RESUMO
GBS and CIDP are important treatable forms of acquired peripheral neuropathies. GBS is a heterogeneous disorder representing at least five different entities. Three are predominantly motor: AIDP, AMSAN, and AMAN. Fisher syndrome and acute panautonomic neuropathy are other variants. Treatment for all of these conditions is the same and includes either plasma exchange or intravenous immunoglobulin. There is no indication that Guillain-Barré patients respond to corticosteroids. At the present time, it is uncertain if CIDP represents one or more disorders. Evidence favors a syndrome composed of more than one entity accounting for (1) clinical variations from subject-to-subject, ranging from symmetrical to focal neurologic deficits; (2) course variations from slowly progressive to step-wise, to relapsing; and, (3) laboratory variations in nerve conduction studies, spinal fluid protein, and nerve biopsy findings. CIDP patients respond to corticosteroids in contrast to those with GBS. CIDP improves with intravenous immunoglobulin and plasma exchange, paralleling the findings in GBS. Specific regimens of treatment for both GBS and CIDP are presented in this article and considerations that might influence one treatment regimen over another are discussed.
Assuntos
Síndrome de Guillain-Barré/terapia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia , Corticosteroides/uso terapêutico , Doenças do Sistema Nervoso Autônomo/terapia , Humanos , Imunoglobulinas Intravenosas , Troca PlasmáticaRESUMO
This is the first detailed description of the neuropathology of a patient with xeroderma pigmentosum/Cockayne syndrome complex (XP/CS). This 6-year-old boy's clinical course, followed from infancy to death, is compared with that of the eight other known cases of XP/CS. Normal at birth, he developed the cutaneous sun sensitivity of XP in infancy and the infantile CS phenotype in early childhood. He had the characteristic CS facies, cachexia, failure of somatic and brain growth, spasticity, ataxia, pigmentary retinopathy, hearing loss, mixed peripheral neuropathy, and myopathy. Like his clinical phenotype, the neuropathology was also that of CS despite an XPG genotype. His brain weighed 350 grams (considerably less than the expected weight at birth) and revealed hydrocephalus, tigroid-type demyelination, dystrophic calcification and widespread neuronal loss and gliosis with hyperchromatic glial and endothelial nuclei. Peripheral nerve showed myelinopathy with axonal degeneration, and skeletal muscle had mixed myopathic and neuropathic features. Ophthalmic pathology disclosed cataracts, iris and ciliary body atrophy, inner retinal atrophy and gliosis, retinal pigment epithelial atrophy, and optic nerve atrophy. Molecular studies, which have appeared elsewhere, do not provide full understanding of the pathophysiology of the postnatal growth failure, cachexia, precocious aging, selectivity of tissues affected (such as myelinated axons), and other manifestations of this devastating illness.
Assuntos
Síndrome de Cockayne/complicações , Xeroderma Pigmentoso/complicações , Atrofia/patologia , Calcinose/patologia , Cerebelo/patologia , Criança , Síndrome de Cockayne/genética , DNA Helicases/genética , Enzimas Reparadoras do DNA , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Olho/patologia , Evolução Fatal , Expressão Gênica/genética , Gliose/patologia , Humanos , Masculino , Músculo Esquelético/patologia , Proteínas Nucleares , Mutação Puntual/genética , Proteínas de Ligação a Poli-ADP-Ribose , Fatores de Transcrição , Xeroderma Pigmentoso/genéticaRESUMO
OBJECTIVES: To review genetic variants of Cockayne syndrome (CS) and xeroderma pigmentosum (XP), autosomal recessive disorders of DNA repair that affect the nervous system, and to illustrate them by the first case of xeroderma pigmentosum-Cockayne syndrome (XP-CS) complex to undergo neuropathologic examination. METHODS: Published reports of clinical, pathologic, and molecular studies of CS, XP neurologic disease, and the XP-CS complex were reviewed, and a ninth case of XP-CS is summarized. RESULTS: CS is a multisystem disorder that causes both profound growth failure of the soma and brain and progressive cachexia, retinal, cochlear, and neurologic degeneration, with a leukodystrophy and demyelinating neuropathy without an increase in cancer. XP presents as extreme photosensitivity of the skin and eyes with a 1000-fold increased frequency of cutaneous basal and squamous cell carcinomas and melanomas and a small increase in nervous system neoplasms. Some 20% of patients with XP incur progressive degeneration of previously normally developed neurons resulting in cortical, basal ganglia, cerebellar, and spinal atrophy, cochlear degeneration, and a mixed distal axonal neuropathy. Cultured cells from patients with CS or XP are hypersensitive to killing by ultraviolet (UV) radiation. Both CS and most XP cells have defective DNA nucleotide excision repair of actively transcribing genes; in addition, XP cells have defective repair of the global genome. There are two complementation groups in CS and seven in XP. Patients with the XP-CS complex fall into three XP complementation groups. Despite their XP genotype, six of nine individuals with the XP-CS complex, including the boy we followed up to his death at age 6, had the typical clinically and pathologically severe CS phenotype. Cultured skin and blood cells had extreme sensitivity to killing by UV radiation, DNA repair was severely deficient, post-UV unscheduled DNA synthesis was reduced to less than 5%, and post-UV plasmid mutation frequency was increased. CONCLUSIONS: The paradoxical lack of parallelism of phenotype to genotype is unexplained in these disorders. Perhaps diverse mutations responsible for UV sensitivity and deficient DNA repair may also produce profound failure of brain and somatic growth, progressive cachexia and premature aging, and tissue-selective neurologic deterioration by their roles in regulation of transcription and repair of endogenous oxidative DNA damage.
Assuntos
Síndrome de Cockayne/genética , Reparo do DNA/genética , Xeroderma Pigmentoso/genética , HumanosRESUMO
We report a case of recurrent critical illness myopathy in an asthmatic patient who was treated for respiratory failure with high doses of intravenous corticosteroids alone without exposure to nondepolarizing neuronmscular-bloclong agents. Each episode was followed by substantial symptomatic improvement. Our experience indicates that intravenous corticosteroids should be used with special caution in patients with a history of critical illness myopathy.