Development of patient-reported outcome for adult spinal deformity: validation study.

Adult spinal deformity (ASD) is a complex condition that combines scoliosis, kyphosis, pain, and postoperative range of motion limitation. The lack of a scale that can successfully capture this complex condition is a clinical challenge. We aimed to develop a disease-specific scale for ASD. The study included 106 patients (mean age; 68 years, 89 women) with ASD. We selected 29 questions that could be useful in assessing ASD and asked the patients to answer them. The factor analysis found two factors: the main symptom and the collateral symptom. The main symptom consisted of 10 questions and assessed activity of daily living (ADL), pain, and appearance. The collateral symptom consisted of five questions to assess ADL due to range of motion limitation. Cronbach's alpha was 0.90 and 0.84, respectively. The Spearman's correlation coefficient between the change of main symptom and satisfaction was 0.48 (p < 0.001). The effect size of Cohen's d for comparison between preoperative and postoperative scores was 1.09 in the main symptom and 0.65 in the collateral symptom. In conclusion, we have developed a validated disease-specific scale for ASD that can simultaneously evaluate the benefits and limitations of ASD surgery with enough responsiveness in clinical practice.

Mid-Term Results of Single-Level Posterior Lumbar Interbody Fusion in Patients with Pelvic Incidence Minus Lumbar Lordosis Mismatch.

BACKGROUND: Recent literature suggests that sagittal imbalance is a risk factor for adjacent segment disease following fusion surgery. This study explored the influence of pelvic incidence minus lumbar lordosis (PI-LL) mismatch on the mid-term results and reoperation rate after single-level posterior lumbar interbody fusion (PLIF). METHODS: The participants of this study included 253 patients (80 men and 173 women; mean age 68.2 years) who underwent L4-5 single-segment PLIF. Preoperative PI-LL mismatch was defined as a PI-LL of 30° or greater. The patients were divided into 2 groups according to the presence or absence of PI-LL mismatch (PI-LL mismatch group; group M, Control group; group C), and the clinical outcomes and radiographic parameters were compared. RESULTS: Of the 253 cases, 25 were classified in group M and 228 in group C. The Japanese Orthopaedic Association score at 5 years postoperatively was 23.0 ± 3.6 in group M and 23.5 ± 5.1 in group C, and the recovery rate was 66.2 ± 32.6% in group M and 64.6 ± 21.4% in group C and there was no significant difference in the recovery rate between the 2 groups. All radiographic parameters except sacral slope were significantly worse in group M. One patient (4.3%) in Group M and 18 patients (7.8%) in Group C required revision surgery at 2.4 years (range 0.0-5.0) and there was no significant difference in the revision rate between the 2 groups. CONCLUSIONS: The mid-term results of L4-5 single-level PLIF were compared with and without PI-LL mismatch, with the threshold defined as 30°; however, there were no significant differences in both the Japanese Orthopaedic Association recovery and reoperation rates between the 2 groups.

Long-term outcomes of spine surgery in dialysis patients, focusing on activities of daily living, life expectancy, and the risk factors for postoperative mortality.

BACKGROUND: Because of the high incidence of major perioperative adverse events, spine surgery in dialysis patients should be recommended carefully after consideration of its risks and benefits. However, the benefits of spine surgery in dialysis patients remain unclear because of the lack of long-term outcomes. The purpose of this study is to elucidate the long-term outcomes of spine surgery in dialysis patients, focusing on activities of daily living (ADLs), life expectancy, and risk factors for postoperative mortality. METHODS: Data for 65 dialysis patients who underwent spine surgery at our institution and were followed up for a mean duration of 6.2 years were retrospectively reviewed. ADLs, number of surgeries, and survival times were recorded. The postoperative survival rate was calculated using the Kaplan-Meier method, and risk factors for postoperative mortality were investigated using a generalized Wilcoxon test and multivariate Cox proportional-hazards model. RESULTS: Compared with preoperative ADLs, ADLs significantly improved at discharge after surgery and at the final follow-up. However, 16 of the 65 patients (24.6%) underwent multiple surgeries, and 34 (52.3%) died during the follow-up period. Kaplan-Meier analysis revealed that the survival rate after spine surgery was 95.4% at 1 year, 86.2% at 3 years, 69.6% at 5 years, 59.7% at 7 years, and 28.7% at 10 years, and the overall median survival time was 99 months. Multivariate Cox regression analysis showed that a dialysis period of ≥10 years was a significant risk factor. CONCLUSIONS: Spine surgery in dialysis patients improved and maintained ADLs in the long term and did not shorten life expectancy. However, dialysis patients undergoing spine surgery require multiple surgeries more frequently, and a dialysis period of ≥10 years is a significant risk factor for postoperative mortality.

Management of Antithrombotic Drugs before Elective Spine Surgery: A Nationwide Web-Based Questionnaire Survey in Japan.

Introduction: The number of patients on antithrombotic drugs for coronary heart disease or cerebrovascular disease has been increasing with the aging of society. We occasionally need to decide whether to continue or discontinue antithrombotic drugs before spine surgery. The purpose of this study is to understand the current perioperative management of antithrombotic drugs before elective spine surgery in Japan. Methods: In 2021, members of the Japanese Society for Spine Surgery and Related Research (JSSR) were asked to complete a web-based questionnaire survey that included items concerning the respondents' surgical experience, their policy regarding discontinuation or continuation of antithrombotic drugs, their reasons for decisions concerning the management of antithrombotic drugs, and their experience of perioperative complications related to the continuation or discontinuation of these drugs. Results: A total of 1,181 spine surgeons returned completed questionnaires, giving a response rate of 32.0%. JSSR board-certified spine surgeons comprised 75.1% of the respondents. Depending on the management policy regarding antithrombotic drugs for each comorbidity, approximately 73% of respondents discontinued these drugs before elective spine surgery, and about 80% also discontinued anticoagulants. Only 4%-5% of respondents reported continuing antiplatelet drugs, and 2.5% reported continuing anticoagulants. Among the respondents who discontinued antiplatelet drugs, 20.4% reported having encountered cerebral infarction and 3.7% reported encountering myocardial infarction; among those who discontinued anticoagulants, 13.6% reported encountering cerebral embolism and 5.4% reported encountering pulmonary embolism. However, among the respondents who continued antiplatelet drugs and those who continued anticoagulants, 26.3% and 27.2%, respectively, encountered an unexpected increase in intraoperative bleeding, and 10.3% and 8.7%, respectively, encountered postoperative spinal epidural hematoma requiring emergency surgery. Conclusions: Our findings indicate that, in principle, >70% of JSSR members discontinue antithrombotic drugs before elective spine surgery. However, those with a discontinuation policy have encountered thrombotic complications, while those with a continuation policy have encountered hemorrhagic complications.

Spinopelvic sagittal realignment and incidence of adjacent segment disease after single-segment posterior lumbar inter-body fusion using 12° lordotic cages-a 2-year prospective cohort study.

Background: The importance of spinopelvic sagittal alignment for adjacent segment disease (ASD) after lumbar fusion surgery has been reported. However, no longitudinal cohort studies have determined the extent to which segmental alignment and spinopelvic global alignment can be achieved using 12° lordotic cages in posterior lumbar inter-body fusion (PLIF) and the extent to which the development of ASD can be prevented. The purpose of this study was to analyze changes in segmental and spinopelvic sagittal alignment after single-segment PLIF with 12° lordotic cages, to clarify the relationship between changes in segmental and spinopelvic sagittal alignment, and to report the incidence of ASD at 2 years postoperatively. Methods: Subjects in this 2-year prospective longitudinal cohort study were 28 patients who had undergone L4/5 PLIF using 12° lordotic cages. Incidence of operative ASD (O-ASD) was evaluated as clinical outcomes. Radiological measurements were examined preoperatively and at 3 months, 1 year and 2 years postoperatively. The following radiographic spinopelvic parameters were measured: segmental lordosis (SL) at L4/5; sagittal vertical axis (SVA); T1 pelvic angle (TPA); thoracic kyphosis (TK); lumbar lordosis (LL); sacral slope (SS); pelvic tilt (PT); and pelvic incidence (PI). With respect to radiological outcomes, changes in SL (ΔSL) and spinopelvic parameters and the incidence of radiological ASD (R-ASD) were evaluated. Correlations of ΔSL and changes in other spinopelvic parameters (ΔSVA, ΔTPA, ΔTK, ΔLL, ΔSS, ΔPT, and ΔPI-LL) between preoperatively and 3 months postoperatively were examined. Results: The follow-up rate was 100% (n=28) at 1 year postoperatively and 96.4% (n=27) at 2 years postoperatively. No cases of O-ASD were seen during 2 years of follow-up. Significant realignment was observed and maintained at 2 years postoperatively in almost all spinopelvic sagittal parameters (SL, SVA, TPA, LL, PT, PI-LL). Regarding the correlation between ΔSL and other parameters, significant correlations were detected with ΔSVA (r=-0.37, P<0.05) and ΔLL (r=0.538, P<0.01). Three cases (11.1%) showed R-ASD at 2 years postoperatively. Conclusions: PLIF with 12° lordotic cages for L4 degenerative spondylolisthesis improved SL and global sagittal realignment, and achieved satisfactory clinical outcomes with a low incidence of ASD during 2 years of follow-up.

[Autologous stem cell transplantation after pola-BR regimen as a salvage therapy in relapsed diffuse large B-cell lymphoma].

A 57-year-old male patient with relapsed/refractory diffuse large B-cell lymphoma received 4 courses of Pola-BR (polatuzumab vedotin-bendamustine-rituximab). After treatment, stem cell collection with G-CSF and plerixafor successfully yielded 4.2×106 cells/kg of CD34-positive cells. The patient underwent autologous peripheral hematopoietic stem cell transplantation. Neutrophil engraftment was achieved on day 12 and the patient was followed up without progression. In this case, stem cell mobilization with G-CSF and plerixafor was effective even in patients who had received chemotherapy including bendamustine, which is known to sometimes complicate stem cell collection. Although bendamustine should generally be avoided in cases where stem cell collection is planned, there are cases in which the decision to perform transplantation is made after chemotherapy including bendamustine. We have reported a case in which we were able to perform stem cell collection after pola-BR regimen.

Striatal-Inoculation of α-Synuclein Preformed Fibrils Aggravated the Phenotypes of REM Sleep without Atonia in A53T BAC-SNCA Transgenic Mice.

Accumulation of α-synuclein (α-syn) is the pathological hallmark of α-synucleinopathy. Rapid eye movement (REM) sleep behavior disorder (RBD) is a pivotal manifestation of α-synucleinopathy including Parkinson's disease (PD). RBD is clinically confirmed by REM sleep without atonia (RWA) in polysomnography. To accurately characterize RWA preceding RBD and their underlying α-syn pathology, we inoculated α-syn preformed fibrils (PFFs) into the striatum of A53T human α-syn BAC transgenic (A53T BAC-SNCA Tg) mice which exhibit RBD-like phenotypes with RWA. RWA phenotypes were aggravated by PFFs-inoculation in A53T BAC-SNCA Tg mice at 1 month after inoculation, in which prominent α-syn pathology in the pedunculopontine nucleus (PPN) was observed. The intensity of RWA phenotype could be dependent on the severity of the underlying α-syn pathology.

Lewy Body Disease Primate Model with α-Synuclein Propagation from the Olfactory Bulb.

BACKGROUND: Lewy body diseases (LBDs), which are pathologically defined as the presence of intraneuronal α-synuclein (α-Syn) inclusions called Lewy bodies, encompass Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies. Autopsy studies have shown that the olfactory bulb (OB) is one of the regions where Lewy pathology develops and initiates its spread in the brain. OBJECTIVE: This study aims to clarify how Lewy pathology spreads from the OB and affects brain functions using nonhuman primates. METHODS: We inoculated α-Syn preformed fibrils into the unilateral OBs of common marmosets (Callithrix jacchus) and performed pathological analyses, manganese-enhanced magnetic resonance imaging, and 18 F-fluoro-2-deoxy-d-glucose positron emission tomography up to 6 months postinoculation. RESULTS: Severe α-Syn pathology was observed within the olfactory pathway and limbic system, while mild α-Syn pathology was seen in a wide range of brain regions, including the substantia nigra pars compacta, locus coeruleus, and even dorsal motor nucleus of the vagus nerve. The brain imaging analyses showed reduction in volume of the OB and progressive glucose hypometabolism in widespread brain regions, including the occipital lobe, and extended beyond the pathologically affected regions. CONCLUSIONS: We generated a novel nonhuman primate LBD model with α-Syn propagation from the OB. This model suggests that α-Syn propagation from the OB is related to OB atrophy and cerebral glucose hypometabolism in LBDs. © 2022 International Parkinson and Movement Disorder Society.

Rapid Induction of Dopaminergic Neuron Loss Accompanied by Lewy Body-Like Inclusions in A53T BAC-SNCA Transgenic Mice.

Parkinson's disease (PD), the most common neurodegenerative movement disorder, is characterized by dopaminergic neuron loss in the substantia nigra pars compacta (SNpc) and intraneuronal α-synuclein (α-syn) inclusions. It is highly needed to establish a rodent model that recapitulates the clinicopathological features of PD within a short period to efficiently investigate the pathological mechanisms and test disease-modifying therapies. To this end, we analyzed three mouse lines, i.e., wild-type mice, wild-type human α-syn bacterial artificial chromosome (BAC) transgenic (BAC-SNCA Tg) mice, and A53T human α-syn BAC transgenic (A53T BAC-SNCA Tg) mice, receiving dorsal striatum injections of human and mouse α-syn preformed fibrils (hPFFs and mPFFs, respectively). mPFF injections induced more severe α-syn pathology in most brain regions, including the ipsilateral SNpc, than hPFF injections in all genotypes at 1-month post-injection. Although these Tg mouse lines expressed a comparable amount of α-syn in the brains, the mPFF-injected A53T BAC-SNCA Tg mice exhibited the most severe α-syn pathology as early as 0.5-month post-injection. The mPFF-injected A53T BAC-SNCA Tg mice showed a 38% reduction in tyrosine hydroxylase (TH)-positive neurons in the ipsilateral SNpc, apomorphine-induced rotational behavior, and motor dysfunction at 2 months post-injection. These data indicate that the extent of α-syn pathology induced by α-syn PFF injection depends on the types of α-syn PFFs and exogenously expressed α-syn in Tg mice. The mPFF-injected A53T BAC-SNCA Tg mice recapitulate the key features of PD more rapidly than previously reported mouse models, suggesting their usefulness for testing disease-modifying therapies as well as analyzing the pathological mechanisms.

Preoperative Pelvic Incidence Minus Lumbar Lordosis Mismatch in Repeat Posterior Lumbar Interbody Fusion Induces Subsequent Corrective Long Fusion.

OBJECTIVE: Only a few studies have addressed clinical outcomes of revision surgery for adjacent segment disease. The purpose of this study was to elucidate clinical outcomes of second (repeat) posterior lumbar interbody fusion (PLIF) by focusing on the relationship between clinical outcomes and spinopelvic parameters and predisposing factors requiring subsequent corrective long fusion after repeat PLIF. METHODS: We analyzed the data of 47 patients ≥40 years old who underwent repeat PLIF after single-segment PLIF owing to adjacent segment disease. The correlation between clinical outcomes and radiographic parameters was investigated. Patient demographics and radiographic parameters were compared between patients with and without subsequent corrective long fusion. RESULTS: Japanese Orthopaedic Association score at final follow-up was 13.4, and the recovery rate was 37.2%. All sagittal parameters except pelvic tilt and C7-central sacral vertical line at final follow-up showed weak to moderate (|r| = 0.30-0.56) correlation with clinical scores. Finally, 11% of patients required subsequent long corrective fusion. Pelvic incidence minus lumbar lordosis (PI-LL) mismatch (cutoff value of 27.5°) and thoracic kyphosis (cutoff value of 12.5°) before repeat PLIF were identified as predisposing factors for subsequent long corrective fusion. CONCLUSIONS: The clinical outcomes of repeat PLIF were inferior to outcomes of primary PLIF. Once PI-LL mismatch occurs after initial PLIF, it will be difficult to resolve the PI-LL mismatch during the second PLIF. To stop the chain of reoperations in patients whose preoperative PI-LL exceeds 27.5° before repeat PLIF, corrective long fusion may be a surgical option to consider.

Effect of segmental lordosis on early-onset adjacent-segment disease after posterior lumbar interbody fusion.

OBJECTIVE: Although several reports have described adjacent-segment disease (ASD) after posterior lumbar interbody fusion (PLIF), there have been only a few reports focusing on early-onset ASD occurring within 3 years after primary PLIF. The purpose of this study was to investigate the prevalence and postoperative pathologies of early-onset ASD and its relation with radiological parameters such as segmental lordosis (SL). METHODS: The authors reviewed a total of 256 patients who underwent single-segment PLIF at L4-5 for degenerative lumbar spondylolisthesis (DLS) and were followed up for at least 5 years. The definition of ASD was a symptomatic condition requiring an additional operation at the adjacent fusion segment in patients who had undergone PLIF. ASD occurring within 3 years after primary PLIF was categorized as early-onset ASD. As a control group, 54 age- and sex-matched patients who had not suffered from ASD for more than 10 years were selected from this series. RESULTS: There were 42 patients with ASD at the final follow-up. ASD prevalence rates at 3, 5, and 10 years postoperatively and at the final follow-up were 5.0%, 8.2%, 14.1%, and 16.4%, respectively. With respect to ASD pathologies, lumbar disc herniation (LDH) was significantly more common in early-onset ASD, while lumbar spinal stenosis and DLS occurred more frequently in late-onset ASD. Significant differences were detected in the overall postoperative range of motion (ROM) and in the changes in ROM (ΔROM) at L3-4 (the cranial adjacent fusion segment) and changes in SL (ΔSL) at L4-5 (the fused segment), while there were no significant differences in other pre- and postoperative parameters. In stepwise logistic regression analysis, ΔSL was identified as an independent variable (p = 0.008) that demonstrated significant differences, especially in early-onset ASD (control 1.1° vs overall ASD -2.4°, p = 0.002; control 1.1° vs early-onset ASD -6.6°, p = 0.00004). CONCLUSIONS: The study results indicated that LDH was significantly more common as a pathology in early-onset ASD and that ΔSL was a major risk factor for ASD, especially early-onset ASD.

α-Synuclein Propagation Mouse Models of Parkinson's Disease.

Parkinson's disease (PD) is pathologically characterized by intraneuronal α-synuclein (α-Syn) inclusions called Lewy bodies (LBs) and the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Autopsy studies have suggested that Lewy pathology initially occurs in the olfactory bulb and enteric nervous system, subsequently spreading in the brain stereotypically. Recent studies have demonstrated that templated fibrillization and intercellular dissemination of misfolded α-Syn underlie this pathological progression. Injection of animals with α-Syn preformed fibrils (PFFs) can recapitulate LB-like inclusions and the subsequent intercellular transmission of α-Syn pathology. Moreover, targeting specific brain regions or body parts enables the generation of unique models depending on the injection sites. These features of α-Syn PFF-injected animal models provide a platform to explore disease mechanisms and to test disease modifying therapies in PD research. Here, we describe a methodology for the generation of α-Syn PFFs and the surgery on mice.

Comparing Investigation Between Bilateral Partial Laminectomy and Posterior Lumbar Interbody Fusion for Mild Degenerative Spondylolisthesis.

STUDY DESIGN: A retrospective comparative study. OBJECTIVE: The present study aims to compare the surgical outcomes between bilateral partial laminectomy (BPL) and posterior lumbar interbody fusion (PLIF) in patients with mild degree of slippage. SUMMARY OF BACKGROUND DATA: To date, there have not been established surgical procedures for patients with mild degree of slippage. Moreover, sufficient studies that have compared surgical outcomes between BPL and PLIF are very few. MATERIALS AND METHODS: In this retrospective study, the authors enrolled 202 consecutive patients with degenerative spondylolisthesis with slippage at L3 or L4 of >3% who underwent spine surgery between 2005 and 2015. Patients were grouped into those who underwent single-segment PLIF (n=106) and those who underwent BPL (n=51). To adjust for potential confounders, the inverse probability of treatment weighting based on the propensity score was used. Surgical outcomes were compared between the BPL and PLIF groups. The threshold age for the final recovery rate of >70% was evaluated using receiver operating characteristic curve analyses to assess the limit of age to achieve good outcomes. Patients who underwent reoperation in both groups were also evaluated. RESULTS: Operation time and blood loss were significantly lower in the BPL group. The final recovery rate was similar between the groups without age stratification. The cutoff age to achieve a final recovery rate of >70% was 75 years in the PLIF group, and the final recovery rate was significantly higher in the PLIF group than in the BPL group in patients aged less than 75 years but not in patients aged 75 years or older. In addition, the reoperation rate was similar between groups, and all reoperations in the PLIF group were for adjacent segment disease. CONCLUSIONS: BPL is one of the useful options in patients with mild degenerative spondylolisthesis, particularly in patients aged more than 75 years.

A Detailed Clinical Course Leading to Hypoxic Ischemic Encephalopathy After Anterior Cervical Spine Surgery: A Case Report.

CASE: A 48-year-old woman underwent anterior cervical discectomy and fusion at C5/6. Extubation was performed immediately after surgery. Tachycardia, limb tremor, and panic attack developed approximately 4 hours after surgery at 16:15. Thirty minutes later, cessation of respiration occurred at 16:50. An experienced anesthesiologist attempted intubation but was unsuccessful because of laryngopharyngeal edema at the C2 level. Finally, an otolaryngologist performed tracheotomy and secured the airway at 17:20 but hypoxic encephalopathy ensued. CONCLUSION: Predicting the airway obstruction caused by laryngopharyngeal edema was very difficult; hence, to prevent critical complications, systematic perioperative management is essential in anterior cervical spine surgery.

Anterior selective stabilization combined with laminoplasty for cervical myelopathy due to massive ossification of the posterior longitudinal ligament: report of early outcomes in 14 patients.

OBJECTIVE: Surgical management of massive ossification of the posterior longitudinal ligament (OPLL) is challenging. To reduce surgical complications, the authors have performed anterior selective stabilization combined with laminoplasty (antSS+LP) for massive OPLL since 2012. This study aimed to elucidate the short-term outcome of the antSS+LP procedure. METHODS: The authors' analysis was based on data from 14 patients who underwent antSS+LP for cervical myelopathy caused by massive OPLL and were followed up for at least 2 years after surgery (mean follow-up duration 3.3 years). Clinical outcome was evaluated preoperatively, at 6 months and 1 year postoperatively, and at the final follow-up using the Japanese Orthopaedic Association (JOA) scoring system for cervical myelopathy and the recovery rate of the JOA score. The following radiographic parameters were measured preoperatively, immediately after surgery, at 1 year after surgery, and at the final follow-up: the C2-7 angle, measured on lateral plain radiographs, and the segmental lordosis angle (SLA), measured on sagittal CT scans. The correlation between radiographic parameters and clinical outcomes was evaluated. RESULTS: The mean JOA score increased from 10.4 before surgery to 13.6 and 13.8 at 6 months and 1 year after surgery, respectively; at the final follow-up the mean score was 13.4. This postoperative recovery was significant (p = 0.004) and was maintained until the final follow-up. No patient required revision surgery due to postoperative neurological deterioration. However, the C2-7 angle gradually deteriorated postoperatively. Similarly, the SLA was significantly increased immediately after surgery, but the improvement was not maintained. The recovery rate at the final follow-up correlated positively with the change in C2-7 angle (r = 0.60, p = 0.03) and the change in SLA (r = 0.72, p < 0.01). CONCLUSIONS: AntSS+LP is safe and effective and may be an alternative to anterior decompression and fusion for the treatment of patients with massive OPLL. No postoperative neurological complications or significant postoperative exacerbation of neck pain were observed in our case series. Not only reducing intervertebral motion and decompressing the canal at the maximal compression level but also acquiring segmental lordosis at the maximal compression level are crucial factors for achieving successful outcomes of antSS+LP.

α-Synuclein BAC transgenic mice exhibit RBD-like behaviour and hyposmia: a prodromal Parkinson's disease model.

Parkinson's disease is one of the most common movement disorders and is characterized by dopaminergic cell loss and the accumulation of pathological α-synuclein, but its precise pathogenetic mechanisms remain elusive. To develop disease-modifying therapies for Parkinson's disease, an animal model that recapitulates the pathology and symptoms of the disease, especially in the prodromal stage, is indispensable. As subjects with α-synuclein gene (SNCA) multiplication as well as point mutations develop familial Parkinson's disease and a genome-wide association study in Parkinson's disease has identified SNCA as a risk gene for Parkinson's disease, the increased expression of α-synuclein is closely associated with the aetiology of Parkinson's disease. In this study we generated bacterial artificial chromosome transgenic mice harbouring SNCA and its gene expression regulatory regions in order to maintain the native expression pattern of α-synuclein. Furthermore, to enhance the pathological properties of α-synuclein, we inserted into SNCA an A53T mutation, two single-nucleotide polymorphisms identified in a genome-wide association study in Parkinson's disease and a Rep1 polymorphism, all of which are causal of familial Parkinson's disease or increase the risk of sporadic Parkinson's disease. These A53T SNCA bacterial artificial chromosome transgenic mice showed an expression pattern of human α-synuclein very similar to that of endogenous mouse α-synuclein. They expressed truncated, oligomeric and proteinase K-resistant phosphorylated forms of α-synuclein in the regions that are specifically affected in Parkinson's disease and/or dementia with Lewy bodies, including the olfactory bulb, cerebral cortex, striatum and substantia nigra. Surprisingly, these mice exhibited rapid eye movement (REM) sleep without atonia, which is a key feature of REM sleep behaviour disorder, at as early as 5 months of age. Consistent with this observation, the REM sleep-regulating neuronal populations in the lower brainstem, including the sublaterodorsal tegmental nucleus, nuclei in the ventromedial medullary reticular formation and the pedunculopontine nuclei, expressed phosphorylated α-synuclein. In addition, they also showed hyposmia at 9 months of age, which is consistent with the significant accumulation of phosphorylated α-synuclein in the olfactory bulb. The dopaminergic neurons in the substantia nigra pars compacta degenerated, and their number was decreased in an age-dependent manner by up to 17.1% at 18 months of age compared to wild-type, although the mice did not show any related locomotor dysfunction. In conclusion, we created a novel mouse model of prodromal Parkinson's disease that showed RBD-like behaviour and hyposmia without motor symptoms.

Effects of Concomitant Decompression Adjacent to a Posterior Lumbar Interbody Fusion Segment on Clinical and Radiologic Outcomes: Comparative Analysis 5 Years After Surgery.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To examine the effects of concomitant decompression adjacent to the posterior lumbar interbody fusion (PLIF) segment on the clinical and radiological outcomes 5 years after surgery. METHODS: Forty-five consecutive patients who had undergone L3/4 decompression with L4/5 PLIF for multilevel stenosis with degenerative spondylolisthesis (DS), and were followed for 5 years, were enrolled (group D). As a control group, 45 age-, sex- and preoperative disc height at L3/4-matched patients who had undergone L4/5 PLIF alone for L4/5DS were randomly selected (group A). Disc height, vertebral slippage, range of motion, posterior opening angle, segmental lordotic angle, presence of the intradiscal vacuum phenomenon (IVP) at the L3/4 level were measured on radiographs. Japanese Orthopaedic Association (JOA) score and the requirement for additional L3/4 surgery were evaluated. RESULTS: In terms of pre-/postoperative radiographic changes between the groups, significant differences were detected regarding disc height narrowing of ≥3 mm (group D 31%, group A 9%) and IVP (group D 33%, group A 11%). There were no significant differences in other radiological parameters. The recovery rate of the JOA score (group D 58%, group A 61%) and reoperation rate (group D 2.2%, group A 6.7%) were not significantly different between the groups. CONCLUSION: Concomitant decompression adjacent to the PLIF segment accelerated adjacent disc degeneration compared to PLIF alone, but it did not predispose to the development of instability 5 years after surgery. Moreover, the JOA score and reoperation rate were not significantly different between groups D and A.

Effect of segmental lordosis on the clinical outcomes of 2-level posterior lumbar interbody fusion for 2-level degenerative lumbar spondylolisthesis.

OBJECTIVE: Although the importance of spinopelvic sagittal balance and its implications for clinical outcomes of spinal fusion surgery have been described, to the authors' knowledge there have been no reports of the relationship between spinopelvic alignment and clinical outcomes for 2-level posterior lumbar interbody fusion (PLIF). The purpose of this study was to elucidate the relationship between clinical outcomes and spinopelvic sagittal parameters after 2-level PLIF for 2-level degenerative spondylolisthesis (DS). METHODS: This study was limited to patients who were treated with 2-level PLIF for 2-level DS at L3-4-5. Between 2005 and 2014, 33 patients who could be followed up for at least 2 years were included in this study. The average age at the time of surgery was 72 years, and the average follow-up period was 5.6 years. Based on clinical assessments, the Japanese Orthopaedic Association (JOA) score and recovery rate were evaluated. The patients were divided into 2 groups based on the recovery rate: the good outcome group (G group; n = 19), with recovery rate ≥ 50%, and the poor outcome group (P group; n = 14) with recovery rate < 50%. Spinopelvic parameters were measured using lateral standing radiographs of the whole spine as follows: sagittal vertical axis (SVA), thoracic kyphosis (TK), sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), lumbar lordosis (LL), and segmental lordosis (SL) at L3-4-5. The clinical outcomes and radiological parameters were assessed preoperatively and at the final follow-up. Radiological parameters were compared between the 2 groups. RESULTS: The mean JOA score improved significantly in all patients from 10.8 points before surgery to 19.6 points at the latest follow-up (mean recovery rate 47.7%). For radiological outcomes, no difference was observed from preoperative assessment to final follow-up in any of the spinopelvic parameters except SVA. Although no significant difference between the 2 groups was detected in any of the spinopelvic parameters, there were significant differences in the change in SL and LL (ΔSL 3.7° vs -2.1° and ΔLL 1.2° vs -5.6° for the G and P groups, respectively). In addition, the number of patients in the G group was significantly larger for the patients with ΔSL-plus than those with ΔSL-minus (p = 0.008). CONCLUSIONS: The clinical outcomes of 2-level PLIF for 2-level DS limited at L3-4-5 appeared to be satisfactory. The results indicate that acquisition of increased SL in surgery might lead to better clinical outcomes.