RESUMO
Fibromyalgia (FM) exhibits characteristics of a neurological disorder, and similarities have been identified between FM and idiopathic intracranial hypertension (IICH). When intracranial pressure rises, the drainage of excess cerebrospinal fluid (CSF) through the subarachnoid space of the cranial and spinal nerves increases. Higher CSF pressure irritates nerve fibers inside nerve root sheaths and may consequently cause radicular pain, as was reported in patients with IICH. Moreover, the cut-off of 20-25â¯cm H20 used to define IICH may be too high, as has been suggested in patients with chronic fatigue syndrome. We hypothesize that the neurological symptoms of FM are caused by the dysregulation of cerebrospinal pressure (CSP) and that spinal fluid drainage can relieve this pain. Exploring the processes underlying increased CSP may provide an alternative explanation for the generation of unexplained widespread pain (WSP) and FM as opposed to central sensitization. Additionally, when performing a lumbar puncture for diagnostic reasons, it is useful to measure opening pressure in patients with chronic WSP.
Assuntos
Síndrome de Fadiga Crônica/fisiopatologia , Fibromialgia/terapia , Manejo da Dor/métodos , Dor/etiologia , Adulto , Líquido Cefalorraquidiano , Síndrome de Ehlers-Danlos/líquido cefalorraquidiano , Síndrome de Ehlers-Danlos/terapia , Síndrome de Fadiga Crônica/líquido cefalorraquidiano , Feminino , Fibromialgia/líquido cefalorraquidiano , Humanos , Pressão Intracraniana , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Pseudotumor Cerebral/terapia , Medula Espinal/fisiopatologia , Punção Espinal , Espaço Subaracnóideo , Adulto JovemRESUMO
We have found mutations in the Menkes disease gene (MNK) which impair, but do not abolish, correct mRNA splicing in patients with less severe clinical phenotypes. In one family, four males aged 2-36 years with a distinctive Menkes variant have a mutation at the +3 position of a splice donor site near the 3' end of the Menkes coding sequence that is associated with exon skipping and a stable mutant transcript. In an unrelated 15-year-old male with typical occipital horn syndrome, a point mutation at the -2 exonic position of a splice donor site in the middle of the gene causes exon-skipping and activation of a cryptic splice acceptor site. In both mutations, maintenance of some normal splicing is demonstrable by RT-PCR, cDNA sequencing and ribonuclease protection.