People with RPON experience different severity of pain, duration of symptoms, and frequency of attacks, which are also dependent on the treatment they received. The attacks of RPON usually occur on the same side of the head in subsequent episodes. Headache
The most common type of headache is migraine-like, usually accompanied by symptoms such as nausea, vomiting, photophobia, or phonophobia. Less commonly, RPON can occur without migrainous headache nor accompanied by the classical migrainous symptoms. The frequency of headaches can range from several times per month to once in several years, while the duration varies from several days to a week, which lasts longer than that of a typical migraine. Ophthalmoplegia
Ophthalmoplegia usually occurs either concurrently or within 1 week after the onset of headache, and less commonly up to 2 weeks. The ocular manifestation of RPON depend on which ocular cranial nerve is being affected. CNIII is involved in the vast majority of cases, but the involvement of CNVI and CNIV is also reported in studies. Typical ocular signs involving CNIII include outwards and downwards drifting of eyes (strabismus), difficulty in controlling inward and upward eye movements, drooping of eyelid (ptosis) and double vision. Pupil dilation (mydriasis) and reduction in pupillary light reflexes can also be observed as pupillomotor fibers are also affected by CNIII paralysis. Rare cases involve abducens nerve paralysis affects lateral eye movement while trochlear nerve paralysis affects vertical eye movement. Similar to headache, ophthalmoplegia usually resolve gradually and completely over time, but recovery may be incomplete after several episodes.
In TPP, the mutations described are single-nucleotide polymorphisms located in the hormone response element responsive to thyroid hormone, implying that transcription of the gene and production of ion channels may be altered by increased thyroid hormone levels. Furthermore, mutations have been reported in the genes coding for potassium voltage-gated channel, Shaw-related subfamily, member 4 (Kv3.4) and sodium channel protein type 4 subunit alpha (Na41.4).Of people with TPP, 33% from various populations were demonstrated to have mutations in KCNJ18, the gene coding for Kir2.6, an inward-rectifier potassium ion channel. This gene, too, harbors a thyroid response element.Certain forms of human leukocyte antigen (HLA)—especially B46, DR9, DQB1*0303, A2, Bw22, AW19, B17, and DRW8—are more common in TPP. Linkage to particular forms of HLA, which plays a central role in the immune response, might imply an immune system cause, but it is uncertain whether this directly causes TPP or whether it increases the susceptibility to Graves disease, a known autoimmune disease. Thyroid disease
The most common underlying form of thyroid disease associated with TPP is Graves disease, a syndrome due to an autoimmune reaction that leads to overproduction of thyroid hormone. TPP has also been described in people with other thyroid problems such as thyroiditis, toxic nodular goiter, toxic adenoma, TSH-producing pituitary adenoma, excessive ingestion of thyroxine or iodine, and amiodarone-induced hyperthyroidism. Mechanism
The muscle weakness and increased risk of irregular heart beat in TPP result from markedly reduced levels of potassium in the bloodstream.