Degenerative L4-L5 spondylolisthesis and stenosis surgery: does over-level flavectomy technique influence clinical outcomes and rates of cranial adjacent segment disease?

BACKGROUND: One of the most dreaded long-term complications related to L4-L5 lumbar arthrodesis is the onset of adjacent segment disease, which most frequently occurs at the cranial level. Few studies have compared the rates of cranial adjacent segment disease (CASD) in patients undergoing lumbar fusion associated with total laminectomy at the same level with those undergoing partial laminectomy. No study has examined the role of selective over-level flavectomy (OLF; i.e., L3-L4). METHODS: A total of 299 patients undergoing posterolateral arthrodesis (PLA) for L4-L5 degenerative spondylolisthesis were retrospectively analyzed with a 5-year follow-up. 148 patients underwent PLA + L4-L5 flavectomy + L4 partial laminectomy (control group), while 151 underwent PLA + L4-L5 flavectomy + total L4 laminectomy + L3-L4 flavectomy (OLF group). Rates of reoperations due to CASD were examined utilizing Cox proportional hazard models, while clinical improvement at follow-up (measured in ODI) was analyzed using generalized linear models (GLMs). Adjustments for potential confounders were made (grade of lumbar lordosis, age, sex, BMI, intervertebral disc degeneration, and presurgical cranial spinal stenosis). RESULTS: At 5 years from the operation, 16 patients (10.8%) in the control group had undergone revision surgery for CASD compared to 5 patients (3.3%) in the OLF group (p = 0.013). Survival analysis and GLM demonstrated that the OLF group had a significantly lower incidence of CASD and presented more favorable clinical outcome. There were no differences in the rate of discal degeneration or the onset of Meyerding's grade I degenerative spondylolisthesis at the adjacent segment. BMI was the only other significant predictor of ODI improvement and of the incidence of CASD. CONCLUSIONS: In patients with L4-L5 degenerative spondylolisthesis and stenosis, the OLF technique may lower rates of CASD and improve clinical outcomes by preventing cranial spinal stenosis without increasing iatrogenic instability or accelerating intervertebral disc degenerative changes.

Fluorescein sodium-guided resection of a cerebellar lymphoma: case report and literature review.

We report on a patient, who underwent the resection of a cerebellar primary central nervous system lymphoma and was administered intraoperative fluorescein sodium to improve the visualization of the tumor and guide surgery. Low-dosage fluorescein was administered prior to opening the dura so to distinguish contrast-enhanced lymphomatous tissue from the surrounding unenhanced brain cerebellar parenchyma. Intraoperatively, the tumor was indistinguishable from cerebellar parenchyma under the white light, however, after the administration of low-dose intravenous fluorescein, it appeared brightly fluorescent under yellow light, and was safely resected. Our protocol of administration allowed for the sampling of the pathological tissue while at the same time avoiding neurological damage. The fluorescein-guided technique for the resection of primary central nervous system lymphomas has only been rarely described, as surgical excision of such tumors is rarely indicated. Starting from our case, we review and discuss the pertinent literature. Furthermore, an intraoperative video detail is provided.

Incidence, prevalence, and factors associated with lymphedema after treatment for cervical cancer: a systematic review.

BACKGROUND: Lower limb lymphedema is a frequent and debilitating complication after cervical cancer treatment. OBJECTIVE: To evaluate the incidence and prevalence of lymphedema after treatment for cervical cancer and evaluate the factors associated with this outcome. METHODS: The study was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines and was registered in the International Prospective Register of Systematic Reviews (PROSPERO). Eligible studies were identified through the databases Medline (via PubMed), LILACS, Scopus, and Web of Science. For the search, descriptors, keywords, and synonyms were used for cervical cancer, lymphedema, and outcomes of interest (incidence, prevalence, frequency, occurrence, morbidity, risk factors, and prognosis). Observational studies were included that were published in English, Portuguese, or Spanish, between January 1, 2013 and December 31, 2019, with frequency data and associated factors for lymphedema after cervical cancer treatment. Studies that evaluated the presence of lymphedema less than 6 months after surgery or radiotherapy and those in which frequency data were not stratified by tumor topography, were excluded. RESULTS: Twenty-three studies were included. The incidence of lymphedema varied between 0% and 69%. Different designs and methods were employed for lymphedema assessment. The main factors associated with lymphedema included extension of lymphadenectomy, number of lymph nodes removed, removal of circumflex iliac lymph nodes, and adjuvant radiotherapy. Other factors associated with lymphedema included cellulitis, lymphocyst formation, increased age, invasive lymph node staging, higher body mass index, and insufficient physical activity. CONCLUSIONS: The frequency of lymphedema after treatment for cervical cancer is variable. The different designs and methodology to measure this complication make it difficult to draw definitive conclusions about its prevalence. The method used for lymphedema assessment is not standardized.

Image-based analysis and long-term clinical outcomes of deep brain stimulation for Tourette syndrome: a multisite study.

BACKGROUND: Deep brain stimulation (DBS) can be an effective therapy for tics and comorbidities in select cases of severe, treatment-refractory Tourette syndrome (TS). Clinical responses remain variable across patients, which may be attributed to differences in the location of the neuroanatomical regions being stimulated. We evaluated active contact locations and regions of stimulation across a large cohort of patients with TS in an effort to guide future targeting. METHODS: We collected retrospective clinical data and imaging from 13 international sites on 123 patients. We assessed the effects of DBS over time in 110 patients who were implanted in the centromedial (CM) thalamus (n=51), globus pallidus internus (GPi) (n=47), nucleus accumbens/anterior limb of the internal capsule (n=4) or a combination of targets (n=8). Contact locations (n=70 patients) and volumes of tissue activated (n=63 patients) were coregistered to create probabilistic stimulation atlases. RESULTS: Tics and obsessive-compulsive behaviour (OCB) significantly improved over time (p<0.01), and there were no significant differences across brain targets (p>0.05). The median time was 13 months to reach a 40% improvement in tics, and there were no significant differences across targets (p=0.84), presence of OCB (p=0.09) or age at implantation (p=0.08). Active contacts were generally clustered near the target nuclei, with some variability that may reflect differences in targeting protocols, lead models and contact configurations. There were regions within and surrounding GPi and CM thalamus that improved tics for some patients but were ineffective for others. Regions within, superior or medial to GPi were associated with a greater improvement in OCB than regions inferior to GPi. CONCLUSION: The results collectively indicate that DBS may improve tics and OCB, the effects may develop over several months, and stimulation locations relative to structural anatomy alone may not predict response. This study was the first to visualise and evaluate the regions of stimulation across a large cohort of patients with TS to generate new hypotheses about potential targets for improving tics and comorbidities.

Is capsulectomy a feasible and useful measure in internal pulse generator replacement procedures? A technical note on the use of the PEAK PlasmaBlade(TM).

BACKGROUND: Implantable pulse generator (IPG) replacement is considered a simple procedure, but in case of extension cable damage or IPG pocket infection, it can dramatically affect a patient's quality of life. Higher risk of infection has been reported after IPG replacement procedures rather than after primary deep brain stimulation lead implantation, and some authors suggested that the IPG pocket capsule could play a pivotal role in causing it. In this technical note we present a capsulectomy technique adopted in IPG replacement procedures. METHODS: Between July and October 2015, we carried out ten outpatient IPG replacement procedures at the chest and abdomen under local anesthesia for battery depletion using the PEAK PlasmaBlade(TM). All patients were followed for at least 2 months to rule out any hardware malfunction and infection. RESULTS: All ten procedures were uneventful. No extension cable damage occurred. No IPG pocket infection occurred, also not in the follow-up. Mean surgical time was 30 min. CONCLUSIONS: Complete capsulectomy is not feasible with basic surgical instruments, and the PEAK PlasmaBlade(TM) pencil appears to be a helpful tool in carrying out the procedure.

Electrophysiological study of medial and lateral branches of the superficial radial nerve.

INTRODUCTION: In this study we sought to establish a new technique for nerve conduction study (NCS) of medial and lateral branches of the superficial radial nerve (SRN). METHODS: Antidromic NCS were performed on 60 healthy subjects, recording the sensory nerve action potential (SNAP) from the dorsomedial and dorsolateral aspects of the phalanx of the thumb. The main trunk of SRN was also investigated. RESULTS: SNAPs were easily recorded in all subjects, and normative latency and amplitude data were collected. CONCLUSIONS: We propose a simple and reliable technique to investigate nerve conduction of the terminal branches of the SRN, which could be useful in some focal and systemic pathologies.

Relationship between lumbar lordosis, pelvic parameters, PI-LL mismatch and outcome after short fusion surgery for lumbar degenerative disease. Literature review, rational and presentation of public study protocol: RELApSE study (registry for evaluation of lumbar artrodesis sagittal alignEment).

Background: Vertebral arthrodesis for degenerative pathology of the lumbar spine still remains burdened by clinical problems with significant negative results. The introduction of the sagittal balance assessment with the evaluation of the meaning of pelvic parameters and spinopelvic (PI-LL) mismatch offered new evaluation criteria for this widespread pathology, but there is a lack of consistent evidence on long-term outcome. Methods: The authors performed an extensive systematic review of literature, with the aim to identify all potentially relevant studies about the role and usefulness of the restoration or the assessment of Sagittal balance in lumbar degenerative disease. They present the study protocol RELApSE (NCT05448092 ID) and discuss the rationale through a comprehensive literature review. Results: From the 237 papers on this topic, a total of 176 articles were selected in this review. The analysis of these literature data shows sparse and variable evidence. There are no observations or guidelines about the value of lordosis restoration or PI-LL mismatch. Most of the works in the literature are retrospective, monocentric, based on small populations, and often address the topic evaluation partially. Conclusions: The RELApSE study is based on the possibility of comparing a heterogeneous population by pathology and different surgical technical options on some homogeneous clinical and anatomic-radiological measures aiming to understanding the value that global lumbar and segmental lordosis, distribution of lordosis, pelvic tilt, and PI-LL mismatch may have on clinical outcome in lumbar degenerative pathology and on the occurrence of adjacent segment disease.

Towards a common language in neurosurgical outcome evaluation: the NEON (NEurosurgical Outcome Network) proposal.

BACKGROUND: The aim of this study was to achieve a consensus on the minimum set of outcome measures and predictors to be used in the neurosurgical practice and on the timing of outcome assessment. METHODS: A consensus building approach was employed. All neurosurgical departments in Lombardy (Italy) were invited to participate by the Carlo Besta Neurologic Institute IRCCS Foundation. Three workshops were organized during which a multidisciplinary group called Neurosurgical Outcome Network (NEON) was created and the methodology to select outcome measures, predictors, and timing of outcome assessment was established. Eight working groups were created for the different neurosurgical diseases (neuro-oncological, skull base, vascular, traumatic, spinal, peripheral nervous system, malformation, functional) and 8 workshops were organized to identify the outcome measures and predictors specific for each of the neurosurgical diseases based on the experts' clinical practice and the existing literature. RESULTS: A total of 20 neurosurgical departments participated in this study. Specific outcome measures, predictors and the timing of outcome assessment were identified for each of the 8 neurosurgical diseases. Moreover, a list of variables common to all pathologies were identified by the NEON group as further data to be collected. CONCLUSIONS: A consensus on the minimum set of outcome measures and predictors and the timing of outcome assessments for 8 neurosurgical diseases was achieved by a group of neurosurgeons of the Lombardy region, called NEON. These sets could be used in future studies for a more homogeneous data collection and as a starting point to reach further agreement also at national and international level.

Psychometric Evaluation of a Brazilian Version of the Lymphedema Functioning, Disability and Health Questionnaire for Lower Limb Lymphedema in Patients After Cancer Treatment.

Background: The aim of this study was to evaluate psychometric properties of the Lymphedema Functioning, Disability and Health Questionnaire for lower limb lymphedema (Lymph-ICF-LL) in Brazilian patients with secondary lower limb lymphedema after cancer treatment. Methods and Results: A diagnostic test study was performed in 30 patients with lower limb lymphedema. To assess the reliability, the intraclass correlation coefficient (ICC) was analyzed through test-retest, Cronbach alpha coefficient, magnitude of intrasubject variability by standard error of measurement (SEM), and smallest real difference (SRD). To assess the face and content validity, a specific questionnaire was applied to assess the clarity of the scoring system and comprehensiveness of questions. To assess construct validity, correlations between the final Brazilian version of the Lymph ICF-LL and the quality of life questionnaire SF-36 (36-Item Short Form Health Survey Questionnaire) were analyzed. The ICCs and general internal consistency scores of Lymph-ICF-LL were high (ICCs >0.90 and the Cronbach alpha coefficient >0.90, respectively). Measurement variability between the tests was acceptable (SEM 5.9) with SRD of 16.4. Face and content validity were considered excellent by the patients as the scoring system was clear and questions were understandable for 97% and 90% of the patients, respectively. Construct validity was classified as good and all hypotheses for assessing convergent validity were accepted (medium to strong correlation, from -0.69 to -0.84). Conclusion: The Brazilian version of the Lymph-ICF-LL is a reliable and valuable instrument for assessing Brazilian patients with secondary lower limb lymphedema associated with cancer treatment.

Basal Ganglia Pathways Associated With Therapeutic Pallidal Deep Brain Stimulation for Tourette Syndrome.

BACKGROUND: Deep brain stimulation (DBS) targeting the globus pallidus internus (GPi) can improve tics and comorbid obsessive-compulsive behavior (OCB) in patients with treatment-refractory Tourette syndrome (TS). However, some patients' symptoms remain unresponsive, the stimulation applied across patients is variable, and the mechanisms underlying improvement are unclear. Identifying the fiber pathways surrounding the GPi that are associated with improvement could provide mechanistic insight and refine targeting strategies to improve outcomes. METHODS: Retrospective data were collected for 35 patients who underwent bilateral GPi DBS for TS. Computational models of fiber tract activation were constructed using patient-specific lead locations and stimulation settings to evaluate the effects of DBS on basal ganglia pathways and the internal capsule. We first evaluated the relationship between activation of individual pathways and symptom improvement. Next, linear mixed-effects models with combinations of pathways and clinical variables were compared in order to identify the best-fit predictive models of tic and OCB improvement. RESULTS: The best-fit model of tic improvement included baseline severity and the associative pallido-subthalamic pathway. The best-fit model of OCB improvement included baseline severity and the sensorimotor pallido-subthalamic pathway, with substantial evidence also supporting the involvement of the prefrontal, motor, and premotor internal capsule pathways. The best-fit models of tic and OCB improvement predicted outcomes across the cohort and in cross-validation. CONCLUSIONS: Differences in fiber pathway activation likely contribute to variable outcomes of DBS for TS. Computational models of pathway activation could be used to develop novel approaches for preoperative targeting and selecting stimulation parameters to improve patient outcomes.

Disentangling the Hypothesis of Host Dysosmia and SARS-CoV-2: The Bait Symptom That Hides Neglected Neurophysiological Routes.

The respiratory condition COVID-19 arises in a human host upon the infection with SARS-CoV-2, a coronavirus that was first acknowledged in Wuhan, China, at the end of December 2019 after its outbreak of viral pneumonia. The full-blown COVID-19 can lead, in susceptible individuals, to premature death because of the massive viral proliferation, hypoxia, misdirected host immunoresponse, microthrombosis, and drug toxicities. Alike other coronaviruses, SARS-CoV-2 has a neuroinvasive potential, which may be associated with early neurological symptoms. In the past, the nervous tissue of patients infected with other coronaviruses was shown to be heavily infiltrated. Patients with SARS-CoV-2 commonly report dysosmia, which has been related to the viral access in the olfactory bulb. However, this early symptom may reflect the nasal proliferation that should not be confused with the viral access in the central nervous system of the host, which can instead be allowed by means of other routes for spreading in most of the neuroanatomical districts. Axonal, trans-synaptic, perineural, blood, lymphatic, or Trojan routes can gain the virus multiples accesses from peripheral neuronal networks, thus ultimately invading the brain and brainstem. The death upon respiratory failure may be also associated with the local inflammation- and thrombi-derived damages to the respiratory reflexes in both the lung neuronal network and brainstem center. Beyond the infection-associated neurological symptoms, long-term neuropsychiatric consequences that could occur months after the host recovery are not to be excluded. While our article does not attempt to fully comprehend all accesses for host neuroinvasion, we aim at stimulating researchers and clinicians to fully consider the neuroinvasive potential of SARS-CoV-2, which is likely to affect the peripheral nervous system targets first, such as the enteric and pulmonary nervous networks. This acknowledgment may shed some light on the disease understanding further guiding public health preventive efforts and medical therapies to fight the pandemic that directly or indirectly affects healthy isolated individuals, quarantined subjects, sick hospitalized, and healthcare workers.

SARS-CoV-2 Aiming for the Heart: A Multicenter Italian Perspective About Cardiovascular Issues in COVID-19.

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the high fatality rate of coronavirus disease 2019 (COVID-19) have been putting a strain on the world since December 2019. Infected individuals exhibit unpredictable symptoms that tend to worsen if age is advanced, a state of malnutrition persists, or if cardiovascular comorbidities are present. Once transmitted, the virus affects the lungs and in predisposed individuals can elicit a sequela of fatal cardiovascular consequences. We aim to present the pathophysiology of COVID-19, emphasizing the major cellular and clinical manifestations from a cardiological perspective. As a roaming viral particle or more likely via the Trojan horse route, SARS-CoV-2 can access different parts of the body. Cardiovascular features of COVID-19 can count myocardial injuries, vasculitis-like syndromes, and atherothrombotic manifestations. Deviations in the normal electrocardiogram pattern could hide pericardial effusion or cardiac inflammation, and dispersed microthrombi can cause ischemic damages, stroke, or even medullary reflex dysfunctions. Tailored treatment for reduced ejection fraction, arrhythmias, coronary syndromes, macrothrombosis and microthrombosis, and autonomic dysfunctions is mandatory. Confidently, evidence-based therapies for this multifaceted nevertheless purely cardiological COVID-19 will emerge after the global assessment of different approaches.

Healthy Eating, Physical Activity, and Sleep Hygiene (HEPAS) as the Winning Triad for Sustaining Physical and Mental Health in Patients at Risk for or with Neuropsychiatric Disorders: Considerations for Clinical Practice.

Neuropsychiatric disorders stem from gene-environment interaction and their development can be, at least in some cases, prevented by the adoption of healthy and protective lifestyles. Once full blown, neuropsychiatric disorders are prevalent conditions that patients live with a great burden of disability. Indeed, the determinants that increase the affliction of neuropsychiatric disorders are various, with unhealthy lifestyles providing a significant contribution in the interplay between genetic, epigenetic, and environmental factors that ultimately represent the pathophysiological basis of these impairing conditions. On one hand, the adoption of Healthy Eating education, Physical Activity programs, and Sleep hygiene promotion (HEPAS) has the potential to become one of the most suitable interventions to reduce the risk to develop neuropsychiatric disorders, while, on the other hand, its integration with pharmacological and psychological therapies seems to be essential in the overall management of neuropsychiatric disorders in order to reduce the disability and improve the quality of life of affected patients. We present an overview of the current evidence in relation to HEPAS components in the prevention and management of neuropsychiatric disorders and provide suggestions for clinical practice.

Critical aspects in the legal defence of patients with Tourette's Syndrome: An Italian case series.

Tourette's syndrome (TS) is a developmental neurobehavioral disorder with childhood onset and relevant burden in terms of disability and reduced quality of life. In Italy the biological basis of this syndrome is still frequently ignored and TS is often recognised as a psychiatric manifestation, or even it is not recognised as pathology, which may result in inadequate treatment, social isolation and improper hospitalization. Indeed, the organic medical nature of TS needs to be taken into great consideration in evaluating causality of committing crimes in affected patients. In addition, delaying the diagnosis and consequently proper treatment has a devastating impact on social as well as legal aspects in patients with TS. The present report is aimed to present an Italian case series of 4 TS patients who faced legal problems related to their mental condition, in the intent to add further evidence, raise the level of awareness and encourage further investigation in the field, as in most of the cases, patients' illness was not taken into adequate account by the Justice. The relevant law is discussed in detail.

Ventral Intermediate Nucleus Versus Zona Incerta Region Deep Brain Stimulation in Essential Tremor.

BACKGROUND: The ventral intermediate nucleus (VIM) is the target of choice for Essential Tremor (ET) deep brain stimulation (DBS). Renewed interest in caudal zona incerta (cZI) stimulation for tremor control has recently emerged and some groups believe this approach may address long-term reduction of benefit seen with VIM-DBS. OBJECTIVES: To compare clinical outcomes and DBS programming in the long-term between VIM and cZI neurostimulation in ET-DBS patients. MATERIALS AND METHODS: A retrospective review of 53 DBS leads from 47 patients was performed. Patients were classified into VIM or cZI groups according to the location of the activated DBS contact. Demographics, DBS settings, and Tremor Rating Scale scores were compared between groups at baseline and yearly follow-up to 4 years after DBS. Student t-tests and analysis of variance (ANOVA) were used to compare variables between groups. RESULTS: Relative to baseline, an improvement in ON-DBS tremor scores was observed in both groups from 6 months to 4 years post-DBS (p < 0.05). Although improvement was still significant at 4 years, scores from month 6 to 2 years were comparable between groups but at 3 and 4 years post-DBS the outcome was better in the VIM group (p < 0.01). Stimulation settings were similar across groups, although we found a lower voltage in the VIM group at 3 years post-DBS. CONCLUSIONS: More ventral DBS contacts in the cZI region do improve tremor, however, VIM-DBS provided better long-term outcomes. Randomized controlled trials comparing cZI vs VIM targets should confirm these results.

Dual floor burr hole technique in deep brain stimulation: A retrospective study on 209 patients.

BACKGROUND: Skin erosion/infections due to deep brain stimulation hardware are highly worrisome complications. They can lead to the removal of the entire deep brain stimulation device, and consequently hold the whole treatment in otherwise pharmacologically refractory patients. Several techniques have been used such as C-shape skin incision and dual floor burr hole or single passage of connecting cables to reduce the incidence of skin complications. METHODS: In this paper, we describe our experience in 209 patients using a dual-floor burr hole technique to reduce skin adverse effects. CONCLUSION: The dual floor burr hole technique is a safe technique with a low incidence of skin erosions and complications.

Handwriting Tics in Tourette's Syndrome: A Single Center Study.

Tourette's syndrome (TS) is a neurodevelopmental disorder typically defined by multiple motor tics and at least one sound tic, beginning in childhood or in adolescence. Handwriting is one of the most impaired school activities for TS patients because of the presence of tics that hamper learning processes. In this paper, we present a case of handwriting tics in a TS patient highlighting the main features.