Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, including muscular dystrophy and inflammatory myopathy. It occurs in neuromuscular junction disorders, such as myasthenia gravis. Pathophysiology
Muscle cells work by detecting a flow of electrical impulses from the brain, which signals them to contract through the release of calcium by the sarcoplasmic reticulum. Fatigue (reduced ability to generate force) may occur due to the nerve, or within the muscle cells themselves. New research from scientists at Columbia University suggests that muscle fatigue is caused by calcium leaking out of the muscle cell. This makes less calcium available for the muscle cell. In addition, the Columbia researchers propose that an enzyme activated by this released calcium eats away at muscle fibers.Substrates within the muscle generally serve to power muscular contractions. They include molecules such as adenosine triphosphate (ATP), glycogen and creatine phosphate. ATP binds to the myosin head and causes the ratchetting that results in contraction according to the sliding filament model. Creatine phosphate stores energy so ATP can be rapidly regenerated within the muscle cells from adenosine diphosphate (ADP) and inorganic phosphate ions, allowing for sustained powerful contractions that last between 5–7 seconds. Glycogen is the intramuscular storage form of glucose, used to generate energy quickly once intramuscular creatine stores are exhausted, producing lactic acid as a metabolic byproduct.
Malum perforans is a long-lasting, usually painless ulcer that penetrates deep into or through the skin, usually on the sole of the foot (in which case it may be called malum perforans pedis). It is often a complication in diabetes mellitus and other conditions affecting the nerves. Presentation
These ulcers have punched-out edge and slough in floor, resembling gummatous ulcer. Surrounding area might have loss of sensation. Cause
This condition results from denervation of areas exposed to day-to-day friction of bony prominences. The denervation may be result of any of the following diseases:
Spinal injuries
Leprosy
Peripheral nerve injury
Diabetic neuropathy
Tabes dorsalis
Transverse myelitis
Meningomyelocele
Syringomyelia

Pathophysiology
Normal pressure and pain sensations are essential for protecting the foot from excessive and prolonged pressures over bony prominences. In insensitive foot, such as in diabetic neuropathy, soft tissues are exposed to excessive pressures without knowledge of the individual. In other words, by nerve damage in the feet, the patients get no feedback on the impact of the feet when walking. These ulcers start with callosity under which suppuration takes place. The pus comes out and a hole forms under which the lesion grows deeper. This leads to punched-out, painless ulcers usually under metatarsal heads, tip of toe, or proximal interphalangeal joint of a hammertoe or on the heel. In non-ambulatory patients, these ulcers are found on buttocks and back of the heel. Diagnosis
Diagnosis is clinical. Sensation is tested using graded monofilament. Treatment
The underlying cause of the neuropathy is first treated. Necrotic portions of the wound are removed and the wound is kept moist at all occasions.