Key pointsr The pathophysiological roles of the CNS in bowel dysfunction in patients with irritable bowel syndrome and Parkinson's disease remain obscure.r In the present study, we demonstrate that dopamine in the lumbosacral defaecation centre causes strong propulsive motility of the colorectum.r The effect of dopamine is a result of activation of sacral parasympathetic preganglionic neurons via D2-like dopamine receptors.r Considering that dopamine is a neurotransmitter of descending pain inhibitory pathways, our results highlight the novel concept that descending pain inhibitory pathways control not only pain, but also the defaecation reflex.r In addition, severe constipation in patients with Parkinson's disease can be explained by reduced parasympathetic outflow as a result of a loss of the effect of dopaminergic neurons. AbstractWe have recently demonstrated that intrathecally injected noradrenaline caused propulsive contractions of the colorectum. We hypothesized that descending pain inhibitory pathways control not only pain, but also the defaecation reflex. Because dopamine is one of the major neurotransmitters of descending pain inhibitory pathways in the spinal cord, we examined the effects of the intrathecal application of dopamine to the spinal defaecation centre on colorectal motility. Colorectal intraluminal pressure and expelled volume were recorded in vivo in anaesthetized rats. Slice patch clamp and immunohistochemistry were used to confirm the existence of dopamine-sensitive neurons in the sacral parasympathetic nuclei. Intrathecal application of dopamine into the L6-S1 spinal cord, where the lumbosacral defaecation centre is located, caused propulsive contractions of the colorectum. Inactivation of spinal neurons using TTX blocked the effect of dopamine. Although thoracic spinal transection had no effect on the enhancement of colorectal motility by intrathecal dopamine, the severing of the pelvic nerves abolished the enhanced motility. Pharmacological experiments revealed that the effect of dopamine is mediated primarily by D2-like dopamine receptors. Neurons labelled with retrograde dye injected at the colorectum showed an inward current in response to dopamine in slice patch clamp recordings. Furthermore, immunohistochemical analysis revealed that neurons immunoreactive to choline acetyltransferase express D2-like dopamine receptors. Taken together, our findings demonstrate that dopamine activates sacral parasympathetic preganglionic neurons via D2-like dopamine receptors and causes propulsive motility of the colorectum in rats. The present study supports the hypothesis that descending pain inhibitory pathways regulate defaecation reflexes.

No abstract

Immunoglobulin helicase μ-binding protein 2 (IGHMBP2) gene is responsible for Charcot-Marie-Tooth disease (CMT) type 2S and spinal muscular atrophy with respiratory distress type 1 (SMARD1). From June 2014 to December 2015, we collected 408 cases, who referred to our genetic laboratory for genetic analysis, suspected with CMT disease or other inherited peripheral neuropathies (IPNs) on the basis of clinical manifestations and electrophysiological studies. Mutation screening was performed using Ion AmpliSeq Custom Panels, which comprise 72 disease-causing or candidate genes of IPNs. We identified novel homozygous or compound heterozygous variants of IGHMBP2 in four patients. Three patients presented with childhood-onset axonal predominant sensorimotor polyneuropathies, whereas the other case was diagnosed with SMARD1, manifesting as low birth weight, weak cry, reduced spontaneous movement and developed respiratory distress 4 months after birth. We present the original report of CMT type 2S in Japan, and illustrate that recessive IGHMBP2 variants account for ~1.6% of axonal CMT in our cohort.

Christianson syndrome (CS) is an X-linked intellectual disorder caused by mutations in the SLC9A6 gene. Clinical features of CS include an inability to speak, truncal ataxia, postnatal microcephaly, hyperkinesis, and epilepsy. Almost all patients with CS develop drug-resistant epilepsy—its most serious complication. We report two cases of CS with drug-resistant epilpesy associated with the Lennox–Gastaut syndrome (LGS). One patient experienced generalized tonic seizures since 9 months of age with cognitive regression, which evolved to include atonic seizures at the age of 7 years. Electroencephalography (EEG) showed generalized slow spike–wave complexes and generalized paroxysmal fast activity. Seizures remained drug-resistant despite multiple anti-seizure drugs. The second patient experienced generalized tonic seizures since the age of 17 months and arrested development. EEG showed generalized slow spike–wave complexes, with frequent atonic seizures since the age of 6 years. Electrical status epilepticus during slow-wave sleep (ESES) developed at the age of 7 years. Our cases illustrate that CS may cause LGS in addition to other developmental and epileptic encephalopathies of the neonatal and infantile period. We suggest that generalized tonic or tonic–clonic seizures and generalized slow spike–wave complexes in interictal EEG be included as potential electroclinical features of epilepsy in CS.

No abstract