In consequence of these "primary genomic changes", an expanding clone of cells develops; overproduces and secretes a monoclonal IgM, IgG, IgA, IgE, or IgD antibody, a κ or λ light chain, an α, γ, or μ heavy chain, or, very rarely, fragments of these proteins; and may accumulate "secondary genomic changes" that cause them to become malignant. The overproduced monoclonal proteins, termed myeloma proteins, commonly circulate in blood, may accumulate in urine, and are the hallmarks of plasma cell dyscrasias including their most malignant forms viz., multiple myeloma, light chain multiple myeloma, and plasma cell leukemia. IgG-secretory, IgA-secretory, and light-chain secretory multiple myeloma represent 52%, 21%, and 16%, respectively, of all multiple myeloma cases; these myelomas are associated with various types of chromosomal aberrancies and mutations. IgD-secretory multiple myeloma occurs in only 1% to 2% of multiple myeloma cases and is commonly associated with somatic mutations in the gene encoding the gV (i.e. variable) region of the monoclonal antibody. IgE-secretory multiple myeloma has been reported in <50 cases as of 2013 and is characteristically associated with translocations between the q arms of chromosome 11 and 14, i.e. t(11;14)(q13;q32) translocations.In other cases, plasma cells and/or lymphoplasmacytoid cells (a type of B cell resembling, and possible precursor to, plasma cells) suffer other kinds of mutations that lead to the production of an IgM myeloma protein. Overproduction of this myeloma protein may progress to a different form of plasma cell/lymphoplasmacytoid cell malignancy, Waldenström macroglobulinaemia.
Partial (minimal to moderate) improvement with monotherapy, augment with another of the first-line recommendations. Stage 2: Monotherapy with an alternative drug, then augmentation. Stage 3: Possible medication combinations—lithium plus Divalproex, lithium plus atypical, or Divalproex plus atypical. Stage 4: Combination of 2-3 mood stabilizers
Stage 5: Alternate monotherapy with oxcarbazepine, ziprasidone, or aripiprazole (all Level D). Stage 6: For nonresponse or intolerable side effects—clozapine for children or adolescents, or electroconvulsive therapy (ECT) for adolescents only. BPD II, manic or mixed, with psychosis
Stage 1: Same as BPD I without psychosis except for first-line treatment warrants a combination of mood stabilizer and an atypical antipsychotic. Stages 2–4: Varying combinations and augmentations. Stage 5: Alternate monotherapy (oxcarbazepine) plus an atypical antipsychotic. (Bipolar Disorder in Children and Adolescents, 2005). Prognosis
Chronic medication is often needed, with relapses of individuals reaching rates over 90% in those not following medication indications and almost to 40% in those complying with medication regimens in some studies. Compared to adults, a juvenile onset has in general a similar or worse course, although age of onset predicts the duration of the episodes more than the prognosis. A risk factor for a worse outcome is the existence of additional (comorbid) pathologies.Children with bipolar disorder are more likely to commit suicide than other children. Epidemiology
The prevalence of bipolar in youth is estimated at 2%. History
Descriptions of children with symptoms similar to contemporary concepts of mania date back to the 18th century.