Polysomnographic and actigraphic evidence of sleep fragmentation in patients with irritable bowel syndrome

STUDY OBJECTIVE: To characterize the function and quality of sleep in patients with irritable bowel syndrome (IBS). DESIGN: A prospective study with a historic comparison group. SETTING: A regional hospital that also serves as a tertiary referral center. PATIENTS: Eighteen patients with IBS and a comparison group of 20 matched adults with mild benign snoring. INTERVENTIONS: A polysomnography study and a wrist actigraphy study. MEASUREMENTS: All subjects underwent sleep studies and completed self-report questionnaires (IBS severity, psychosocial variables, sleep function, and Epworth Sleepiness Scale). Fourteen IBS and 11 comparison patients underwent actigraphy. RESULTS: The IBS patients had more than 70% less slow-wave stage sleep (4.5 +/- 7.3% vs 19.3 +/- 12.9%; P = 0.006), compensated by increased stage 2 sleep (72.2 +/- 6.6% vs 60.1 +/- 16.8%; P = 0.01). The IBS group had significant sleep fragmentation with a significantly higher arousal and awakening index (P < 0.001), a longer wake period after sleep onset (P = 0.02), and more downward shifts to lighter sleep stages (P = 0.01). The 4-night actigraphy study supported the polysomnography findings. The sleep fragmentation index was significantly higher (P = 0.008) in the IBS group. The IBS patients reported greater daytime sleepiness (9.0 +/- 4.8 vs 6.4 +/- 4.8, Epworth Sleepiness Scale score, P < 0.01) and greater impairment in quality of life, which correlated significantly with the sleep fragmentation indexes. The difference between the groups was not due to differences in baseline anxiety/depression levels. CONCLUSIONS: Patients with IBS have impaired sleep quality, reduced slow-wave sleep activity, and significant sleep fragmentation. The cause-and-effect relationship of these findings with patients' daytime symptoms should be studied further.     

Molecular characterization of a 1p36 chromosomal duplication and in utero interference define ENO1 as a candidate gene for polymicrogyria

While chromosome 1p36 deletion syndrome is one of the most common terminal subtelomeric microdeletion syndrome, 1p36 microduplications are rare events. Polymicrogyria (PMG) is a brain malformation phenotype frequently present in patients with 1p36 monosomy. The gene whose haploinsufficiency could cause this phenotype remains to be identified. We used high-resolution arrayCGH in patients with various forms of PMG in order to identify chromosomal variants associated to the malformation and characterized the genes included in these regions in vitro and in vivo. We identified the smallest case of 1p36 duplication reported to date in a patient presenting intellectual disability, microcephaly, epilepsy, and perisylvian polymicrogyria. The duplicated segment is intrachromosomal, duplicated in mirror and contains two genes: enolase 1 (ENO1) and RERE, both disrupted by the rearrangement. Gene expression analysis performed using the patient cells revealed a reduced expression, mimicking haploinsufficiency. We performed in situ hybridization to describe the developmental expression profile of the two genes in mouse development. In addition, we used in utero electroporation of shRNAs to show that Eno1 inactivation in the rat causes a brain development defect. These experiments allowed us to define the ENO1 gene as the most likely candidate to contribute to the brain malformation phenotype of the studied patient and consequently a candidate to contribute to the malformations of the cerebral cortex observed in patients with 1p36 monosomy.Subject terms: Gene regulation, Genetics research     

Severe classical congenital muscular dystrophy and merosin expression

Vajsar J, Chitayat D, Becker LE, Ho M, Ben-Zeev B, Jay V. Severe classical congenital muscular dystrophy and merosin expression. Clin Genet 1998: 54: 193–198. 0 Munksgaard, 1998
It has been suggested that patients with autosomal recessive merosin deficient congenital muscular dystrophy (CMD), as opposed to the merosin positive cases form a homogeneous subgroup of a clinically more severe form of CMD. We examined merosin expression in muscle biopsies from five children with the severe classical form of CMD. Merosin deficiency was found only in 1 patient, a 6–year-old female, with abnormal brain myelination. However, her initial biopsy did not reveal the classical picture of dystrophy. The four merosin positive cases exhibited severe muscle weakness but their brain imagings were normal. There were no familial cases, except for the mother of 1 patient who had a milder form of the disease, suggesting an autosomal dominant mode of inheritance.
In contrast to previous reports, the merosin deficient CMD cases were rare in our group. Furthermore, merosin positive cases were also associated with severe phenotype suggesting that a severe phenotype is not exclusive to merosin deficient cases. Finally, the absence of merosin in a neonate with hypotonia and weakness can be helpful in making a definitive diagnosis of CMD, even though the dystrophic process may not be evident yet and histology may be non-specific.     

The additive miotic effects of dapiprazole and pilocarpine

Background: Since dapiprazole on alpha-adrenergic agent, produces miosis by paralyzing the dilator muscle, and pilocarpine, a parasympathetic drug, causes miosis by affecting the sphincter, we speculated that the two drugs might have additive effects. Methods: The additive miotic actions of pilocarpine 2% and dapiprazole 0.5% were evaluated by comparing the effects of two drugs given together and alone on the reversal of mydriasis induced by tropicamide (0.5%) and phenylephrine (10%) in one eye each of 60 healthy volunteers. Results: Dapiprazole and pilocarpine together induced miosis significantly faster than each drug alone, showing additive effects. Conclusion: Co-administration of dapiprazole and pilocarpine at the end of the eye examination will induce fast pupillary constriction, which might be useful in preventing the development of an acute attack of angle-closure glaucoma in patients with anatomically narrow angles.     

Assessment of multiple sclerosis lesions with spherical harmonics: comparison of MR imaging and pathologic findings

Spherical harmonics (SH) were used to approximate the volume and three-dimensional geometry of multiple sclerosis (MS) lesions in deceased patients. The institutional ethical committee does not require its approval for studies involving pathologic specimens. Pathologic findings were used as the reference standard. In addition, lesion volume was measured with cylindrical approximation (CA). Volumetric comparisons of biases were based on summary statistics, Spearman correlation, Wilcoxon test, and two-way analysis of variance. Shape comparison metrics included mean distance and Dice similarity coefficient (DSC). Eight of 11 lesions had smaller biases with SH method (P < .001). Median biases with SH and CA did not differ significantly, as compared with pathologic findings (r = 1.00 vs 0.99, respectively). Variances of the biases were significantly smaller for SH (P = .04). Ranges of normalized distance and DSC were 0.1%-2.5% and 75%-96%, respectively. Mean DSC was significantly higher than 70% (P < .001). SH method provided unbiased lesion volume and added geometric information that may enable a better understanding of the pathogenesis and lesion evolution over time.     

Congenital hydrocephalus and continuous spike wave in slow-wave sleep--a common association?

Early-onset hydrocephalus was identified as the common denominator in 5 of 12 consecutive patients with Landau-Kleffner syndrome or continuous spike wave in slow-wave sleep who presented during the last 6 years. This association seems to be more common than expected, and the course of epileptic disease and outcome differs from that of previous reports. We present the clinical cases and discuss the possible connection between early hydrocephalus and epilepsy, especially continuous spike wave in slow-wave sleep. A retrospective analysis was undertaken of the clinical course and electroencephalographic (EEG) data before and after the development of continuous spike wave in slow-wave sleep in a group of five children with early-onset hydrocephalus identified in three epilepsy clinics in Israel. Landau-Kleffner syndrome or continuous spike wave in slow-wave sleep was identified in 12 patients during 6 years (1995-2000). Five patients had a history of early-onset hydrocephalus. Three patients had ventriculoperitoneal shunts; two of them were never shunted. Patients' seizures and continuous spike wave in slow-wave sleep epileptiform activity was resistant to appropriate anticonvulsant treatment. Pediatric neurologists and neurosurgeons should be aware of the association between continuous spike wave in slow-wave sleep and early-onset hydrocephalus. When a child with hydrocephalus presents with behavioral, cognitive, or motor deterioration, he or she should undergo sleep EEG in addition to investigation of shunt function. Our series demonstrated the presence of continuous spike wave in slow-wave sleep and localization-related epilepsy that did not originate from the shunt site. This group of patients is heterogeneous, and the exact trigger for continuous spike wave in slow-wave sleep development is still unclear.