Lumbar Spine Abnormalities in Patients With Obstructive Sleep Apnoea

Previous studies suggested cervical spondylosis as a risk factor for development of obstructive sleep apnoea (OSA). We aimed to assess lumbar disc degeneration in patients with OSA and correlate the findings with symptoms and disease severity. Twenty-seven patients with OSA and 29 non-OSA controls underwent sleep studies and lumbar magnetic resonance imaging (MRI), and completed the Epworth Sleepiness Scale and the 24-item Roland‐Morris Disability Questionnaire questionnaires. Plasma klotho was determined with enzyme-linked immunosorbent assay.Patients with OSA had higher number of disc bulges (4.6±3.7 vs. 1.7±2.5, p<0.01) and anterior spondylophytes (2.7±4.2 vs. 0.8±2.1, p<0.01), increased Pfirrmann score (16.7±4.7 vs. 13.2±4.1, p<0.01) and vertebral fatty degeneration (7.8±4.7 vs. 3.8±3.7, p<0.01). Markers of OSA severity, including the apnoea-hypopnoea index, oxygen desaturation index and percentage of total sleep time spent with saturation <90% as well as plasma levels of klotho were correlated with the number of disc bulges and anterior spondylophytes following adjustment on age, gender and body mass index (all p<0.05). Markers of disc degeneration were related to chronic pain.OSA is associated with lumbar spondylosis likely through chronic intermittent hypoxaemia inducing inflammation in the lumbar discs. Our study highlights the importance of lumbar imaging in patients with OSA reporting lower back pain.

Lumbar spine abnormalities and facet joint angles in asymptomatic elite junior tennis players

Background Lumbar spine abnormalities, in particular stress fractures to the pars interarticularis, are common in elite junior tennis players, though the difference in prevalence between males and females remains unclear. Further, facet joint orientation appears to be a possible option for recognizing which players might go on to present with a pars stress fracture. Given the link between pars stress fractures and low back pain in tennis players, it appears logical to explore the link between facet joint angle and pars abnormalities. Thus, the purpose of this study was to describe the prevalence of lumbar spine abnormalities and explore the relationship between facet joint orientation and pars abnormalities in elite adolescent tennis players. Methodology Lumbar spine MRI images of 25 elite junior tennis players were obtained and distributed between five radiologists for analysis. Descriptive comparisons and confidence intervals were used to describe the prevalence of the abnormalities. A generalized linear regression model was conducted to investigate the relationship between lumbar pars abnormalities and lumbar facet joint angles. Results Sixteen (64%) of 25 players were found to have at least one lumbar spine abnormality. Pars abnormalities affected 36% of players while bone marrow edema was found in 24% of players. Disc herniation, disc degeneration, and facet joint degeneration were diagnosed in 20%, 44%, and 24% of players respectively. Lastly, one player (4%) was diagnosed with spondylolisthesis. Females had significantly larger facet joint angles across L3/4 L5/S1 compared to males (p < 0.01). Further, those who had pars abnormalities had larger facet joint angles compared to those who did not (p < 0.001). Conclusion Disc degeneration, pars abnormalities, including bone marrow edema, and facet joint degeneration were common findings among elite adolescent tennis players. Additionally, this study is the first to discover that pars abnormalities are linked to facet joint angle in elite adolescent tennis players. This finding might assist in identifying tennis players at a greater risk of developing lumbar spine pars abnormalities in the future.

Headache in a Child with Pseudohypoparathyroidism: An Alarming Symptom Not to Miss

Background. While the endocrine manifestations of pseudohypoparathyroidism are well known, less is known about the associated brain and spine abnormalities. These abnormalities may present with nonspecific symptoms in the paediatric population, and lack of awareness to these uncommon manifestations of the disease may result in a delay in necessary intervention. Case Presentation. We herein present a case of known pseudohypoparathyroidism type 1a who presented initially with minor head injury. She later developed progressive worsening headache, increased irritability, and vomiting. Repeated imaging showed hydrocephalus and Chiari malformation type 1 necessitating emergency craniectomy. Conclusion. Growth hormone deficiency, a common manifestation of pseudohypoparathyroidism type 1a, results in underdevelopment of the posterior cranial fossa and may account for the higher incidence of Chiari malformation in this group of patients. Other associated neurological features reported in pseudohypoparathyroidism type 1a include spinal stenosis, syringomyelia, and craniosynostosis. While less commonly seen, awareness to these associations is important in order to optimize the multidisciplinary care to this group of patients.

SAK3 Administration Improves Spine Abnormalities and Cognitive Deficits in AppNL-G-F/NL-G-F Knock-in Mice by Increasing Proteasome Activity through CaMKII/Rpt6 Signaling

Alzheimer’s disease (AD) is the most common form of dementia and is characterized by neuropathological hallmarks consisting of accumulation of extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles (NFT). Recently, we have identified a new AD therapeutic candidate, ethyl-8′-methyl-2′,4-dioxo-2-(piperidin-1-yl)-2′H-spiro[cyclopentane-1,3′-imidazo [1,2-a] pyridin]-2-ene-3-carboxylate (SAK3), which ameliorates the AD-like pathology in AppNL-F/NL-F knock-in mice. However, the detailed mechanism underlying the therapeutic effects of SAK3 remains unclear. In this study, we found that SAK3 administration improved the reduced proteasome activity through the activation of CaMKII/Rpt6 signaling in AppNL-F/NL-F knock-in (NL-G-F) mice. Moreover, spine abnormalities observed in NL-G-F mice were significantly reversed by SAK3 administration. Along with this, cognitive impairments found in NL-G-F mice were markedly ameliorated by SAK3. In summary, our data suggest that SAK3 administration increases the activity of the proteasome via activation of the CaMKII/Rpt6 signaling pathway, contributing to improvements in spine abnormalities and cognitive deficits in NL-G-F mice. Overall, our findings suggest that SAK3 might be a new attractive drug candidate, representing a new mechanism for the treatment of AD pathology.

Knockdown of Son, a mouse homologue of the ZTTK syndrome gene, causes neuronal migration defects and dendritic spine abnormalities.

Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome, a rare congenital anomaly syndrome characterized by intellectual disability, brain malformation, facial dysmorphism, musculoskeletal abnormalities, and some visceral malformations is caused by de novo heterozygous mutations of the SON gene. The nuclear protein SON is involved in gene transcription and RNA splicing; however, the roles of SON in neural development remain undetermined. We investigated the effects of Son knockdown on neural development in mice and found that Son knockdown in neural progenitors resulted in defective migration during corticogenesis and reduced spine density on mature cortical neurons. The induction of human wild-type SON expression rescued these neural abnormalities, confirming that the abnormalities were caused by SON insufficiency. We also applied truncated SON proteins encoded by disease-associated mutant SON genes for rescue experiments and found that a truncated SON protein encoded by the most prevalent SON mutant found in ZTTK syndrome rescued the neural abnormalities while another much shorter mutant SON protein did not. These data indicate that SON insufficiency causes neuronal migration defects and dendritic spine abnormalities, which seem neuropathological bases of the neural symptoms of ZTTK syndrome. In addition, the results support that the neural abnormalities in ZTTK syndrome are caused by SON haploinsufficiency independent of the types of mutation that results in functional or dysfunctional proteins.