Evaluation for CSF histamine levels in many disorders and measurements of hypothalamic neuropeptides in the patients with Kleine-Levin syndrome

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(1) We first reported that histamine decreases in the primary CNS hypersomnia, such as narcolepsy and idiopathic hypersomnia (Kanbayashi 2009). However, the histamine levels in other diseases are still unknown. We have further estimated the histamine in CSF of several neurological diseases. Histaminergic neurons are located exclusively in the tuberomammillary nucleus (TMN) of the posterior hypothalamus and project their axons to various brain regions. Histamine is released in the brain not only from TMN histamine neurons, but also from brain mast cell enriched in the choroid plexus, and peripheral blood transferred to central nervous system (CNS). Histamine release by these cells may contribute to CSF histamine levels. Increased CSF histamine levels have been reported in meningitis and encephalitis (Ito 2010). In the demyelinating diseases, histamine levels of MS were low but those of ADEM were high. In addition, we found reductions in CSF histamine levels in PSP and CBD compared to MSA (Kanbayashi2012). The differences of histamine levels in these disorders may be caused by the dysfunctions of posterior hypothalamus. (2) Kleine-Levin Syndrome (KLS) is a neurological disorder characterized by recurring periods of excessive amounts of sleeping and eating. We hypothesized that this disorder is caused by the damage to hypothalamic neuropeptides. The refore, we measured hypothalamic peptides and neurotransmitters, such as, αMSH, AgRP, MCH, nesfatin-1, orexin and histamine. There were no specific findings in the levels of neuropeptides and neurotransmitters (Kanbayashi2010). While we found that CSF AgRP were elevated in the patients with anorexia nervosa, the histamine levels are relatively low among the patiets with KLS (Ito2010).