RESUMO
We report on a 45-year-old man with a history of multiple psychiatric admissions for a gait disorder and episodic weakness thought to be psychogenic who was subsequently diagnosed with status cataplecticus due to narcolepsy. The gait difficulties resolved with venlafaxine. This case demonstrates that status cataplecticus can be misdiagnosed as a psychogenic gait disorder.
Assuntos
Cataplexia/complicações , Erros de Diagnóstico , Distúrbios Distônicos/complicações , Distúrbios Distônicos/diagnóstico , Marcha , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Transporte/líquido cefalorraquidiano , Diagnóstico Diferencial , Distúrbios Distônicos/líquido cefalorraquidiano , Antígenos HLA-DQ/líquido cefalorraquidiano , Cadeias beta de HLA-DQ , Humanos , Masculino , Pessoa de Meia-Idade , Neuropeptídeos/líquido cefalorraquidiano , Orexinas , Sono REM/fisiologiaRESUMO
Hypocretins (orexins) are hypothalamic neuropeptides involved in sleep and energy homeostasis. Hypocretin mutations produce narcolepsy in animal models. In humans, narcolepsy is rarely due to hypocretin mutations, but this system is deficient in the cerebrospinal fluid (CSF) and brain of a small number of patients. A recent study also indicates increased body mass index (BMI) in narcolepsy. The sensitivity of low CSF hypocretin was examined in 38 successive narcolepsy-cataplexy cases [36 human leukocyte antigen (HLA)-DQB1*0602-positive] and 34 matched controls (15 controls and 19 neurological patients). BMI and CSF leptin levels were also measured. Hypocretin-1 was measurable (169 to 376 pg/ml) in all controls. Levels were unaffected by freezing/thawing or prolonged storage and did not display any concentration gradient. Hypocretin-1 was dramatically decreased (<100 pg/ml) in 32 of 38 patients (all HLA-positive). Four patients had normal levels (2 HLA-negative). Two HLA-positive patients had high levels (609 and 637 pg/ml). CSF leptin and adjusted BMI were significantly higher in patients versus controls. We conclude that the hypocretin ligand is deficient in most cases of human narcolepsy, providing possible diagnostic applications. Increased BMI and leptin indicate altered energy homeostasis. Sleep and energy metabolism are likely to be functionally connected through the hypocretin system.
Assuntos
Proteínas de Transporte/líquido cefalorraquidiano , Metabolismo Energético , Homeostase , Peptídeos e Proteínas de Sinalização Intracelular , Leptina/líquido cefalorraquidiano , Narcolepsia/líquido cefalorraquidiano , Neuropeptídeos/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Análise de Variância , Índice de Massa Corporal , Proteínas de Transporte/sangue , Metabolismo Energético/fisiologia , Feminino , Antígenos HLA-DQ/líquido cefalorraquidiano , Humanos , Masculino , Pessoa de Meia-Idade , Narcolepsia/diagnóstico , Neuropeptídeos/sangue , OrexinasRESUMO
Equal numbers of CD4+ T cells recognizing myelin basic protein (MBP) and proteolipid protein (PLP) are found in the circulation of normal individuals and multiple sclerosis (MS) patients. We hypothesized that if myelin-reactive T cells are critical for the pathogenesis of MS, they would exist in a different state of activation as compared with myelin-reactive T cells cloned from the blood of normal individuals. This was investigated in a total of 62 subjects with definitive MS. While there were no differences in the frequencies of MBP- and PLP-reactive T cells after primary antigen stimulation, the frequency of MBP or PLP but not tetanus toxoid-reactive T cells generated after primary recombinant interleukin (rIL-2) stimulation was significantly higher in MS patients as compared with control individuals. Primary rIL-2-stimulated MBP-reactive T cell lines were CD4+ and recognized MBP epitopes 84-102 and 143-168 similar to MBP-reactive T cell lines generated with primary MBP stimulation. In the cerebrospinal fluid (CSF) of MS patients, MBP-reactive T cells generated with primary rIL-2 stimulation accounted for 7% of the IL-2-responsive cells, greater than 10-fold higher than paired blood samples, and these T cells also selectively recognized MBP peptides 84-102 and 143-168. In striking contrast, MBP-reactive T cells were not detected in CSF obtained from patients with other neurologic diseases. These results provide definitive in vitro evidence of an absolute difference in the activation state of myelin-reactive T cells in the central nervous system of patients with MS and provide evidence of a pathogenic role of autoreactive T cells in the disease.