Occipitocervical Fusion.

Occipitocervical fusion is a surgical technique in continuous evolution due to the innovation of devices, operative and instrumentation techniques. The aetiologies responsible for occipitocervical instability are trauma, neoplastic disease, metabolic disease or congenital disease. A variety of stabilization techniques are currently available depending on the type of patient and surgeon's experience. Each of these techniques requires thorough knowledge of the anatomy of the craniovertebral junction.

Occipital Nerve Stimulation for Refractory Pain after Occipitocervical Fusion.

Occipital nerve stimulation (ONS) is electric stimulation of the distal branches of the greater occipital nerve by cylindrical or paddle leads implanted in subcutaneous occipital tissue. This surgical option has emerged as a promising treatment for different types of disabling medical refractory headache and recently also for residual occipital and nuchal pain after previous occipitocervical fusion. The mechanisms of action have not yet been clearly explained: electrical stimulation of the occipital nerve has both peripheral and central effects on the nervous system, which may modulate nociception. ONS is a well-tolerated and safe procedure in comparison with other invasive modalities of treatment. Lead migration/dislodgement is a common complication, but use of new surgical techniques and leads may reduce the rate of this complication.

Metalloproteinase-9 and neutrophil gelatinase-associated lipocalin plasma and tissue levels evaluation in middle cerebral artery aneurysms.

Background. Cerebral aneurysms are relatively common in adults, with a prevalence ranging between 1% and 5%. Subarachnoid hemorrhage, following aneurismal rupture, is a major cause of death and disability in these patients. Matrix Metalloproteinases (MMPs) and Neutrophil Gelatinase-Associated Lipocalin (NGAL) seem to be involved in the pathogenesis and in the clinical course of aneurysms. In this study, we evaluated the relationship between tissue and plasma levels of MMP-9 and NGAL in patient with ruptured and unruptured middle cerebral artery aneurysms. Methods. An open label study was conducted on 7 patients with middle cerebral aneurysms. Three patients had ruptured aneurysms (Group I) and four patients had unruptured aneurysms (Group II). All patients underwent aneurysm clipping. Plasma levels of MMP-9 and NGAL were evaluated through ELISA Test. During the surgery, biopsies of the aneurysmatic arteries were taken and frozen (- 80°C) for Western blot evaluation of MMPs and NGAL expression. Four healthy volunteers (Group III) represented the control group for ELISA testing. Results. Both plasma MMP-9 and NGAL levels were significantly high in aneurysmatic patients respect to those of control patients, and these levels were higher (P < 0.01) in patients with ruptured aneurysms respect to patients with unruptured aneurysms (P < 0.01). The latest findings were similarly evident in tissue evaluation of MMP-9 and NGAL between ruptured and unruptured aneurysms. Conclusion. This study suggests that MMP-9 and NGAL plasma levels may be useful to predict the clinical course of a cerebral aneurysms in order to evaluate the progression of the disease and the tendency of an aneurysm to rupture.

Spinal Cord Stimulation in Chronic Low Back Pain Syndrome: Mechanisms of Modulation, Technical Features and Clinical Application.

Chronic low-back pain (CLBP) is a common disease with several negative consequences on the quality of life, work and activity ability and increased costs to the health-care system. When pharmacological, psychological, physical and occupational therapies or surgery fail to reduce CLBP, patients may be a candidate for Spinal Cord Stimulation (SCS). SCS consists of the transcutaneous or surgical implantation of different types of electrodes in the epidural space; electrodes are then connected to an Implanted Pulse Generator (IPG) that generates stimulating currents. Through spinal and supraspinal mechanisms based on the "gate control theory for pain transmission", SCS reduces symptoms of CLBP in the almost totality of well-selected patients and its effect lasts up to eight years in around 75% of patients. However, the evidence in favor of SCS still remains weak, mainly due to poor trial methodology and design. This narrative review is mainly addressed to those professionals that may encounter patients with CLBP failing conventional treatments. For this reason, we report the mechanisms of pain relief during SCS, the technical features and some clinical considerations about the application of SCS in patients with CLBP.

Pilocytic Astrocytoma-Derived Cells in Peripheral Blood: A Case Report.

Imaging limitations, invasive tissue biopsies and poor information over the course of treatment to evaluate 'real-time' tumor dynamics justify the emerging use of liquid biopsies in the field of brain tumors. Circulating tumor cells (CTCs) from high-grade astrocytomas might reach the circulation by crossing the blood-brain barrier. Here, for the first time, CTCs cytology in a case of pylocitic astrocytoma is described. An obstructive hydrocephalous due to a lateral mesencephalic tectum mass occluding the Silvio Aqueduct was diagnosed in a young, 18 years old, male. Considering the location of the tumor and the rapid deterioration of the neurological status, it has been decided to urgency treat the patient with ventriculoperitoneal shunting. Magnetic resonance imaging showed a nodular shaped lesion localized within the left lateral mesencephalic tectum. Stereotactic biopsy was not approachable due significant risk of neurological consequences. The diagnosis was performed by blood sampling, a non-invasive procedure for the patient, in order to provide tumor information. Cytopathological features on detected circulating atypical GFAP positive cells led to pilocytic diagnosis confirmed by the patient's 68 months outcome.

Percutaneous intradiscal injection of radiopaque gelified ethanol: short- and long-term functional outcome and complication rate in a consecutive series of patients with lumbar disc herniation.

Lumbar disc herniation (LDH) is a common cause of low back pain (LBP) and/or radicular pain (RP). Over the years, different therapies have been proposed to treat symptomatic LDH, including different minimally invasive techniques and open surgical methods. Recently, percutaneous intradiscal injection of radiopaque gelified ethanol (RGE) DiscoGel® has emerged as an effective therapeutic option in patients with LDH. Nevertheless, only few studies addressed the reliability of this technique. The purpose of this study was to evaluate the efficacy and safety of this procedure. We analysed surgical and outcome data of patients with small or medium LDH treated by DiscoGel between 2012 to 2015. Outcome variables included pain relief, the limitation on physical activity and severity of depression status. Overall, complication rate was defined as the occurrence of any perioperative adverse events. A total of 94 consecutive patients were enrolled in the study. Pain relief was achieved in 90.6% and 88.8% of patients at 1- and 4-year follow-up, respectively. At the last follow-up, at least a satisfactory result was achieved in 92.5% of patients. Similar results were obtained in the limitation on physical activity. Depression status did not significantly change after treatment. There was no mortality, and no patients experienced permanent sequelae. In well-selected patients, DiscoGel has proved effective in maintaining excellent functional results in terms of pain relief and limitation on physical activity while minimizing the overall rate of complications related to these kinds of surgical procedures.

Deep brain stimulation for treatment-resistant depression: a safe and effective option.

Introduction: Major depressive disorder (MDD) is the leading cause of years lost to disability worldwide. Pharmacotherapy and psychotherapy are effective treatments in most depressive episodes; but, about 30% of MDD patients remain symptomatic, and relapse is a common event. Recently, deep brain stimulation (DBS) has emerged as a valid therapeutic option in treatment-resistant depression (TRD) patients.Areas covered: In this paper, the authors summarize the findings of studies focused on these pathophysiologic phenomena and specifically on the role of DBS as a therapeutic option in TRD patients. The authors simply reviewed RCTs, open-label studies, neurophysiological mechanisms of DBS in MDD, and the possible role of different targets. Finally, we suggest possible future options.Expert opinion: Depression is a systems-level disorder, involving several brain structures. Neuroimaging studies demonstrate multiple interconnected regions that modulate different neural networks. DBS can modulate different targets, and others are under investigation. Among these subcallosal cingulate gyrus (SCG), ventral capsule and ventral striatum (VC/VS) seems to be the most relevant targets. We believe that, in the next future, DBS for TRD might become a first-line of treatment, especially using directional leads, that may help us to improve therapeutic effects.

Suspected Pulmonary Embolism after Oxygen-Ozone Therapy for Low Back Pain.

Oxygen-ozone therapy is used to treat degenerative pathology of the spine when surgery is not needed (e.g., removal of a herniated disk). Some authors have described it as a safe and effective procedure in ∼ 70 to 90% of patients. The aim of the therapy is to dehydrate the intervertebral disk and alter its contents. However, this treatment has been associated with some rare but very serious side effects. Both cardiac damage and a case of fulminant septicemia were reported. We describe a case of suspected pulmonary embolism, followed by sudden death, in an elderly woman treated with oxygen-ozone therapy for lumbar pain caused by disk protrusion. We believe a massive pulmonary embolism occurred, probably caused by an intradiskal injection that accidentally punctured a venous vessel and created emboli.

Cervical spinal cord compression from delayed epidural scar tissue formation around plate lead for SCS.

Cervical spinal compression is a serious and rare complication of spinal cord stimulation (SCS) that can occur using leads placed via open surgical approach. The present report describe a case of cervical plate lead implant that developed spinal and radicular compression symptoms after seven years due to the growth of fibrotic epidural mass at the level of lead. A review of literature is provided. A 59-year­old woman with 3-year history of left arm post­traumatic complex regional pain syndrome (CRPS) was treated with SCS performed with the implant of paddle lead in the epidural space from C3-C5. Seven years later she reported progressive paresthesia along the spine and the limbs, gait ataxia with sensation of weakness in the legs, increased muscle tone and tendon reflexes in the lower extremities and decrease in effectiveness of stimulation. Cervical CT showed a tissue mass into the cervical canal posteriorly to the lead. This finding was confirmed by MR performed after lead removal that also allowed to document the amount of spinal cord compression. The patient underwent C4-C5-C6 laminectomy and a thick scar was removed from the dura. After surgery there was progressive and incomplete improvement of neurological signs but symptoms related to algodystrophy recurred partly. The formation of hypertrophic epidural scar tissue at the level of lead implant must be taken into consideration in presence of the onset of progressive cervical myelopathy in patient treated with SCS using laminectomy lead.

DBS in Treatment of Post-Traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition for which pharmacological therapy is not always solvable. Various treatments have been suggested and deep brain stimulation (DBS) is currently under investigation for patients affected by PTSD. We review the neurocircuitry and up-to-date clinical concepts which are behind the use of DBS in posttraumatic stress disorder (PTSD). The role of DBS in treatment-refractory PTSD patients has been investigated relying on both preclinical and clinical studies. DBS for PTSD is in its preliminary phases and likely to provide hope for patients with medical refractory PTSD following the results of randomized controlled studies.

Minimally invasive motor cortex stimulation for Parkinson's disease.

Extra/intradural strip electrode implantation on motor cortex may be possible minimally invasive neurosurgical method for therapeutic neuromodulation in Parkinson's disease (PD). The aim of this review is to assess motor cortex stimulation (MCS) efficacy and safety in advanced PD. Sixteen published articles were included with a total of 130 PD patients treated. In almost all results are from prospective observational open labeled study, only in two studies blinded assessment was carried out. Negative results are reported in three studies. Significant improvement in motor symptoms with remarkable effect on axial symptoms, L-dopa-induced dyskinesia and quality of life are outlined in thirteen studies. Surgical technique involved implant of four-contact strip electrode over M1 in epidural space with exception of few cases in which implant was carried out in subdural space. Surgical procedure was performed contralateral to most affected side with exception of five patients in which it was carried at dominant hemisphere; in four patients electrode implant was bilateral but stimulation was carried out simultaneously on both sides only in two cases. Complications and adverse events occurred very rarely for extradural MCS whereas with higher rate for subdural MCS. Based on review of current literature extra/intradural MCS represents an alternative to deep brain stimulation (DBS) to surgically treat PD patients who are not candidate for DBS. MCS is a minimally invasive neuromodulation procedure with low morbidity-mortality that can relieve all three major symptoms of PD on both sides simultaneously and bilaterally; it has significant effectiveness on axial symptoms, gait disturbances and therapy complications.

Critical reappraisal of DBS targeting for movement disorders.

Deep brain stimulation (DBS) is used as a surgical treatment of movement disorders such as Parkinson's disease, dystonia and essential tremor. Fundamental understanding of DBS effects on the pathological neural circuitry remains insufficient. In 2002 DBS of the subthalamic nucleus (STN) and the globus pallidus internus (GPi) was approved for use in patients with PD. Next year, DBS of Gpi and STN for dystonia received a Humanitarian Device exemption from the FDA. The commonly targets for DBS are subthalamic nucleus (STN) or globus pallidus internus (GPi) for Parkinson's disease, Gpi for dystonia and ventro-intermediate (VIM) nucleus of the thalamus for essential tremor. However, VIM DBS cannot sufficiently improve akinesia and rigidity. Pedunculopontine nucleus (PPN) is currently investigated as potential target to improve gait and posture. It is determined that DBS sometimes influences not only motor functions but also the cognitive and affective functions of patients. In this article we review the present state of DBS for movement disorders, appropriate indications, practical effects and stimulation-induced adverse events established in previous studies. We discuss target selection and the effect of DBS on motor and non-motor symptoms of Parkinson's disease, dystonia and essential tremor.

Administration of palmitoylethanolamide in combination with topiramate in the preventive treatment of nummular headache.

Nummular headache has been recently described as a primary disorder characterized by head pain exclusively felt in a small rounded area typically 2-6 cm in diameter, not attributed to another disorder. Both size and shape of the painful area remain constant since the onset of symptoms. A 57-year-old woman presented with a history of focal episodic pain in a circumscribed area on the right parietal region. The administration of standard oral doses of palmitoylethanolamide and topiramate in combination showed an improvement in pain symptoms and on pain measuring scales.

High mobility group A1 expression correlates with the histological grade of human glial tumors.

Glioblastoma is one of the most aggressive tumors in mankind with 50% of patients dying within the 1st year of diagnosis, and being refractory to conventional therapies. The aim of our work has been to analyse the expression of the HMGA1 proteins in human astrocytomas and glioblastomas in order to verify whether the detection of these proteins might be of some help in the diagnosis of these neoplasias. Here we report the analysis of 27 cases, including 12 astrocytomas and 15 glioblastomas, for HMGA1 expression. All the neoplastic samples showed positive staining even though the number of positive cells and the staining intensity was higher in glioblastomas compared to astrocytomas. Conversely, HMGA1 proteins were not detected in normal brain. Accordingly, expression of the hmga1 gene, analysed by RT-PCR, was higher in glioblastomas than in astrocytomas.

Motor cortex stimulation in Parkinson's disease.

Motor Cortex Stimulation (MCS) is less efficacious than Deep Brain Stimulation (DBS) in Parkinson's disease. However, it might be proposed to patients excluded from DBS or unresponsive to DBS. Ten patients with advanced PD underwent unilateral MCS contralaterally to the worst clinical side. A plate electrode was positioned over the motor cortex in the epidural space through single burr hole after identification of the area with neuronavigation and neurophysiological tests. Clinical assessment was performed by total UPDRS, UPDRS III total, UPDRS III-items 27-31, UPDRS IV, and UPDRS II before implantation in off-medication and on-medication states and after surgery at 1, 3, 6, 12, 18, 24, and 36 months in on-medication/on-stimulation and off-medication/on-stimulation states. We assessed changes of quality of life, throughout the Parkinson's disease quality of life scale (PDQoL-39), and the dose of anti-Parkinson's disease medications, throughout the Ldopa equivalent daily dose (LEDD). During off-medication state, we observed moderate and transitory reduction of total UPDRS and UPDRS total scores and significant and long-lasting improvement in UPDRS III items 27-31 score for axial symptoms. There was marked reduction of UPDRS IV score and LEDD. PDQL-39 improvement was also significant. No important complications and adverse events occurred.

Sacral nerve stimulation with percutaneous dorsal transforamenal approach in treatment of isolated pelvic pain syndromes.

Objectives. The aim of the study was to test the effectiveness of sacral nerve stimulation (SNS) performed by a transforamenal approach in patients with isolated chronic intractable pelvic pain. Materials. Sevenpatients with intractable pelvic pain underwent implantation of self-anchoring leads by way of the dorsal S3 foramen in four cases and of the dorsal S4 foramen in three cases. Patients with pain improvement > 50% underwent sacral nerve root stimulation device implantation. SNS therapeutic efficacy was measured using a visual analog scale (VAS) and its effects on quality of life (QoL) using the SF-36 scale. Results. During test stimulation five patients had significant and permanent pain relief and subsequently underwent implantation of a permanent device. VAS score improvement was evident in these patients and remained unchanged at 3, 6, and 12 months (median 8 months); SF-36 QoL questionnaire also revealed significant improvement in many domains of QoL including all the four physical domains and three of the four mental domains. There were three complications in our seven patients: one lead fracture, one lead displacement in the presacral space, and one patient who developed pain at the implantable pulse generator site. Conclusions. Transforamenal SNS is effective in relieving isolated pelvic pain but a high complication rate was found.