Accordingly, the disease is thought not to be caused by inadequate production of Htt, but by a toxic gain-of-function of mHtt in the body. Cellular changes
The toxic action of mHtt may manifest and produce the HD pathology through multiple cellular changes. In its mutant (polyglutamine expanded) form, the protein is more prone to cleavage that creates shorter fragments containing the polyglutamine expansion. These protein fragments have a propensity to undergo misfolding and aggregation, yielding fibrillar aggregates in which non-native polyglutamine β-strands from multiple proteins are bonded together by hydrogen bonds. These aggregates share the same fundamental cross-beta amyloid architecture seen in other protein deposition diseases. Over time, the aggregates accumulate to form inclusion bodies within cells, ultimately interfering with neuronal function. Inclusion bodies have been found in both the cell nucleus and cytoplasm. Inclusion bodies in cells of the brain are one of the earliest pathological changes, and some experiments have found that they can be toxic for the cell, but other experiments have shown that they may form as part of the bodys defense mechanism and help protect cells.Several pathways by which mHtt may cause cell death have been identified. These include effects on chaperone proteins, which help fold proteins and remove misfolded ones; interactions with caspases, which play a role in the process of removing cells; the toxic effects of glutamine on nerve cells; impairment of energy production within cells; and effects on the expression of genes.Mutant huntingtin protein has been found to play a key role in mitochondrial dysfunction.
Medical imaging, consisting of x-ray, CT, MRI, or ultrasound may detect chondrocalcinosis within the affected joint, indicating a substantial amount of calcium crystal deposition within the cartilage or ligaments. Ultrasound is a reliable method to diagnose CPPD. Using ultrasound, chondrocalcinosis may be depicted as echogenic foci with no acoustic shadow within the hyaline cartilage or fibrocartilage. By x-ray, CPPD can appear similar to other diseases such as ankylosing spondylitis and gout. Arthrocentesis, or removing synovial fluid from the affected joint, is performed to test the synovial fluid for the calcium pyrophosphate crystals that are present in CPPD. When stained with H&E stain, calcium pyrophosphate crystals appears deeply blue ("basophilic"). However, CPP crystals are much better known for their rhomboid shape and weak positive birefringence on polarized light microscopy, and this method remains the most reliable method of identifying the crystals under the microscope. However, even this method has poor sensitivity, specificity, and inter-operator agreement.These two modalities currently define CPPD disease, but lack diagnostic accuracy. Thus, the diagnosis of CPPD disease is potentially epiphenomenological. Treatment
Because any medication that could reduce the inflammation of CPPD bears a risk of causing organ damage, treatment is not advised if the condition is not causing pain. For acute pseudogout, treatments include intra-articular corticosteroid injection, systemic corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), or, on occasion, high-dose colchicine. In general, NSAIDs are administered in low doses to help prevent CPPD. However, if an acute attack is already occurring, higher doses are administered. If nothing else works, hydroxychloroquine or methotrexate may provide relief.