A Rare Case of Postpartum Paraplegia: A Case Report.

In this case report, a 27-year-old woman who had pre-eclampsia in the past and had a cesarean section as a result of the condition presents with an uncommon and difficult form of postpartum paraplegia. She experienced bilateral lower limb paralysis and urine incontinence soon after the surgery, which quickly led to unconsciousness and required mechanical ventilator support and intensive care treatment. Comprehensive diagnostic testing, which included magnetic resonance imaging scans of the brain and spinal cord, identified signs typical of "Posterior Reversible Encephalopathy Syndrome (PRES)" and spinal cord infarction affecting segments C3 to D2. "Antiphospholipid Antibody Syndrome (APLA)" was identified by laboratory testing, highlighting the significance of taking a thorough approach to comprehending this uncommon clinical condition. Treatment included anticoagulant therapy, high-dose steroid therapy, and antihypertensive drugs, emphasizing the crucial importance of inter-disciplinary care in handling such complex situations. Even if the patient's symptoms have partially improved, their condition is still being closely monitored in the intensive care unit. In the context of postpartum neurological problems and the complex interplay between pre-eclampsia, spinal cord infarction, and related clinical symptoms, this case emphasizes the need for increased awareness and prompt management.

Apprehension of Paraplegia after Undergoing Spinal Anesthesia in the Central Region Population of Saudi Arabia: A Cross-Sectional Study.

Aim: The aim of the present study was to determine the prevalence of paraplegia-related fear in spinal anesthesia among the general population in the central region of Saudi Arabia. Materials and Methods: A total of 371 participants were given a pretested, precoded, questionnaire was used to collect data to assess the prevalence of fear of paraplegia in spinal anesthesia. The questionnaire contained questions to assess variables like the extent of fear, causes, gender preponderance, any false information about paraplegia in spinal anesthesia, and complications experienced after receiving spinal anesthesia. Results: It was noted that 80.1% of the respondents were familiar with the term spinal/regional/epidural anesthesia. Forty one point eight percent of the respondents their reference of knowledge about regional anesthesia was family of friends. Thirteen point nine percent of the responses were paralysis, 8.2% of the responses were feeling of pain during the operation, and 7.9% of the responses were nausea or vomiting. Conclusion: The present study revealed that the participants exhibited a certain degree of apprehension stemming from their inadequate understanding and awareness regarding spinal anesthesia.

Acute Paraplegia Caused by Spinal Epidural Empyema Following Infectious Cellulitis of the Hand: Case Report and Literature Review.

Background Spinal epidural abscess is a rare but serious condition that can cause spinal cord compression and neurological deficits. Case Description and Methods The article reports a case of a 31-year-old patient who presented with an infectious cellulitis in the left hand, which progressed to a spinal epidural abscess. The diagnosis was confirmed by clinical examination and magnetic resonance imaging. Treatment involved laminectomy, after which the patient had complete recovery of neurological deficits. This article is a case report with a literature review. Patient data and images were collected by the researchers who participated in the patient's care. The literature was reviewed by one of the researchers based on the search for articles in the PubMed database. For the research, the following keywords were inserted: "Spinal epidural empyema," "Spinal epidural abscess." Conclusion Spinal epidural abscess is often underdiagnosed, which can lead to delays in treatment and serious complications. The relationship between cellulitis and spinal epidural abscess may be related to the spread of infection through the lymphatic or blood system.

KCNJ3 is a novel candidate gene for autosomal dominant pure hereditary spastic paraplegia identified using whole genome sequencing.

Hereditary spastic paraplegia (HSP) is a group of familial diseases characterized by progressive corticospinal tract degeneration. Clinically, patients present with lower-limb spasticity and weakness. To date, more than 80 genetic HSP types have been identified. Despite advances in molecular genetics, novel HSP gene discoveries are ongoing, with a low genetic diagnostic yield. In this study, we aimed to determine pathogenic variants in a family with HSP, which was not diagnosed through conventional genetic testing. We clinically characterized a large family and conducted whole genome sequencing (WGS) analysis of four affected and three unaffected individuals in the family to identify the genetic cause of HSP. This family had autosomal dominant pure (uncomplicated) late childhood-onset HSP. The patients' symptoms accelerated between the ages of 20 and 30. Brain magnetic resonance images typically showed white matter changes, a thin corpus callosum, and cerebellar atrophy. We identified a heterozygous missense variant, KCNJ3 c.1297T>G (p.Leu433Val), through WGS and family genetic analysis, confirmed by Sanger sequencing. We suggest that the identification of KCNJ3 c.1297T>G (p.Leu433Val) constitutes the discovery of a potential novel gene responsible for HSP in this family. This is the first study to report the possible role of a KCNJ3 variant in HSP pathogenesis. Our findings further expand the phenotypic and genotypic spectrum of HSP.

Spinal Cord Infarction Thrombolysed at Seven Hours: A Case Report and Review of Literature.

We report a case of acute spinal cord infarction treated with intravenous (IV) thrombolysis at seven hours from symptom onset. Nineteen previously thrombolysed cases are reviewed. The patient underwent a clinical assessment, followed by an MRI of the spine. He was thrombolysed with a recombinant tissue plasminogen activator. Neurological severity was assessed at presentation and 24 hours using the National Institute of Health Stroke Scale (NIHSS), and disability at three months was evaluated using a modified Rankin scale (mRS). A middle-aged man presented with acute-onset paraplegia (NIHSS 9). MRI with T2-weighted sagittal, axial, and diffusion-weighted images showed hyperintensity from D10 to LI vertebral levels. He was thrombolysed at 428 minutes, leading to mild clinical improvement at 24 hours (NIHSS 7). At three months, he could walk with support (mRS 3). Nineteen cases of acute spinal cord infarction treated with IV thrombolysis have been reported. Clinical outcome at three months is available for 16 patients: seven (44%) had a good outcome (mRS 0-2); this is the first reported case of spinal cord infarction treated with thrombolysis at seven hours. Clinical trials to confirm the efficacy and safety of thrombolysis in spinal cord infarcts are needed.

Thoracic spinal cord injury after surgical removal of a ruptured cerebellar arteriovenous malformation in a patient in the Concorde position: illustrative case.

BACKGROUND: Thoracic spinal cord injury after posterior cranial fossa surgery in younger patients is a rare complication. There have been reports of this complication in tumor and spine fields but not in vascular surgery. OBSERVATIONS: A 22-year-old-man experienced cerebellar arteriovenous malformation rupture, and the malformation was surgically removed with the man in the Concorde position. After surgery, the man had severe paraplegia, and a thoracic spinal cord injury was diagnosed. LESSONS: In younger patients, cervical hyperflexion in the Concorde position can cause thoracic spinal cord injury even in surgery for cerebrovascular disease.

Selenoprotein I is indispensable for ether lipid homeostasis and proper myelination.

Selenoprotein I (SELENOI) catalyzes the final reaction of the CDP-ethanolamine branch of the Kennedy pathway, generating the phospholipids phosphatidylethanolamine (PE) and plasmenyl-PE. Plasmenyl-PE is a key component of myelin and is characterized by a vinyl ether bond that preferentially reacts with oxidants, thus serves as a sacrificial antioxidant. In humans, multiple loss-of-function mutations in genes affecting plasmenyl-PE metabolism have been implicated in hereditary spastic paraplegia, including SELENOI. Herein, we developed a mouse model of nervous system-restricted SELENOI deficiency that circumvents embryonic lethality caused by constitutive deletion and recapitulates phenotypic features of hereditary spastic paraplegia. Resulting mice exhibited pronounced alterations in brain lipid composition, which coincided with motor deficits and neuropathology including hypomyelination, elevated reactive gliosis, and microcephaly. Further studies revealed increased lipid peroxidation in oligodendrocyte lineage cells and disrupted oligodendrocyte maturation both in vivo and in vitro. Altogether, these findings detail a critical role for SELENOI-derived plasmenyl-PE in myelination that is of paramount importance for neurodevelopment.

Value and Limitations of Urethrotech Catheterisation Device to Manage Difficult Urethral Catheterisation in Male Spinal Cord Injury Patients.

Methods: We used a Urethrotech catheterisation device in 57 male patients with spinal cord injury, in whom urethral catheterisation was unsuccessful or previous catheterisation was difficult. Results: Urethrotech catheter could be inserted in 51 patients. No patient developed urinary tract infection. In one patient, the guidewire could not be introduced into the bladder, and a coude Foley catheter was inserted. In two patients, the guidewire was inserted into the bladder, but a 16 CH catheter could not be advanced over the guidewire. Emergency suprapubic cystostomy was performed in one case; in the other, urethral stricture was dilated; a size 12 CH catheter was inserted. In three patients, the guidewire curled back into the urethra because of severe spasm of the urethral sphincter. Catheterisation with a Tiemann catheter was successful after administration of diazepam and/or stretching of the anal sphincter by another health professional, which caused reflex relaxation of the urethral sphincter. Complications of Urethrotech catheterisation included urethral bleeding, haematuria, pain, doubling back of the guidewire due to spasm of the urethral sphincter or from an empty bladder. We adopted variations in technique, eg filling the bladder with saline prior to catheterisation when feasible, insertion of the guidewire by the side of the old catheter, use of Tiemann tip catheters, administration of antibiotics, diazepam to control spasms, nifedipine to control autonomic dysreflexia, analgesics, stretching of the anal sphincter to induce reflex relaxation of the urethral sphincter, urgent imaging studies to confirm correct positioning of the catheter, omitting anticoagulants and monitoring patients, who developed bleeding. Conclusion: Use of Urethrotech in spinal injury patients warranted adaptations to the technique, which required expertise, experience, and backup facilities. To ensure patient safety, Urethrotech catheter should be used in a hospital setting, and by medical personnel with experience in the management of spinal cord injury patients.

Improving shoulder function and pain in a paraplegic patient with massive irreparable rotator cuff tear using a subacromial balloon spacer.

The subacromial balloon spacer is a promising treatment option for alleviating symptoms in patients with massive irreparable rotator cuff tears (MIRCTs). The balloon provides faster pain relief and easier rehabilitation than other options (such as arthroscopic partial rotator cuff repair). For a paraplegic MIRCT patient, the need for speedy recovery and rehabilitation is crucial, as these patients rely on their upper limbs for daily life activities and independence. In this report, we present a 60-year-old male paraplegic patient who presented to the clinic with an MIRCT of the right shoulder. After a holistic investigation and assessment of the patient, a subacromial balloon spacer with an upper border subscapularis repair was chosen as the treatment of choice. The patient had an uneventful recovery, and at the 1-year mark, had forward elevation of 170°, an American Shoulder and Elbow Surgeons score of 95, and a visual analogue scale pain score of 0.

Expanding SPG18 clinical spectrum: autosomal dominant mutation causes complicated hereditary spastic paraplegia in a large family.

BACKGROUND: SPG18 is caused by mutations in the endoplasmic reticulum lipid raft associated 2 (ERLIN2) gene. Autosomal recessive (AR) mutations are usually associated with complicated hereditary spastic paraplegia (HSP), while autosomal dominant (AD) mutations use to cause pure SPG18. AIM: To define the variegate clinical spectrum of the SPG18 and to evaluate a dominant negative effect of erlin2 (encoded by ERLIN2) on oligomerization as causing differences between AR and AD phenotypes. METHODS: In a four-generation pedigree with an AD pattern, a spastic paraplegia multigene panel test was performed. Oligomerization of erlin2 was analyzed with velocity gradient assay in fibroblasts of the proband and healthy subjects. RESULTS: Despite the common p.V168M mutation identified in ERLIN2, a phenoconversion to amyotrophic lateral sclerosis (ALS) was observed in the second generation, pure HSP in the third generation, and a complicated form with psychomotor delay and epilepsy in the fourth generation. Erlin2 oligomerization was found to be normal. DISCUSSION: We report the first AD SPG18 family with a complicated phenotype, and we ruled out a dominant negative effect of V168M on erlin2 oligomerization. Therefore, our data do not support the hypothesis of a relationship between the mode of inheritance and the phenotype, but confirm the multifaceted nature of SPG18 on both genetic and clinical point of view. Clinicians should be aware of the importance of conducting an in-depth clinical evaluation to unmask all the possible manifestations associated to an only apparently pure SPG18 phenotype. We confirm the genotype-phenotype correlation between V168M and ALS emphasizing the value of close follow-up.

Late-onset Kjellin syndrome: Diagnosis of SPG11 on fundus examination.

INTRODUCTION: Spastic paraplegia (SPG) is a heterogenous group of neurodegenerative disorders, that may include ocular involvement. Here we report the clinical data of a patient with late-onset Kjellin syndrome, a peculiar form of hereditary SPG with macular dystrophy. MATERIALS AND METHODS: Clinical, functional and multimodal retinal imaging data were collected. Genetic testing was performed by Whole Exome Sequencing (WES). RESULTS: A 52-year-old female patient with SPG of unknown origin was referred for a progressive visual acuity loss. Multimodal fundus imaging revealed a peculiar macular dystrophy. Given the specific association of macular dystrophy and SPG, a Kjellin syndrome was suspected and genetic testing performed. WES revealed biallelic pathogenic variants in SPG11, co-segregating with disease in the family. CONCLUSION: Careful ophthalmological examination prompted the diagnosis and guided molecular testing. This case underlines the importance of a neuro-ophthalmologic assessment in patients with SPG.

Utility of Motor Evoked Potentials in Contemporary Open Thoracoabdominal Aortic Repair.

OBJECTIVES: Paraplegia remains one of the major complications of contemporary open thoracoabdominal aortic aneurysm (TAAA) repair. Intraoperative motor-evoked potentials (MEPs) act as a surrogate measure for spinal cord homeostasis. The purpose of this study was to evaluate the results of intraoperative neuromonitoring in contemporary TAAA repair and its association with postoperative spinal cord ischemia. METHODS: Patients who underwent open type 2 or 3 TAAA or completion aortic repair utilizing intraoperative neuromonitoring were identified between May 2006 and November 2023. Patient demographics, comorbidities, indication for the procedure, procedural details, and outcomes were recorded. The groups were divided based on type of repair, and univariate statistics were then utilized to evaluate the association of these metrics versus the type of repair. RESULTS: Seventy-nine patients underwent open type 2 (N=41) and 3 (N=23) TAAA and completion aortic (N=15; open in 14, endovascular in 1) repairs by a single surgeon. The cohort was predominantly male (N=48, 60.8%) with a mean age of 52.5±16.2 years. There was a high incidence of hypertension (N=53, 67.1%), smoking history (N=42, 53.1%), and connective tissue disorders (N=37, 46.8%). Operative indications included dissection-related (N=50, 63.3%) and degenerative (N=26, 32.9%) TAAA and dissection-related malperfusion (N=3, 3.8%). Left heart bypass was often (N=73, 92.4%) utilized for distal aortic perfusion, and cerebrospinal fluid drainage (N=77, 97.5%) was a common adjunct. MEPs were classified as no change (N=43, 54.4%), reversible change (N=26, 32.9%), irreversible change (N=4, 5.1%), and unreliable (N=6, 7.6%). MEP changes were predominantly bilateral (N=70, 88.6%) and occurred most often during repair of the abdominal aortic segment (N= 13, 16.5%). The median number of replaced vertebral levels was associated with MEP changes (P=0.013). SCI was only observed in repairs greater than 6 replaced vertebral levels with an overall frequency of 17.7%. It was most prevalent in completion aortic repairs (26.7%). Immediate and delayed SCI occurred in 10.1% and 7.6% of patients, respectively; it was most commonly (71.8%) reversible. Permanent paraplegia occurred in 4 patients (5.1%), with equal immediate and delayed onsets. MEPs demonstrated poor sensitivity (53.9%) and specificity (62.3%) for SCI, however there was a high negative predictive value (86.4%) in this population. In-hospital mortality occurred in 5 (6.3%). CONCLUSIONS: No changes in intraoperative MEPs are highly predictive of spinal cord homeostasis. The number of replaced vertebral levels and previous aortic repair should guide intraoperative neuroprotective measures including intercostal reimplantation and should take precedence over intraoperative monitoring, especially when MEP changes occur.

Relationship between brain white matter damage and grey matter atrophy in hereditary spastic paraplegia types 4 and 5.

BACKGROUND AND PURPOSE: White matter (WM) damage is the main target of hereditary spastic paraplegia (HSP), but mounting evidence indicates that genotype-specific grey matter (GM) damage is not uncommon. Our aim was to identify and compare brain GM and WM damage patterns in HSP subtypes and investigate how gene expression contributes to these patterns, and explore the relationship between GM and WM damage. METHODS: In this prospective single-centre cohort study from 2019 to 2022, HSP patients and controls underwent magnetic resonance imaging evaluations. The alterations of GM and WM patterns were compared between groups by applying a source-based morphometry approach. Spearman rank correlation was used to explore the associations between gene expression and GM atrophy patterns in HSP subtypes. Mediation analysis was conducted to investigate the interplay between GM and WM damage. RESULTS: Twenty-one spastic paraplegia type 4 (SPG4) patients (mean age 50.7 years ± 12.0 SD, 15 men), 21 spastic paraplegia type 5 (SPG5) patients (mean age 29.1 years ± 12.8 SD, 14 men) and 42 controls (sex- and age-matched) were evaluated. Compared to controls, SPG4 and SPG5 showed similar WM damage but different GM atrophy patterns. GM atrophy patterns in SPG4 and SPG5 were correlated with corresponding gene expression (ρ = 0.30, p = 0.008, ρ = 0.40, p < 0.001, respectively). Mediation analysis indicated that GM atrophy patterns were mediated by WM damage in HSP. CONCLUSIONS: Grey matter atrophy patterns were distinct between SPG4 and SPG5 and were not only secondary to WM damage but also associated with disease-related gene expression. CLINICAL TRIAL REGISTRATION NO: NCT04006418.

Phenotypic variability in a large kindred with spastic paraplegia associated with a novel REEP1 variant.

Background and objectives: The aim of this study is to provide a comprehensive characterization of a large Estonian family spanning five generations with seventeen individuals affected by spastic paraplegia associated with a novel variant in the receptor expression-enhancing protein-1 (REEP1) gene. Methods: Comprehensive clinical evaluation, neuroimaging, and neurophysiological studies were performed on six patients who provided oral and written consent. Whole-exome sequencing was performed on the index case. Targeted carrier testing was done in all other available affected and at-risk relatives. Results: Four individuals presented with pure spastic paraplegia, with onset from early childhood to adult age. None had bladder or bowel dysfunction. Two subjectively asymptomatic mutation carriers displayed pyramidal signs on examination. Imaging of the neuroaxis was normal in three patients, three had MRI findings interpreted as unrelated. Motor evoked potential (MEP) was abnormal in five; the patient with the longest disease duration had additional somatosensory evoked potential (SSEP) abnormalities. The novel splice-site variant, c.32 + 1G > C in the REEP1 gene, found in the index case, co-segregates with disease in the family. Expressivity in this family is variable. Conclusion: Our findings are in keeping with previous descriptions of the SPG31 spectrum. The phenotype associated with splice variants is not necessarily more severe than other conventional REEP1 variants. As for other forms of familial spastic paraplegias, the factors modulating variable expressivity in SPG31 are still unknown.

Reticulon 2 deficiency results in an autosomal recessive distal motor neuropathy with lower limb spasticity.

Heterozygous RTN2 variants have been previously identified in a limited cohort of families affected by autosomal dominant spastic paraplegia (SPG12-OMIM:604805) with a variable age of onset. Nevertheless, the definitive validity of SPG12 remains to be confidently confirmed due to scarcity of supporting evidence. In our study, we identified and validated seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven consanguineous families with distal hereditary motor neuropathy (dHMN) using exome, genome and Sanger sequencing coupled with deep-phenotyping. All affected individuals (seven males and seven females, aged 9-50 years) exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography. Despite a slowly progressive disease course, all patients remained ambulatory over a mean disease duration of 19.71 ± 13.70 years. Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain. Treatment of the mutant with an endoplasmic/sarcoplasmic reticulum Ca2+ reuptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences, suggesting a potential therapeutic benefit for RTN2-disorder. Despite Reticulon-2 being an endoplasmic reticulum (ER)-resident membrane shaping protein, our analysis of patient fibroblast cells did not find significant alterations in ER structure or the response to ER stress. Our findings delineate a distinct form of autosomal recessive dHMN with pyramidal features associated with Reticulon-2 deficiency. This phenotype shares similarities with SIGMAR1-related dHMN, and Silver-like syndromes, providing valuable insights into the clinical spectrum and potential therapeutic strategies for RTN2-related dHMN.

Whole exome sequencing in Serbian patients with hereditary spastic paraplegia.

Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases with a high genetic and clinical heterogeneity. Numerous HSP patients remain genetically undiagnosed despite screening for known genetic causes of HSP. Therefore, identification of novel variants and genes is needed. Our previous study analyzed 74 adult Serbian HSP patients from 65 families using panel of the 13 most common HSP genes in combination with a copy number variation analysis. Conclusive genetic findings were established in 23 patients from 19 families (29%). In the present study, nine patients from nine families previously negative on the HSP gene panel were selected for the whole exome sequencing (WES). Further, 44 newly diagnosed adult HSP patients from 44 families were sent to WES directly, since many studies showed WES may be used as the first step in HSP diagnosis. WES analysis of cohort 1 revealed a likely genetic cause in five (56%) of nine HSP families, including variants in the ETHE1, ZFYVE26, RNF170, CAPN1, and WASHC5 genes. In cohort 2, possible causative variants were found in seven (16%) of 44 patients (later updated to 27% when other diagnosis were excluded), comprising six different genes: SPAST, SPG11, WASCH5, KIF1A, KIF5A, and ABCD1. These results expand the genetic spectrum of HSP patients in Serbia and the region with implications for molecular genetic diagnosis and future causative therapies. Wide HSP panel can be the first step in diagnosis, alongside with the copy number variation (CNV) analysis, while WES should be performed after.

Outcome of Endovascular and Open Treated Penetrating Aortic Ulcers.

PURPOSE: Penetrating aortic ulcer (PAU) is a rare etiology of acute aortic syndrome. Few studies exist regarding the perioperative outcome. The aim was to analyze clinical outcome and risk factors of mortality in this treatment population. METHODS: Retrospective, monocentric study from 2010 to 2021. Clinical data of endovascular or open treated PAU were analyzed. In-hospital mortality was selected as the primary study endpoint. Angio-morphologies were analyzed and risk factors for mortality were identified by using univariate analysis. RESULTS: Overall, 133 patients were identified. 29% (n=38) of patients presented symptomatically. In 64% (n=85), the PAU was localized in the thoracic aorta. On average, PAUs had a depth of 15.4±10.1 mm and a width of 17.9±9.6 mm. The patients had a median of 2 (95% confidence interval [CI]=2-3) high-risk features (HRF) as PAU depth >10 mm, PAU width >20 mm, aortic diameter >40 mm, symptomatic, intramural hematoma (IMH), pleural effusion. Significantly more HRF were observed in symptomatic patients (p=0.01). 53% (n=71) of patients were treated with thoracic endovascular aortic repair (TEVAR), 41% (n=54) by endovascular aortic repair (EVAR), and 6% (n=8) by open surgery. A hybrid procedure with cervical debranching was performed in 16% (n=21) and complex endovascular repair with fenestrated or branched endografts in 15% (n=20). Overall, complications greater than grade II according to the Clavien-Dindo classification occurred in 19% (n=25) and of the patients. In-hospital mortality manifested in 6% (n=8). Factors associated with increased mortality were the diameter of the aorta >40 mm (88% vs 39%, p=0.03), as well as symptomatic patients (63% vs 26%, p=0.04), coincident IMHs (38% vs 10%, p=0.05), and complex endovascular procedures (50% vs 50% p<0.01). Penetrating aortic ulcer width >20 mm tended to show higher mortality (75% vs 40%, p=0.06). Routine follow-up was available for 89% (n=117) for a median of 39 months (95% CI=25-42). One-year and 5-year survival were 83% and 60%, respectively, with 1 aortic pathology-related death. CONCLUSIONS: Treatment of PAU is associated with an acceptable perioperative morbidity and mortality. Risk factors associated with increased mortality are an elevated aortic diameter, the presence of IMHs, clinical symptomatology at presentation, and complex endovascular procedures.

Use of an upright power wheelchair in spinal cord injury: a case series.

Objective: To explore independence, usability, and self-reported quality of life (QOL) in eligible persons with spinal cord injury (SCI) who used a standing powered wheelchair over a 12-week period. Setting: VA SCI research facility. Participants: Four participants with chronic SCI who use a wheelchair as the primary means of mobility. Intervention: A standing power wheelchair was used three times a week (3.5 h/session) for 12 weeks in a supervised setting. Main Outcome Measures: safety, usability and feasibility, blood pressure in seated and standing positions, bowel, bladder, and pain item banks from the SCI-QOL Physical-Medical-Health domain, and overall user satisfaction with the device. Results: Participants consistently maintained normal blood pressure responses between seated and standing positions throughout the training sessions and learned to perform all the mobility tasks safely and independently. Participants reported improvements on the SCI-QOL and were generally satisfied with the upright standing power wheelchair. Conclusions: In this small case series of chronic, non-ambulatory individuals with SCI, the standing powered wheelchair was shown to be safe and efficacious.

Cul-4 inhibition rescues spastin levels and reduces defects in hereditary spastic paraplegia models.

Hereditary spastic paraplegias (HSPs) are degenerative motor neuron diseases characterized by progressive spasticity and weakness in the lower limbs. The most common form of HSP is due to SPG4 gene haploinsufficiency. SPG4 encodes the microtubule severing enzyme spastin. Although, there is no cure for SPG4-HSP, strategies to induce a spastin recovery are emerging as promising therapeutic approaches. Spastin protein levels are regulated by poly-ubiquitination and proteasomal-mediated degradation, in a neddylation-dependent manner. However, the molecular players involved in this regulation are unknown. Here, we show that the Cullin-4-Ring E3 ubiquitin ligase complex (CRL4) regulates spastin stability. Inhibition of CRL4 increases spastin levels by preventing its poly-ubiquitination and subsequent degradation in spastin-proficient and in patient derived SPG4 haploinsufficient cells. To evaluate the role of CRL4 complex in spastin regulation in vivo, we developed a Drosophila melanogaster model of SPG4 haploinsufficiency which show alterations of synapse morphology and locomotor activity, recapitulating phenotypical defects observed in patients. Downregulation of the CRL4 complex, highly conserved in Drosophila, rescues spastin levels and the phenotypical defects observed in flies. As a proof of concept of possible pharmacological treatments, we demonstrate a recovery of spastin levels and amelioration of the SPG4-HSP-associated defects both in the fly model and in patient-derived cells by chemical inactivation of the CRL4 complex with NSC1892. Taken together, these findings show that CRL4 contributes to spastin stability regulation and that it is possible to induce spastin recovery and rescue of SPG4-HSP defects by blocking the CRL4-mediated spastin degradation.

How Elite Athletes with a Spinal Cord Injury Sweat during Exercise-An Exploratory Study.

BACKGROUND: Sweat and thermal responses in individuals with spinal cord injury (SCI) are impaired depending on lesion characteristics. This is particularly problematic for athletes and may ultimately lead to reduced performance. This exploratory study investigated the feasibility of field-usable methods to objectively collect data relevant to sweat response in elite athletes with SCI. Differences in sweat response were also evaluated for different athlete characteristics. METHODS: Measurements were performed during exercise and included core temperature (Tc), heart rate, urine specific gravity, fluid intake, sweat rate, and sweat electrolyte concentration. Differences for sex, lesion level (tetraplegia versus paraplegia), motor impairment (complete versus incomplete), and sport type (endurance versus team/skill) were evaluated. RESULTS: Fifteen athletes (median (Q1-Q3) age, 30 (28-36) years; three females; 11 with complete lesions) were included. Endurance athletes were measured during indoor performance tests (n = 10), whereas team/skill athletes were measured during training sessions (n = 5). In the mixed exercise intensities, the average Tc was 37.7 (37.3-37.8) °C and the average heart rate was 126 (100-146) bpm. Dehydration, defined as a urine specific gravity > 1.020 ng/mL, was prevalent in six athletes before exercise and in five athletes after exercise. The sweat rate was lower in athletes with tetraplegia (p = 0.02) and in team/skill athletes (p = 0.008). CONCLUSIONS: Collecting sweat and thermal response data from athletes with SCI in the field is feasible. Given the suboptimal hydration status of many athletes, raising awareness of the importance of hydration seems valuable.