Peripheral Neuropathy: Evaluation and Differential Diagnosis.

Peripheral neuropathy, a common neurologic problem encountered by family physicians, can be classified clinically by the anatomic pattern of presenting symptoms and, if indicated, by results of electrodiagnostic studies for axonal and demyelinating disease. The prevalence of peripheral neuropathy in the general population ranges from 1% to 7%, with higher rates among those older than 50 years. Common identifiable causes include diabetes mellitus, nerve compression or injury, alcohol use, toxin exposure, hereditary diseases, and nutritional deficiencies. Peripheral neuropathy is idiopathic in 25% to 46% of cases. Diagnosis requires a comprehensive history, physical examination, and judicious laboratory testing. Early peripheral neuropathy may present as sensory alterations that are often progressive, including sensory loss, numbness, pain, or burning sensations in a "stocking and glove" distribution of the extremities. Later stages may involve proximal numbness, distal weakness, or atrophy. Physical examination should include a comprehensive neurologic and musculoskeletal evaluation. If the peripheral nervous system is identified as the likely source of the patient's symptoms, evaluation for potential underlying etiologies should initially focus on treatable causes. Initial laboratory evaluation includes a complete blood count; a comprehensive metabolic profile; fasting blood glucose, vitamin B12, and thyroid-stimulating hormone levels; and serum protein electrophoresis with immunofixation. If the initial evaluation is inconclusive, referral to a neurologist for additional testing (e.g., electrodiagnostic studies, specific antibody assays, nerve biopsy) should be considered. Treatment of peripheral neuropathy focuses on managing the underlying etiology. Several classes of medications, including gabapentinoids and antidepressants, can help alleviate neuropathic pain.

A dominant negative form of Rac1 affects myogenesis of adult thoracic muscles in Drosophila.

Blocking Rac1 function in precursors of the indirect flight muscle of Drosophila severely disrupts muscle formation. The DLM fibers that develop using larval scaffolds are reduced in number and fiber size, while the DVMs, which develop using founder cells, are mostly absent. These adult muscle phenotypes are in part due to a reduced myoblast pool present at the third larval instar. BrDU labeling studies indicated that this is primarily due to a reduction in proliferation. In addition, DVM myoblasts display altered morphology and are unable to segregate into primordia. This defect precedes the evident block in fusion. We also show that the recently described DVM founder cells can be labeled with 22C10 and beta-3 tubulin, and that they are present under conditions of dominant negative Rac1(N17) expression. Despite the presence of founder cells, DVM fiber formation is rarely observed. Although DLM myoblasts are able to segregate around their larval scaffolds, the pace of fusion is reduced and consequently there is a delay in DLM fiber formation. Thus, in addition to its well-established role in fusion, Rac1 is also involved in the regulation of myoblast proliferation and segregation during adult myogenesis. These are two new roles for Rac1 in Drosophila.