Innovative Discoveries in Neurosurgical Treatment of Neurodegenerative Diseases: A Narrative Review.

Neurodegenerative diseases (NDDs) encapsulate conditions in which neural cell populations are perpetually degraded and nervous system function destroyed. Generally linked to increased age, the proportion of patients diagnosed with a NDD is growing as human life expectancies rise. Traditional NDD therapies and surgical interventions have been limited. However, recent breakthroughs in understanding disease pathophysiology, improved drug delivery systems, and targeted pharmacologic agents have allowed innovative treatment approaches to treat NDDs. A common denominator for administering these new treatment options is the requirement for neurosurgical skills. In the present narrative review, we highlight exciting and novel preclinical and clinical discoveries being integrated into NDD care. We also discuss the traditional role of neurosurgery in managing these neurodegenerative conditions and emphasize the critical role of neurosurgery in effectuating these newly developed treatments.

Complications, readmissions, reoperations and patient-reported outcomes in patients with multiple sclerosis undergoing elective spine surgery - a propensity matched analysis.

BACKGROUND CONTEXT: Multiple sclerosis (MS) is an autoimmune, neurodegenerative disease that can lead to significant functional disability. Improving treatment regimens have extended life expectancy and led to an increase in the number of elective spine surgeries for degenerative conditions in the MS population. Recent literature has reported mixed results regarding the efficacy of elective spine surgery for patients with MS. There is also a paucity of literature comparing postoperative patient reported outcomes (PROs) and reoperation rates between patients with and without MS. PURPOSE: To determine if patients with MS have worse PROs and higher complication, readmission and reoperation rates after elective spine surgery compared with patients without neurodegenerative conditions when adjusting for baseline covariates through propensity matching. STUDY DESIGN/SETTING: Retrospective review of prospectively collected data from the Quality Outcomes Database (QOD), a national, longitudinal, multicenter spine outcomes registry. PATIENT SAMPLE: For the lumbar cohort, 312 patients with MS and 46,738 patients without MS were included. The cervical myelopathy cohort included 91 patients with MS and 6,426 patients without MS. The cervical radiculopathy cohort consisted of 103 patients with MS and 13,751 patients without MS. OUTCOME MEASURES: 1) complication rates, 2) readmission rates, 3) reoperation rates, and 4) PROs at 3- and 12-months including ODI/NDI, NRS back/neck/arm/leg pain, mJOA scores and patient satisfaction ratings. METHODS: Data from the QOD was queried for patients with surgeries occurring between 04/2013-01/2019. Three surgical groups were included: 1) Elective lumbar surgery, 2) Elective cervical surgery for myelopathy, 3) Elective cervical surgery for radiculopathy. Patients with any neurodegenerative condition other than MS were excluded. Patients without MS were propensity matched against patients with MS in a 5 to 1 ratio without replacement based on ASA grade, arthrodesis, surgical approach, number of operated levels, age, and baseline ODI/NDI, NRS leg/arm pain, NRS back/neck pain, and EQ-5D. Multivariable regressions with cluster-robust standard errors were used to estimate average effect of how the outcome would change if the MS patient didn't have the disease. The mean difference was used for continuous outcomes and the risk difference was used for binary outcomes. RESULTS: For the lumbar cohort, no differences were found between the 2 groups at 3 or 12 months in any of the outcome measures. For the myelopathy cohort, patients with MS patients had a lower rate of reoperation at 12 months (risk difference=-0.036, p=.007) and worse 3-month mJOA scores (mean difference=-1.044, p=.004) compared with patients without MS. For the radiculopathy cohort, patients with MS had a lower rate of reoperation at 3 months (risk difference=-0.019, p=.018) and 12 months (risk difference=-0.029, p=.007) compared with those without MS. CONCLUSIONS: Patients with MS had similar PROs compared with patients without MS when adjusting for baseline covariates through propensity matching, except for 3-month mJOA scores in the myelopathy cohort. Reoperation rates were found to be lower in patients with MS undergoing elective cervical surgery for both myelopathy and radiculopathy. These results suggest that when analyzed independently, a diagnosis of MS does not significantly impact complication, readmission and reoperation rates or PROs, and therefore should not represent a major contraindication to elective spine surgery. Surgical decisions in this patient population should be made based on careful consideration of patient factors including other comorbidities as well as baseline patient functional status.

The influence of ApoE4 on the clinical outcomes and pathophysiology of degenerative cervical myelopathy.

Degenerative cervical myelopathy (DCM) is the most common cause of nontraumatic spinal cord injury in adults worldwide. Surgical decompression is generally effective in improving neurological outcomes and halting progression of myelopathic deterioration. However, a subset of patients experience suboptimal neurological outcomes. Given the emerging evidence that apolipoprotein E4 (ApoE4) allelic status influences neurodegenerative conditions, we examined whether the presence of the ApoE4 allele may account for the clinical heterogeneity of treatment outcomes in patients with DCM. Our results demonstrate that human ApoE4+ DCM patients have a significantly lower extent of improvement after decompression surgery. Functional analysis of our DCM mouse model in targeted-replacement mice expressing human ApoE4 revealed delayed gait recovery, forelimb grip strength, and hind limb mechanical sensitivity after decompression surgery, compared with their ApoE3 counterparts. This was accompanied by an exacerbated proinflammatory response resulting in higher concentrations of TNF-α, IL-6, CCL3, and CXCL9. At the site of injury, there was a significant decrease in gray matter area, an increase in the activation of microglia/macrophages, and increased astrogliosis after decompression surgery in the ApoE4 mice. Our study is the first to our knowledge to investigate the pathophysiological underpinnings of ApoE4 in DCM, which suggests a possible personalized medicine approach for the treatment of DCM in ApoE4 carriers.

Stem Cells: Innovative Therapeutic Options for Neurodegenerative Diseases?

Neurodegenerative diseases are characterized by the progressive loss of structure and/or function of both neurons and glial cells, leading to different degrees of pathology and loss of cognition. The hypothesis of circuit reconstruction in the damaged brain via direct cell replacement has been pursued extensively so far. In this context, stem cells represent a useful option since they provide tissue restoration through the substitution of damaged neuronal cells with exogenous stem cells and create a neuro-protective environment through the release of bioactive molecules for healthy neurons, as well. These peculiar properties of stem cells are opening to potential therapeutic strategies for the treatment of severe neurodegenerative disorders, for which the absence of effective treatment options leads to an increasingly socio-economic burden. Currently, the introduction of new technologies in the field of stem cells and the implementation of alternative cell tissues sources are pointing to exciting frontiers in this area of research. Here, we provide an update of the current knowledge about source and administration routes of stem cells, and review light and shadows of cells replacement therapy for the treatment of the three main neurodegenerative disorders (Amyotrophic lateral sclerosis, Parkinson's, and Alzheimer's disease).

Role of the cerebellum in the phenotype of neurodegenerative diseases: Mitigate or exacerbate?

Degenerative diseases alter brain activity and functional connectivity. In this issue of the Neuroscience Letters, Yin and others (2021) [6] present data showing increased activity in lobules VIII and IX of the cerebellar vermis in Parkinson's patients with visuospatial disorders. The study refines the fMRI mapping of the cerebellum, but the functional interpretation of the findings remains complex. The architecture and connectivity of the cerebellum set it apart from the rest of the brain and should be considered when interpreting the functional connectivity data. In degenerative diseases, the cerebellum suffers from the same pathology as the cerebral cortex; hence, it is unlikely that changes in the cerebellum could ameliorate clinical symptoms in degenerative diseases. Clinical, surgical data indicate that the primary function of the cerebellum is motor, not cognition or affective. The cerebellar anatomy buttresses these observations. The cerebellum receives direct motor-related inputs but no direct information from the sensory system. Hence, it likely contributes to the behavioral components of emotions and cognition.

Patient journey following lumbar spinal fusion surgery (FuJourn): A multicentre exploration of the immediate post-operative period using qualitative patient diaries.

The aim of this study was to capture and understand the immediate recovery journey of patients following lumbar spinal fusion surgery and explore the interacting constructs that shape their journey. A qualitative study using Interpretive Phenomenological Analysis (IPA) approach. A purposive sample of 43 adult patients (≥16 years) undergoing ≤4 level instrumented fusion for back and/or leg pain of degenerative cause, were recruited pre-surgery from 4 UK spinal surgery centres. Patients completed a weekly diary expressed in their own words for the first 4 weeks following surgery to capture their life as lived. Diary content was based on previous research findings and recorded progress, recovery, motivation, symptoms, medications, healthcare appointments, rehabilitation, positive/negative thoughts, and significant moments; comparing to the previous week. To maximise completion and data quality, diaries could be completed in paper form, word document, as online survey or as audio recording. Strategies to enhance diary adherence included a weekly prompt. A framework analysis for individual diaries and then across participants (deductive and inductive components) captured emergent themes. Trustworthiness was enhanced by strategies including reflexivity, attention to negative cases and use of critical co-investigators. Twenty-eight participants (15 female; n = 18 (64.3%) aged 45-64) contributed weekly diaries (12 withdrew post-surgery, 3 did not follow through with surgery). Adherence with diaries was 89.8%. Participants provided diverse and vivid descriptions of recovery experiences. Three distinct recovery trajectories were identified: meaningful recovery (engagement in physical and functional activities to return to functionality/mobility); progressive recovery (small but meaningful improvement in physical ability with increasing confidence); and disruptive recovery (limited purpose for meaningful recovery). Important interacting constructs shaped participants' recovery including their pain experience and self-efficacy. This is the first account of immediate recovery trajectories from patients' perspectives. Recognition of a patient's trajectory may inform patient-centred recovery, follow-up and rehabilitation to improve patient outcomes.

Neurologic Clinical Manifestations of Fahr Syndrome and Hypoparathyroidism.

A 41-year-old female with a history of chronic hypoparathyroidism with Fahr syndrome presented with complaints of weakness and muscle spasticity. Brain imaging demonstrated diffuse intracranial calcifications. In addition, cervical spine imaging revealed extensive calcification along the anterior and posterior cervical vertebral bodies causing multilevel stenosis and cord compression. The patient underwent a multilevel posterior cervical decompression and fusion. Postoperatively, the patient had noted improvement in her upper and lower extremity strength and spasticity. This illustrative case demonstrates rare clinical and radiographic neurologic sequelae of long-standing hypoparathyroidism.

Hypermetabolic Syndrome and Dyskinesia After Neurologic Surgery for Labrune Syndrome: A Case Report.

A 20-year-old man with a rare neurodegenerative disease developed hypermetabolic symptoms with dyskinesia after a third ventriculostomy for hydrocephalus. The initial presentation was concerning for an acute dystonic reaction after metoclopramide was administered for nausea. He concurrently developed hypermetabolic symptoms, including hyperthermia, tachycardia, and a lactic acidosis. The diagnosis was broadened to include neuroleptic malignant syndrome, serotonin syndrome, and malignant hyperthermia. Although perhaps less intellectually satisfying but more true to clinical reality, we did not isolate a single diagnosis but treated effectively all 3 with dantrolene sodium and benzodiazepine.

Therapeutic potential of stem cells for treatment of neurodegenerative diseases.

Neurodegenerative diseases are caused by a loss of neurons within the peripheral or central nervous system. Inadequate repairability in the central nervous system and failure of treatments are the significant hurdles for several neurological diseases. The regenerative potential of stem cells drew the attention of researchers to cell-based therapy for treating neurodegenerative diseases. The clinical application of stem cells may help to substitute new cells and overcome the inability of the endogenous repairing system to repair the damaged brain. However, the clinical application induced pluripotent stem cells are restricted due to the risk of tumor formation by residual undifferentiated upon transplantation. In this focused review, we briefly discussed different stem cells currently being studied for therapeutic development. Moreover, we present supporting evidence for the utilization of stem cell therapy for the treatment of neurodegenerative diseases. Also, we described the key issues that should be considered to transplantation of stem cells for different neurodegenerative diseases. In our conclusion, stem cell therapy probably would be the only treatment strategy that offers a cure for neurodegenerative disease. Although, further study is required to identify ideal stem cells candidate, dosing and the ideal method of cell transplantation. We suggest that all grafted cells would be transgenically armed with a molecular kill-switch that could be activated by the event of adverse side effects.

Subfascial drainage and clipping technique for treatment of cerebrospinal fluid leak following spinal surgery.

OBJECTIVE: To investigate the treatment of iatrogenic cerebrospinal fluid (CSF) leak that develops after degenerative lumbar spinal surgery with a subfascial drainage and clipping (SDC) technique. METHODS: This study retrospectively reviewed the medical records of 46 patients who developed iatrogenic CSF leak after surgery for lumbar degenerative spine disease from 2007 to 2019. Twenty-five patients were treated with the SDC procedure (SDC group), whereas 21 were not (control group). Outcomes were compared between the two groups. RESULTS: CSF leakage ceased within 6-9 days (average 7.4+/-1) after the procedure in the SDC group. In the control group, CSF leakage was controlled with conservative measures in 14 patients, and in 7 patients, lumbar external drainage was performed. Among these 7, the CSF leak was controlled by lumbar external drainage in 3, and 4 required reoperation to repair the dural defect. No infection occurred in either group. Length of hospital stay was also shorter in SDC group (8.4+/-1 vs 10.0+/-1.3 days, p less than 0.001). CONCLUSION: The SDC technique is effective for the treatment of iatrogenic CSF leak that develops after degenerative lumbar spinal surgery.

Prevalence of Osteoporosis in Patients Undergoing Lumbar Fusion for Lumbar Degenerative Diseases: A Combination of DXA and Hounsfield Units.

STUDY DESIGN: Retrospective analysis. OBJECTIVE: To investigate the prevalence of osteoporosis (OP) in patients undergoing lumbar fusion for lumbar degenerative diseases (LDD). SUMMARY OF BACKGROUND DATA: OP is related to many complications after lumbar fusion for patients with LDD. There are sparse data on the prevalence of OP among this specific population. Moreover, LDD can falsely elevate the bone mineral density measured by dual energy x-ray absorptiometry (DXA), leading to unreliable diagnostic results. Computed tomography (CT) Hounsfield unit (HU) values can help identify osteoporotic patients undetected by DXA. METHODS: A total of 479 patients aged≥50 years undergoing lumbar fusion for LDD were reviewed. The diagnosis of OP using DXA was based on World Health Organization criterion. The criterion for OP diagnosed on CT scan was the L1-HU value≤110. RESULTS: The prevalence of OP diagnosed on lumbar DXA, hip DXA, and both was 32.4%, 19.6%, 39.7%, respectively. The females had higher prevalence of OP diagnosed on DXA (spine and hip) than males (48.9% vs. 27.1%, P < 0.001). In females but not males, the prevalence of OP significantly increased with age (females, 50-59: 28.0%, 60-69: 58.1%, ≥70: 78.8%, P < 0.001). Patients having primary diagnosis of degenerative lumbar scoliosis had the higher prevalence of OP than the rest patients (56.5% vs. 36.8%, P = 0.002). Among the 324 patients diagnosed with non-OP by lumbar DXA, the prevalence of OP diagnosed on CT scan was 25.9%, it increased with age and was also highest in patients with degenerative lumbar scoliosis. CONCLUSION: OP was quite common among patients aged≥50 years undergoing lumbar fusion for LDD, especially for females aged≥60 years or patients having degenerative lumbar scoliosis. Older patients or patients having degenerative lumbar scoliosis are more likely to have unreliable lumbar T-scores. Measurements of HU values can help identify more osteoporotic patients in this population. LEVEL OF EVIDENCE: 3.

Risk Factors for Postsurgical Foot Complaints One Year Following Degenerative Lumbar Spinal Surgery.

MINI: Postsurgical foot complaints occurred frequently in 853 degenerative lumbar surgeries (prevalence, 20.6%; n = 176). Risk factor analysis showed that the incidence of postsurgical foot complaint was significantly higher in patients with preoperative foot symptoms (adjusted odds ratio, 5.532) and in those with preoperative sensory deficits on the leg (adjusted odds ratio, 1.904). STUDY DESIGN: Retrospective. OBJECTIVE: To investigate the prevalence and risk factors of postsurgical foot complaints (PFCs) following spinal surgery by using a modified pain drawing (PD) instrument. SUMMARY OF BACKGROUND DATA: Although many patients report nonspecific foot symptoms with various clinical presentation, there is not a well defined diagnostic criterion. PDs are essential for measuring spinal surgery outcomes. We created a modified patient-physician communication-based PD instrument to overcome the limitations of the previous system. METHODS: We included 853 consecutive patients who underwent decompression with or without fusion. PFCs were defined as sensory foot symptoms, including ambiguous sensations that were not clearly due to spinal pathology. Patients who complained of postoperative foot symptoms at more than two consecutive visits were assigned to the PFC group. The remaining patients were assigned to the asymptomatic group. We collected medical records using our PD instrument and compared variables between the two groups. RESULTS: In total, 176 (20.6%) of the 853 patients had PFCs. The duration of preoperative leg pain was significantly longer in the PFC group than in the asymptomatic group (2.8 vs. 2.2 years; P = 0.048). The proportions of preoperative foot symptoms (82.9% vs. 43.3%) and sensory deficits on the leg (48.6% vs. 27%) were significantly greater in the PFC group than in the asymptomatic group (P < 0.001). Multivariable logistic regression analysis revealed two independent risk factors: the presence of preoperative foot symptoms (adjusted odds ratio, 5.532) and preoperative sensory deficits on the leg (adjusted odds ratio, 1.904). CONCLUSION: PFCs occurred frequently after degenerative lumbar spinal surgery (prevalence, 20.6%). Based on our data using PD instrument, it can help reduce the incidence of PFCs if patients are informed and educated that preoperatively existing foot symptom and sensory deficits on the leg are significant risk factors for PFC development. LEVEL OF EVIDENCE: 4.

Retrospective. To investigate the prevalence and risk factors of postsurgical foot complaints (PFCs) following spinal surgery by using a modified pain drawing (PD) instrument. Although many patients report nonspecific foot symptoms with various clinical presentation, there is not a well defined diagnostic criterion. PDs are essential for measuring spinal surgery outcomes. We created a modified patient-physician communication-based PD instrument to overcome the limitations of the previous system. We included 853 consecutive patients who underwent decompression with or without fusion. PFCs were defined as sensory foot symptoms, including ambiguous sensations that were not clearly due to spinal pathology. Patients who complained of postoperative foot symptoms at more than two consecutive visits were assigned to the PFC group. The remaining patients were assigned to the asymptomatic group. We collected medical records using our PD instrument and compared variables between the two groups. In total, 176 (20.6%) of the 853 patients had PFCs. The duration of preoperative leg pain was significantly longer in the PFC group than in the asymptomatic group (2.8 vs. 2.2 years; P = 0.048). The proportions of preoperative foot symptoms (82.9% vs. 43.3%) and sensory deficits on the leg (48.6% vs. 27%) were significantly greater in the PFC group than in the asymptomatic group (P < 0.001). Multivariable logistic regression analysis revealed two independent risk factors: the presence of preoperative foot symptoms (adjusted odds ratio, 5.532) and preoperative sensory deficits on the leg (adjusted odds ratio, 1.904). PFCs occurred frequently after degenerative lumbar spinal surgery (prevalence, 20.6%). Based on our data using PD instrument, it can help reduce the incidence of PFCs if patients are informed and educated that preoperatively existing foot symptom and sensory deficits on the leg are significant risk factors for PFC development. Level of Evidence: 4.

Half of Unplanned Readmissions Following One or Two-Level Anterior Cervical Decompression and Fusion Are Unrelated to Surgical Site.

MINI: In this study we analyze rates of readmission, and the timing and reasons for readmission after one to two level anterior cervical decompression and fusion. Among 18,833 patients who underwent anterior cervical decompression and fusion, 3% were readmitted to the hospital within 30 days. 39.5% of readmissions were for reasons related to surgical site. STUDY DESIGN: Retrospective review of a national database. OBJECTIVE: In this study we analyze rates of readmission, and the timing and reasons for readmission after one to two level anterior cervical decompression and fusion (ACDF). SUMMARY OF BACKGROUND DATA: The safety profile of ACDF has been previously described with readmission rates typically between 2% and 4%. However no studies have investigated the primary diagnoses driving readmission, and whether these diagnoses are related to the surgical site. METHODS: Demographics, comorbidities, and procedural characteristics were collected for all patients undergoing one or two-level ACDF for degenerative indications identified by Current Procedural Terminology (CPT) coding in the National Surgical Quality Improvement Program (NSQIP) database. The incidence of 30-day complications and readmissions was calculated, and the reasons for readmission as well as the timing of readmission were reviewed. Multivariate logistic regression analyses were performed to identify risk factors associated with complications or readmissions within 30 days of surgery. RESULTS: Eighteen thousand eight hundred thirty three patients underwent ACDF (15,464 single-level and 3369 two-level, mean age 53.7 yrs, standard deviation [SD]: 11.6; 50% male). Postoperative complication rate of was 4.3% in two-level fusions and 3.5% in single-level fusion (P = 0.027). Five hundred sixty nine unplanned readmissions were identified (3.0%), of which 39.5% were related to the surgical site and 49.7% were unrelated to the surgical site (10.5% unknown cause of readmission). The most frequent reason for 30-day readmission was pneumonia (9.3%, mean time to readmission of 11.3 d) followed by dysphagia (7.4%, 6.3 d), and acute postoperative pain (7.2%, 11.4 d). CONCLUSION: In this nationwide analysis of 18,833 ACDF cases, 3.0% of patients were readmitted within 30 days, of which at least 49.7% were for reasons unrelated to the surgical site. LEVEL OF EVIDENCE: 3.

Retrospective review of a national database. In this study we analyze rates of readmission, and the timing and reasons for readmission after one to two level anterior cervical decompression and fusion (ACDF). The safety profile of ACDF has been previously described with readmission rates typically between 2% and 4%. However no studies have investigated the primary diagnoses driving readmission, and whether these diagnoses are related to the surgical site. Demographics, comorbidities, and procedural characteristics were collected for all patients undergoing one or two-level ACDF for degenerative indications identified by Current Procedural Terminology (CPT) coding in the National Surgical Quality Improvement Program (NSQIP) database. The incidence of 30-day complications and readmissions was calculated, and the reasons for readmission as well as the timing of readmission were reviewed. Multivariate logistic regression analyses were performed to identify risk factors associated with complications or readmissions within 30 days of surgery. Eighteen thousand eight hundred thirty three patients underwent ACDF (15,464 single-level and 3369 two-level, mean age 53.7 yrs, standard deviation [SD]: 11.6; 50% male). Postoperative complication rate of was 4.3% in two-level fusions and 3.5% in single-level fusion (P = 0.027). Five hundred sixty nine unplanned readmissions were identified (3.0%), of which 39.5% were related to the surgical site and 49.7% were unrelated to the surgical site (10.5% unknown cause of readmission). The most frequent reason for 30-day readmission was pneumonia (9.3%, mean time to readmission of 11.3 d) followed by dysphagia (7.4%, 6.3 d), and acute postoperative pain (7.2%, 11.4 d). In this nationwide analysis of 18,833 ACDF cases, 3.0% of patients were readmitted within 30 days, of which at least 49.7% were for reasons unrelated to the surgical site. Level of Evidence: 3.

Effects of pre-surgery physiotherapy on walking ability and lower extremity strength in patients with degenerative lumbar spine disorder: Secondary outcomes of the PREPARE randomised controlled trial.

BACKGROUND: Degenerative lumbar spine disorders are common among musculoskeletal disorders. When disabling pain and radiculopathy persists after adequate course of rehabilitation and imaging confirms compressive pathology, surgical decompression is indicated. Prehabilitation aiming to augment functional capacity pre-surgery may improve physical function and activity levels pre and post-surgery. This study aims to evaluate the effect and dose-response of pre-surgery physiotherapy on quadriceps femoris strength and walking ability in patients with degenerative lumbar spine disorders compared to waiting-list controls and their association with postoperative physical activity level. METHOD: In this single blinded, 2-arm randomised controlled trial, 197 patients were consecutively recruited. Inclusion criteria were: MRI confirmed diagnosis and scheduled for surgery due to disc herniation, lumbar spinal stenosis, degenerative disc disease or spondylolisthesis, ages 25-80 years. Patients were randomised to 9 weeks of pre-surgery physiotherapy or to waiting-list. Patient reported physical activity level, walking ability according to Oswestry Disability Index item 4, walking distance according to the SWESPINE national register and physical outcome measures including the timed ten-meter walk test, maximum voluntary isometric quadriceps femoris muscle strength, patient-rated were collected at baseline and follow-up. Parametric or non-parametric within and between group comparisons as well as multivariate regression was performed. RESULTS: Patients who received pre-surgery physiotherapy significantly improved in all variables from baseline to follow-up (p < 0.001 - p < 0.05) and in comparison to waiting-list controls (p < 0.001 - p < 0.028). Patients adhering to ≥12 treatment sessions significantly improved in all variables (p < 0.001 - p < 0.032) and those receiving 0-11 treatment session in only normal walking speed (p0.035) but there were no significant differences when comparing dosages. Physical outcome measures after pre-surgery physiotherapy together significantly explain 27.5% of the variation in physical activity level 1 year after surgery with pre-surgery physical activity level having a significant multivariate association. CONCLUSION: Pre-surgery physiotherapy increased walking ability and lower extremity strength in patients with degenerative lumbar spine disorders compared to waiting-list controls. A clear treatment dose-response response relationship was not found. These results implicate that pre-surgery physiotherapy can influence functional capacity before surgical treatment and has moderate associations with maintained postoperative physical activity levels mostly explained by physical activity level pre-surgery. TRIAL REGISTRATION: NCT02454400 . Trial registration date: August 31st 2015, retrospectively registered.

Comparison of bilateral decompression via unilateral laminotomy and conventional laminectomy for single-level degenerative lumbar spinal stenosis regarding low back pain, functional outcome, and quality of life - A Randomized Controlled, Prospective Trial.

BACKGROUND: Conventional posterior open lumbar surgery is associated with considerable trauma to the paraspinal muscles. Severe damage to the paraspinal muscles could cause low back pain (LBP), resulting in poor functional outcomes. Thus, several studies have proposed numerous surgical techniques that can minimize damage to the paraspinal muscles, particularly unilateral laminotomy for bilateral decompression. The purpose of this study is to compare the degree of postoperative LBP, functional outcome, and quality of life of patients between bilateral decompression via unilateral laminotomy (BDUL; group U) and conventional laminectomy (CL; group C). METHODS: Of 87 patients who underwent diagnostic and decompression surgery, 50 patients who met the inclusion and exclusion criteria and were followed up for > 2 years were enrolled. The patients were asked to record their visual analog scale pain score after 6, 12, and 24 months postoperatively. BDUL was used for group U, whereas CL was used for group C. The patients were randomly divided based on one of the two techniques, and they were followed up for over 2 years. Functional outcomes were assessed by the Oswestry Disability Index (ODI), Roland-Morris Disability Questionnaire (RMDQ), and SF-36. RESULTS: Operation time was significantly shorter in group U than in group C (p = 0.003). At 6, 12, and 24 months, there was no significant difference between the two groups in terms of spine-related pain (all p > 0.05). Functional outcomes using ODI and RMDQ and quality of life using SF-36 were not significantly different between the groups (all p > 0.05). CONCLUSIONS: Regarding single-level decompression for degenerative lumbar spinal stenosis, group U had the advantages of shorter operation time than group C, but not in terms of back pain, functional outcome, and quality of life.

Neurodegenerative disease treatments by direct TNF reduction, SB623 cells, maraviroc and irisin and MCC950, from an inflammatory perspective - a Commentary.

Introduction: The importance of excessive cerebral tumor necrosis factor (TNF) concentrations as one of the central tenets of the pathogenesis of the neurodegenerative diseases is now widely known, but variably accepted. Areas covered: Here we update the field by including material that is freely available on the large databases, particularly PubMed. We include the therapeutic outcomes with etanercept (a widely used specific anti-TNF biological), XPro1595 (a new double negative TNF inhibitor), 3,61-dithiothalidomide, implanted SB623 stem cells, maraviroc (a CCR5 inhibitor used to treat AIDS), MCC950 (an NLRP3 inhibitor), and changes in the hormone irisin. Expert opinion: Remarkably, considering the ample literature that links SB623 cells, maraviroc, MCC950 and irisin to TNF, these publications do not mention this cytokine, and therefore not their implicit involvement with controlling its cerebral levels. With regard to developments demonstrated by MCC950, we note that DAMPs and PAMPs recognize and activate both TLRs and inflammasomes in these disease states. Here, as in other illnesses, data suggests that preventing a pathogenic interaction could be achieved through shutting down either of these arms of innate immunity.

Route to diagnosis of degenerative cervical myelopathy in a UK healthcare system: a retrospective cohort study.

OBJECTIVES: Degenerative cervical myelopathy (DCM) presents insidiously, making initial diagnosis challenging. Surgery has been shown to prevent further disability but existing spinal cord damage may be permanent. Delays in surgery lead to increased disability and reduced postoperative improvements. Therefore, rapid surgical assessment is key to improving patient outcomes. Unfortunately, diagnosis of DCM in primary care is often delayed. This study aimed to characterise patients with DCM route to diagnosis and surgical assessment as well as to plot disease progression over time. DESIGN: Retrospective, observational cohort study. SETTING: Single, tertiary centre using additional clinical records from primary and secondary care centres. PARTICIPANTS: One year of cervical MRI scans conducted at a tertiary neurosciences centre (n=1123) were screened for cervical cord compression, a corresponding clinical diagnosis of myelopathy and sufficient clinical documentation to plot a route to diagnosis (n=43). PRIMARY OUTCOME MEASURES: Time to diagnosis from symptom onset, route to diagnosis and disease progression were the primary outcome measures in this study. Disease severity was approximated using a prospectively validated method for inferring modified Japanese Orthopaedic Association (i-mJOA) functional scoring from clinical documentation. RESULTS: Patients received a referral to secondary care 6.4±7.7 months after symptom onset. Cervical MRI scanning and neurosurgical review occurred 12.5±13.0 and 15.8±13.5 months after symptom onset, respectively. i-mJOA was 16.0±1.7 at primary care assessment and 14.8±2.5 at surgical assessment. 61.0% of patients were offered operations. For those who received surgery, time between onset and surgery was 22.1±13.2 months. CONCLUSIONS: Route to surgical assessment was heterogeneous and lengthy. Some patients deteriorated during this period. This study highlights the need for a streamlined pathway by which patients with cervical cord compression can receive timely assessment and treatment by a specialist. This would improve outcomes for patients using existing treatments.

Predictors of Return to Normal Neurological Function After Surgery for Moderate and Severe Degenerative Cervical Myelopathy: An Analysis of A Global AOSpine Cohort of Patients.

BACKGROUND: Multiple studies have established the safety and efficacy of surgical intervention for degenerative cervical myelopathy (DCM). Although the main goal of surgery is symptom stabilization, a subset of patients achieves remarkable improvements. OBJECTIVE: To identify predictors of return to normal neurological function after surgery for moderate or severe DCM. METHODS: This is an analysis of 2 prospective multicenter studies (the AOSpine CSM-North America and CSM-International studies) conducted between 2005 and 2011. For patients with complete preoperative magnetic resonance imaging (MRI) and 2-yr follow-up, characteristics were compared between those who achieved a modified Japanese Orthopaedic Association (mJOA) score of 18 at 2 yr (no signs of myelopathy) vs controls. Only patients with baseline mJOA ≤ 14 (moderate and severe myelopathy) were included to minimize ceiling effects. RESULTS: A total of 51 patients (20.3%) out of 251 with moderate or severe baseline myelopathy achieved an mJOA score of 18 at 2 yr. On stepwise multiple logistic regression analysis, T1-weighted (T1W1)-hypointensity (odds ratio [OR] 0.10; 95% confidence interval [CI], 0.01-0.79; P = .03) and longer walking time on the 30-m walking test (OR 0.95; 95% CI, 0.92-0.99; P = .03) were independent predictors of outcome, with an area under the curve of 0.71 for the model. CONCLUSION: In this study, T1W-hypointensity on MRI and longer walking time were found to predict a less likelihood of achieving return to normal neurological function after surgery for moderate or severe DCM. These findings may provide useful information for patient counseling and perioperative expectations.

Robot-Assisted Versus Fluoroscopy-Guided Pedicle Screw Placement in Transforaminal Lumbar Interbody Fusion for Lumbar Degenerative Disease.

OBJECTIVE: To compare the clinical accuracy and perioperative outcomes for pedicle screw placement in transforaminal lumbar interbody fusion (TLIF) between the robot-assisted (RA) technique and fluoroscopy-guided (FG) technique. METHODS: Seventy-seven patients scheduled to undergo RA (n = 43) and FG (n = 44) TLIF surgery were included. Patient demographics, radiographic accuracy, and perioperative outcomes were recorded and compared. The accuracy of pedicle screw placement was according to the Gertzbein and Robbins scale and facet joint violation. Perioperative outcomes mainly included operative time, radiation exposure, and revisions. RESULTS: Of the 176 screws in the RA group, 164 screws were grade A, and 9, 2, and 1 screws were grades B, C, and D, respectively. Of the 204 screws in the FG group, 175 screws were grade A, with 16 screws scored as grade B, 8 screws scored as grade C, 3 screws scored as grade D, and 2 screws scored as grade E. The rate of perfect screw position (grade A) was higher in the RA group than in the FG group (93.2% vs. 85.8%, respectively; P = 0.020). In the FG group, 191 screws (93.6%) were clinically acceptable (groups A and B), whereas more acceptable screw positions were achieved in the RA group (98.3%; P = 0.024). Fewer screws in the RA group violated the proximal facet joint (5 vs. 24 screws, respectively; P = 0.001). The radiation dose was lower in the RA group (25.9 ± 14.2 vs. 70.5 ± 27.3 µSv, respectively; P < 0.001). Two screws in the FG group required a revision, but no revision was required in the RA group. CONCLUSIONS: RA pedicle screw placement is an accurate and safe procedure in TLIF for lumbar degenerative disease.

The Effect and Safety of Polymethylmethacrylate-Augmented Sacral Pedicle Screws Applied in Osteoporotic Spine with Lumbosacral Degenerative Disease: A 2-Year Follow-up of 25 Patients.

BACKGROUND: A high rate of instrumentation failure is frequently seen in osteoporotic spines, especially at the sacral segment because of the great shear stress. Several techniques of sacral pedicle screw placement, such as bicortical and tricortical fixation, have been developed; however, the problems of loosening and pulling out of the screws are still a concern. Recently, the polymethylmethacrylate (PMMA)-augmented pedicle screws have been shown to strengthen the purchase in osteoporotic spine, but there are few reports on the effect of S1 pedicle screw with PMMA augmentation. METHODS: Seventy-five patients receiving cement-augmented pedicle screws at lumbosacral vertebra were enrolled and divided into 3 groups by different patterns of S1 pedicle screw placement: S1 pedicle screw with PMMA augmentation (group A, 25 patients), S1 bicortical pedicle screw fixation (group B, 25 patients), and S1 tricortical pedicle screw fixation (group C, 25 patients). The Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores were assessed preoperatively and at the last follow-up. Besides, the complications, loosening rate, and fusion rate were recorded. RESULTS: The VAS and ODI scores at the last follow-up were significantly improved in the 3 groups compared with preoperative results. Better pain relief and functional improvement at the last follow-up was seen in group A compared with the other 2 groups; however, no significant difference was detected between groups B and C. Although the lowest screws loosening rates and the highest fusion rate were found in group A, no significant difference among these 3 groups. Furthermore, longer fusion segments and larger postoperative pelvic incidence-lumbar lordosis (PL-LL) were found as risks related to S1 screw loosening without cement augmentation. CONCLUSIONS: The S1 pedicle screws with PMMA augmentation achieved better stability with less screw loosening in the osteoporotic spine with lumbosacral degenerative diseases compared with bicortical/tricortical fixation at S1. This procedure is especially recommended for patients with long segment fixation and large postoperative PI-LL, but there is also a risk of bone cement leakage and a learning curve.