on pediatric CD or CD in veterinary disciplines or studies with very small sample size (patient number < 10) were excluded. Also, papers on CD in pregnancy were not included in this review. Results and conclusions Because of the high incidence of recurrence in CD, annual clinical and biochemical follow-up is paramount. 50% of recurrences occur during the first 50 months after first surgery. In case of recurrence, treatment options include second surgery, pituitary radiation, targeted medical therapy to control hypercortisolism, and bilateral adrenalectomy. Success rates of all these treatment options vary between 25 (some of the medical therapy) and 100% (bilateral adrenalectomy). All treatment options have specific advantages, limitations, and side effects. Therefore, treatment decisions have to be individualized according to the specific needs of the patient.

Based on these results, we conclude that risperidone and paliperidone have a similar therapeutic range and similar intra-individual variability in terms of trough serum levels. For treatment optimization, monitoring of plasma concentrations may be as useful for paliperidone as for risperidone.