IMF®-Therapy (Intention controlled Myo-Feedback) — an innovative method in the treatment of peripheral nerve lesions

Physiotherapy is a well established part of the rehabilitation of peripheral nerve paralysis. The aim of this type of treatment is to re-establish arbitrary functions by improving the patients’ active and passive mobility as well as their strength and stamina. IMF®-Therapy (Intention controlled Myo-Feedback) is an innovative method in the treatment of peripheral nerve lesions that goes beyond the purely neuro-scientific framework and also takes into account methods and concepts of the psychology of learning. The essential assumption is that things learnt in the past are firmly established in the long term motor memory and can be reactivated by the patient. From results achieved in 32 patients treated with this therapy it can be concluded that IMF®-Therapy may be a promising additional rehabilitation tool in peripheral nerve lesion.

Engineering a multimodal nerve conduit for repair of injured peripheral nerve

Injury to nerve tissue in the peripheral nervous system (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-co-glycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons; 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate hydrogel. This indicates return of some feeling to the limb via the fully-configured conduit. Immunohistochemical analysis of the implanted conduits removed from the rats after the four-week implantation period confirmed the presence of myelinated axons within the conduit and distal to the site of implantation, further supporting that the conduit promoted nerve repair over this period of time. This study describes the design considerations and fabrication of a novel multicomponent, multimodal bio-engineered synthetic conduit for peripheral nerve repair.

Nerve guidance conduits from aligned nanofibers: improvement of nerve regeneration through longitudinal nanogrooves on a fiber surface

A novel fibrous conduit consisting of well-aligned nanofibers with longitudinal nanogrooves on the fiber surface was prepared by electrospinning and was subjected to an in vivo nerve regeneration study on rats using a sciatic nerve injury model. For comparison, a fibrous conduit having a similar fiber alignment structure without surface groove and an autograft were also conducted in the same test. The electrophysiological, walking track, gastrocnemius muscle, triple-immunofluorescence, and immunohistological analyses indicated that grooved fibers effectively improved sciatic nerve regeneration. This is mainly attributed to the highly ordered secondary structure formed by surface grooves and an increase in the specific surface area. Fibrous conduits made of longitudinally aligned nanofibers with longitudinal nanogrooves on the fiber surface may offer a new nerve guidance conduit for peripheral nerve repair and regeneration.

Adamts5, the gene encoding a proteoglycan-degrading metalloprotease, is expressed by specific cell lineages during mouse embryonic development and in adult tissues.

The secreted metalloprotease ADAMTS5 is implicated in destruction of the cartilage proteoglycan aggrecan in arthritis, but its physiological functions are unknown. Its expression profile during embryogenesis and in adult tissues is therefore of considerable interest. &beta;-Galactosidase (&beta;-gal) histochemistry, enabled by a LacZ cassette inserted in the Adamts5 locus, and validated by in situ hybridization with an Adamts5 cRNA probe and ADAMTS5 immunohistochemistry, was used to profile Adamts5 expression during mouse embryogenesis and in adult mouse tissues. Embryonic expression was scarce prior to 11.5 days of gestation (E11.5) and noted only in the floor plate of the developing brain at E9.5. After E11.5 there was continued expression in brain, especially in the choroid plexus, peripheral nerves, dorsal root ganglia, cranial nerve ganglia, spinal and cranial nerves, and neural plexuses of the gut. In addition to nerves, developing limbs have Adamts5 expression in skeletal muscle (from E13.5), tendons (from E16.5), and inter-digital mesenchyme of the developing autopod (E13.5&ndash;15.5). In adult tissues, there is constitutive Adamts5 expression in arterial smooth muscle cells, mesothelium lining the peritoneal, pericardial and pleural cavities, smooth muscle cells in bronchi and pancreatic ducts, glomerular mesangial cells in the kidney, dorsal root ganglia, and in Schwann cells of the peripheral and autonomic nervous system. Expression of Adamts5 during neuromuscular development and in smooth muscle cells coincides with the broadly distributed proteoglycan versican, an ADAMTS5 substrate. These observations suggest the major contexts in which developmental and physiological roles could be sought for this protease.<br />

Neurological complication of systemic cancer

Neurological complications of systemic cancer&mdash;those arising outside the nervous system&mdash;can be distressing, disabling, and sometimes fatal. Diagnosis is often difficult because different neurological disorders may present with similar signs and symptoms. Furthermore, comorbid neurological illnesses, common in elderly patients with cancer, can complicate diagnosis. Early diagnosis and aggressive treatment can improve neurological symptoms and can substantially enhance a patient's quality of life. We approach the problem of neurological complications of systemic cancer as would a neurologist: first by identifying the anatomical area or areas that are affected (ie, brain, spinal cord, peripheral nerve), then by evaluating the diagnostic approach, considering the symptoms and signs and including appropriate laboratory tests, and finally, by recommending treatment. We focus on disorders that are difficult to diagnose, need neurological consultation, and for which effective treatments exist.

Retinal nerve fibre layer thinning associated with diabetic peripheral neuropathy

<b>Aims <br /></b>To investigate the relationship between retinal nerve fibre layer thickness and peripheral neuropathy in patients with&nbsp;Type 2 diabetes, particularly in those who are at higher risk of foot ulceration.<br /><br /><b>Methods <br /></b>Global and sectoral retinal nerve fibre layer thicknesses were measured at 3.45 mm diameter around the optic&nbsp;nerve head using optical coherence tomography (OCT). The level of neuropathy was assessed in 106 participants (82 with&nbsp;Type 2 diabetes and 24 healthy controls) using the 0&ndash;10 neuropathy disability score. Participants were stratified into four&nbsp;neuropathy groups: none (0&ndash;2), mild (3&ndash;5), moderate (6&ndash;8), and severe (9&ndash;10). A neuropathy disability score &Dagger; 6 was used to&nbsp;define those at higher risk of foot ulceration. Multivariable regression analysis was performed to assess the effect of&nbsp;neuropathy disability scores, age, disease duration and retinopathy on RNFL thickness.<br /><br /><b>Results</b> <br />Inferior (but not global or other sectoral) retinal nerve fibre layer thinning was associated with higher neuropathy&nbsp;disability scores (P = 0.03). The retinal nerve fibre layer was significantly thinner for the group with neuropathy disability&nbsp;scores &Dagger; 6 in the inferior quadrant (P &lt; 0.005). Age, duration of disease and retinopathy levels did not significantly influence&nbsp;retinal nerve fibre layer thickness. Control participants did not show any significant differences in thickness measurements&nbsp;from the group with diabetes and no neuropathy (P &gt; 0.24 for global and all sectors).<br /><b><br />Conclusions <br /></b>Inferior quadrant retinal nerve fibre layer thinning is associated with peripheral neuropathy in patients with&nbsp;Type 2 diabetes, and is more pronounced in those at higher risk of foot ulceration.

Peripheral injected cholecystokinin-8S modulates the concentration of serotonin in nerve fibers of the rat brainstem

Serotonin and cholecystokinin (CCK) play a role in the short-term inhibition of food intake. It is known that peripheral injection of CCK increases c-Fos-immunoreactivity (Fos-IR) in the nucleus of the solitary tract (NTS) in rats, and injection of the serotonin antagonist ondansetron decreases the number of c-Fos-IR cells in the NTS. This supports the idea of serotonin contributing to the effects of CCK. The aim of the present study was to elucidate whether peripherally injected CCK-8S modulates the concentration of serotonin in brain feeding-regulatory nuclei. Ad libitum fed male Sprague-Dawley rats received 5.2 and 8.7 nmol/kg CCK-8S (n = 3/group) or 0.15 M NaCl (n = 3-5/group) injected intraperitoneally (ip). The number of c-Fos-IR neurons, and the fluorescence intensity of serotonin in nerve fibers were assessed in the paraventricular nucleus (PVN), arcuate nucleus (ARC), NTS and dorsal motor nucleus of the vagus (DMV). CCK-8S increased the number of c-Fos-ir neurons in the NTS (mean &plusmn; SEM: 72 &plusmn; 4, and 112 &plusmn; 5 neurons/section, respectively) compared to vehicle-treated rats (7 &plusmn; 2 neurons/section, P &lt; 0.05), but did not modulate c-Fos expression in the DMV or ARC. Additionally, CCK-8S dose-dependently increased the number of c-Fos-positive neurons in the PVN (218 &plusmn; 15 and 128 &plusmn; 14, respectively vs. 19 &plusmn; 5, P &lt; 0.05). In the NTS and DMV we observed a decrease of serotonin-immunoreactivity 90 min after injection of CCK-8S (46 &plusmn; 2 and 49 &plusmn; 8 pixel/section, respectively) compared to vehicle (81 &plusmn; 8 pixel/section, P &lt; 0.05). No changes of serotonin-immunoreactivity were observed in the PVN and ARC. Our results suggest that serotonin is involved in the mediation of CCK-8's effects in the brainstem. &copy; 2014 Elsevier Inc.

Retinal tissue thickness is reduced in diabetic peripheral neuropathy

AIM: To investigate the relationship between diabetic peripheral neuropathy (DPN) and retinal tissue thickness. <br /><br />METHODS: Full retinal thickness in the central retinal, parafoveal, and perifoveal zones and thickness of the ganglion cell complex and retinal nerve fiber layer (RNFL) were assessed in 193 individuals (84 with type 1 diabetes, 67 with type 2 diabetes, and 42 healthy controls) using spectral domain optical coherence tomography. Among those with diabetes, 44 had neuropathy defined using a modified neuropathy disability score recorded on a 0-10 scale. Multiple regression analysis was performed to investigate the relationship between diabetic neuropathy and retinal tissue thickness, adjusted for the presence of diabetic retinopathy (DR), age, sex, duration of diabetes, and HbA1c levels. <br /><br />RESULTS: In individuals with diabetes, perifoveal thickness was inversely related to the severity of neuropathy (p &lt; 0.05), when adjusted for age, sex, duration of diabetes, and HbA1c levels. DR was associated with reduced thickness in parafovea (p &lt; 0.01). The RNFL was thinner in individuals with greater degrees of neuropathy (p &lt; 0.04). <br /><br />CONCLUSIONS: DPN is associated with structural compromise involving several retinal layers. This compromise may represent a threat to visual integrity and therefore warrants examination of functional correlates.