Autoimmune nodo-paranodopathies 10 years later: Clinical features,pathophysiology and treatment

Background and Aims

Autoimmune neuropathies are classified, on the basis of pathophysiology, as demyelinating or axonal. The term nodo-paranodopathy, introduced in 2013 to better categorize the neuropathies with antiganglioside antibodies and later expanded to include neuropathies with antibodies to nodal and paranodal axoglial complexes, characterizes disorders in which the nodal region is critical in the pathogenesis. These neuropathies, although presenting electrophysiologic demyelinating features do not show pathologic evidence of segmental demyelination, or, although being classified as axonal, can show reversible nerve conduction failure and rapid recovery contrary with the communal concept of an axonal neuropathy.

Methods

In this personal view is reported, with a splitting approach, an update on autoimmune nodo-paranodopathies, classified according to the domains of peripheral nerve fiber, the target antigens and the antibody class and subclass involved. The clinical features, the electrophysiologic findings, the results of the immunopathological and ultrastructural studies, the pathophysiology and treatment are also described.

Results and Interpretation

The nodo-paranodopathy category integrates the clinical classification of autoimmune neuropathies and expands the traditional dichotomous demyelinating and axonal classification. It helps to a better systematization pointing to the domain and target antigens of the autoimmune process, it resolves conflicting pathologic and electrophysiologic findings, reconciles the contradiction that axonal neuropathies may be rapidly reversible, avoids taxonomical confusion and possible misdiagnoses. Finally this categorization, through the identification of the specific antibody and its prevalent class and subclass, clarifies the pathophysiological mechanisms and addresses to a more targeted therapeutic approach.     

Delta EEG Band as a Marker of Left Hypofrontality for Language in Schizophrenia Patients

Frontal hypoactivation has consistently been demonstrated in schizophrenia patients. We hypothesized that this well-known deficit is asymmetrical, ie, centered over left frontal locations and, in-line with Crow''s theory, associated with both loss of linguistic asymmetry and correlated with positive symptoms. Electroencephalography delta band was used as a quantitative index of cortical inhibition in 17 paranoid schizophrenia patients with prevailing positive symptoms and 17 matched control subjects. Delta amplitude was measured by 38 electrodes, while participants performed 3 linguistic tasks, visuoperceptual, rhyming, and semantic judgment. Compared with control subjects, patients did not show overall delta band differences, revealing no detrimental effects of pharmacological treatment. In healthy participants, analysis of 4 quadrants/regions of interest revealed higher delta amplitude in right vs left anterior sites, indicating significant left anterior disinhibition during linguistic processing. Instead, patients showed bilateral delta band distribution and, compared with control subjects, significant greater delta amplitude (ie, brain inhibition) in linguistic left anterior centers. Patients’ left hypofrontality was functionally related to their lack of hemispheric specialization for language and was positively correlated with higher levels of delusions (P1) and conceptual disorganization (P2) Positive and Negative Syndrome Scale subscales. Results suggest, in schizophrenia patients, a functional deficit of Broca''s area, a region playing a fundamental hierarchical role between and within hemispheres by integrating many basic processes in linguistic and conceptual organization. The significant correlation between lack of anterior asymmetry and increased positive symptoms is in-line with Crow''s hypothesis postulating the etiological role of disrupted linguistic frontal asymmetry on the onset of the key symptoms of schizophrenia.     

Taper-wedge stem suitable for anterior approach total hip arthroplasty: Adequate biomechanical reconstruction parameters and excellent clinical outcome at mid-term follow-up

BACKGROUNDThe direct anterior approach (DAA) for total hip arthroplasty (THA) is a less invasive and muscle-sparing approach that seems to improve early function and patient satisfaction. Several studies, however, have reported high complication and revision rates due to the technical difficulties related to the femoral preparation. AIMTo evaluate the usefulness and safety of a new stem equipped with a morphometric design and a size-specific medial curvature in DAA for THA.METHODSThis retrospective study was based on 130 patients that underwent mini-invasive DAA procedures for THA using the Accolade II stem. A total of 144 procedures were included in the assessment, which was based on postoperative complications, survival rates, functional parameters, and patient related outcomes. RESULTSOverall complications were recorded in 6 procedures (4.2%). There were no complications related to the stem implantation and no intraoperative fractures. Only one patient was revised for deep infection. On radiographs, biomechanical hip reconstruction was satisfactory and no stem showed any subsidence greater than 2 mm. Full osseointegration based on Engh scores was seen in all of the implanted stems. Median Harris hip score at final follow-up was 99 points (range 44-100 points), which resulted excellent in 91.3% of patients. The median values of the osteaorthritis outcome score ranged from 87.5 to 95.CONCLUSIONThe mid-term positive outcomes and low complication rate in our consecutive series of patients support the safety and suitability of this new stem design in DAA for THA.     

Fragrant bioethanol: A valued bioproduct from orange juice and essential oil extraction

We identify the composition of a less known, yet important bioproduct obtained in relatively high amount during orange fruit processing for juice and essential oil extraction comprised of bioethanol dissolving valued terpenes. Green cosmetic, perfume and biosolvent applications are anticipated.     

Hippocampal hypoglycaemia-activated K+ channels: single-channel analysis of glucose and voltage dependence

The effect of glucose on kinetics and the voltage-dependent characteristics of glucose-sensitive channels in hippocampal neurons were examined with the cell-attached mode of the patch-clamp technique. Recordings of a 100-pS K⁺ channel in the presence or absence of glucose demonstrate that the increase in channel open state probability (P _o) induced by glucose deprivation (40- to 400-times the control in high-glucose medium) was largely due to a decrease in the global amount of time spent by the channel in a long-lived closed state. TheP _o value of the same 100-pS channel was also found to increase (by approx. 80-times) following a depolarization of 40 mV from rest, the main factor responsible for this being a dramatic shortening of the long closed-times on depolarization. Another glucose-sensitive channel of smaller conductance (approx. 10 pS) showed a similar dependence ofP _o on glucose, but different dependence on voltage, with long openings at the same hyperpolarized potentials where the 100-pS channel was almost always closed. Our results indicate that the action of glucose on the kinetics of hippocampal channels closely resembles that of ATP-sensitive channels in pancreaticβ-cells. Furthermore, they indicate that the two types of glucose-sensitive channels found in hippocampal neurons, differing not only in their single-channel conductance but also in the dependence on voltage, could play different roles in the responses of these cells to modified energetic supply.