Altered cutaneous nerve regeneration in a simian immunodeficiency virus / macaque intracutaneous axotomy model.

To characterize the regenerative pattern of cutaneous nerves in simian immunodeficiency virus (SIV)-infected and uninfected macaques, excisional axotomies were performed in nonglabrous skin at 14-day intervals. Samples were examined after immunostaining for the pan-axonal marker PGP 9.5 and the Schwann cell marker p75 nerve growth factor receptor. Collateral sprouting of axons from adjacent uninjured superficial dermal nerve bundles was the initial response to axotomy. Both horizontal collateral sprouts and dense vertical regeneration of axons from the deeper dermis led to complete, rapid reinnervation of the epidermis at the axotomy site. In contrast to the slower, incomplete reinnervation previously noted in humans after this technique, in both SIV-infected and uninfected macaques epidermal reinnervation was rapid and completed by 56 days postaxotomy. p75 was densely expressed on the Schwann cells of uninjured nerve bundles along the excision line and on epidermal Schwann cell processes. In both SIV-infected and uninfected macaques, Schwann cell process density was highest at the earliest timepoints postaxotomy and then declined at a similar rate. However, SIV-infection delayed epidermal nerve fiber regeneration and remodeling of new sprouts at every timepoint postaxotomy, and SIV-infected animals consistently had lower mean epidermal Schwann cell densities, suggesting that Schwann cell guidance and support of epidermal nerve fiber regeneration may account for altered nerve regeneration. The relatively rapid regeneration time and the completeness of epidermal reinnervation in this macaque model provides a useful platform for assessing the efficacy of neurotrophic or regenerative drugs for sensory neuropathies including those caused by HIV, diabetes mellitus, medications, and toxins.

Penn State screen exam for the detection of frontal and temporal dysfunction syndromes: application to ALS.

We improved standard treatment approaches by systematically addressing cognitive and behavioral change in association with frontal and temporal dysfunction in ALS. We evaluated the profile of inchange 198 ALS patients with a 20-minute screen exam. Significant deficiencies in letter fluency and reading comprehension (N=59) were found in 22.7% and 12.8% of limb onset and 36.4% and 20% of bulbar-onset patients. Deficiencies in abstract reasoning and judgment were found in 17%, and 29.5% of limb onset and 19.2%, and 46.7% of bulbar-onset patients. Significant behavioral change (N=89) was also reported in 2.4% of limb onset and 4.3% of bulbar-onset patients. Accommodations were provided from the time of initial detection of acquired deficiencies, with the goal of optimizing the patient's role in decision making throughout the process of treatment planning and implementation. This screen is of practical clinical value for assessment and intervention of deficiencies that affect treatment and quality of life.