Neurodevelopmental profile of siblings with Angelman syndrome due to pathogenic UBE3A variants.

BACKGROUND: Angelman syndrome (AS) is a neurodevelopmental disorder caused by a lack of expression of the maternally inherited UBE3A gene on chromosome 15. Individuals with AS due to a UBE3A mutation are more likely to have siblings who also have AS compared with those with AS due to other cytogenetic/molecular mechanisms, but it is unknown whether the developmental outcome of siblings who have AS is similar. METHODS: Through an ongoing AS Natural History Study, we identified seven pairs of siblings with AS due to a UBE3A mutation. We compared the neurodevelopment of the first-born and second-born siblings with AS participants who have a UBE3A mutation and have either typically developing siblings or no siblings. RESULTS: Second-born AS participants due to a UBE3A mutation were more likely to be diagnosed at an earlier age. With the exception of higher expressive language scores among the second-born participants, no other differences were observed in the developmental and adaptive functioning skills across the different groups. CONCLUSIONS: The presence of an older sibling with the same neurodevelopmental disorder is associated with an earlier age of diagnosis and may be associated with an improvement in expressive language skills; the developmental outcome of siblings with AS due to a UBE3A mutation is otherwise comparable.

A systematic review of severe morbidity in infants born late preterm.

OBJECTIVE: Late-preterm infants (34 weeks 0/7 days-36 weeks 6/7 days' gestation) represent the largest proportion of singleton preterm births. A systematic review was performed to access the short- and/or long-term morbidity of late-preterm infants. STUDY DESIGN: An electronic search was conducted for cohort studies published from January 2000 through July 2010. RESULTS: We identified 22 studies studying 29,375,675 infants. Compared with infants born at term, infants born late preterm were more likely to suffer poorer short-term outcomes such as respiratory distress syndrome (relative risk [RR], 17.3), intraventricular hemorrhage (RR, 4.9), and death <28 days (RR, 5.9). Beyond the neonatal period, late-preterm infants were more likely to die in the first year (RR, 3.7) and to suffer from cerebral palsy (RR, 3.1). CONCLUSION: Although the absolute incidence of neonatal mortality and morbidity in infants born late preterm is low, its incidence is significantly increased as compared with infants born at term.

Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia between 34 and 37 weeks' gestation (HYPITAT-II): a multicentre, open-label randomised controlled trial.

BACKGROUND: Gestational hypertension (GH) and pre-eclampsia (PE) can result in severe complications such as eclampsia, placental abruption, syndrome of Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) and ultimately even neonatal or maternal death. We recently showed that in women with GH or mild PE at term induction of labour reduces both high risk situations for mothers as well as the caesarean section rate. In view of this knowledge, one can raise the question whether women with severe hypertension, pre-eclampsia or deterioration chronic hypertension between 34 and 37 weeks of gestation should be delivered or monitored expectantly. Induction of labour might prevent maternal complications. However, induction of labour in late pre-term pregnancy might increase neonatal morbidity and mortality compared with delivery at term. METHODS/DESIGN: Pregnant women with severe gestational hypertension, mild pre-eclampsia or deteriorating chronic hypertension at a gestational age between 34+0 and 36+6 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant monitoring. In the expectant monitoring arm, women will be induced only when the maternal or fetal condition detoriates or at 37+0 weeks of gestation. The primary outcome measure is a composite endpoint of maternal mortality, severe maternal complications (eclampsia, HELLP syndrome, pulmonary oedema and thromboembolic disease) and progression to severe pre-eclampsia. Secondary outcomes measures are respiratory distress syndrome (RDS), neonatal morbidity and mortality, caesarean section and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be intention to treat. The power calculation is based on an expectant reduction of the maternal composite endpoint from 5% to 1% for an expected increase in neonatal RDS from 1% at 37 weeks to 10% at 34 weeks. This implies that 680 women have to be randomised. DISCUSSION: This trial will provide insight as to whether in women with hypertensive disorders late pre-term, induction of labour is an effective treatment to prevent severe maternal complications without compromising the neonatal morbidity. TRIAL REGISTRATION: NTR1792 CLINICAL TRIAL REGISTRATION: http://www.trialregister.nl.

Axially loaded magnetic resonance image of the lumbar spine in asymptomatic individuals.

STUDY DESIGN: For this study, 43 asymptomatic individuals underwent magnetic resonance imaging of the lumbar spine in both supine psoas-relaxed position and supine axial compression in extension. The change in dural cross-sectional area between positions at each disc level was calculated. OBJECTIVES: To evaluate the effect of axial loading on asymptomatic individuals, as compared with the effect on patients who have clinical signs of lumbar spinal canal stenosis, and to assess the effect that different magnitude and duration of the applied load have on the dural cross-sectional area. SUMMARY OF BACKGROUND DATA: Degenerative changes in the spine are found in both symptomatic and asymptomatic individuals. A study of patients with suspected clinical lumbar spine encroachment examined in both psoas-relaxed position and axial compression in extension with computed tomographic myelography or magnetic resonance imaging of the lumbar spine is reported. A significant decrease in dural cross-sectional area was found, respectively, in 80% and 76% of the patients. METHODS: The study subjects underwent magnetic resonance imaging examinations in both psoas-relaxed position and axial compression in extension. The examination of the subject under axial compression in extension was performed with the lumbar spine in a supine position using a compression device. Degenerative changes in and adjacent to the spinal canal were registered. The dural cross-sectional areas were determined for psoas-relaxed position and axial compression in extension, then compared. In seven reexamined individuals, the dural cross-sectional area was calculated after an axial load corresponding to 25% and 50% of their body weight and a loading time of 5 to 60 minutes. RESULTS: A significant decrease in dural cross-sectional area from psoas-relaxed position to axial compression in extension was found in 24 individuals (56%), most frequently at L4-L5, and increasingly with age. In four individuals (5 disc levels), a decrease in dural cross-sectional area to less than 100 mm2 from psoas-relaxed position to axial compression in extension was found. In seven reexamined individuals, a significant decrease in dural cross-sectional area was found: in five after 5 minutes load of 25% of their body weight, and in two with 50% of their body weight. CONCLUSIONS: Using magnetic resonance imaging, a significant decrease in dural cross-sectional area after axial loading was found less frequently in asymptomatic than in symptomatic subjects. The decrease was more frequent at L4-L5, and increasingly with age. The load should be 50% of the subject's body weight applied for at least 5 minutes.

The diagnostic effect from axial loading of the lumbar spine during computed tomography and magnetic resonance imaging in patients with degenerative disorders.

STUDY DESIGN: Patients with low back pain, sciatica, and neurogenic claudication were observed during computed tomographic myelography or magnetic resonance imaging in psoas-relaxed position and axially compressed supine position of the lumbar spine. OBJECTIVE: To estimate the clinical value of axially loaded imaging in patients with degenerative disorders of the lumbar spine. SUMMARY OF BACKGROUND DATA: Computed tomography and magnetic resonance imaging still are performed with the lumbar spine in a supine relaxed position, which results in unloading of the spine and enlargement of the canal. METHODS: A device for axial loading of the lumbar spine in computed tomography and magnetic resonance imaging was used. Altogether, 172 patients were examined in psoas-relaxed position and axially compressed supine position of the lumbar spine: 50 patients with computed tomographic myelography and 122 patients with magnetic resonance imaging. If a significant decrease (>15 mm2) in the dural sac cross-sectional area to values smaller than 75 mm2 (the borderline value for stenosis) was found during examination in axial loading, or if a suspected disc herniation, narrow lateral recess, narrow intervertebral foramen, or intraspinal synovial cyst changed to being obvious at the axial loading examination, this was regarded as additional information important for the treatment. RESULTS: Additional valuable information was found in 50 of 172 patients (29%) during examination in axial loading. In the different diagnostic groups, additional valuable information was found in 69% of the patients with neurogenic claudication, in 14% of the patients with sciatica, and in 0% of the patients with low back pain. The percentage of additional valuable information increased to 50% in the patients with sciatica, if recommended inclusion criteria for examinations in axial loading were used. A narrowing of the lateral recess causing compression of the nerve root was found at 42 levels in 35 patients at axial loading. CONCLUSION: According to the study results, axially loaded imaging adds frequent additional valuable information, as compared with conventional imaging methods, especially in patients with neurogenic claudication, but also in patients with sciatica if defined inclusion criteria are used.

Imaging lumbar spinal stenosis.

The entire concept of spinal stenosis is based on the assumption that there is a minimal space necessary for the function of the neural content of the spinal canal, and this space, under certain circumstances, gets too small. This may seem self evident, but it was not until the middle of the previous century that there was sufficient focus on this concept to establish the diagnosis of lumbar spine stenosis.

Colour adaptation modifies the temporal properties of the long- and middle-wave cone signals in the human luminance mechanism.

The human luminance mechanism (LUM) detects rapid flicker and motion, summating the neurally integrated L' and M' 'contrast' signals from the long- and middle-wave cones, respectively. We previously observed large temporal phase shifts between the L' and M' signals in LUM, which were maximal and of reversed sign on green versus orange background fields and which were accompanied by large variations in the relative L' and M' contrast weights. The effects were modelled with phasic magnocellar retinal ganglion cells. The changing L' versus M' contrast weights in the model predict that the temporal dynamics of the L' and M' luminance signals will differ on green and orange fields. This is assessed with several protocols. Motion thresholds for 1 cycle deg(-1) drifting gratings or static pulsed gratings on the orange field show that the M' signal is more temporally bandpass than the L' signal; this reverses on the green field. Strong motion due to the different dynamics of the L' and M' signals is even seen with a pair of L' and M' gratings pulsed simultaneously. Impulse response functions were measured with gratings pulsed spatially in phase or antiphase. The impulse response was clearly biphasic for the M' signal on the orange field and L' signal on the green field, while the other signals were more sustained. The impulse responses predicted the motion seen with gratings pulsed in spatial quadrature.

Axial loading of the spine during CT and MR in patients with suspected lumbar spinal stenosis.

PURPOSE: To evaluate the effect of compressive axial loading in imaging of the lumbar spine in patients with clinically suspected spinal stenosis. MATERIAL AND METHODS: A total of 84 patients were examined, 50 with CT (after intrathecal contrast administration) and 34 with MR. First the dural sac cross-sectional area (CSA) was determined with the patient in the supine psoas relaxed position (PRP). Then the CSA was determined during supine axial compression in slight extension (ACE), obtained with a specially designed loading device. A measurement error study was performed. RESULTS: A minimum difference in CSA of 15 mm2 between PRP and ACE was found to be significant. In 40/50 (80%) of CT-examined patients and in 26/34 (76%) of MR-examined patients a significant difference in CSA was found. In 25/84 (30%) of the patients there was a significant difference at more than one level. CONCLUSION: For an adequate evaluation of the CSA, CT or MR studies should be performed with axial loading in patients who have symptoms of lumbar spinal stenosis.

The effects of external compression by three different retractors on pressure in the erector spine muscles during and after posterior lumbar spine surgery in humans.

STUDY DESIGN: An experimental study on patients undergoing posterior lumbar spine surgery. OBJECTIVES: To study the relation between external compression and muscle strain induced by spinal retractors and intramuscular pressure in the dorsolumbar compartment during posterior spinal surgery. SUMMARY OF BACKGROUND DATA: Pressures were studied as a function of the distance between the retractor blades during surgery. METHODS: Intramuscular pressure was measured bilaterally in the erector spinae muscle with intermittent microcapillary infusion technique in 12 patients undergoing posterior lumbar spine surgery during 271 (range 90-420) minutes. Three self-retaining retractors were tested; the McCulloch, the Viking, and the Richard retractors. RESULTS: Intramuscular pressure was 7.7 mm Hg before surgery. It varied between 35 mm Hg and 69 mm Hg during surgical exposure of the laminas and facet joints. Intramuscular pressure varied between 61 mm Hg and 158 mm Hg depending on which retractor was used and on the distance between the retractor blades. Intramuscular pressure never exceeded 30 mm Hg at rest after the operation. CONCLUSIONS: External compression and muscle strain from retractor blades during surgery increased intramuscular pressure in the paravertebral muscles to levels that, according to other studies, induce ischemia in the muscles.

Dynamic effects on the lumbar spinal canal: axially loaded CT-myelography and MRI in patients with sciatica and/or neurogenic claudication.

STUDY DESIGN: In patients with sciatica or neurogenic claudication, the structures in and adjacent to the lumbar spinal canal were observed by computed tomographic myelography or magnetic resonance imaging in psoas-relaxed position and during axial compression in slight extension of the lumbar spine. OBJECTIVES: To determine the mechanical effects on the lumbar spinal canal in a simulated upright position. SUMMARY OF BACKGROUND DATA: For years, functional myelographic investigation techniques were shown to be of value in the evaluation of suspected encroachment of the spinal canal. Since the advent of computed tomography and magnetic resonance imaging, there have been few clinical and experimental attempts that have imitated these techniques. The data indicate that the space within the canal is posture dependent. METHODS: Portable devices for axial loading of the lumbar spine in computed tomographic and magnetic resonance examinations were developed. Fifty patients (94 sites) were studied with computed tomographic myelography, and 34 patients (80 sites) with magnetic resonance in psoas-relaxed position followed by axial compression in slight extension. The dural sac cross-sectional area at L2 to S1, the deformation of the dural sac and the nerve roots, and the changes of the tissues surrounding the canal were observed. RESULTS: In 66 of the investigated 84 patients, there was a statistically significant reduction of the dural sac cross-sectional area in at least one site during axial compression in slight extension. Of the investigated patients, 29 passed the borderlines for relative (100 mm2) or absolute stenosis (75 mm2) in 40 sites. In 30 patients, there was deformation of the dural sac in 46 sites. In 11 of the patients investigated with magnetic resonance imaging, there was a narrowing of the lateral recess in 13 sites, during axial compression in slight extension. CONCLUSIONS: Axial loading of the lumbar spine in computed tomographic scanning and magnetic resonance imaging is recommended in patients with sciatica or neurogenic claudication when the dural sac cross-sectional area at any disc location is below 130 mm2 in conventional psoas-relaxed position and when there is a suspected narrowing of the dural sac or the nerve roots, especially in the ventrolateral part of the spinal canal in psoas-relaxed position. The diagnostic specificity of the spinal stenosis will increase considerably when the patient is subjected to an axial load.

Acute burst fractures. A comparative analysis of a modern fracture classification and pathologic findings.

Ten acute thoracolumbar burst fractures (T11-L3) in eight spinal specimens were investigated regarding injuries to the bony, ligamentous, and neural structures. The fractures were subdivided into three groups, which were compared to the different burst fractures proposed by Denis in 1983. In the specimens, it was impossible to separate Denis Type A and B fractures. The Type D fractures showed pronounced instability. These latter fractures were subdivided into two groups: one with rupture of the bony vertebral arch (D) and one with rupture of the posterior ligaments (D2). The Denis A or B fractures were not associated with macroscopic or microscopic damage to the spinal cord or cauda equina, or both. However, in the six Denis D fractures, the neural tissue was transected in one case and severely compressed in four cases.

Unstable thoracolumbar injuries.

The treatment of thoracolumbar fractures was traditionally conservative. With increasing demands for early mobilization, operative reduction and stabilization has become more popular, even in less severe injuries. The Harrington instrumentation is still useful and efficient. However, in fractures with posterior element ruptures, the internal fixator is superior in stabilizing the fracture. Early mobilization in a body cast is an equivalent treatment to surgery in less severe burst fractures if the neurology is intact. A treatment program for different fractures is presented.

The natural history of burst fractures at the thoracolumbar junction.

Conservative management of 54 patients with thoracolumbar (T12 and/or L1) burst fractures was investigated. The fractures were subdivided according to the Denis classification and a modification was suggested. Most type A and B fractures showed good results regarding reduction and neurological improvement. However, severe type B (with anterior column compression and spinal canal narrowing exceeding 50%), D, and E fractures were to a large extent complicated by intractable low back pain, neurological involvement, and signs of instability. This study suggests predictors for complications in patients with burst fractures in the thoracolumbar junction. These are (a) compression rate of the anterior column exceeding 50%, (b) narrowing of the spinal canal exceeding 50%, (c) signs of rotational malalignment in fracture level, and (d) level of the injury (L1 fractures).

Burst fractures in the thoracic and lumbar spine. A clinico-neuropathologic analysis.

Neuropathologic analysis of eight acute and 12 chronic burst fractures was performed. In the acute cases, the injury to the bony, ligamentous, and neural tissues was investigated. Serious Denis B or D fractures showed signs of pronounced instability, and all had a large bone fragment rotated into the spinal canal. The neural tissues were compressed in two cases and transected in one. The Denis A fractures had relatively well-restored ligamentous structures and the bone fragment in the spinal canal was narrowing the spinal canal less than 50% in all cases. Three of four had normal neural tissue macroscopically and microscopically. The majority of the patients with chronic burst fractures did not show any sign of bone fragment resorption. Six out of eight patients with thoracolumbar (T12 and L1) and lumbar (L3) fractures experienced intractable burning pain and/or rhizopathy. The pain seemed to be caused by entrapment of the nerve roots in adhesions.

Intermittent parasympathetic symptoms in lumbar spinal stenosis.

Symptoms related to autonomic nervous dysfunction are uncommon in spinal stenosis. Involvement of nerve roots S2-S5 has previously been reported only in a few cases. Of great interest is the occurrence of phenomena such as intermittent penile erections and fecal incontinence on walking in patients with compromise of the lower lumbar spinal canal. We report on two patients, one of whom presented because of fecal incontinence and the other with penile erections on walking. In both cases, these manifestations resolved after decompressive laminectomy. These patients are compared to six other patients, with parasympathetic disturbances due to lumbar spinal stenosis, described previously.

Radiologic study of the influence of zygapophyseal joint orientation on spinal injuries at the thoracolumbar junction.

The change from coronal to sagittal plane orientation of the zygapophyseal (facet) joints at the thoracolumbar junction, coupled with differences in lumbar and thoracic spine mobility, may predispose the T10 to L2 segments to injury. To test for an association between the level of injury and variations in orientation of the zygapophyseal joints, CT investigations of 44 spinal injured patients were studied. Of these, 28 sustained burst/compression fractures and 16 demonstrated a rotation injury with disruption to one or both zygapophyseal joints. Injuries were examined to determine whether more congruent "mortice" joints localised the segmental level of trauma. The Chi-square statistic was used: to compare the transitional characteristics of 44 clinical cases with a "normal" patient database (n = 630); to examine differences in transition patterns between the "compression" and "rotation" injury groups; and to compare the incidence of mortice joints between the clinical and normal series. A significant difference between the transition patterns of the clinical and normal series (p less than 0.001) appeared to account for the higher frequency of abrupt transitions in the 44 injury cases. No significant differences distinguished the transition patterns of the two injury groups. A higher incidence of mortice joints was demonstrated in the injury group compared with the normal population (p less than 0.02). These findings suggest that individuals with an abrupt transition have a greater predisposition to injuries at the thoracolumbar junction.

Dynamic changes in the dimensions of the lumbar spinal canal: an experimental study in vitro.

The variation in the dimensions of the lumbar spinal canal under both flexion-extension and axial compression-distraction was studied using computerized tomography (CT) scans in human cadaver lumbar spine specimens. In 3-mm-thick CT slices through the disk at L3-L4, the cross-sectional area of the spinal canal was reduced by around 40 mm2, corresponding to a 16% reduction of the initial area when the lumbar spines were moved both from flexion to extension and from distraction to compression. A corresponding reduction in the midsagittal diameter of the canal of 2 mm was found. During these motions, the ligamentum flavum did not appear to be a significant factor for the dynamic changes affecting the dimensions of the canal. This held true even after the disk had been excised in order to produce a total collapse of the disk space.

A test of the spatial-frequency explanation of the Müller-Lyer illusion.

Previous investigations have shown that the response of spatial-frequency-specific channels in the human visual system is differentially affected by adaptation to gratings of distinct spatial frequencies and/or orientations. A study is reported of the effects of adaptation to vertical or horizontal gratings of a high or a low spatial frequency on the extent of the Brentano form of the Müller-Lyer illusion in human observers. It is shown that the illusion decreases after adaptation to vertical gratings of low spatial frequency, but seems unaffected otherwise. These results are consistent with the notion of visual channels that are spatial-frequency and orientation specific, and support the argument that the Müller-Lyer illusion may be due primarily to lower-spatial-frequency components in the Fourier spectra of the image.