A simple and objective marker for stress.

OBJECTIVE: To examine the association between pressure pain sensitivity (PPS) at sternum and various well established physiological stress measures among opera singers during a performance as a measure for transitional stress, and resting values in out-clinic patients as a measure for persistent stress. METHODS: Changes in PPS on the index finger and sternum, middle blood pressure (MAP), heart rate (HR), pressure-rate-product (PRP) and salivary cortisol (SCO) were recorded in 26 opera solo singers during a performance. Resting PPS, HR, MAP, PRP and presence of a noxious withdrawal reflex (NWR) were recorded in 181 out-clinic patients. RESULTS: During opera performance, the PPS on sternum changed concomitantly with MAP (correlation coefficient (r) r=0.42, p<0.005), HR (r=0.55, p<0.001), PRP (r=0.54, p<0.001) and SCO (r=0.26, p=0.066). During rest, a significant correlation was found between PPS on sternum and HR, PRP and presence of noxious withdrawal reflex (all p<0.01). CONCLUSIONS: The PPS measurement at sternum was associated with well established physiological stress measures and may represent a simple, objective and reliable measure of physiological stress used by both non-professional and professionals.

Multifocal motor neuropathy with conduction block: slow but not benign.

OBJECTIVE: To describe a patient with multifocal motor neuropathy with conduction block who had annual clinical and physiological examinations for 18 years but declined treatment for personal reasons. DESIGN: Case report. SETTING: Collaboration between 2 academic tertiary care hospitals. Patient One patient with multifocal motor neuropathy with conduction block. RESULTS: At age 44 years, there was weakness and wasting of the left biceps with conduction block in the left musculocutaneous and right ulnar nerves. The left median nerve was inexcitable. The right median, ulnar, and left peroneal nerves developed axonal change (loss of distal compound muscle action potential amplitude) at years 5, 12, and 13. By 2005, new weakness had appeared in 20 muscles (16 in the arms); he could not use a keyboard, button buttons, or write his name. Nerves that initially showed conduction block became inexcitable over the course of the illness. CONCLUSIONS: Multifocal motor neuropathy with conduction block is a disease that may be "only" slowly progressive but is not always benign. Nerves showing conduction block may develop axonal change. Better markers for this disease are needed.

Electrophysiologic techniques in critical illness-associated weakness.

Neuromuscular disorders are increasingly recognized in the critically ill but conventional electrodiagnostic techniques often provide non-specific results or are hampered by local conditions that prevent adequate disease classification. Muscle fiber inexcitability is a common phenomenon in critical illness myopathy possibly secondary to disordered sodium channel fast inactivation and associated with loss of myosin staining. Direct muscle stimulation techniques, measuring evoked response amplitudes and comparison of nerve and muscle stimulated responses, are recognized methods of demonstrating this phenomenon. Other measures studied in this population include increased compound motor action potential duration, motor unit number estimates and mean step area of individual motor unit potentials during motor unit number estimate studies. An electrophysiologic approach to the study of patients with critical illness associated weakness is proposed.

Antagonism of RAGE suppresses peripheral nerve regeneration.

Axotomy of peripheral nerve triggers events that coordinate a limited inflammatory response to axonal degeneration and initiation of neurite outgrowth. Inflammatory and neurite outgrowth-promoting roles for the receptor for advanced glycation end products (RAGE) have been suggested, so we tested its role in peripheral nerve regeneration. Analysis of immunohistochemical localization of RAGE by confocal microscopy revealed that RAGE was expressed in axons and infiltrating mononuclear phagocytes upon unilateral sciatic nerve crush in mice. Administration of soluble RAGE, the extracellular ligand binding domain of RAGE, or blocking F(ab')2 fragments of antibodies raised to either RAGE or its ligands, S100/calgranulins or amphoterin, reduced functional recovery as assessed by motor and sensory nerve conduction velocities and sciatic functional index and reduced regeneration, as assessed by myelinated fiber density after acute crush of the sciatic nerve. In parallel, in mice subjected to RAGE blockade, decreased numbers of mononuclear phagocytes infiltrated the distal nerve segments after crush. These findings provide the first evidence of an innate function of the ligand/RAGE axis and suggest that RAGE plays an important role in regeneration of the peripheral nervous system.

RAGE modulates peripheral nerve regeneration via recruitment of both inflammatory and axonal outgrowth pathways.

Axotomy of peripheral nerve stimulates events in multiple cell types that initiate a limited inflammatory response to axonal degeneration and simultaneous outgrowth of neurites into the distal segments after injury. We found that pharmacological blockade of RAGE impaired peripheral nerve regeneration in mice subjected to RAGE blockade and acute crush of the sciatic nerve. As our studies revealed that RAGE was expressed in axons and in infiltrating mononuclear phagocytes upon injury, we tested the role of RAGE in these distinct cell types on nerve regeneration. Transgenic mice expressing signal transduction-deficient RAGE in mononuclear phagocytes or peripheral neurons were generated and subjected to unilateral crush injury to the sciatic nerve. Transgenic mice displayed decreased functional and morphological recovery compared with littermate controls, as assessed by motor and sensory conduction velocities; and myelinated fiber density. In double transgenic mice expressing signal transduction deficient RAGE in both mononuclear phagocytes and peripheral neurons, regeneration was even further impaired, suggesting the critical interplay between RAGE-modulated inflammation and neurite outgrowth in nerve repair. These findings suggest that RAGE signaling in inflammatory cells and peripheral neurons plays an important role in plasticity of the peripheral nervous system.

Congenital Guillain-Barré syndrome associated with maternal inflammatory bowel disease is responsive to intravenous immunoglobulin.

A 34-week floppy preterm infant born to a mother with acute ulcerative colitis presented with a progressive reduction in spontaneous limb movements, severe generalized hypotonia, areflexia, autonomic dysfunction and respiratory failure. Electromyography revealed pronounced denervation activity and markedly slow nerve conduction velocity (3 m/s) with evidence of conduction block. These findings indicated demyelination with additional axonal features. The infant was diagnosed with congenital Guillain-Barré syndrome, was treated with intravenous immunoglobulin and showed clinical improvement within 48 hours of treatment. The relationship between inflammatory bowel syndrome and inflammatory demyelinating polyneuropathy is discussed.

Motor Unit Estimate Number in the Anterior Tibial Muscle: Normative Data versus Findings in Critically Ill Patients in Intensive Care Units.

OBJECTIVES: To determine the number of motor units (MUNEs) in the anterior tibial muscle of normal subjects for comparison with those of severely paretic or paralytic muscles of critically ill patients in intensive care units. RESULTS: The mean MUNE for 24 normal subjects (194 +/- 5; mean +/- standard deviation) was similar to that of the 22 patients with critical illness (184 +/- 10). However, both the mean amplitude of the evoked compound muscle action potential (CMAP) and of the single motor unit action potential (S-MUAP) among patients were approximately one third of those in normal subjects. CONCLUSION: Critically ill patients in this study demonstrated normal MUNEs with reduced CMAP and S-MUAP amplitudes in the setting of severe clinical weakness, suggestive of predominantly myopathic injury. MUNE may provide a valuable tool for distinguishing between neuropathy and myopathy in critically ill patients.