Dynamic Brain Imaging Response to Spinal Cord Stimulation Differential Frequencies DiFY SCS-PET Clinical Trial.

OBJECTIVES: This study with sequential 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-computed tomography (CT) scanning was designed to investigate any objective measurable effect of differential frequency stimulation (40 Hz, 4000 Hz, and 10,000 Hz) on specific pain matrix areas in patients who underwent spinal cord stimulation (SCS) for intractable lumbar neuropathic pain. MATERIALS AND METHODS: In this single-center, randomized, blinded study, four brain 18F-FDG PET scans were performed for each patient-at baseline before SCS implant and after 40-Hz, 4000-Hz, and 10,000-Hz stimulation. After 40-Hz stimulation for four weeks, patients were randomized 1:1 (4000 Hz/10,000 Hz), crossing over at another four weeks. 18F-FDG PET-CT brain scans acquired on the GE-Discovery 710 PET system (GE Healthcare, Chicago, IL) with 128-slice CT (250-MBq dose) were analyzed using the PMOD software (PMOD Technologies Ltd, Zurich, Switzerland). A total of 18 pain regions, the right and left prefrontal cortex (PFC), insula, anterior cingulate cortex (ACC), hippocampus, amygdala, primary somatosensory cortices, secondary somatosensory cortices (SSCII), thalami, parabrachial, and periaqueductal gray (PAG), were analyzed. RESULTS: A total of 14 patients received 40 Hz for four weeks before crossing over to 10,000 Hz/4000 Hz. A total of 57 PET-CT scans (15 for baseline and 14 each for 40 Hz, 4000 Hz, and 10,000 Hz) were analyzed for maximum standardized uptake value (SUVmax), with a statistically significant difference in SUVmax between 40 Hz and baseline (p = 0.002) and 4000 Hz and baseline (p = 0.001) when pooled across 18 pain matrices. There was no statistical difference in SUVmax between 10,000 Hz and baseline. The pooled analysis showed a proportionately higher thalamic region reduction (59.5%) in metabolic activity than other pain matrices, PFC (52%), insula (50%), ACC (52%), SSCII (49%), and PAG (52%). CONCLUSION: This large cohort of brain PET scans (n = 57) shows statistically significant differences in brain metabolic activity at 40 Hz and 4000 Hz from baseline, with effect on both nociceptive and affect-cognitive pathways (proportionately higher reduction in the thalamus), highlighting the possible mechanism of SCS. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03716557.

Effectiveness of high dose spinal cord stimulation for non-surgical intractable lumbar radiculopathy - HIDENS Study.

OBJECTIVES: Spinal cord stimulation (SCS) is being increasingly used in non-surgical intractable low back pain. This study was designed to evaluate the efficacy of high-dose (HD) SCS utilizing sub-perception stimulation with higher frequency and pulse width in non-surgical predominant low-back pain population at 12 months. MATERIALS AND METHODS: A total of 20 patients were recruited (280 screened between March 2017 and July 2018) to undergo percutaneous fluoroscopic-guided SCS (Medtronic 8 contact standard leads and RestoreR IPG), with T8 and T9 midline anatomical parallel placement. Sixteen patients completed 12 months follow-up (500 Hz frequency, 500 µs pulse width, and 25% pulse density). Differences in patients' clinical outcome (NRS back, NRS leg, ODI, PGIC, and PSQ) and medication usage (MQS) at 1, 3, and 12 months from the baseline were assessed using non-parametric Wilcoxon paired test. RESULTS: The mean NRS scores for back pain (baseline 7.53) improved significantly at 1, 3, and 12 months; 2.78 (p < 0.001), 4.45 (p = 0.002), and 3.85 (p = 0.002), respectively. The mean NRS score for leg pain (baseline 6.09) improved significantly at 1 and 3 months; 1.86 (p < 0.001) and 3.13 (p = 0.010), respectively. Mean NRS for leg pain at 12 months was 3.85 (p = 0.057). ODI and sleep demonstrated significant improvement as there was consistent improvement in medication particularly opioid usage (MQS) at 12 months. CONCLUSIONS: This study demonstrates that anatomical placement of leads with sub-perception HD stimulation could provide effective pain relief in patients who are not candidates for spinal surgery.

An overview of the neurosurgical implications, pathophysiology, diagnosis and recent treatment strategies for Grade IV idiopathic osteolysis, also known as Gorham-Stout or phantom bone disease.

OBJECTIVE: Gorham-Stout disease (GSD), commonly referred as vanishing bone or phantom bone disease, is a rare disorder characterized by spontaneous bone osteolysis due to proliferation of lymphangiomatous tissue. This disease can involve multiple bones and cause pathologic fractures. The exact cause of GSD is unknown and its severity is unpredictable; the disorder can potentially cause disfigurement or functional disability. According to CARE guidelines, we studied a 46 years old lady with a progressive defect of the skull. Differential diagnosis included: benign and malignant diploic lesions (eosinophylic granuloma of the skull, myeloma, lytic metastasis from unknown primary tumour, etc) and osteomyelitis. A suspicion of GSD was raised by coupling information from laboratory and nuclear medicine investigations, and eventually confirmed histologically. CONCLUSION: We included early in the investigation protocols a total body fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) scan that was extremely helpful to promptly rule out malignant or infective nature of osteolysis. An update on the diagnostic and management options available for GSD, with particular reference to the role of nuclear medicine and the latest clinical trials from international patients registries and classification of idiopathic osteolysis is provided.

Pain and functional outcomes following vertebroplasty for vertebral compression fractures - A tertiary centre experience.

OBJECTIVES: There is a dearth of comparative outcome data on vertebroplasty for the treatment of vertebral compression fractures (VCF) according to vertebral level, the number of levels and aetiology. The aim of this study was to investigate the improvement of pain and function following vertebroplasty for a heterogeneous cohort of patients with medically refractory VCF. METHODS: A prospective observational study was conducted on a cohort of consecutive patients undergoing vertebroplasty following at least 4 weeks of failed medical management, between April 2007 and March 2012 at a single neurosurgical centre. Pain visual analogue scale (VAS) scores, Oswestry Disability Index (ODI) scores, analgesic usage and complications were recorded preoperatively and at day 1, week 1, 1 month, 6 months and 1 year postoperatively. Intraoperative vertebral body biopsy was performed routinely. RESULTS: Two hundred and two levels were augmented in 147 patients. The most common levels augmented were T12 (17%), L1 (18%) and L4 (10%). Significant reductions in pain VAS and ODI scores were evident at day 1 and sustained at up to 1 year postoperatively (p < 0.001). They were not dependent on the level of fracture (T3-10, T11-L2 and L3-S1) (p > 0.05), the number of levels treated (single level, two-level and > two level) (p > 0.05) or aetiology of VCF (p > 0.05). At 1 year postoperatively, 79% (113/142) had no or reduced analgesic usage. The complication rate was 6% (9/147). There were five mortalities, none of which was directly related to surgery. CONCLUSION: Vertebroplasty for medically refractory VCF may offer sustained improvement in pain and function. The procedure is associated with low morbidity and mortality.

Utility of routine biopsy at vertebroplasty in the management of vertebral compression fractures: a tertiary center experience.

OBJECT: The authors assess the utility of routine biopsy at vertebroplasty for vertebral compression fracture (VCF) as a tool in the early detection of malignancy in presumed benign VCF. METHODS: A prospective observational study was conducted on a cohort of consecutive patients undergoing vertebroplasty over a 5-year period between April 2006 and March 2011 at the Royal London Hospital. Polymethylmethacrylate cement injection was used in every procedure. Intraoperative vertebral body biopsy was performed routinely at every level of VCF. Pain visual analog scale (VAS) scores, Oswestry Disability Index (ODI) scores, analgesic usage, and complications were recorded preoperatively and at 1 day, 1 week, 1 month, 6 months, and 1 year postoperatively. RESULTS: A total of 202 levels were augmented in 147 patients. The most common levels augmented were T-12 (17%), L-1 (18%), and L-4 (10%). Analysis of 184 routine vertebral biopsies in 135 patients revealed that in 86 patients with presumed osteoporosis and no prior cancer diagnosis, 4 (4.7%) had a malignant VCF. In 20 known cancer patients presumed to be in remission, 2 (10%) had a malignant VCF. Routine vertebral biopsy returned an overall cancer diagnosis rate of 5.5% (6 of 109) when combining the 2 groups (patients with no prior history of cancer or cancer thought to be in remission). In these 6 patients, history, examination, laboratory tests, and preprocedure imaging all failed to suggest malignancy diagnosed at routine biopsy. Significant reductions in pain VAS and ODI scores were evident at Day 1 and were sustained at up to 1 year postoperatively (p < 0.001). They were not dependent on the level of fracture (T3-10, T11-L2, or L3-S1) (p > 0.05), number of levels treated (single level, 2 levels, or > 2 levels) (p > 0.05), or etiology of VCF (p > 0.05). The complication rate was 6% (9 of 147). There were 5 deaths, none of which were directly related to surgery. CONCLUSIONS: Routine vertebral biopsy performed at vertebroplasty may demonstrate cancer-related VCFs in unsuspected patients with no previous cancer diagnosis or active malignancy in patients previously thought to be in remission. This early diagnosis of cancer or relapsed disease will play an important role in expediting patients' subsequent cancer management. In cases of multiple-level VCF, the authors advocate biopsy at each level to maximize the diagnostic yield from the specimens and to avoid missing a malignancy at a single level.

Lentiviral mediated expression of a NGF-soluble Nogo receptor 1 fusion protein promotes axonal regeneration.

Nogo receptor 1 (NgR1) mediates the inhibitory effects of several myelin-associated inhibitors (MAIs) on axonal regeneration in the central nervous system. A truncated soluble NgR1 (sNgR) has been reported to act as a decoy receptor to block the actions of MAIs. In this study, we fused the sNgR to nerve growth factor (NGF) and used NGF as a carrier to deliver sNgR to the intercellular space to neutralize MAIs. NGF in NGF-sNgR remained biologically active and induced sprouting of calcitonin gene related peptide containing axons when expressed in the spinal cord using a lentiviral vector (LV). Secreted NGF-sNgR promoted neurite outgrowth of dissociated dorsal root ganglion neurons on myelin protein substrate. In a rat dorsal column transection model, regenerating sensory axons were found to grow into the lesion cavity in animals injected with LV/NGF-sNgR, while in animals injected with LV/GFP or LV/NGF-GFP few sensory axons entered the lesion cavity. The results indicate that NGF-sNgR fusion protein can reduce the inhibition of MAIs and facilitate sensory axon regeneration. The fusion constructs may be modified to target other molecules to promote axonal regeneration and the concept may also be adapted to develop gene therapy strategies to treat other disorders.

Mitigating effects of external ventricular drain usage in the management of severe head injury.

BACKGROUND: Cerebrospinal fluid (CSF) drainage has been variably employed to lower intracranial pressure (ICP) in patients with severe head injury. The efficacy of this manoeuvre remains under-explored (Brain Trauma Foundation Recommendation-optional treatment). This work seeks to report the results of CSF drainage via external ventricular drain (EVD) in severe head injury in comparison to other treatment options. METHODS: Retrospective observational comparative study of all consecutive patients admitted to a major trauma centre with severe traumatic brain injury over a period of 12 months. RESULTS: Out of a total 139 patients, 33 had delayed elevation of ICP despite conventional medical therapy, 16 patients were treated with EVD insertion (4 placed under AxiEM image guidance [Medtronic]) and 17 received either decompressive craniectomy or barbiturate coma. Subsequently, two patients with decompression had further ICP elevation and needed EVD. Two patients with EVD had raised ICP-one underwent decompression and the other was treated with barbiturate coma. One patient with EVD developed infection, which was successfully treated. Patients treated with EVD had a lower risk of needing definitive treatment for ICP control, i.e. decompressive craniectomy or barbiturate coma. CONCLUSIONS: EVD was a safe and less invasive procedure, and achieved sustained control of ICP in this patient group.

Balloon kyphoplasty treatment for a spontaneous vertebral fracture in renal osteodystrophy.

Renal osteodystrophy is a spectrum of musculoskeletal abnormalities. Bony fractures can occur spontaneously or with minor trauma in this condition. The authors report the first case of balloon kyphoplasty treatment for painful renal osteodystrophy vertebral body collapse secondary to end-stage renal failure on dialysis. The authors have demonstrated that kyphoplasty is a safe procedure for pain management in severe dystrophic patients. In addition, pain treatment with kyphoplasty can be achieved without anatomical restoration of vertebral body height.

Traumatic intraspinal extradural ganglion cyst in a teenager: case report and review of the literature.

Spinal extradural cyst is a rare cause of spinal cord or nerve root compression. We present a case which is unique due to both the young age of the patient and its distinctly acute haemorrhagic presentation. In what is normally considered a degenerative disease in older patients this has implications for the possibility of a traumatic aetiology in children. The literature on the classification of extradural cysts is reviewed.

Cushing's disease in children and adolescents: 20 years of experience in a single neurosurgical center.

OBJECTIVE: This is a retrospective analysis of 25 consecutive pediatric patients with Cushing's disease who underwent transsphenoidal surgery performed by a single neurosurgeon in a specialist center during a 20-year period. This article discusses the presentation of Cushing's disease, the endocrinological investigation with particular reference to bilateral inferior petrosal sinus sampling (BIPSS), the operative management with reference to specific pediatric difficulties of the transsphenoidal approach and the use of intraoperative image guidance, and the analysis of these cases as regards postoperative complications and outcomes of this rare condition in young patients. METHODS: All patients underwent detailed endocrine investigation and imaging in the form of computed tomography and/or magnetic resonance imaging. BIPSS was performed in 19 patients (76%), with successful lateralization of the side of the microadenoma in 14 (74%) and prediction of a central tumor in four (94% total prediction rate). Surgical removal was via the sublabial, paraseptal, transsphenoidal route. RESULTS: There were 15 male and 10 female patients, with a mean age of 13.4 years (range, 6.6-17.8 yr). Weight gain was the most common presentation (100%), and then growth impairment (96%), fatigue and skin changes (64%), and hypertension (32%). Postoperative complications included growth hormone deficiency (36%), transient diabetes insipidus (12%), panhypopituitarism (4%), and transient cerebrospinal fluid rhinorrhea (4%). The median follow-up period was 59.5 months (range, 6-126 mo). Overall, 15 patients (60%) achieved surgical cure or remission, of which 14 outcomes were obtained using the results of BIPSS. Ten patients (40%) required postoperative radiotherapy to achieve "remission." There were no cases of meningitis, no neurological deficits, no reoperations, and no mortality. CONCLUSION: Cushing's disease in children and adolescents is a rare illness. The accurate preoperative localization of the adenoma is essential for achieving good results. In this series, BIPSS was far more accurate in localizing the adenoma than computed tomography or magnetic resonance imaging. Imaging, however, is useful for the exclusion of other intracranial problems. Transsphenoidal surgery was safe and efficacious in achieving cure in the majority of cases. The challenge of transsphenoidal surgery in this age group is the small pituitary fossa and the absence of sphenoid sinus aeration in some cases. We found the use of intraoperative neuronavigation to be an excellent aid in overcoming such anatomic difficulties.

Trigeminal neuralgia secondary to Chiari's malformation--treatment with ventriculoperitoneal shunt.

BACKGROUND: Trigeminal neuralgia (TN) is most commonly related to vascular compression of the trigeminal nerve. Trigeminal neuralgia associated with Chiari's malformation and associated hydrocephalus are rare. CASE DESCRIPTION: A 31-year-old male presented with classical TN affecting the mandibular division of the right trigeminal nerve. His symptoms were poorly controlled with increasing doses of carbamazepine. Magnetic resonance imaging scan of brain revealed Chiari's type I malformation and associated hydrocephalus. Approximately 1 month after insertion of a programmable ventriculoperitoneal shunt, his TN resolved. CONCLUSIONS: Chiari's malformation and hydrocephalus are rare associates of TN. The pathophysiology of TN in these cases may be due to neurovascular conflict, related to raised intracranial pressure from the hydrocephalus and/or the small posterior fossa volume in these patients. Drainage of associated hydrocephalus may be an effective surgical treatment.