High-precision control of static magnetic field magnitude, orientation, and gradient using optically pumped vapour cell magnetometry

An integrated system of hardware and software allowing precise definition of arbitrarily oriented magnetic fields up to |B| = 1 μT within a five-layer Mumetal shield is described. The system is calibrated with reference to magnetic resonance observed between Zeeman states of the 6S1/2 F = 4 133Cs ground state. Magnetic field definition over the full 4π solid angle is demonstrated with one-sigma tolerances in magnitude, orientation, and gradient of δ|B| = 0.94 nT, δθ = 5.9 mrad, and δ|∇B|=13.0δ|∇B|=13.0 pT/mm, respectively. This field control is used to empirically map Mx magnetometer signal amplitude as a function of the static field (B0) orientation

In vivo effects of antibodies from patients with anti-NMDA receptor encephalitis: further evidence of synaptic glutamatergic dysfunction

Background: A severe encephalitis that associates with auto-antibodies to the NR1 subunit of the NMDA receptor (NMDA-R) was recently reported. Patients' antibodies cause a decrease of the density of NMDA-R and synaptic mediated currents, but the in vivo effects on the extracellular glutamate and glutamatergic transmission are unknown. Methods. We investigated the acute metabolic effects of patients' CSF and purified IgG injected in vivo. Injections were performed in CA1 area of Ammon's horn and in premotor cortex in rats. Results: Patient's CSF increased the concentrations of glutamate in the extracellular space. The increase was dose-dependent and was dramatic with purified IgG. Patients' CSF impaired both the NMDA- and the AMPA-mediated synaptic regulation of glutamate, and did not affect the glial transport of glutamate. Blockade of GABA-A receptors was associated with a marked elevation of extra-cellular levels of glutamate following a pretreatment with patients' CSF. Conclusion: These results support a direct role of NMDA-R antibodies upon altering glutamatergic transmission. Furthermore, we provide additional evidence in vivo that NMDA-R antibodies deregulate the glutamatergic pathways and that the encephalitis associated with these antibodies is an auto-immune synaptic disorder. © 2010 Manto et al; licensee BioMed Central Ltd.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Consensus Paper: Latent Autoimmune Cerebellar Ataxia (LACA)

Immune-mediated cerebellar ataxias (IMCAs) have diverse etiologies. Patients with IMCAs develop cerebellar symptoms, characterized mainly by gait ataxia, showing an acute or subacute clinical course. We present a novel concept of latent autoimmune cerebellar ataxia (LACA), analogous to latent autoimmune diabetes in adults (LADA). LADA is a slowly progressive form of autoimmune diabetes where patients are often initially diagnosed with type 2 diabetes. The sole biomarker (serum anti-GAD antibody) is not always present or can fluctuate. However, the disease progresses to pancreatic beta-cell failure and insulin dependency within about 5 years. Due to the unclear autoimmune profile, clinicians often struggle to reach an early diagnosis during the period when insulin production is not severely compromised. LACA is also characterized by a slowly progressive course, lack of obvious autoimmune background, and difficulties in reaching a diagnosis in the absence of clear markers for IMCAs. The authors discuss two aspects of LACA: (1) the not manifestly evident autoimmunity and (2) the prodromal stage of IMCA’s characterized by a period of partial neuronal dysfunction where non-specific symptoms may occur. In order to achieve an early intervention and prevent cell death in the cerebellum, identification of the time-window before irreversible neuronal loss is critical. LACA occurs during this time-window when possible preservation of neural plasticity exists. Efforts should be devoted to the early identification of biological, neurophysiological, neuropsychological, morphological (brain morphometry), and multimodal biomarkers allowing early diagnosis and therapeutic intervention and to avoid irreversible neuronal loss

Early detection of poor glycemic control in patients with diabetes mellitus in sub-Saharan Africa: a cohort study in Mozambique

Introduction: WHO estimates 422 million cases of diabetes mellitus worldwide. Mozambique has the second-highest mortality related to DM in the African region. Objectives of the present study are to provide data about a DM care service in Mozambique and to evaluate early outcomes of treatment. Methods: The new patients diagnosed with DM in a two-years period in a health centre in Maputo (Mozambique) were included in a retrospective cohort study. Fasting blood glucose (FBG), waist circumference (WC) and BMI were collected at baseline and after three months. Results: 188 patients were enrolled. Median BMI, WC and FBG at baseline were respectively 28 kg/m2(Inter Quartile Range [IQR]23.4-31.8), 98cm (IQR 87-105) and 209mg/dL (IQR 143-295). A non-pharmacological intervention was prescribed for six patients, while 182 patients received metformin 500 mg b.i.d. FBG was significantly reduced at control (226[±103.7]mg/dL vs 186[±93.2]mg/dL, p<0.000); however, glycemic control was reached in 74 patients (39.4%); not controlled patients changed regimen. Elderly patients had a higher glycemic control (adjusted Odds Ratio 2.50, 95% CI 1.11-5.06, p=0.002). Conclusion: Strategies for early detection of scarce glycemic control are feasible in Mozambique and could lead to prompt regimen switch; an invasive therapeutic approach could be preferable in selected cases to achieve control

Tremorgenesis: a new conceptual scheme using reciprocally innervated circuit of neurons

Neural circuits controlling fast movements are inherently unsteady as a result of their reciprocal innervation. This instability is enhanced by increased membrane excitability. Recent studies indicate that the loss of external inhibition is an important factor in the pathogenesis of several tremor disorders such as essential tremor, cerebellar kinetic tremor or parkinsonian tremor. Shaikh and colleagues propose a new conceptual scheme to analyze tremor disorders. Oscillations are simulated by changing the intrinsic membrane properties of burst neurons. The authors use a model neuron of Hodgkin-Huxley type with added hyperpolarization activated cation current (Ih), low threshold calcium current (It), and GABA/glycine mediated chloride currents. Post-inhibitory rebound is taken into account. The model includes a reciprocally innervated circuit of neurons projecting to pairs of agonist and antagonist muscles. A set of four burst neurons has been simulated: inhibitory agonist, inhibitory antagonist, excitatory agonist, and excitatory antagonist. The model fits well with the known anatomical organization of neural circuits for limb movements in premotor/motor areas, and, interestingly, this model does not require any structural modification in the anatomical organization or connectivity of the constituent neurons. The authors simulate essential tremor when Ih is increased. Membrane excitability is augmented by up-regulating Ih and It. A high level of congruence with the recordings made in patients exhibiting essential tremor is reached. These simulations support the hypothesis that increased membrane excitability in potentially unsteady circuits generate oscillations mimicking tremor disorders encountered in daily practice. This new approach opens new perspectives for both the understanding and the treatment of neurological tremor. It provides the rationale for decreasing membrane excitability by acting on a normal ion channel in a context of impaired external inhibition

Diabetes and severity of COVID-19: What is the link?

In Diabetes Mellitus the loss of capacity to regulate immunity, the reduction of pulmonary functions and the pro-thrombotic state determine the severity of COVID19

Cerebellar Ataxia With Anti-DNER Antibodies: Outcomes and Immunologic Features

BACKGROUND AND OBJECTIVES: There is no report on the long-term outcomes of ataxia with antibodies against Delta and Notch-like epidermal growth factor-related (DNER). We aimed to describe the clinical-immunologic features and long-term outcomes of patients with anti-DNER antibodies. METHODS: Patients tested positive for anti-DNER antibodies between 2000 and 2020 were identified retrospectively. In those with available samples, immunoglobulin G (IgG) subclass analysis, longitudinal cerebellum volumetry, human leukocyte antigen isotyping, and CSF proteomic analysis were performed. Rodent brain membrane fractionation and organotypic cerebellar slices were used to study DNER cell-surface expression and human IgG binding to the Purkinje cell surface. RESULTS: Twenty-eight patients were included (median age, 52 years, range 19-81): 23 of 28 (82.1%) were male and 23 of 28 (82.1%) had a hematologic malignancy. Most patients (27/28, 96.4%) had cerebellar ataxia; 16 of 28 (57.1%) had noncerebellar symptoms (cognitive impairment, neuropathy, and/or seizures), and 27 of 28 (96.4%) became moderately to severely disabled. Half of the patients (50%) improved, and 32.1% (9/28) had no or slight disability at the last visit (median, 26 months; range, 3-238). Good outcome significantly associated with younger age, milder clinical presentations, and less decrease of cerebellar gray matter volumes at follow-up. No human leukocyte antigen association was identified. Inflammation-related proteins were overexpressed in the patients' CSF. In the rodent brain, DNER was enriched in plasma membrane fractions. Patients' anti-DNER antibodies were predominantly IgG1/3 and bound live Purkinje cells in vitro. DISCUSSION: DNER ataxia is a treatable condition in which nearly a third of patients have a favorable outcome. DNER antibodies bind to the surface of Purkinje cells and are therefore potentially pathogenic, supporting the use of B-cell-targeting treatments