Zonisamide improves axial symptoms in dementia with Lewy bodies with parkinsonism: Post hoc analysis of clinical trials.

Patients with dementia with Lewy bodies (DLB) experience worsening axial symptoms with disease progression, which can negatively affect quality of life. Previous phase 2 and 3 clinical trials conducted in Japan showed that zonisamide improved parkinsonism in patients with DLB. In the present study, we performed a post hoc analysis of pooled data from the previous phase 2 and 3 trials to examine the effect of zonisamide on axial symptoms in this patient group. In our pooled analysis, the primary outcome was the change from baseline to 12 weeks in axial symptom score, measured as the sum of Unified Parkinson's Disease Rating Scale Part III items relevant to gait/balance/midline function. A total of 498 patients were included in this analysis. Zonisamide 25 mg and 50 mg significantly reduced the axial symptom score at week 12 compared with placebo (p < 0.01 and p < 0.001, respectively, by mixed model of repeated measures). Our findings indicate that zonisamide may improve axial symptoms in DLB with parkinsonism and, thus, may potentially reduce the risk of falls and improve quality of life in this vulnerable patient population.

[Effect of modified lateral mass screws implantation strategy on axial symptoms in cervical expansive open-door laminoplasty].

OBJECTIVE: To investigate the effect of modified lateral mass screws implantation strategy on axial symptoms in cervical expansive open-door laminoplasty. METHODS: A clinical data of 166 patients, who underwent cervical expansive open-door laminoplasty between August 2011 and July 2016 and met the selection criteria, was retrospective analyzed. Among them, 81 patients were admitted before August 2014 using the traditional mini-plate placement and lateral mass screws implantation strategy (control group), and 85 patients were admitted after August 2014 using modified lateral mass screws implantation strategy (modified group). There was no significant difference in the gender composition, age, clinical diagnosis, disease duration, diseased segment, and preoperative Japanese Orthopaedic Association (JOA) score, pain visual analogue scale (VAS) score, Neck Disability Index (NDI), cervical curvature and range of motion, spinal canal diameter and cross-sectional areas, and Pavlov's value between the two groups ( P>0.05). The operation time, intraoperative blood loss, the number of facet joints penetrated by lateral mass screws, effectiveness evaluation indexes (JOA score and improvement rate, VAS score, NDI), imaging evaluation indexes (cervical curvature and range of motion, spinal canal diameter and cross-sectional areas, Pavlov's value, and lamina open angle), and complications were recorded and compared between the two groups. RESULTS: The modified group had shorter operation time and lower intraoperative blood loss than the control group ( P<0.05). There were 121 (29.9%, 121/405) and 10 (2.4%, 10/417) facet joints penetrated by lateral mass screws in control and modified groups, respectively; and the difference in incidence was significant ( χ 2=115.797, P=0.000). Eighteen patients in control group had 3 or more facet joints penetrated while no patients in modified group suffered 3 or more facet joint penetrated. The difference between the two groups was significant ( P=0.000). All patients were followed up, the follow-up time was (28.7±4.9) months in modified group and (42.4±10.7) months in control group, showing significant difference ( t=10.718, P=0.000). The JOA score, VAS score, and NDI at last follow-up of the two groups were significantly improved compared with preoperative ( P<0.05); there was no significant difference in JOA score and improvement rate and VAS score between the two groups ( P>0.05), but the NDI was significantly lower in modified group than in control group ( P<0.05). There were significant differences in cervical curvature and range of motion, spinal canal diameter, Pavlov's value, and cross-sectional areas at last follow-up when compared with those before operation in both groups ( P<0.05). There was no significant difference in the above indicators and lamina open angle between the two groups ( P>0.05). The modified group has a relative lower axial symptom rate (23/85, 27.1%) than the control group (27/81, 33.3%), but the difference was not significant ( Z=-1.446, P=0.148). There was no significant differences between the two groups in the incidences of C 5 nerve root palsy, cerebrospinal fluid leakage, wound infection, and lung or urinary tract infection ( P>0.05). CONCLUSION: In the cervical expansive open-door laminoplasty, the modified lateral mass screws implantation strategy can effectively reduce the risk of lateral mass screw penetrated to the cervical facet joints, and thus has a positive significance in avoiding the axial symptoms caused by facet joint destruction.

Factors associated with postoperative axial symptom after expansive open-door laminoplasty: retrospective study using multivariable analysis.

PURPOSE: The aim of the present study was to investigate the factors associated with axial symptom using multivariable analysis. METHODS: The authors retrospectively assessed 249 patients treated by open-door laminoplasty. The patients were classified into two groups: axial symptom and no axial symptom group. The possible factors included demographic variables (age, sex, BMI, smoking, heart disease, diabetes, preoperative neck pain, preoperative JOA scores, preoperative NDI, course of disease and pathogenesis) and surgical and radiological variables [operation time, intraoperative blood loss, collar wear time, preoperative cervical curvature, postoperative cervical curvature, T1 slope, preoperative and postoperative C2 sagittal vertical axis (C2 SVA)]. RESULTS: The prevalence of axial symptom was 34.9% (89/249). The collar wear time, preoperative and postoperative C2 SVA were risk factors for axial symptom. A cutoff value of 22.6 mm for preoperative C2 SVA and 3.5 weeks for collar wear time predicted the development of axial symptom. CONCLUSIONS: The longer collar wear time, larger preoperative and postoperative C2 SVA were positively correlated with the higher incidence of axial symptom.

A Phase 2a Trial Investigating the Safety and Tolerability of the Novel Cortical Enhancer IRL752 in Parkinson's Disease Dementia.

BACKGROUND: IRL752 is a novel small-molecule compound that acts to regioselectively enhance norepinephrine, dopamine, and acetylcholine neurotransmission in the cerebral cortex. OBJECTIVE: The primary objective of the trial was to investigate the safety and tolerability of IRL752 in patients with Parkinson's disease and dementia. METHODS: Patients with Parkinson's disease and dementia were randomized to IRL752 or placebo treatment (3:1 ratio) for 28 days. The study drug was given as an adjunct treatment to the patients' regular stable antiparkinsonian medication. Dosing was individually titrated for 14 days after which the dose was kept stable for an additional 14 days. RESULTS: A total of 32 patients were randomized to treatment, and 29 patients completed the 4-week treatment. Adverse events were generally mild and transient and were mostly reported during the dose titration phase. There were 2 serious adverse events, and none of them were related to the experimental treatment. The average dose achieved in the stable dose phase was 600 mg daily, yielding a 2-hour postdose plasma concentration of about 4 µM on day 28. Exploratory assessment of secondary outcomes indicated efficacy for symptoms and signs known to be poorly responsive to levodopa. CONCLUSIONS: IRL752 appears to be safe and well tolerated for a 4-week treatment in patients with Parkinson's disease and dementia. © 2020 International Parkinson and Movement Disorder Society.

Comparison of Axial Symptoms and Limitations of Activities of Daily Living Accompanying Reduced Neck Mobility After Cervical Laminoplasty Preserving C2 Muscle Attachments With and Without C2 to T1 Instrumented Fusion.

OBJECTIVE: Muscles are usually detached from C2 to facilitate C2 pedicle screw insertion. The aim of this study was to compare 1-year postoperative axial symptoms and limitations in activities of daily livings (ADLs) accompanying reduced neck mobility between 2 procedures in which all C2 muscle attachments are preserved: laminoplasty and C2 to T1 fusion (LPF group: n=15) and laminoplasty alone (LP group: n=26). METHODS: We examined axial symptoms and limitations in ADLs using the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire. We also examined related factors, including the occiput (O)-C7 angle in extension and flexion, and the rotational and O-C2 ranges of motion (ROM). RESULTS: The postoperative decreases in the O-C7 angle in flexion (27.8° vs. 9.4°) and rotational ROM (40° vs. 15°), as well as the compensating postoperative increase in the O-C2 ROM (11.7° vs. 2.3°), were significantly greater in the LPF group. Most of the axial symptoms were similar between groups. The ability to perform ADLs tended to worsen more frequently in the LPF group, but the difference did not achieve significance. CONCLUSION: Postoperative changes in axial symptoms and loss of ROM were not obstacles affecting patients' ability to perform ADLs after laminoplasty with muscle-sparing C2 to T1 fusion.

[Application of modified micro titanium plate for extensor attachment point reconstruction in open-door laminoplasty].

Objective: To observe the effect of modified micro titanium plate for extensor attachment point reconstruction in open-door laminoplasty. Methods: From January 2016 to February 2017, 26 patients with cervical spondylotic myelopathy underwent open-door laminoplasty+modified micro-titanium plate fixation+extensor muscle attachment point reconstruction at Tianjin Hospital were enrolled in this study. There were 14 males and 12 females in this group, aged (59±18) years. The improvement of neurological function based on the Japanese Orthopedic Association (JOA) score and the changes cervical curvature based on the cervical curvature index (CCI), especially the atrophy of the back muscles and the occurrence axial symptoms were recorded and analyzed. Intra-group comparisons were performed by using repeated measures of variance analysis or paired t-test. Results: The operations were performed well without injury to spinal cord. The operation time was (116±32) min with a blood loss of (196±41) ml. The JOA scores was improved form 7.8±2.1 preoperatively to 13.5±3.4 three months after surgery, and 13.9±3.7 at the final follow up (F=30.619, P<0.05). The improvement rate of neurological function was 66%±13%. The CCI decreased from 14.3%±3.9% preoperatively to 13.7%±3.7% three months after surgery and 13.0%±3.3% at the last follow-up (F=0.829, P>0.05). The cross-sectional area of the posterior cervical muscle was (35.9±7.6) cm(2) before surgery, and it was (33.5±6.7) cm(2) at the last follow-up (t=1.208, P>0.05). The spinal cord drift distance was (2.6±0.5) mm. The axial symptoms occurred in three patients, the incidence rate was 11.5%. Conclusion: In the open-door laminectomy, modified micro titanium plate can maintain the stability of the cervical spine, it also can rebuild the extensor attachment points and reduce the atrophy of the posterior cervical muscles, which avoid the occurrence of kyphotic deformity and reduce the occurrence of axial symptoms.

[Analysis of influencing factors the postoperative axial symptoms of cervical single open-door laminoplasty].

OBJECTIVE: To explore the influencing factors and possible mechanism of axial symptoms(AS) after C3-C7 single open-door laminoplasty in patients with chronic compression cervical myelopathy. METHODS: The clinical data of 32 patients with multi-segment chronic compression cervical cord disease treated by C3-C7 single open-door laminectomy from May 2012 to July 2016 were retrospectively analyzed. Including cervical spondylotic myelopathy of 14 cases, developmental cervical stenosis complicated with cervical myelopathy of 8 cases, ossification of posterior longitudinal ligament(OPLL) of 10 cases. There were 17 males and 15 females, aged from 47 to 82 years old with an average of 57.46 year, the course of disease was 5 to 35 months with an average of 22.4 months. The opening angle(OA), cervical curvature angle(CA), preoperative spinal cord compression rate(PSCR) and postoperative spinal cord shift (PSCS) were recorded. After 2 weeks of surgery, determining whether occurred an AS condition according to the AS assessment criteria, the patients were divided into a axial symptom group and a non-axial symptom group, the general data and imaging parameters of the two groups were compared and the factors that may be postoperative AS were analyzed by binary Logistic regression analysis. RESULTS: At 2 weeks after operation, 13 patients occurred AS. There was no significant difference in gender, age and course of disease between axial symptom group and a non-axial symptom group (P>0.05). In axial symptom group, OA was(36.76±9.35)°, CA was(11.53±4.36)°, PSCR was(27.83±1.72)%, PSCS was (3.17±0.81) mm, while in non-axial symptom group, above items were (33.03±10.52)°, (7.71±4.73)°, (25.16±3.59)%, (2.43±0.95) mm, respectively, there was significant difference in CA, PSCR, PSCS between two groups(P<0.05), and there was no significant difference in OA between two groups(P>0.05). The results of the binary Logistic regression analysis of 3 parameters(OA, PSCR, PSCS) and AS showed OA and PSCR were eliminated in dependent variables, and the partial regression coefficient of PSCR was 0.311, and P=0.031. CONCLUSIONS: CA, PSCR, and PSCS are related influencing factors of AS, and PSCS is a high risk factor for AS. C4,5 nerve traction caused by posterior spinal movement, postoperative dural self-expansion causes greater traction of the spinal cord, excessive deformation of the cervical spinal cord causes autonomic nerve damage or necrosis that dominates blood vessels may be the pathogenesis of AS, but this is only a theoretical inference, and further improved experiment is necessary to verify it in the future.

Analysis of influencing factors the postoperative axial symptoms of cervical single open-door laminoplasty / 中国骨伤

OBJECTIVE@#To explore the influencing factors and possible mechanism of axial symptoms(AS) after C₃-C₇ single open-door laminoplasty in patients with chronic compression cervical myelopathy.@*METHODS@#The clinical data of 32 patients with multi-segment chronic compression cervical cord disease treated by C₃-C₇ single open-door laminectomy from May 2012 to July 2016 were retrospectively analyzed. Including cervical spondylotic myelopathy of 14 cases, developmental cervical stenosis complicated with cervical myelopathy of 8 cases, ossification of posterior longitudinal ligament(OPLL) of 10 cases. There were 17 males and 15 females, aged from 47 to 82 years old with an average of 57.46 year, the course of disease was 5 to 35 months with an average of 22.4 months. The opening angle(OA), cervical curvature angle(CA), preoperative spinal cord compression rate(PSCR) and postoperative spinal cord shift (PSCS) were recorded. After 2 weeks of surgery, determining whether occurred an AS condition according to the AS assessment criteria, the patients were divided into a axial symptom group and a non-axial symptom group, the general data and imaging parameters of the two groups were compared and the factors that may be postoperative AS were analyzed by binary Logistic regression analysis.@*RESULTS@#At 2 weeks after operation, 13 patients occurred AS. There was no significant difference in gender, age and course of disease between axial symptom group and a non-axial symptom group (>0.05). In axial symptom group, OA was(36.76±9.35)°, CA was(11.53±4.36)°, PSCR was(27.83±1.72)%, PSCS was (3.17±0.81) mm, while in non-axial symptom group, above items were (33.03±10.52)°, (7.71±4.73)°, (25.16±3.59)%, (2.43±0.95) mm, respectively, there was significant difference in CA, PSCR, PSCS between two groups(0.05). The results of the binary Logistic regression analysis of 3 parameters(OA, PSCR, PSCS) and AS showed OA and PSCR were eliminated in dependent variables, and the partial regression coefficient of PSCR was 0.311, and =0.031.@*CONCLUSIONS@#CA, PSCR, and PSCS are related influencing factors of AS, and PSCS is a high risk factor for AS. C₄,₅ nerve traction caused by posterior spinal movement, postoperative dural self-expansion causes greater traction of the spinal cord, excessive deformation of the cervical spinal cord causes autonomic nerve damage or necrosis that dominates blood vessels may be the pathogenesis of AS, but this is only a theoretical inference, and further improved experiment is necessary to verify it in the future.

Influence on postoperative axial symptom by unilateral laminoplasty combined with different fixations / 医疗卫生装备

Objective To observe the influence of preoperatively physical curvature abnormality and different fixation systems on postoperative axial symptom (PAS) and union rate of hinge groove after unilateral expansive laminoplasty for the patient with cervical spondylotic myelopathy (CSM).Methods The study reviewed 106 CSM patients who underwent unilateral laminoplasty supplemented by lateral mass or pedicle screw/rod fixation with a minimum of 36 months of follow-up.According to being complicated with physical curvature abnormality or not,the incidence,initial onset,severity,duration of PAS and union rate of hinge groove at postoperative 6 months were respectively compared to analyze the influences of two internal methods on the features of PAS.Results For 50 cases without physical curvature abnormality,fusion rates of hinge groove in pedicle placement group was higher than that in lateral mass fixation group,the P value reached statistical difference (t=142.2,P=0.032).Duration of PAS in pedicle group was shorter than that in lateral mass group,the difference reached statistic significance (t=147.2,P=0.019).For 56 cases of with physical curvature abnormality,incidence of PAS in pedicle group presented was lower than that in lateral mass group,the difference achieved statistic significance (x2=3.89,P=-0.042).Conclusion Whether concomitant with physical curvature abnormality or not,pedicle fixation would be beneficial to promoting bony fusion of hinge groove,shortening duration of PAS and reducing incidence of PAS in contrast to lateral mass fixation to some extent after unilateral laminoplasty for treating CSM patients.

Prevalence of axial symptoms after posterior cervical decompression: a meta-analysis.

PURPOSE: To investigate the prevalence of axial symptoms (AS) in patients following posterior cervical decompression. METHODS: We searched the PubMed, Embase, and Cochrane databases for relevant studies that reported the incidence of AS after posterior cervical decompression, and manually screened reference lists for additional studies. Relevant prevalence estimates were calculated. Subgroup analysis, sensitivity analysis and publication bias assessment were also performed. RESULTS: Our meta-analysis included 44 studies, with 893 AS cases in 2984 patients. The pooled AS prevalence was 28 % (95 % CI 24-32). The prevalence of AS was higher after expansive open-door laminoplasty (39 %) than after modified open-door laminoplasty (MOLP, 23 %) and laminectomy instrumented fusion (29 %). AS prevalence was also higher in those that wore a neck collar for 2-3 months (34 %) compared with 2 weeks (21 %). The lowest AS prevalence (9 %) was found in patients who underwent MOLP with C3 laminectomy and C7 spinous processes conserved. There was an intermediate AS prevalence after MOLP with C7 spinous processes conserved (16 %), MOLP with preservation of the unilateral posterior muscular-ligament complex (19 %), MOLP with C3 laminectomy (22 %), and MOLP with plate fixation (23 %). Prevalence of AS might be higher in patients <60 years and increased in populations with a higher proportion of females. CONCLUSIONS: Posterior cervical surgery carries a high risk of postoperative AS. Postoperative AS may be reduced through preserving posterior muscles and structures, stabilizing cervical vertebrae, and reducing external cervical immobilization time.

Correlation of height change of intervertebral space of fused segment with axial synptoms after anterior cervical fusion / 中国矫形外科杂志

[Objective] To investigate the height change of intervertebral space after anterior cervical fusion and its relation to neck axial symptoms.[Method]Totally 122 patients receiving anterior cervical fusion were followed up for 2 to 5 years,average 3.9 years.The height change of intervertebral space of the fused segment on X-rays were evaluated before,3 months and 2 years after operation.All patients were classified into 3 groups by means of the postoperative height change of intervertebral space.The axial symptoms after operation were observed and analyzed during follow-up.[Result]The incidence of neck axial symptoms was 54.55%,25.84% and 45.45%,respectively.There were significant differences in statistical analysis in group A group B,group B to group C(x2=7.18,P0.0125).[Conclusion]There is significant relation between height change of intervertebral space and neck axial symptoms after anterior cervical fusion.