Major Motor Deficits Research Articles

875 Comparison of Anterior Versus Posterior Approaches for Management of Cervical Trauma: A National Database Study

INTRODUCTION: Cervical spine injuries are a major cause of long-term disability, accounting for almost 65% of all spinal injuries. They often result in major motor and sensory deficits and chronic pain. Prompt surgical intervention is often required to prevent further neurological deterioration and instability, yet there is no definitive evidence for the optimal operative approach. METHODS: The National Trauma Data Bank was queried from 2017 to 2019 for all patients with cervical trauma who underwent subsequent spinal fusion surgery with anterior or posterior approaches. Patients receiving combination management were excluded. Paired Student’s t-tests and Pearson’s Chi-squared analyses were used to compare differences in patient demographics, in-hospital complications, and lengths of stay between the two groups. Relative risks for the in-hospital complications were also calculated. Alpha was set to 0.05. RESULTS: A total of 10,593 patients meeting the inclusion criteria were identified, with 6,803 patients undergoing fusion with an anterior approach and 3,226 patients with a posterior approach. Patients with a posterior approach were significantly older, had a higher proportion of white and female patients, and a lower total GCS score (p < 0.05 for all). They also had higher rates of comorbidities such as hematologic disorders, COPD, CHF, Hypertension, PAD, MI, and renal disease (p < 0.05 for all). After surgery, the anterior approach group had a shorter hospital stay and a significantly lower risk of developing SSI, requiring unplanned reoperation, and experiencing MI (p < 0.05 for all). CONCLUSIONS: To our knowledge, this is the largest study assessing differences in in-hospital morbidities between surgical approaches for cervical trauma. Our findings suggest that the anterior approach has a lower risk of short-term complications, emphasizing its clinical advantage. Further research is needed to elucidate the long-term effects.

Intracapsular Enucleation of Brachial Plexus Schwannoma With Intraoperative Neuromonitoring: A Case Series Study and a Review of Literature.

Brachial plexus schwannoma (BPS) is a rare clinical entity that poses a significant challenge for head and neck surgeons due to its neuroanatomical complexity and potential severe complications, such as major motor or sensory neurological deficits or pain of the corresponding upper extremity. This article summarizes our experience in its diagnosis and intracapsular enucleation with intraoperative neuromonitoring (INM). A retrospective review of BPS cases treated at our tertiary medical institution was conducted between April 2020 and May 2023. The clinical and demographic data were retrieved from case notes. Totally, 3 cases were included. All 3 patients were male, aged 43 to 54 years (median age = 52). The presenting symptom was a palpable supraclavicular mass in all these cases (2 on the left side and 1 on the right side). Neuromonitoring was performed with a 4-channel nerve integrity monitor, with the electrodes placed in the upper arm and forearm muscles, as demonstrated in the literature. After exposing the mass and identifying its origin from the brachial plexus, a unipolar stimulating probe was used to stimulate the tumor surface or the nerves with a 1.0-mA current, and a longitudinal incision into the tumor capsule was made along a carefully mapped line with no INM response. Then the mass was carefully exposed and meticulously dissected from its capsule to achieve an intact enucleation. Immediate postoperative neurological deficit was documented in Case 1 as a mild grasping weakness. The recovery of the other 2 patients was uneventful. The follow-up duration was 7 to 38 months (median = 8 months). The minor motor deficit of Case 1 recovered completely 1 month after surgery. No recurrence of BPS was observed. Intracapsular enucleation with INM could result in complete removal of BPS and minimal postoperative neurological deficit, whose recovery was quick and satisfactory.

Mobility related confidence level in chronic stroke patients through task oriented walking intervention

Introduction
 Stroke is a neurological insufficiency caused by cerebrovascular injury resulting in major motor deficits in lower limbs. Different therapeutic interventions are being used for stroke rehabilitation. Task oriented walking intervention is a unique approach used for stroke rehabilitation. This research work was planned to study the effects of Task-Oriented walking Interventions on improving the mobility related confidence level in chronic stroke patients.
 Method
 This randomized control trial study was conducted on 48 stroke patients in hospital settings. Informed consent was taken from all the study participants before inclusion in the study population and the data from the study subjects was collected through a specially designed questionnaire, 06 minutes-walk test (6MWT), Timed "Up and Go" test (TUG), and Activity-specific Balance Confidence (ABC) Scale. The study population was randomly divided into two groups as experimental group and control group. Experimental group received Task-Oriented Walking Interventions and conventional treatment while control group received conventional interventions only.
 Results
 On statistical analysis, significant improvement in mobility related confidence level for all the three scales TUG, ABC and 6MWT was observed on experimental group as compared to the control group after six weeks of interventions.
 Conclusion
 The study concluded that task oriented walking interventions is an effective approach for improving mobility related confidence level in post stroke patients.
 Keywords: Task oriented training, Mobility related confidence, Stroke, Activity-specific Balance Confidence Scale

Short term effects of anodal cerebellar vs. anodal cerebral transcranial direct current stimulation in stroke patients, a randomized control trial.

Balance and gait impairments are major motor deficits in stroke patients that require intensive neuro-rehabilitation. Anodal transcranial direct current stimulation is a neuro-modulatory technique recently used in stroke patients for balance and gait improvement. Majority of studies focusing on tDCS have assessed its effects on cerebral motor cortex and more recently cerebellum as well but to our best knowledge the comparison of stimulating these two regions in stroke patients is not investigated so far. The current study aimed to compare the effect of anodal transcranial direct current stimulation on cerebellar and cerebral motor cortex M1 in stroke patients. This double-blinded, parallel, randomized, sham controlled trial included 66 patients with a first-ever ischemic stroke were recruited into three groups; Cerebellar stimulation group (CbSG), M1 Stimulation Group (MSG), and Sham stimulation group (SSG). A total of three sessions of anodal transcranial direct current stimulation were given on consecutive days in addition to non-immersive virtual reality using Xbox 360 with kinect. Anodal tDCS with an intensity of 2 mA was applied for a duration of 20 min. Primary outcome measures berg balance scale (BBS), timed up and go test (TUG), BESTest Balance Evaluation-Systems Test (BESTest) and secondary outcomes measures montreal cognitive assessment (MoCA), mini mental state examination (MMSE), Johns Hopkins Fall Risk Assessment Tool (JHFRAT), twenty five feet walk test (25FWT), six minute walk test (6MWT), and tDCS Adverse Effects was assessed before initiation of treatment (T0) and at the end of third session of stimulation (T1). The results of between group's analysis using mean difference showed a significant difference with p-value <0.05 for balance (BBS, TUG, BESTest), walking ability (6MWT, 25FWT), risk of fall (JHFRAT). Cognitive function did not show any significant change among the groups for MoCA with p-value >0.05 but MMSE was improved having significant p-value (p = 0.013). However, 6MWT and 25FWT showed non-significant results for both between group and within group analysis. In pairwise comparison both the cerebellar and cerebral stimulation groups showed Significant difference with p-value <0.05 in comparison to sham stimulation; BBS (cerebellar vs. sham p ≤ 0.001, cerebral vs. sham p = 0.011), TUG (cerebellar vs. sham p = 0.001, cerebral vs. sham p = 0.041), Bestest (cerebellar vs. sham p = 0.007, cerebral vs. sham p = 0.003). Whereas for JHFRAT only cerebellar stimulation in comparison to sham and motor cortex stimulation showed significant improvements (cerebellar vs. M1 p = 0.037, cerebellar vs. sham p = 0.037). MMSE showed significant improvement in M1 stimulation (M1 vs. cerebellar p = 0.036, M1 vs. sham p = 0.011). Findings of the study suggest anodal tDCS stimulation of the cerebellum and cerebral motor cortex both improves gait, balance and risk of fall in stroke patients. However, both stimulation sites do not induce any notable improvement in cognitive function. Effects of both stimulation sites have similar effects on mobility in stroke patients.

Long-Term Outcome Following Decompressive Craniectomy in Pediatric Penetrating Blast Brain Injury; a Prospective Study

Background: Brain penetrating blast injury is a leading cause of early death due to excessively elevated intracranial pressure (ICP), culminating in trans-tentorial herniation. The role of craniectomy to decrease ICP and secondary injuries has been controversial particularly in pediatric patients. Three cases of pediatric penetrating blast injuries undergoing decompressive craniectomy are reported in Methods: The current study was a prospective series, including fifteen cases of pediatric blast-related brain injury referred to the emergency ward during a period of two years. Three survived patients had a Glasgow Coma Scale (GCS) of four along with anisocoric pupillary light reflex (PLR). Decompressive craniectomy and ventriculostomy (EVD) were performed. The patients underwent ICP monitoring for two weeks. Results: Early postoperative GCS (5 days) was 7/15 in all three patients. Two weeks and one month’s GCS were 9 and 14, respectively. After three months, cranioplasty was performed. Long-term follow-up detected no major motor deficits after one year and was associated with excellent school performance. Neuroplasticity resulted in contralateral dominancy and handedness in one case. Conclusions: Survivors of pediatric blast brain injury had a favorable outcome after decompressive craniectomy in the current paper. However, there was a limited number of patients, and the results could not be generalized. Further research in this regard with larger sample size is recommended.

Major motor and gait deficits with sexual dimorphism in a Shank3 mutant mouse model

BackgroundContrasting findings were reported in several animal models with a Shank3 mutation used to induce various autism spectrum disorder (ASD) symptoms. Here, we aimed at investigating behavioral, cellular, and molecular consequences of a C-terminal (frameshift in exon 21) deletion in Shank3 protein in mice, a mutation that is also found in clinical conditions and which results in loss of major isoforms of Shank3. A special focus was made on cerebellar related parameters.MethodsAll three genotypes were analyzed [wild type (WT), heterozygote (Shank3+/ΔC) and homozygote (Shank3 ΔC/ΔC)] and males and females were separated into two distinct groups. Motor and social behavior, gait, Purkinje cells (PC) and glutamatergic protein levels were determined. Behavioral and cellular procedures used here were previously validated using two environmental animal models of ASD. ANOVA and post-hoc analysis were used for statistical analysis.ResultsShank3 ΔC/ΔC mice showed significant impairments in social novelty preference, stereotyped behavior and gait. These were accompanied by a decreased number of PC in restricted cerebellar sub-regions and decreased cerebellar expression of mGluR5. Females Shank3 ΔC/ΔC were less affected by the mutation than males. Shank3+/ΔC mice showed impairments only in social novelty preference, grooming, and decreased mGluR5 expression and that were to a much lesser extent than in Shank3 ΔC/ΔC mice.LimitationsAs Shank3 mutation is a haploinsufficiency, it is of interest to emphasize that Shank3+/ΔC mice showed only mild to no deficiencies compared to Shank3 ΔC/ΔC.ConclusionsOur findings indicate that several behavioral, cellular, and molecular parameters are affected in this animal model. The reported deficits are more pronounced in males than in females. Additionally, male Shank3 ΔC/ΔC mice show more pronounced alterations than Shank3+/ΔC. Together with our previous findings in two environmental animal models of ASD, our studies indicate that gait dysfunction constitutes a robust set of motor ASD symptoms that may be considered for implementation in clinical settings as an early and quantitative diagnosis criteria.

Treatment Outcomes of Endovascular Embolization Only in Patients with Unruptured Brain Arteriovenous Malformations: A Subgroup Analysis of ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations).

Endovascular embolization only has been advocated for treatment of brain arteriovenous malformations in recent trials. Our aim was to evaluate the results of embolization only in a cohort of patients who were enrolled in the A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) study at 39 clinical sites in 9 countries. We analyzed the rates and severity of stroke and death in patients who underwent embolization only. Events were identified through in-person neurologic follow-up visits performed at 6-month intervals during the first 2 years and annually, with telephone contact every 6 months thereafter. All event-related data were reviewed by independent adjudicators. Among 30 patients who had embolization planned, 26 underwent embolization only. A total of 13 stroke events were reported in the follow-up period among 26 subjects (ischemic, hemorrhagic, or both in 4, 7, and 2 subjects, respectively). The adverse event occurred after the first embolization in 11 of 13 patients. One patient had a major motor deficit, and 2 patients developed major visual field deficits. One event was fatal. The modified Rankin Scale score was 0-2 at last follow-up in 11 of the 12 stroke survivors. Estimated stroke-free survival was 46% at 12 months. Although the rates of stroke and/or death were high in patients treated with embolization only in ARUBA, the rates of favorable outcomes following stroke were high during follow-up.

Unilateral lesion of the nigroestriatal pathway with 6-OHDA induced allodynia and hyperalgesia reverted by pramipexol in rats

Pain is the non-motor symptom with the highest prevalence in patients with Parkinson's Disease (PD) affecting 40–85%. This study aimed to investigate the development of tactile allodynia and mechanical hyperalgesia after the nigrostriatal dopaminergic lesion induced by the unilateral 6-hydroxydopamine (6-OHDA) injection at different doses in the substantia nigra pars compacta (SNpc). Moreover, we studied the possible antiallodynic and antihyperalgesic effect with the acute and the subacute treatment of the pramipexole (PPX) in rats. First, dopaminergic lesion was realized by the unilateral injection of 6-OHDA (6, 10 and 16 μg/μl) into the SNpc. To know the establishment of motor deficits, we measure several turns and forelimb-use asymmetry by rotational behavior and cylinder, respectively. On the other hand, to investigate allodynia and hyperalgesia induced by 6-OHDA, we used the von Frey filaments. Moreover, antiallodynic and antihyperalgesic effect induced by PPX (0.03, 0.3 and 3 mg/kg, s.c.) was examined on acute and subacute conditions. We found that major dopaminergic lesion with 16 μg/μl of 6-OHDA caused the highest allodynia and hyperalgesia effects in both paws, as well as the major motor deficits. In addition, the treatment with PPX at 0.3 mg/kg reverts the allodynia and the hyperalgesia induced by 6-OHDA. In conclusion, the dopaminergic lesion into SNpc induce allodynia and hyperalgesia in both paws; interestingly the treatment with PPX can be suggested as an analgesic drug for patients with PD.

Emerging Roles of miRNAs in Brain Development and Perinatal Brain Injury.

In human beings the immature brain is highly plastic and depending on the stage of gestation is particularly vulnerable to a range of insults that if sufficiently severe, can result in long-term motor, cognitive and behavioral impairment. With improved neonatal care, the incidence of major motor deficits such as cerebral palsy has declined with prematurity. Unfortunately, however, milder forms of injury characterized by diffuse non-cystic white matter lesions within the periventricular region and surrounding white matter, involving loss of oligodendrocyte progenitors and subsequent axonal hypomyelination as the brain matures have not. Existing therapeutic options for treatment of preterm infants have proved inadequate, partly owing to an incomplete understanding of underlying post-injury cellular and molecular changes that lead to poor neurodevelopmental outcomes. This has reinforced the need to improve our understanding of brain plasticity, explore novel solutions for the development of protective strategies, and identify biomarkers. Compelling evidence exists supporting the involvement of microRNAs (miRNAs), a class of small non-coding RNAs, as important post-transcriptional regulators of gene expression with functions including cell fate specification and plasticity of synaptic connections. Importantly, miRNAs are differentially expressed following brain injury, and can be packaged within exosomes/extracellular vesicles, which play a pivotal role in assuring their intercellular communication and passage across the blood–brain barrier. Indeed, an increasing number of investigations have examined the roles of specific miRNAs following injury and regeneration and it is apparent that this field of research could potentially identify protective therapeutic strategies to ameliorate perinatal brain injury. In this review, we discuss the most recent findings of some important miRNAs in relation to the development of the brain, their dysregulation, functions and regulatory roles following brain injury, and discuss how these can be targeted either as biomarkers of injury or neuroprotective agents.

Cervical Spondylotic Radiculopathy: The Role of Conservative Management

Introduction: Cervical spondylotic radiculopathy is common and most patients experiencing an acute episode of unilateral radiculopathy without major motor deficit and no evidence of cord compression can be managed by non-operative measures. This study aimed to determine the severity of degenerative changes on plain radiograph among patients with cervical spondylotic radiculopathy and patient's self rated outcomes following conservative treatment. This study also looked into the correlation between pain with disability of patient, severity of degenerative changes of the cervical spine and different level of root compression. Materials and Methods: An observational cohort study where all patients with newly diagnosed cervical spondylotic radiculopathy were recruited from December 2016 to January 2018. Patient rated pain score and neck disability index at presentation and three months after conservative treatment were evaluated. Demographic data, radiographic severity grade, neck disability index and pain score were documented and analyzed via descriptive analysis and Pearson correlation test. Results: There were 29 patients recruited, with mean age of 49 years old. Forty one percent of patients had Grade 2 radiographic severity changes. Patient rated outcomes with neck disability index and pain score showed moderate improvement after conservative treatment (r=0.523, p&lt;0.01). There was significant correlation between pain score and neck disability index (p&lt;0.001). However, pain score showed no significant correlation between radiographic severity grade and different level nerve root compression. The power of this study is 0.8 with PASS 11 calculation. Conclusion: Patients with cervical spondylotic radiculopathy who were treated conservatively showed favorable clinical outcome.

The Vienna psychosocial assessment procedure for bionic reconstruction in patients with global brachial plexus injuries.

BackgroundGlobal brachial plexopathies cause major sensory and motor deficits in the affected arm and hand. Many patients report of psychosocial consequences including chronic pain, decreased self-sufficiency, and poor body image. Bionic reconstruction, which includes the amputation and prosthetic replacement of the functionless limb, has been shown to restore hand function in patients where classic reconstructions have failed. Patient selection and psychological evaluation before such a life-changing procedure are crucial for optimal functional outcomes. In this paper we describe a psychosocial assessment procedure for bionic reconstruction in patients with complete brachial plexopathies and present psychosocial outcome variables associated with bionic reconstruction.MethodsBetween 2013 and 2017 psychosocial assessments were performed in eight patients with global brachial plexopathies. We conducted semi-structured interviews exploring the psychosocial adjustment related to the accident, the overall psychosocial status, as well as motivational aspects related to an anticipated amputation and expectations of functional prosthetic outcome. During the interview patients were asked to respond freely. Their answers were transcribed verbatim by the interviewer and analyzed afterwards on the basis of a pre-defined item scoring system. The interview was augmented by quantitative evaluation of self-reported mental health and social functioning (SF-36 Health Survey), body image (FKB-20) and deafferentation pain (VAS). Additionally, psychosocial outcome variables were presented for seven patients before and after bionic reconstruction.ResultsQualitative data revealed several psychological stressors with long-term negative effects on patients with complete brachial plexopathies. 88% of patients felt functionally limited to a great extent due to their disability, and all of them reported constant, debilitating pain in the deafferented hand. After bionic reconstruction the physical component summary scale increased from 30.80 ± 5.31 to 37.37 ± 8.41 (p-value = 0.028), the mental component summary scale improved from 43.19 ± 8.32 to 54.76 ± 6.78 (p-value = 0.018). VAS scores indicative of deafferentation pain improved from 7.8 to 5.6 after prosthetic hand replacement (p-value = 0.018). Negative body evaluation improved from 60.71 ± 12.12 to 53.29 ± 11.03 (p-value = 0.075). Vital body dynamics increased from 38.57 ± 13.44 to 44.43 ± 16.15 (p-value = 0.109).ConclusionsBionic reconstruction provides hope for patients with complete brachial plexopathies who have lived without hand function for years or even decades. Critical patient selection is crucial and the psychosocial assessment procedure including a semi-structured interview helps identify unresolved psychological issues, which could preclude or delay bionic reconstruction. Bionic reconstruction improves overall quality of life, restores an intact self-image and reduces deafferentation pain.

Mutant A53T α-Synuclein Improves Rotarod Performance Before Motor Deficits and Affects Metabolic Pathways.

The protein α-synuclein (α-Syn) interferes with glucose and lipid uptake and also activates innate immune cells. However, it remains unclear whether α-Syn or its familial mutant forms contribute to metabolic alterations and inflammation in synucleinopathies, such as Parkinson's disease (PD). Here, we address this issue in transgenic mice for the mutant A53T human α-Syn (α-SynA53T), a mouse model of synucleinopathies. At 9.5months of age, mice overexpressing α-SynA53T (homozygous) had a significant reduction in weight, exhibited improved locomotion and did not show major motor deficits compared with control transgenic mice (heterozygous). At 17months of age, α-SynA53T overexpression promoted general reduction in grip strength and deficient hindlimb reflex and resulted in severe disease and mortality in 50% of the mice. Analysis of serum metabolites further revealed decreased levels of cholesterol, triglycerides and non-esterified fatty acids (NEFA) in α-SynA53T-overexpressing mice. In fed conditions, these mice also showed a significant decrease in serum insulin without alterations in blood glucose. In addition, assessment of inflammatory gene expression in the brain showed a significant increase in TNF-α mRNA but not of IL-1β induced by α-SynA53T overexpression. Interestingly, the brain mRNA levels of Sirtuin 2 (Sirt2), a deacetylase involved in both metabolic and inflammatory pathways, were significantly reduced. Our findings highlight the relevance of the mechanisms underlying initial weight loss and hyperactivity as early markers of synucleinopathies. Moreover, we found that changes in blood metabolites and decreased brain Sirt2 gene expression are associated with motor deficits.

Novel Rat Model of Weight Drop-Induced Closed Diffuse Traumatic Brain Injury Compatible with Electrophysiological Recordings of Vigilance States.

Traumatic brain injury (TBI) is a major cause of persistent disabilities such as sleep-wake disorders (SWD). Rodent studies of SWD after TBI are scarce, however, because of lack of appropriate TBI models reproducing acceleration-deceleration forces and compatible with electroencephalography/myography (EEG/EMG)-based recordings of vigilance states. We therefore adapted the Marmarou impact acceleration model to allow for compatibility with EEG-headset implantation. After implantation of EEG/EMG electrodes, we induced closed TBI by a frontal, angular hit with a weight-drop device (56 rats, weight 2500 g, fall height 25 cm). Subsequently, we tested our model's usefulness for long-term studies on a behavioral, electrophysiological, and histological level. Neurological, motor, and memory deficits were assessed with the neurological severity score, open field, and novel object recognition tests, respectively. EEG/EMG recordings were performed in both Sham (n = 7) and TBI (n = 7) rats before and 1, 7, and 28 days after trauma to evaluate sleep-wake proportions and post-traumatic implant stability. Histological assessments included hematoxylin and eosin staining for parenchymal damage and hemorrhage and amyloid precursor protein staining for diffuse axonal damage. All rats survived TBI without major neurological or motor deficits. Memory function was impaired after TBI at weeks 1, 2, and 3 and recovered at week 4. EEG implants were stable for at least 1 month and enabled qualitative and quantitative sleep analyses. Histological assessments revealed no major bleedings or necrosis but intense diffuse axonal damage after TBI. This approach fulfills major pre-conditions for experimental TBI models and offers a possibility to electrophysiologically study behavioral states before and after trauma.

In reply: paralysis developing as a paradoxical response during the treatment for tuberculous spondylitis.

We appreciate your valuable comments. At the time of diagnosis, the orthopedic surgeon recommended an operation (anterior debridement and fusion) for the patient with vertebral collapse [1]. However, the patient refused the surgery and wanted to receive conservative treatment. Kotil et al. [2] reported that 44 patients with tuberculous spondylitis were managed conservatively with anti-tuberculous medication and spinal orthosis. Exclusion criteria were major motor deficit, deteriorating neurologic function, or spinal deformity greater than 30° at the affected level of spine. Forty-two patients (95.4%) were treated well without any progression of the spinal deformity. Consequently, the authors suggested indications for surgery in tuberculous spondylitis with the following conditions: 1) gross neurologic impairment and instability or deformity, 2) treatment failure, 3) neurologic deterioration, 4) paradoxical response, or 5) intolerance to anti-tuberculous medication. Additionally, Zhang et al. [3] suggested that there was no significant difference in the outcomes between the anti-tuberculous medication plus surgery and the medication alone, in a meta-analysis. However, there have been only two randomized controlled trials (331 patients) which were conducted in the 1970s and 1980s. Thus, a large, well-conducted, randomized controlled trial is needed to conclude the indications for surgery in tuberculous spondylitis. Therefore, conservative treatment including anti-tuberculous medication and rigid thoracolumbosacral orthosis (TLSO) was chosen for the patient.

Spinal cord transection-induced allodynia in rats--behavioral, physiopathological and pharmacological characterization.

In humans, spinal cord lesions induce not only major motor and neurovegetative deficits but also severe neuropathic pain which is mostly resistant to classical analgesics. Better treatments can be expected from precise characterization of underlying physiopathological mechanisms. This led us to thoroughly investigate (i) mechanical and thermal sensory alterations, (ii) responses to acute treatments with drugs having patent or potential anti-allodynic properties and (iii) the spinal/ganglion expression of transcripts encoding markers of neuronal injury, microglia and astrocyte activation in rats that underwent complete spinal cord transection (SCT). SCT was performed at thoracic T8–T9 level under deep isoflurane anaesthesia, and SCT rats were examined for up to two months post surgery. SCT induced a marked hyper-reflexia at hindpaws and strong mechanical and cold allodynia in a limited (6 cm2) cutaneous territory just rostral to the lesion site. At this level, pressure threshold value to trigger nocifensive reactions to locally applied von Frey filaments was 100-fold lower in SCT- versus sham-operated rats. A marked up-regulation of mRNAs encoding ATF3 (neuronal injury) and glial activation markers (OX-42, GFAP, P2×4, P2×7, TLR4) was observed in spinal cord and/or dorsal root ganglia at T6-T11 levels from day 2 up to day 60 post surgery. Transcripts encoding the proinflammatory cytokines IL-1β, IL-6 and TNF-α were also markedly but differentially up-regulated at T6–T11 levels in SCT rats. Acute treatment with ketamine (50 mg/kg i.p.), morphine (3–10 mg/kg s.c.) and tapentadol (10–20 mg/kg i.p.) significantly increased pressure threshold to trigger nocifensive reaction in the von Frey filaments test, whereas amitriptyline, pregabalin, gabapentin and clonazepam were ineffective. Because all SCT rats developed long lasting, reproducible and stable allodynia, which could be alleviated by drugs effective in humans, thoracic cord transection might be a reliable model for testing innovative therapies aimed at reducing spinal cord lesion-induced central neuropathic pain.

Outcome assessment in conservatively managed patients with cervical spine tuberculosis.

Cervical spine tuberculosis is a relatively less frequent form of spinal tuberculosis. Cervical spine tuberculosis has a greater propensity to involve the spinal cord and results in major sensory motor deficit. In this prospective study, we aimed to evaluate the clinical and imaging predictors of outcome in conservatively managed patients. In this study, 42 patients of cervical spine tuberculosis were included. Patients were subjected to a detailed clinical evaluation and magnetic resonance imaging. Patients were treated with antituberculosis treatment and were followed up for 18 months. The Modified Barthel index (MBI) was used to assess the disability. Good outcome was defined as MBI >12 and poor outcome as MBI ⩽12. Clinical and imaging characteristics were used to analyze the predictors of outcome, using univariate and multivariate analysis. Four (9.5%) patients required surgery. Data from 38 patients, who were conservatively managed, were analyzed for predictors of outcome. Among conservatively managed patients, at presentation, 29 patients had an MBI score of ⩽12. At 18 months, the majority of patients (81.6%) had a good outcome. On univariate analysis, a duration of illness >3 months, a major motor deficit, bladder involvement, flexor spasms, significant cord compression and spinal extension of the abscess were significantly associated with a poor outcome. However, on multivariate analysis significant cord compression (P=0.003) and spinal extension (P=0.02) showed a significant correlation with a poor outcome. Medical management was effective in cervical spine tuberculosis. Patients with significant cord compression and spinal extension of the abscess showed poorer outcome.

Health-related Quality of Life in Pediatric Cancer Survivors

We aimed to evaluate the health-related quality of life (HRQOL) and the effect of associated factors such as cancer type, treatment strategies, sex, age, and parental factors like education and psychopathology in pediatric cancer survivors and make a comparison with healthy children. "Pediatric Quality of Life Inventory (PedsQL) 4.0 TM, Generic Core Scale" for children and parents, and "Brief Symptom Inventory" for parents were used. Three hundred and two survivors without major mental or motor deficit and 272 healthy controls of 8 to 18 years of age were enrolled to study. Comparison of scores according to child self-report between survivor and control groups revealed lower points in physical and school subscale of survivor group (P<0.01 and P<0.001, respectively). Female survivors had reported significantly worse HRQOL in physical and emotional subscales of PedsQL than male survivors (P<0.001). Female survivors of ≥16 years of age had reported worse scores in school subscale than females of younger age groups and male survivors of same age group. Parents of control group reported better results in school subscales (P<0.001) and social functioning subscales (P<0.05) than parents of survivor group. Brief Symptom Inventory score had significant effect on child self-report and parent proxy-report of physical functioning (P<0.001), emotional functioning (P<0.001), social functioning (P<0.001), and school subscales (P<0.001) of PedsQL. Significantly better scores of physical functioning subscale in the survivors whose parents are university graduate than the survivors whose parents are primary school graduate were detected (P<0.001). The survivors with central nervous system tumors had reported lower scores in the social, emotional, physical, and school functioning subscales of PedsQL than patients with non-Hodgkin and Hodgkin lymphoma (P<0.001). Child self-report school subscale scores were lower in survivors treated with radiotherapy in combination or as sole therapy than survivors in whom radiotherapy was not given (P<0.001). Our study has provided evidence about less-studied determinants of HRQOL like parental factors such as psychopathology or educational level in childhood cancer survivors. Future research can build on this evidence to obtain additional factors other than well-known medical and treatment-related factors.

Gene transfer provides a practical means for safe, long-term, targeted delivery of biologically active neurotrophic factor proteins for neurodegenerative diseases.

Efforts to develop neurotrophic factors to restore function and protect dying neurons in chronic neurodegenerative diseases like Alzheimer's (AD) and Parkinson's (PD) have been attempted for decades. Despite abundant data establishing nonclinical proof-of-concept, significant delivery issues have precluded the successful translation of this concept to the clinic. The development of AAV2 viral vectors to deliver therapeutic genes has emerged as a safe and effective means to achieve sustained, long-term, targeted, bioactive protein expression. Thus, it potentially offers a practical means to solve those long-standing delivery/translational issues associated with neurotrophic factors. Data are presented for two AAV2 viral vector constructs expressing one of two different neurotrophic factors: nerve growth factor (NGF) and neurturin (NRTN). One (AAV2-NGF; aka CERE-110) is being developed as a treatment to improve the function and delay further degeneration of cholinergic neurons in the nucleus basalis of Meynert, the degeneration of which has been linked to cognitive deficits in AD. The other (AAV2-NRTN; aka CERE-120) is similarly being developed to treat the degenerating nigrostriatal dopamine neurons and major motor deficits in PD. The data presented here demonstrate: (1) 2-year, targeted, bioactive-protein in monkeys, (2) persistent, bioactive-protein throughout the life-span of the rat, and (3) accurately targeted bioactive-protein in aged rats, with (4) no safety issues or antibodies to the protein detected. They also provide empirical guidance to establish parameters for human dosing and collectively support the idea that gene transfer may overcome key delivery obstacles that have precluded successful translation of neurotrophic factors to the clinic. More specifically, they also enabled the AAV-NGF and AAV-NRTN programs to advance into ongoing multi-center, double-blind clinical trials in AD and PD patients.

Aspectos percepto-motores e cognitivos do desenvolvimento de crianças com síndrome de Down

O desenvolvimento na Síndrome de Down ocorre com atraso quando comparado com o de crianças com desenvolvimento neuropsicomotor típico. Mas, estudos têm mostrado que a estimulação é importante no processo de desenvolvimento dessa população específica ao oferecer maiores oportunidades de experiências, minimizando as grandes defasagens associadas a ela. O objetivo é avaliar o desenvolvimento percepto-motor e cognitivo de crianças com Síndrome de Down, investigando a possível interdependência entre a motricidade e a estruturação intelectual. Participaram 10 crianças com síndrome de Down , com idade entre um e cinco anos. Para a coleta de dados foi utilizado um roteiro de observação do comportamento motor para descrever os padrões de locomoção, de manipulação, de estabilidade e de percepção, e provas piagetianas adaptadas para a descrição da construção das noções de objeto permanente, de causalidade física, de espaço e de tempo concernentes ao estágio sensório-motor do desenvolvimento cognitivo. Os itens referentes às duas avaliações foram categorizados de forma qualitativa a partir de critérios pré-estabelecidos. Os dados foram tratados utilizando análise estatística exploratória e descritiva. Observou-se que os principais déficits motores e as maiores defasagens cognitivas foram apresentadas pelas crianças mais novas da amostra. Da mesma forma, uma maior interdependência na relação entre os diferentes itens avaliados ocorreu nesses mesmos participantes. Acredita-se que, com o passar da idade, o processo de desenvolvimento dessas crianças tenda a se aproximar do que é tipicamente esperado, ratificando a importância das estimulações em longo prazo para as crianças com Síndrome de Down.

Neuro-rehabilitation robot-assisted assessments of synergy patterns of forearm, elbow and shoulder joints in chronic stroke patients

Background Abnormal synergy is one of the major motor deficits in stroke patients. Abnormal muscle synergies, in conjunction with weakness and spasticity, interfere with voluntary movements and restrict the range of motion. This study aimed to quantify abnormal synergies in the affected upper limbs of chronic stroke patients by using a neuro-rehabilitation robot. Methods Twelve chronic stroke patients and eight age-matched control subjects were recruited to perform rectilinear tracking movements in four horizontal directions (back–forth, two oblique directions at 45°, and right–left). Kinematic, kinetic and electromyogram data were recorded and used to develop two biomechanical indices and one electromyogram assessment index based on principal component analysis. Findings Significant differences between upper limbs of control subjects and the affected side of stroke patients were observed in all three assessment indices. Higher correlation between the elbow joint angle and the forearm pronation/supination torque, higher variation of the forearm torque, and abnormal co-contraction of the elbow and shoulder muscles were observed in the affected limbs of stroke patients. The difference was more prominent in the right–left direction and the oblique direction contra-proximal to ipsi-distal. Interpretation The proposed assessment indices could be employed to quantify the abnormal synergies in stroke patients. Rectilinear tracking along the right–left direction and the oblique direction of contra-proximal to ipsi-distal is more suitable for assessing abnormal synergies.