Abstract
We have examined brainstem lesions in patients with refractory epilepsy disorders, including West syndrome (WS), Lennox-Gastaut syndrome (LGS), and dentatorubral-pallidoluysian atrophy (DRPLA). Acetylcholinergic neurons (AchNs) in the pedunculopontine tegmental nucleus (PPN) are involved in mental development, and disruption of neuronal nicotinic acetylcholine receptors can lead to epilepsy. In order to investigate the involvement of lesions of AchNs in refractory epilepsy, we performed immunohistochemical analyses of AchNs in the PPN in autopsy cases who had a past history of WS and/or LGS and in DRPLA cases who showed progressive myoclonic epilepsy. In addition, we performed a preliminary quantification of the levels of acetylcholine, neuropeptides, and monoamine metabolites in the cerebrospinal fluid (CSF) of patients with WS and benign convulsions associated with mild gastroenteritis (CwG). In the PPN analysis, the total number of neurons and the number of AchNs were reduced in WS/LGS and WS cases, while DRPLA cases showed a decrease in the number and percentage of AchNs. In the CSF analysis, WS patients demonstrated a reduction in the levels of inhibitory neuropeptides, while CwG patients showed increased levels of acetylcholine and decreased levels of serotonin metabolites. These data suggest the possible involvement of lesions of AchNs in WS and DRPLA.
Highlights
West syndrome (WS), which consists of tonic spasms, psychomotor developmental delay, and characteristic electroencephalography changes involving hypsarrhythmia, can have various causes, including congenital brain anomalies and sequelae after perinatal hypoxic and ischemic encephalopathy (HIE) [1]
In order to investigate the involvement of the acetylcholinergic neuronal system in epileptogenesis, we performed an immunohistochemical analysis of Acetylcholinergic neurons (AchNs), CANs, and GABAergic interneurons (GABAis) in the pedunculopontine tegmental nucleus (PPN) in autopsy cases with a history of WS and/or Lennox-Gastaut syndrome (LGS) and Dentatorubral-pallidoluysian atrophy (DRPLA)
There were no significant differences between controls and WS cases in the number and percentages of either CANs or GABAi, which were immunoreactive for tyrosine hydroxylase (TH) or CD, respectively (Table 3 and Figures 1(c) and 1(d))
Summary
West syndrome (WS), which consists of tonic spasms, psychomotor developmental delay, and characteristic electroencephalography changes involving hypsarrhythmia, can have various causes, including congenital brain anomalies and sequelae after perinatal hypoxic and ischemic encephalopathy (HIE) [1]. In order to clarify the epileptogenesis and contribute to the development of new treatments of refractory epilepsy, we have examined lesions of monoaminergic neurons in the brainstem of autopsy cases of WS/LGS and DRPLA [6, 7]. We have performed an immunohistochemical analysis and clarified the selective lesioning of AchNs in the PPN and/or the NbM in patients with perinatal disorders [11], PraderWilli syndrome [12], and xeroderma pigmentosum [13], which is caused by inherited disturbances in nucleotide excision repair. In order to investigate the involvement of the acetylcholinergic neuronal system in epileptogenesis, we performed an immunohistochemical analysis of AchNs, CANs, and GABAis in the PPN in autopsy cases with a history of WS and/or LGS and DRPLA. We preliminarily evaluated the CSF levels of acetylcholine, neuropeptides, and monoamine metabolites in patients with WS and benign convulsions associated with mild gastroenteritis (CwG) (disease controls)
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