-
Neurology. Genetics Jun 2024Spinocerebellar ataxia type 3 (SCA3) is a hereditary ataxia that occurs worldwide. Clinical patterns were observed, including the one characterized by marked spastic...
BACKGROUND AND OBJECTIVES
Spinocerebellar ataxia type 3 (SCA3) is a hereditary ataxia that occurs worldwide. Clinical patterns were observed, including the one characterized by marked spastic paraplegia. This study investigated the clinical features, disease progression, and multiparametric imaging aspects of patients with SCA3.
METHODS
We retrospectively analyzed 249 patients with SCA3 recruited from the Organization for Southeast China for cerebellar ataxia research between October 2014 and December 2020. Of the 249 patients, 145 were selected and assigned to 2 groups based on neurologic examination: SCA3 patients with spastic paraplegia (SCA3-SP) and SCA3 patients with nonspastic paraplegia (SCA3-NSP). Participants underwent 3.0-T brain MRI examinations, and voxel-wise and volume-of-interest-based approaches were used for the resulting images. A tract-based spatial statistical approach was used to investigate the white matter (WM) alterations using diffusion tensor imaging, neurite orientation dispersion, and density imaging metrics. Multiple linear regression analyses were performed to compare the clinical and imaging parameters between the 2 groups. The longitudinal data were evaluated using a linear mixed-effects model.
RESULTS
Forty-three patients with SCA3-SP (mean age, 37.58years ± 11.72 [SD]; 18 women) and 102 patients with SCA3-NSP (mean age, 47.42years ± 12.50 [SD]; 39 women) were analyzed. Patients with SCA3-SP were younger and had a lower onset age but a larger cytosine-adenine-guanine repeat number, as well as higher clinical severity scores (all corrected < 0.05). The estimated progression rates of the Scale for the Assessment and Rating of Ataxia (SARA) and International Cooperative Ataxia Rating Scale scores were higher in the SCA3-SP subgroup than in the SCA3-NSP subgroup (SARA, 2.136 vs 1.218 points; ICARS, 5.576 vs 3.480 points; both < 0.001). In addition, patients with SCA3-SP showed gray matter volume loss in the precentral gyrus with a decreased neurite density index in the WM of the corticospinal tract and cerebellar peduncles compared with patients with SCA3-NSP.
DISCUSSION
SCA3-SP differs from SCA3-NSP in clinical features, multiparametric brain imaging findings, and longitudinal follow-up progression.
PubMed: 38841628
DOI: 10.1212/NXG.0000000000200162 -
Surgical Neurology International 2024Congenital, acquired, and iatrogenic spinal epidermoid cysts (EC) are very rare.
BACKGROUND
Congenital, acquired, and iatrogenic spinal epidermoid cysts (EC) are very rare.
METHODS
A 62-year-old female patient presented with a 5-month history of progressive paraparesis leading to paraplegia secondary to a posterior compressive intradural extramedullary lesion at the T7 level. The patient underwent a laminectomy/durotomy for gross total tumor excision.
RESULTS
Histopathology confirmed the lesion was an epidermoid cyst. Although her spasticity improved within 5 weeks, she only regained partial lower extremity motion (i.e., 3/5 motor function).
CONCLUSION
Patients presenting with the acute/subacute onset of paraparesis secondary to spinal EC should undergo timely gross total cyst resections to optimize neurological outcomes.
PubMed: 38840622
DOI: 10.25259/SNI_280_2024 -
Annals of Clinical and Translational... Jun 2024Krabbe disease (KD) is a multisystem neurodegenerative disorder with severe disability and premature death, mostly with an infancy/childhood onset. In rare cases of...
OBJECTIVE
Krabbe disease (KD) is a multisystem neurodegenerative disorder with severe disability and premature death, mostly with an infancy/childhood onset. In rare cases of late-onset phenotypes, symptoms are often milder and difficult to diagnose. We here present a translational approach combining diagnostic and biochemical analyses of a male patient with a progressive gait disorder starting at the age of 44 years, with a final diagnosis of late-onset KD (LOKD).
METHODS
Additionally to cerebral MRI, protein structural analyses of the β-galactocerebrosidase protein (GALC) were performed. Moreover, expression, lysosomal localization, and activities of β-glucocerebrosidase (GCase), cathepsin B (CTSB), and cathepsin D (CTSD) were analyzed in leukocytes, fibroblasts, and lysosomes of fibroblasts.
RESULTS
Exome sequencing revealed biallelic likely pathogenic variants: GALC exons 11-17: 33 kb deletion; exon 4: missense variant (c.334A>G, p.Thr112Ala). We detected a reduced GALC activity in leukocytes and fibroblasts. While histological KD phenotypes were absent in fibroblasts, they showed a significantly decreased activities of GCase, CTSB, and CTSD in lysosomal fractions, while expression levels were unaffected.
INTERPRETATION
The presented LOKD case underlines the age-dependent appearance of a mildly pathogenic GALC variant and its interplay with other lysosomal proteins. As GALC malfunction results in reduced ceramide levels, we assume this to be causative for the here described decrease in CTSB and CTSD activity, potentially leading to diminished GCase activity. Hence, we emphasize the importance of a functional interplay between the lysosomal enzymes GALC, CTSB, CTSD, and GCase, as well as between their substrates, and propose their conjoined contribution in KD pathology.
PubMed: 38837642
DOI: 10.1002/acn3.52078 -
Annals of Clinical and Translational... Jun 2024TFG mutations have previously been implicated in autosomal recessive hereditary spastic paraplegia (HSP), also known as SPG57. This study aimed to investigate the...
OBJECTIVE
TFG mutations have previously been implicated in autosomal recessive hereditary spastic paraplegia (HSP), also known as SPG57. This study aimed to investigate the clinical and molecular features of TFG mutations in a Taiwanese HSP cohort.
METHODS
Genetic analysis of TFG was conducted in 242 unrelated Taiwanese HSP patients using a targeted resequencing panel covering the entire coding regions of TFG. Functional assays were performed using an in vitro cell model to assess the impact of TFG variants on protein function. Additionally, other representative TFG mutant proteins were examined to understand the broader implications of TFG mutations in HSP.
RESULTS
The study identified a novel homozygous TFG c.177A>C (p.(Lys59Asn)) variant in a family with adolescent-onset, pure form HSP. Functional analysis revealed that the Lys59Asn TFG variant, similar to other HSP-associated TFG mutants, exhibited a low affinity between TFG monomers and abnormal assembly of TFG homo-oligomers. These structural alterations led to aberrant intracellular distribution, compromising TFG's protein secretion function and resulting in decreased cellular viability.
INTERPRETATION
These findings confirm that the homozygous TFG c.177A>C (p.(Lys59Asn)) variant is a novel cause of SPG57. The study expands our understanding of the clinical and mutational spectrum of TFG-associated diseases, highlighting the functional defects associated with this specific TFG variant. Overall, this research contributes to the broader comprehension of the genetic and molecular mechanisms underlying HSP.
PubMed: 38837630
DOI: 10.1002/acn3.52113 -
Alternative Therapies in Health and... Jun 2024To explore the recovery effect of acupuncture combined with rehabilitation therapy on muscle spasms in patients with spinal cord injury through a systematic review of...
OBJECTIVE
To explore the recovery effect of acupuncture combined with rehabilitation therapy on muscle spasms in patients with spinal cord injury through a systematic review of meta-analysis methods.
METHODS
Use "acupuncture," "electronic-acupuncture," "spinal cord," "spasm," and "paraplegia" as keywords, CNKI, Google, Wanfang, VIP, sci-hub, Web of Science, PubMed, and other Chinese or English databases were searched. To collect the domestic and foreign research on acupuncture combined with rehabilitation for muscle spasms in patients with spinal cord injury. Preliminary screening was conducted, and data extraction and quality evaluation were carried out on the included literature, including publication time, sample size, treatment methods, recovery effects, etc. According to the literature, the influence of acupuncture combined with rehabilitation therapy on muscle spasms in patients with spinal cord injury and related indices was analyzed. The search period was from January 2018 to June 2023, and the selected research results were tested by RevMan5.3 software and data consolidation for consistency. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS).
RESULTS
A preliminary literature search yielded 172 papers. 53 papers from sci-hub, 71 papers from HowNet, 36 papers from Wanfang, and 12 papers from VIP. Finally, 10 articles that met the criteria were included, including 594 patients. According to different treatment methods, the literature about acupuncture combined with rehabilitation therapy for muscle spasms in patients with spinal cord injury was analyzed for consistency, and data were merged. It was concluded that acupuncture combined with rehabilitation The clinical curative effect of the experimental group of patients is higher than that of the control group MD=5.31, 95%CI (2.94, 7.81), Z=5.64, P < .001; the clinical effective rate of the experimental group is higher than that of the control group. The improvement of the clinical spasticity index (CSI) score index of the patients in the experimental group was better than that of the control group MD = -3.09, 95%CI (-4.51, -1.67), Z =4.28, P < .001; the MAS score of the patients in the experimental group The improvement was better than that of the control group MD =-0.76, 95%CI (-1.16, -0.38), Z=8.13, P < .001; the improvement of Barthel index (BI) in the experimental group was better than that of the control group MD=9.81, 95%CI (7.84,11.71), Z=12.71, P < .001; no adverse events were reported in the experimental group and the control group.
CONCLUSION
This study shows that acupuncture and rehabilitation are more effective than other therapeutic methods in the treatment of muscle spasms after spinal cord injury, and more randomized controlled trials are needed to verify this in the future.
PubMed: 38836735
DOI: No ID Found -
Frontiers in Surgery 2024Pyogenic vertebral osteomyelitis (VO) represents a clinical challenge and is linked to substantial morbidity and mortality. This study aimed to examine mortality as well...
BACKGROUND
Pyogenic vertebral osteomyelitis (VO) represents a clinical challenge and is linked to substantial morbidity and mortality. This study aimed to examine mortality as well as potential risk factors contributing to in-hospital mortality among patients with VO.
METHODS
This retrospective analysis involved patients receiving treatment for VO at University Regensburg in Germany from January 1, 2000, to December 3, 2020. It included in-hospital mortality rate, comorbidities and pathogens. Patients were identified using ICD-10 diagnosis codes: M46.2, M46.3, M46.4, and M46.5. Kaplan-Meier probability plots and odds ratios (OR) for mortality were calculated.
RESULTS
Out of the total cohort of 155 patients with VO, 53 patients (34.1%) died during a mean follow-up time of 87.8 ± 70.8 months. The overall mortality was 17.2% at one year, 19.9% at two years and 28.3% at five years. Patients with congestive heart failure ( = 0.005), renal disease ( < 0.001), symptoms of paraplegia ( = 0.029), and sepsis ( = 0.006) demonstrated significantly higher overall mortality rates. In 56.1% of cases, pathogens were identified, with and other unidentified pathogens being the most common. Renal disease (OR 1.85) and congestive heart failure (OR 1.52) were identified as significant risk factors.
CONCLUSION
Early assessment of the specific risk factors for each patient may prove beneficial in the management and treatment of VO to reduce the risk of mortality. These findings demonstrate the importance of close monitoring of VO patients with underlying chronic organ disease and early identification and treatment of sepsis. Prioritizing identification of the exact pathogens and antibiotic sensitivity testing can improve outcomes for patients in this high-risk group.
PubMed: 38835852
DOI: 10.3389/fsurg.2024.1357318 -
European Journal of Cardio-thoracic... Jun 2024The aim of this multicentre study was to demonstrate the safety and clinical performance of E-vita OPEN NEO Stent Graft System (Artivion, Inc.) in the treatment of... (Observational Study)
Observational Study
OBJECTIVES
The aim of this multicentre study was to demonstrate the safety and clinical performance of E-vita OPEN NEO Stent Graft System (Artivion, Inc.) in the treatment of aneurysm or dissection, both acute and chronic, in the ascending aorta, aortic arch and descending thoracic aorta.
METHODS
In this observational study of 12 centres performed in Europe and in Asia patients were enrolled between December 2020 and March 2022. All patients underwent frozen elephant trunk using E-vita OPEN NEO Stent Graft System. Primary end point was the rate of all-cause mortality at 30 days and secondary end points included further clinical and safety data are reported up to 3-6 months postoperatively.
RESULTS
A total of 100 patients (66.7% male; mean age, 57.7 years) were enrolled at 12 sites. A total of 99 patients underwent surgery using the E-vita OPEN NEO for acute or subacute type A aortic dissection (n = 37), chronic type A aortic dissection (n = 33) or thoracic aortic aneurysm (n = 29), while 1 patient did not undergo surgery. Device technical success at 24 h was achieved in 97.0%. At discharge, new disabling stroke occurred in 4.4%, while new paraplegia and new paraparesis was reported in 2.2% and 2.2%, respectively. Renal failure requiring permanent (>90 days) dialysis or hemofiltration at discharge was observed in 3.3% of patients. Between discharge and the 3-6 months visit, no patients experienced new disabling stroke, new paraplegia or new paraparesis. The 30-day mortality was 5.1% and the estimated 6-month survival rate was 91.6% (standard deviation: 2.9).
CONCLUSIONS
Total arch replacement with the E-vita OPEN NEO can be performed with excellent results in both the acute and chronic setting. This indicates that E-vita OPEN NEO can be used safely, including in the setting of acute type A aortic dissection.
Topics: Humans; Male; Female; Middle Aged; Aortic Dissection; Aortic Aneurysm, Thoracic; Aged; Blood Vessel Prosthesis Implantation; Chronic Disease; Stents; Acute Disease; Blood Vessel Prosthesis; Treatment Outcome; Aorta, Thoracic; Postoperative Complications; Europe; Adult; Endovascular Procedures
PubMed: 38830042
DOI: 10.1093/ejcts/ezae206 -
Journal of Surgical Case Reports Jun 2024We present a 20-year-old patient with subglottic and tracheal stenosis was taken for a tracheal resection and end-to-end anastomosis. The patient's neck was positioned...
We present a 20-year-old patient with subglottic and tracheal stenosis was taken for a tracheal resection and end-to-end anastomosis. The patient's neck was positioned in hyperflexion using chin stitches to minimize tension at the anastomosis. On post-operative period, the patient developed paresthesias in upper and lower extremities associated with motor weakness. Magnetic resonance imaging was performed showing lesions compromising ventral spinal cord at the level of C4-C5 and C6-C7. Chin stitches were removed and neck flexion was reduced. The patient remained in the intensive care unit with vasopressors, physical therapy and intravenous fluid-therapy to maintain mean arterial pressure above 90 mmHg. After 3 weeks, the patient was discharged with no neurologic deficit. There are few cases reported of acute ischemic spinal injury following tracheal reconstruction. If this complication arises, neck posture should be corrected, maintenance of MAP above 90 mmHg and implementation of early physical therapy is key to improve neurologic outcomes.
PubMed: 38828406
DOI: 10.1093/jscr/rjae253 -
Cureus May 2024More than 100% of the traumatic subluxation of one vertebral body over another in the coronal or sagittal plane is known as traumatic spondyloptosis, which typically...
More than 100% of the traumatic subluxation of one vertebral body over another in the coronal or sagittal plane is known as traumatic spondyloptosis, which typically results in the contusion of the spinal cord. It is an uncommon yet severe spinal column injury. Here, we present traumatic lumbosacral spondyloptosis at the L5 and S1 levels with complete spinal cord compression with paraplegia and bowel and bladder involvement. The patient underwent posterior spinal fusion (delta fixation) and decompression. The patient improved his motor and sensory deficits at one-month follow-up. By the eighth-month follow-up, the patient had recovered entirely from his motor and sensory deficits and was stable for the entire year.
PubMed: 38826881
DOI: 10.7759/cureus.59494 -
American Journal of Surgery May 2024The optimal cannulation strategy for patients with acute type A aortic dissections (ATAAD) is unclear. (Review)
Review
OBJECTIVE
The optimal cannulation strategy for patients with acute type A aortic dissections (ATAAD) is unclear.
METHODS
A systematic search was performed to identify all studies comparing aortic and non-aortic cannulation in patients undergoing ATAAD repair. The primary endpoint was overall survival. The secondary endpoints were operative mortality, postoperative stroke, renal failure, renal replacement therapy, paraplegia, and mesenteric ischemia. Pooled meta-analyses with aggregated and reconstructed time-to-event data were performed.
RESULTS
Twenty-three studies were included (aortic: 3904; non-aortic: 10,719). Ten-year overall survival was 61.1 % and 58.4 % for aortic and non-aortic cannulation, respectively (HR 1.07; 95 % CI 0.92-1.25; p = 0.38). No statistically significant difference was observed for operative mortality (p = 0.10), stroke (p = 0.89), renal failure (p = 0.83), or renal replacement therapy (p = 0.77).
CONCLUSION
Patients undergoing surgery for ATAAD can undergo aortic cannulation with similar outcomes to those who undergo non-aortic cannulation.
PubMed: 38825544
DOI: 10.1016/j.amjsurg.2024.115780