Peroneal nerve orthodromic sensory conduction technique: normative data

In some definite patients, a standard neurophysiological tool may not solve a complete differential diagnosis in common nerve peroneal neuropathy. In this study we have assessed a new simple procedure to study the orthodromic sensory conduction of both the superficial peroneal nerves (SPN) and deep peroneal nerves (DPN) in a heterogeneous group of 55 normal subjects. The mean sensory orthodromic conduction velocity of the SPN was 58.35 m/s. The mean sensory orthodromic conduction velocity of the mixed nerve action potential (MNAP) of the DPN was 55.27 m/s. The sensory conduction velocity, the amplitude of sensory-evoked potentials of SPN and DPN across the fibular head and the normative values are discussed. Our results confirm that these recording methods are easy to repeat and reliable in identifying peroneal neuropathy. An erratum to this article can be found at     

Cell therapy and stem cells in animal models of motor neuron disorders

Amyotrophic lateral sclerosis (ALS), spinal bulbar muscular atrophy (or Kennedy's disease), spinal muscular atrophy and spinal muscular atrophy with respiratory distress 1 are neurodegenerative disorders mainly affecting motor neurons and which currently lack effective therapies. Recent studies in animal models as well as primary and embryonic stem cell models of ALS, utilizing over-expression of mutated forms of Cu/Zn superoxide dismutase 1, have shown that motor neuron degeneration in these models is in part a non cell-autonomous event and that by providing genetically non-compromised supporting cells such as microglia or growth factor-excreting cells, onset can be delayed and survival increased. Using models of acute motor neuron injury it has been shown that embryonic stem cell-derived motor neurons implanted into the spinal cord can innervate muscle targets and improve functional recovery. Thus, a rationale exists for the development of cell therapies in motor neuron diseases aimed at either protecting and/or replacing lost motor neurons, interneurons as well as non-neuronal cells. This review evaluates approaches used in animal models of motor neuron disorders and their therapeutic relevance.     

Myelin protein zero Val102fs mutation manifesting with isolated spinal root hypertrophy

The Val102fs mutation of the myelin protein zero gene (MPZ) has been associated with Charcot–Marie–Tooth disease type 1B (CMT1B). Here we describe an unusual presentation of the Val102fs mutation characterized by symptoms of spinal root hypertrophy with no overt peroneal muscular atrophy. Two sisters aged 41 and 35 years complained of neck pain and presented only pes cavus or deep-tendon hyporeflexia. In both of them magnetic resonance imaging revealed non-enhancing hypertrophy of spinal roots misdiagnosed as neurofibromatosis; neurophysiology disclosed a demyelinating neuropathy and addressed the correct molecular diagnosis. This report adds new data concerning the clinical presentations of MPZ mutations.     

Saturday night brachial plexus palsy

An unusual case of brachial plexopathy following an alcohol binge is presented. The patient developed numbness and weakness of his right hand and neurophysiological tests demonstrated that the lesion level was at the brachial plexus. MRI of the brachial plexus, cerebrospinal fluid examination and DNA analysis for hereditary neuropathy with liability to pressure palsies were normal. Repeated neurological examination and neurophysiological studies 60 days later were normal. A diagnosis of brachial plexus neuropathy consequent to non-traumatic stretching of the middle and the lower trunks was made.     

Changes in spinal ganglia satellite and Schwann cells after aortic occlusion

Ultrastructural ischemic changes of satellite and Schwann cells in lumbar spinal ganglia were studied in dog after single 80-minute and repeated 40-minute ligation of the abdominal aorta 3-48 hours survival. Satellite cells undergo greater changes than the Schwann cells. After a single ligation for eighty minutes, the satellite cell cytoplasm reveals lengthened or slightly vacuolated cisterns of the endoplasmic reticulum and more numerous lysosomes. The adneuronal surface of satellite cells shows retraction of the processes. Schwann cells, investing large myelinated axons contain markedly vacuolated endoplasmic reticulum and some osmiophilic inclusions. Three hours after repeated ligation the density of satellite cell cytoplasm is decreased and the cell processes of the adneuronal surface are less numerous. Some satellite cells containing large vacuoles undergo acute degeneration. Three hours after repeated ligation the Schwann cell cytoplasm reveals numerous lamellar bodies. Following 1-2 days survival after repeated ligation, strongly vacuolized satellite cells or those with lower cytoplasmic density are more frequent, but also hypertrophic satellite cells are visible. The changes of the Schwann cells are less advanced and manifest by the vacuolization of the organelles and the presence of lamellar bodies and other osmiophilic inclusions.     

Influence of ischemia on retrograde axonal transport in the posterior column fibers of the dog

The retrograde axonal transport rate in the posterior spinal root was studied by means of the horseradish peroxidase injection in the control dogs and the dogs with the ischemia induced by the lumbal aorta ligature. As the results show, the increase in the retrograde axonal transport rate after 4 h ischemia occured from 141 +/- 6 mm/24 h to 270 +/- 31 mm/24 h. The retrograde transport rate after 7 d ischemia being 137 +/- 7 mm/24h reaches approximately the control values.     

The spinal biology in humans and animals of pain states generated by persistent small afferent input.

Behavioral models indicate that persistent small afferent input, as generated by tissue injury, results in a hyperalgesia at the site of injury and a tactile allodynia in areas adjacent to the injury site. Hyperalgesia reflects a sensitization of the peripheral terminal and a central facilitation evoked by the persistent small afferent input. The allodynia reflects a central sensitization. The spinal pharmacology of these pain states has been defined in the unanesthetized rat prepared with spinal catheters for injection and dialysis. After tissue injury, excitatory transmitters (e.g., glutamate and substance P) acting though N-methyl-D-aspartate (NMDA) and neurokinin 1 receptors initiate a cascade that evokes release of (i) NO, (ii) cyclooxygenase products, and (iii) activation of several kinases. Spinal dialysis show amino acid and prostanoid release after cutaneous injury. Spinal neurokinin 1, NMDA, and non-NMDA receptors enhance spinal prostaglandin E2 release. Spinal prostaglandins facilitate release of spinal amino acids and peptides. Activation by intrathecal injection of receptors on spinal C fiber terminals (mu,/delta opiate, alpha2 adrenergic, neuropeptide Y) prevents release of primary afferent peptides and spinal amino acids and blocks acute and facilitated pain states. Conversely, consistent with their role in facilitated processing, NMDA, cyclooxygenase 2, and NO synthase inhibitors act to diminish only hyperalgesia. Importantly, spinal delivery of several of these agents diminishes human injury pain states. This efficacy emphasizes (i) the role of facilitated states in humans, (ii) shows the importance of spinal systems in human pain processing, and (iii) indicates that these preclinical mechanisms reflect processes that regulate the human pain experience.     

Suppression of stretch reflex activity after spinal or systemic treatment with AMPA receptor antagonist NGX424 in rats with developed baclofen tolerance

BACKGROUND AND PURPOSE

Baclofen (a GABA_B receptor agonist) is the most commonly used anti-spasticity agent in clinical practice. While effective when administered spinally or systemically, the development of progressive tolerance represents a serious limitation for its long-term use. The goal of the present study was to characterize the treatment potency after intrathecal or systemic treatment with the selective AMPA receptor antagonist NGX424 on stretch reflex activity (SRA) and background muscle activity (BMA) in rats with developed baclofen tolerance.

EXPERIMENTAL APPROACH

Animals were exposed to 10 min of spinal ischaemia to induce an increase in BMA and SRA. Selected animals were implanted with an intrathecal PE-5 catheter and infused intrathecally with baclofen (1 µg·h⁻¹) for 14 days. Before and after baclofen infusion, changes in BMA and SRA were measured at 2 day intervals. After development of baclofen tolerance, the animals were injected intrathecally (1 µg) or subcutaneously (3, 6 or 12 mg·kg⁻¹) with NGX424, and changes in BMA and SRA were measured.

KEY RESULTS

Intrathecal or systemic delivery of NGX424 significantly suppressed the BMA and SRA in baclofen-tolerant animals. This effect was dose dependent. The magnitude of BMA and SRA suppression seen after 1 µg (intrathecal) or 12 mg·kg⁻¹ (s.c.) of NGX424 injection was similar to that seen during the first 5 days of baclofen infusion.

CONCLUSIONS AND IMPLICATIONS

These data demonstrate that the use of NGX424 can represent an effective therapy to modulate chronic spasticity in patients who are refractory or tolerant to baclofen treatment.

LINKED ARTICLE

This article is commented on by Gómez-Soriano et al., pp. 972–975 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2010.00964.x     

The effects of OP-1206 alpha-CD on walking dysfunction in the rat neuropathic intermittent claudication model

IV prostaglandin E1 improves clinical symptoms in patients with spinal canal stenosis. In the present study, we assessed the effects of OP-1206 alpha-CD, an orally active prostaglandin E1 analog, on walking dysfunction in the rat neuropathic intermittent claudication model. To induce spinal stenosis, two pieces of silicon rubber were placed in the lumbar (L4-6) epidural space in rats. Postsurgical walking function was measured using a treadmill apparatus. Spinal cord blood flow (SCBF) and skin blood flow (SKBF) were measured using a laser-Doppler flowmeter. OP-1206 alpha-CD was administered orally bid for 11 days from postoperative Day 3. In Control nontreated rats, a significant walking dysfunction was observed from Day 1 after the induction of spinal stenosis and persisted for 14 days when compared with the Sham-Operated group. On postoperative Day 15, SCBF revealed a significant reduction in the territory of spinal stenosis, although SKBF was not affected. OP-1206 alpha-CD significantly improved walking dysfunction on postoperative Days 5 (300 microg/kg), 7 (150 and 300 microg/kg), and 14 (150 and 300 microg/kg) when compared with the Vehicle-Treated group. On postoperative Day 15, the decrease in SCBF was significantly (150 and 300 microg/kg) improved by OP-1206 alpha-CD treatment, albeit SKBF remained unaffected. These data show that oral treatment with OP-1206 alpha-CD is effective in improving walking dysfunction induced by spinal canal stenosis, and this therapeutic effect is likely mediated by improved SCBF at the territory of spinal stenosis. IMPLICATIONS:Intermittent motor dysfunction is a clinical symptom associated with partial spinal compression. The present study provides evidence that oral treatment with the prostaglandin E1 analog (OP-1206 alpha-CD) is effective in improving motor dysfunction and spinal cord blood flow in rats with spinal compression.