Purpose
Regarding the close interaction between the spinal alignment and the pelvis orientation, no parameter is routinely used to describe and to evaluate the global spinopelvic balance, taking into ...account simultaneously the spinal part and the pelvic part of the global alignment. We described the global tilt (GT) that could analyze malalignment considering the spine and the pelvis simultaneously. From a geometrical point of view, the global tilt is the sum of the pelvic tilt (PT) and the C7 vertical tilt (angular value of sagittal vertical axis). The aim of this study is to evaluate the global tilt with comparison to PT and sagittal vertical axis (SVA), with the hypothesis that GT would be the least sensitive to positional changes.
Methods
A cohort of 22 patients with sagittal malalignment was identified from a multicentric database of adult spinal deformities (ASD). Inclusion criteria were age >30 years, SVA > 40 mm and/or PT > 20°. All patients had full spine EOS radiographs in positions 1 and 2 (P1 and P2), in which the patient was asked to stand and put his hands on his shoulders without any effort (P1), or to make an effort to be as straight as possible (P2). PT, SVA and GT were measured in both positions and changes between P1 and P2 were calculated and compared using Student’s
t
test with significance level at
p
< 0.05.
Results
No significant changes were observed for GT; SVA and PT were significantly influenced by patient positioning. SVA decreased and PT increased for all cases in P2 whereas the changes in GT were in either direction. The average increase in PT was 7.1° (±5.4) or 30.8 % (±24.9); decrease in SVA was 45.1 mm (±25.6) or 60.0 % (±44.2) while the change in GT was 4.4° (±3.3) or 12.6 % (±9.3).
Discussion
GT appears to be less affected by the patient’s position compared to SVA and PT. This seems logical because GT contains both spinal alignment and pelvic compensation; it is not affected by their changes in opposing directions.
Conclusion
GT appears to be the most reliable single sagittal plane parameter in ASD. It is the least affected by patient position and incorporates both the pelvic and the spinal alignment within one measure.
Abstract Alpha-tubulin 4A encoding gene (TUBA4A) has been associated with familial amyotrophic lateral sclerosis (fALS) and fronto-temporal dementia (FTD), based on identification of likely ...pathogenic variants in patients from distinct ALS and FTD cohorts. By screening a multicentric French cohort of 448 unrelated probands presenting with cerebellar ataxia, we identified ultra-rare TUBA4A missense variants, all being absent from public databases and predicted pathogenic by multiple in-silico tools. In addition, gene burden analyses in the 100,000 genomes project (100KGP) showed enrichment of TUBA4A rare variants in the inherited ataxia group compared to controls (OR: 57.0847 10.2- 576.7; p = 4.02 x10-07). Altogether, we report 12 patients presenting with spasticity and/or cerebellar ataxia and harboring a predicted pathogenic TUBA4A missense mutation, including 5 confirmed de novo cases and a mutation previously reported in a large family presenting with spastic ataxia. Cultured fibroblasts from 3 patients harboring distinct TUBA4A missense showed significant alterations in microtubule organisation and dynamics, providing insight of TUBA4A variants pathogenicity. Our data confirm the identification of a hereditary spastic ataxia disease gene with variable age of onset, expanding the clinical spectrum of TUBA4A associated phenotypes.
Several strands of evidence question the dogma that human mitochondrial DNA (mtDNA) is inherited exclusively down the maternal line, most recently in three families where several individuals harbored ...a 'heteroplasmic haplotype' consistent with biparental transmission. Here we report a similar genetic signature in 7 of 11,035 trios, with allelic fractions of 5-25%, implying biparental inheritance of mtDNA in 0.06% of offspring. However, analysing the nuclear whole genome sequence, we observe likely large rare or unique nuclear-mitochondrial DNA segments (mega-NUMTs) transmitted from the father in all 7 families. Independently detecting mega-NUMTs in 0.13% of fathers, we see autosomal transmission of the haplotype. Finally, we show the haplotype allele fraction can be explained by complex concatenated mtDNA-derived sequences rearranged within the nuclear genome. We conclude that rare cryptic mega-NUMTs can resemble paternally mtDNA heteroplasmy, but find no evidence of paternal transmission of mtDNA in humans.
Purpose
Degenerative foraminal stenosis of the cervical spine can lead to cervicobrachial neuralgias. Computed tomography (CT)-scan assists in the diagnosis and evaluation of foraminal stenosis. The ...main objective of this study is to determine the bony dimensions of the cervical intervertebral foramen and to identify which foraminal measurements are most affected by degenerative disorders of the cervical spine. These data could be applied to the surgical treatment of this pathology, helping surgeons to focus on specific areas during decompression procedures.
Methods
A descriptive study was conducted between two groups: an asymptomatic one (young people with no evidence of degenerative cervical spine disorders) and a symptomatic one (experiencing cervicobrachial neuralgia due to degenerative foraminal stenosis). Using CT scans, we determined a method allowing measurements of the following foraminal dimensions: foraminal height (FH), foraminal length (FL), foraminal width in its lateral part ((UWPP, MWPP and IWPP (respectively Upper, Medial and Inferior Width of Pedicle Part)) and medial part (UWMP, MWMP and IWMP (respectively Upper, Medial and Inferior Width of Medial Part)), and disk height (DH). Foraminal volume (FV) was calculated considering the above data. Mean volumes were measured in the asymptomatic group and compared to the values obtained in the symptomatic group.
Results
Both groups were made up of 10 patients, and a total of 50 intervertebral discs (100 intervertebral foramina) were analyzed in each group. Comparison of C4C5, C5C6 and C6C7 levels between both groups showed several significant decreases in foraminal dimensions (
p
< 0.05) as well as in foraminal volume (
p
< 0.001) in the symptomatic group. The most affected dimensions were UWPP, MWPP, UWMP, MWMP and FV. The most stenotic foraminal areas were the top of the uncus and the posterior edge of the lower plate of the overlying vertebra.
Conclusion
Using a new protocol for measuring foraminal volume, the present study refines the current knowledge of the normal and pathological anatomy of the lower cervical spine and allows us to understand the foraminal sites most affected by degenerative stenosis. Those findings can be applied to foraminal stenosis surgeries. According to our results, decompression of the foramen in regard of both uncus osteophytic spurs and inferior plate of the overlying vertebra might be an important step for spinal nerves release.
Purpose
Objectives in scoliosis corrective surgery include restoration of normal sagittal and coronal parameters to achieve patient satisfaction. HRQLs improvements remain limited after corrective ...surgery. The aim of this study was to evaluate the HRQL subclass variability specific to the sagittal and coronal correction in adult scoliosis surgery.
Methods
This multi-centre prospective analysis of consecutive adult spinal deformity (ASD) patients, from five European centres, only included multilevel instrumentation for scoliosis. d-(delta) values for each parameter represented pre to post-operative changes. Parameters included demographics, baseline, 1- and 2-year. HRQL outcomes (Oswestry disability index (ODI), Scoliosis Research Society (SRS)-22 and Short Form (SF36)), sagittal correction including relative spinopelvic alignment (dRSA) and coronal correction including major Cobb (dCobb) angles.
Results
A total of 353 patients reached 1-year and 2-year follow up. All HRQL total scores significantly improved postoperatively, including ODI, SRS-22 and SF36. HRQL subclasses which displayed persistent improvements correlated to dRSA included sex-life, self-image, fatigue, vitality, social functioning. The only HRQL subclass improvement that correlated with dCobb was self-image.
Conclusion
Adult scoliosis surgery improves overall HRQL, having a minimal effect on each variable. Importantly, greater coronal deformity correction affects only greater self-image scores, whereas with greater sagittal correction there are many greater HRQL sub-class impacts. Correction and restoration of coronal balance is one of the surgical goals in adult scoliosis but the degree to which Cobb angle is corrected, apart from self-image, does not correlate with gains in sub-classes of HRQL. These results need to be taken into account when planning surgery.
Ocular coloboma arises from genetic or environmental perturbations that inhibit optic fissure (OF) fusion during early eye development. Despite high genetic heterogeneity, 70% to 85% of patients ...remain molecularly undiagnosed. In this study, we have identified new potential causative genes using cross-species comparative meta-analysis.
Evolutionarily conserved differentially expressed genes were identified through in silico analysis, with in situ hybridization, gene knockdown, and rescue performed to confirm spatiotemporal gene expression and phenotype. Interrogation of the 100,000 Genomes Project for putative pathogenic variants was performed.
Nine conserved differentially expressed genes between zebrafish and mouse were identified. Expression of zebrafish ank3a, bmpr1ba/b, cdh4, and pdgfaa was localized to the OF, periocular mesenchyme cells, or ciliary marginal zone, regions traversed by the OF. Knockdown of ank3, bmpr1b, and pdgfaa revealed a coloboma and/or microphthalmia phenotype. Novel pathogenic variants in ANK3, BMPR1B, PDGFRA, and CDH4 were identified in 8 unrelated coloboma families. We showed BMPR1B rescued the knockdown phenotype but variant messenger RNAs failed, providing evidence of pathogenicity.
We show the utility of cross-species meta-analysis to identify several novel coloboma disease-causing genes. There is a potential to increase the diagnostic yield for new and unsolved patients while adding to our understanding of the genetic basis of OF morphogenesis.
Cilia are highly specialized cellular organelles that serve multiple functions in human development and health. Their central importance in the body is demonstrated by the occurrence of a diverse ...range of developmental disorders that arise from defects of cilia structure and function, caused by a range of different inherited mutations found in more than 150 different genes. Genetic analysis has rapidly advanced our understanding of the cell biological basis of ciliopathies over the past two decades, with more recent technological advances in genomics rapidly accelerating this progress. The 100,000 Genomes Project was launched in 2012 in the UK to improve diagnosis and future care for individuals affected by rare diseases like ciliopathies, through whole genome sequencing (WGS). In this review we discuss the potential promise and medical impact of WGS for ciliopathies and report on current progress of the 100,000 Genomes Project, reviewing the medical, technical and ethical challenges and opportunities that new, large scale initiatives such as this can offer.
•The respective effects of direct and indirect decompression in the clinical outcome after anterior cervical disc fusion is still debated.•Increase in disc height is significantly associated with ...increase in foraminal height and foraminal volume.•Increase in foraminal height is significantly correlated with improvement in NDI score at 3 months post-surgery.•Indirect decompression results in increased foraminal volume and contributes to clinical improvement after anterior cervical disc fusion.
The respective effects of direct and indirect decompression in the clinical outcome after anterior cervical disc fusion (ACDF) is still debated. The main purpose of this study was to analyze the effects of indirect decompression on foraminal volumes during ACDF performed in patients suffering from cervico-brachial neuralgias due to degenerative foraminal stenosis, i.e. to determine whether implant height was associated with increased postoperative foraminal height and volume.
A prospective follow-up of patients who underwent ACDF for cervicobrachial neuralgias due to degenerative foraminal stenosis was conducted. Patient had performed a CT-scan pre and post-operatively. Disc height, foraminal heights and foraminal volumes were measured pre and post operatively.
37 cervical disc fusions were successfully performed in 20 patients, with a total of 148 foramina studied. Foraminal height and volume were measured bilaterally on the pre- and post-operative CT scans (148 foramina studied). After univariate analysis, it was found a significant improvement for every radiological parameter, with a significant increase in disc height, foraminal height and foraminal volume being respectively +3,22 mm (p < 0,001), +2,12 mm (p < 0,001) and +54 mm3 (p < 0,001). Increase in disc height was significantly associated with increase in foraminal height (p < 0,001) and foraminal volume (p < 0,001). At the same time, increase in foraminal height was significantly correlated with foraminal volume (p < 0,001), and seems to be the major component affecting increasing in foraminal volume.
Indirect decompression plays an important part in the postoperative foraminal volume increase after ACDF performed for cervicobrachial neuralgias.
Supercritically dried aerogels of several polysaccharides (chitin, chitosan, alginate, alginic acid, κ-carrageenan, and agar) have been characterised by physisorption of N
2. Surface areas as high as ...570
m
2
g
−1 have been measured. The nature of the functional groups of the polysaccharide significantly influences the adsorption of N
2 on the surface of the aerogel. The net enthalpy of adsorption increases with the polarity of the surface groups of the polymer, in the order chitin
<
agar
≤
chitosan
<
carrageenan
<
alginic acid
∼
alginate. The surface area and the mesopore distribution of the aerogels depend both on the dispersion of the parent hydrogel and on the behaviour of each polymer in the drying treatment. Aerogels which retain the dispersion of the parent hydrogel are mainly macroporous (pores larger than 50
nm) while materials liable to shrink upon solvent exchange form mesoporous structures.
Germline loss-of-function mutations in DEPDC5, and in its binding partners (NPRL2/3) of the mammalian target of rapamycin (mTOR) repressor GATOR1 complex, cause focal epilepsies and increase the risk ...of sudden unexpected death in epilepsy (SUDEP). Here, we asked whether DEPDC5 haploinsufficiency predisposes to primary cardiac defects that could contribute to SUDEP and therefore impact the clinical management of patients at high risk of SUDEP.
Clinical cardiac investigations were performed in 16 patients with pathogenic variants in DEPDC5, NPRL2, or NPRL3. Two novel Depdc5 mouse strains, a human HA-tagged Depdc5 strain and a Depdc5 heterozygous knockout with a neuron-specific deletion of the second allele (Depdc5
), were generated to investigate the role of Depdc5 in SUDEP and cardiac activity during seizures.
Holter, echocardiographic, and electrocardiographic (ECG) examinations provided no evidence for altered clinical cardiac function in the patient cohort, of whom 3 DEPDC5 patients succumbed to SUDEP and 6 had a family history of SUDEP. There was no cardiac injury at autopsy in a postmortem DEPDC5 SUDEP case. The HA-tagged Depdc5 mouse revealed expression of Depdc5 in the brain, heart, and lungs. Simultaneous electroencephalographic-ECG records on Depdc5
mice showed that spontaneous epileptic seizures resulting in a SUDEP-like event are not preceded by cardiac arrhythmia.
Mouse and human data show neither structural nor functional cardiac damage that might underlie a primary contribution to SUDEP in the spectrum of DEPDC5-related epilepsies. ANN NEUROL 2022;91:101-116.
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