A systematic review and computational modelling analysis of unilateral montages in electroconvulsive therapy.

OBJECTIVE: To examine the clinical outcomes of ECT unilateral placements compared in prior studies and apply insights from computational modelling to understand differences between placements. METHODS: PubMed, Embase, Scopus and PsycINFO and reference lists were systematically searched for studies of depressed patients where two unilateral placements were compared and clinical outcomes were reported. Computational modelling was done to generate electric field maps for each unilateral placement identified in the systematic review. RESULTS: A total of 29 studies met criteria for inclusion. Eight studies reported efficacy outcomes and 23 studies reported cognitive outcomes. Most studies found no significant difference in efficacy between right unilateral (RUL) and left unilateral (LUL) ECT, and no difference was found between temporo-parietal and fronto-temporal ECT. For the majority of studies, RUL placements had better verbal anterograde memory outcomes compared with the LUL placements. There was some evidence suggestive of cognitive advantages for fronto-frontal and fronto-parietal placements relative to temporo-parietal ECT. CONCLUSIONS: For efficacy, studies mainly focused on the comparison of right vs. left hemispheric stimulation, with the available evidence suggesting no substantive difference. RUL placements tended to have better verbal anterograde memory outcomes relative to LUL placements, though limited differences were found between the RUL placements.

Expression profile of pattern recognition receptors in skeletal muscle of SOD1(G93A) amyotrophic lateral sclerosis (ALS) mice and sporadic ALS patients.

AIMS: Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motoneurons and progressive muscle wasting. Inflammatory processes, mediated by non-neuronal cells, such as glial cells, are known to contribute to disease progression. Inflammasomes consist of pattern recognition receptors (PRRs), apoptosis-associated speck-like protein (ASC) and caspase 1 and are essential for interleukin (IL) processing and a rapid immune response after tissue damage. Recently, we described inflammasome activation in the spinal cord of ALS patients and in SOD1(G93A) ALS mice. Since pathological changes in the skeletal muscle are early events in ALS, we hypothesized that PRRs might be abnormally expressed in muscle fibre degeneration. METHODS: Western blot analysis, real-time PCR and immunohistochemistry were performed with muscle tissue from presymptomatic and early-symptomatic male SOD1(G93A) mice and with muscle biopsies of control and sporadic ALS (sALS) patients. Analysed PRRs include nucleotide-binding oligomerization domain-like (NOD-like) receptor protein 1 (NLRP1), NLR protein 3 (NLRP3), NLR family CARD domain-containing 4 (NLRC4) and absent in melanoma 2. Additionally, expression levels of ASC, caspase 1, interleukin 1 beta (IL1ß) and interleukin 18 (IL18) were evaluated. RESULTS: Expression of PRRs and ASC was detected in murine and human tissue. The PRR NLRC4, caspase 1 and IL1ß were significantly elevated in denervated muscle of SOD1(G93A) mice and sALS patients. Furthermore, levels of caspase 1 and IL1ß were already increased in presymptomatic animals. CONCLUSION: Our findings suggest that increased inflammasome activation may be involved in skeletal muscle pathology in ALS. Furthermore, elevated levels of NLRC4, caspase 1 and IL1ß reflect early changes in the skeletal muscle and may contribute to the denervation process.

ALS-Associated Endoplasmic Reticulum Proteins in Denervated Skeletal Muscle: Implications for Motor Neuron Disease Pathology.

Alpha-motoneurons and muscle fibres are structurally and functionally interdependent. Both cell types particularly rely on endoplasmic reticulum (ER/SR) functions. Mutations of the ER proteins VAPB, SigR1 and HSP27 lead to hereditary motor neuron diseases (MNDs). Here, we determined the expression profile and localization of these ER proteins/chaperons by immunohistochemistry and immunoblotting in biopsy and autopsy muscle tissue of patients with amyotrophic lateral sclerosis (ALS) and other neurogenic muscular atrophies (NMAs) and compared these patterns to mouse models of neurogenic muscular atrophy. Postsynaptic neuromuscular junction staining for VAPB was intense in normal human and mouse muscle and decreased in denervated Nmd2J mouse muscle fibres. In contrast, VAPB levels together with other chaperones and autophagy markers were increased in extrasynaptic regions of denervated muscle fibres of patients with MNDs and other NMAs, especially at sites of focal myofibrillar disintegration (targets). These findings did not differ between NMAs due to ALS and other causes. G93A-SOD1 mouse muscle fibres showed a similar pattern of protein level increases in denervated muscle fibres. In addition, they showed globular VAPB-immunoreactive structures together with misfolded SOD1 protein accumulations, suggesting a primary myopathic change. Our findings indicate that altered expression and localization of these ER proteins and autophagy markers are part of the dynamic response of muscle fibres to denervation. The ER is particularly prominent and vulnerable in both muscle fibres and alpha-motoneurons. Thus, ER pathology could contribute to the selective build-up of degenerative changes in the neuromuscular axis in MNDs.

[Neurogenic muscular atrophy and selective fibre type atrophies : Groundbreaking findings in the biopsy diagnosis of neuromuscular disease]. / Neurogene Muskelatrophien und selektive Muskelfasertypenatrophien : Wegweisende Befunde in der Biopsiediagnostik neuromuskulärer Erkrankungen.

Neurogenic muscular atrophy (NMA) is the most frequent diagnosis obtained from reading a muscle biopsy. It is characterized by specific histological changes which distinguish NMA from other important muscle pathologies including the primary myopathies such as the muscular dystrophies as well as the inflammatory muscle disorders. Within the group of denervation atrophies, NMAs due to motor neuron diseases are associated with particular histological patterns. The diagnosis of NMA in muscle biopsies requires special methods, mainly enzyme and immunohistochemistry, but also resin histology and in some cases electron microscopy. Analysis of a combined muscle and sural nerve biopsy provides the opportunity to compare the extent of degeneration in the motor and sensory systems, respectively. Muscle fiber typing by enzyme and immunohistochemistry also leads to the detection of selective type 1 and type 2 muscle fiber atrophies which are relevant in the differential diagnosis of neuromuscular diseases.