Cerebrospinal fluid-lymphatic fistula in a child with generalized lymphatic anomaly treated with targeted blood patch - a rare case report and review of the literature.

Spontaneous intracranial hypotension may result in debilitating postural headaches and severe neurological symptoms due to secondary cerebellar sagging. The most common cause is the cerebrospinal fluid (CSF) leak within the spinal canal. Although previously reported in only a few cases, also paraspinal lymphatic malformations causing vertebral bone destruction may occasionally result in CSF leak to these pathological formations. Here, we present a case of a 9-year-old girl with generalized lymphatic anomaly (GLA) presenting with severe postural headache. Radiological imaging revealed a typical feature of cerebellar sagging. Myelography localized the CSF leakage into vertebral bodies of C7 and Th1, which both were partly involved in pathological paravertebral masses of known lymphatic anomaly, and from there along the right C8 nerve root sleeve into the anomaly. As the C8-nerve root could not be ligated due to the risk of significant neurological injury, we attempted image-guided targeted percutaneous epidural placement of a blood patch directly into the foramen at the affected level. The procedure resulted in obliteration of the fistula and regression of cerebellar sagging, with significant relief of symptoms. Although it is an extremely rare coincidence, patients with paraspinal lymphatic malformations may develop intraspinal CSF leak into these pathological formations. The present case report suggests that besides a direct surgical obliteration of the fistula and sacrificing the nerve root, a targeted percutaneous epidural blood patch may be a possible alternative in the case of a functionally important nerve root.

Disseminated central nervous system hemangioblastoma in a patient with no clinical or genetic evidence of von Hippel-Lindau disease-a case report and literature review.

BACKGROUND: Hemangioblastomas (HB) are benign tumors of the central nervous system (CNS) that can appear sporadic or as part of von Hippel-Lindau (VHL) disease. It is often curable with surgical resection, but upon relapse, the disease exhibits a treatment-refractory course. CASE REPORT: A patient treated for sporadic cerebellar HB relapsed 12 years post-surgery. She developed disseminated disease throughout the CNS, including leptomeningeal manifestations. Repeat surgery and craniospinal radiation therapy were unsuccessful. CONCLUSION: This case is in line with previous publications on disseminated non-VHL HB. Available treatment options are inefficient, emphasizing the need for improved understanding of HB biology to identify therapeutic targets.

Rapid recovery and altered neurochemical dependence of locomotor central pattern generation following lumbar neonatal spinal cord injury.

KEY POINTS: Spinal compression injury targeted to the neonatal upper lumbar spinal cord, the region of highest hindlimb locomotor rhythmogenicity, leads to an initial paralysis of the hindlimbs. Behavioural recovery is evident within a few days and approaches normal function within about 3 weeks. Fictive locomotion in the isolated injured spinal cord cannot be elicited by a neurochemical cocktail containing NMDA, dopamine and serotonin 1 day post-injury, but can 3 days post-injury as readily as in the uninjured spinal cord. Low frequency coordinated rhythmic activity can be elicited in the isolated uninjured spinal cord by NMDA + dopamine (without serotonin), but not in the isolated injured spinal cord. In both the injured and uninjured spinal cord, eliciting bona fide fictive locomotion requires the additional presence of serotonin. ABSTRACT: Following incomplete compression injury in the thoracic spinal cord of neonatal mice 1 day after birth (P1), we previously reported that virtually normal hindlimb locomotor function is recovered within about 3 weeks despite substantial permanent thoracic tissue loss. Here, we asked whether similar recovery occurs following lumbar injury that impacts more directly on the locomotor central pattern generator (CPG). As in thoracic injuries, lumbar injuries caused about 90% neuronal loss at the injury site and increased serotonergic innervation below the injury. Motor recovery was slower after lumbar than thoracic injury, but virtually normal function was attained by P25 in both cases. Locomotor CPG status was tested by eliciting fictive locomotion in isolated spinal cords using a widely used neurochemical cocktail (NMDA, dopamine, serotonin). No fictive locomotion could be elicited 1 day post-injury, but could within 3 days post-injury as readily as in age-matched uninjured control spinal cords. Burst patterning and coordination were largely similar in injured and control spinal cords but there were differences. Notably, in both groups there were two main locomotor frequencies, but injured spinal cords exhibited a shift towards the higher frequency. Injury also altered the neurochemical dependence of locomotor CPG output, such that injured spinal cords, unlike control spinal cords, were incapable of generating low frequency rhythmic coordinated activity in the presence of NMDA and dopamine alone. Thus, the neonatal spinal cord also exhibits remarkable functional recovery after lumbar injuries, but the neurochemical sensitivity of locomotor circuitry is modified in the process.

Spinal cord stimulation for the treatment of peripheral neuropathic pain. / Ryggmargsstimulering mot perifere nevropatiske smerter.

Spinal cord stimulation with weak electric current is a neuromodulatory treatment suitable for subgroups of patients with chronic neuropathic pain and certain other pain conditions. Neuropathic pain can reduce quality of life, and the effectiveness of pharmacological treatment is often limited. Studies of spinal cord stimulation have shown significant pain relief and improved functioning at group level, and recent years have seen the development of new stimulation methods which are currently under evaluation.

From wires to waves, a novel sensor system for in vivo pressure monitoring.

Pressure monitoring in various organs of the body is essential for appropriate diagnostic and therapeutic purposes. In almost all situations, monitoring is performed in a hospital setting. Technological advances not only promise to improve clinical pressure monitoring systems, but also engage toward the development of fully implantable systems in ambulatory patients. Such systems would not only provide longitudinal time monitoring to healthcare personnel, but also to the patient who could adjust their way-of-life in response to the measurements. In the past years, we have developed a new type of piezoresistive pressure sensor system. Different bench tests have demonstrated that it delivers precise and reliable pressure measurements in real-time. The potential of this system was confirmed by a continuous recording in a patient that lasted for almost a day. In the present study, we further characterized the functionality of this sensor system by conducting in vivo implantation experiments in nine female farm pigs. To get a step closer to a fully implantable system, we also adapted two different wireless communication solutions to the sensor system. The communication protocols are based on MICS (Medical Implant Communication System) and BLE (Bluetooth Low Energy) communication. As a proof-of-concept, implantation experiments in nine female pigs demonstrated the functionality of both systems, with a notable technical superiority of the BLE.

Volume and densities of chronic subdural haematoma obtained from CT imaging as predictors of postoperative recurrence: a prospective study of 107 operated patients.

BACKGROUND: Chronic subdural haematoma (CSDH) is a common entity in neurosurgery with a considerable postoperative recurrence rate. Computerised tomography (CT) scanning remains the most important diagnostic test for this disorder. The aim of this study was to characterise the relationship between the recurrence of CSDH after treatment with burr-hole irrigation and closed-system drainage technique and CT scan features of these lesions to assess whether CT findings can be used to predict recurrence. METHODS: We investigated preoperative and postoperative CT scan features and recurrence rate of 107 consecutive adult surgical cases of CSDH and assessed any relationship with univariate and multivariate regression analyses. RESULTS: Seventeen patients (15.9 %) experienced recurrence of CSDH. The preoperative haematoma volume, the isodense, hyperdense, laminar and separated CT densities and the residual total haematoma cavity volume on the 1st postoperative day after removal of the drainage were identified as radiological predictors of recurrence. If the preoperative haematoma volume was under 115 ml and the residual total haematoma cavity volume postoperatively was under 80 ml, the probability of no recurrence was very high (94.4 % and 97.4 % respectively). CONCLUSIONS: These findings from CT imaging may help to identify patients at risk for postoperative recurrence.

Atlantoaxial rotatory fixation--a cause of torticollis.

BACKGROUND: A rare, but important cause of torticollis in children is atlantoaxial rotatory fixation. If the patient remains undiagnosed for more than three months, surgery is generally the only therapeutic alternative. In this article we present our experiences of surgical treatment of late-diagnosed atlantoaxial rotatory fixation in children. MATERIAL AND METHOD: This article is based on a review of the case notes of patients who underwent surgery for atlantoaxial rotatory fixation in the Department for Neurosurgery at Oslo University Hospital, Rikshospitalet, during the period 2004-10. RESULTS: The material sample consists of six children aged from seven to 14 years. Five had suffered minor trauma to the upper neck region, while one had had an upper respiratory tract infection. The diagnosis was made 5-36 months after the onset of symptoms. In three of the patients, an attempt was made at closed reduction without success. A CT scan one year postoperatively showed a normal position of the atlantoaxial joint in two patients and partial reduction in three. In the sixth patient there was bone fusion at the time of the operation, and open reduction was unsuccessful. All six patients had reduced rotational movement of the neck at the one-year check-up. INTERPRETATION: All our patients were diagnosed more than five months after the onset of symptoms. Full or partial reduction was achieved in five of the six.

How to generate graded spinal cord injuries in swine - tools and procedures.

Spinal cord injury (SCI) is a medically, psychologically and socially disabling condition. A large body of our knowledge on the basic mechanisms of SCI has been gathered in rodents. For preclinical validation of promising therapies, the use of animal models that are closer to humans has several advantages. This has promoted the more-intensive development of large-animal models for SCI during the past decade. We recently developed a multimodal SCI apparatus for large animals that generated biomechanically reproducible impacts in vivo. It is composed of a spring-load impactor and support systems for the spinal cord and the vertebral column. We now present the functional outcome of farm pigs and minipigs injured with different lesion strengths. There was a correlation between the biomechanical characteristics of the impact, the functional outcome and the tissue damage observed several weeks after injury. We also provide a detailed description of the procedure to generate such a SCI in both farm pigs and minipigs, in the hope to ease the adoption of the swine model by other research groups.

Locomotor central pattern generator excitability states and serotonin sensitivity after spontaneous recovery from a neonatal lumbar spinal cord injury.

The spinal locomotor central pattern generator (CPG) in neonatal mice exhibits diverse output patterns, ranging from sub-rhythmic to multi-rhythmic to fictive locomotion, depending on its general level of excitation and neuromodulatory status. We have recently reported that the locomotor CPG in neonatal mice rapidly recovers the ability to produce neurochemically induced fictive locomotion following an upper lumbar spinal cord compression injury. Here we address the question of recovery of multi-rhythmic activity and the serotonin-sensitivity of the CPG. In isolated spinal cords from control and 3 days post-injury mice, application of dopamine and NMDA elicited multi-rhythmic activity with slow and fast components. The slow component comprised 10-20 s episodes of activity that were synchronous in ipsilateral or all lumbar ventral roots, and the fast components involved bursts within these episodes that displayed coordinated patterns of alternation between ipsilateral roots. Rhythm strength was the same in control and injured spinal cords. However, power spectral analysis of signal within episodes showed a reduced peak frequency after recovery. In control spinal cords, serotonin triggered fictive locomotion only when applied at high concentration (30 µM, constant NMDA). By contrast, in about 50% of injured preparations fictive locomotion was evoked by 2-3 times lower serotonin concentrations (10-15 µM). This increased serotonin sensitivity was correlated with post-injury changes in the expression of specific serotonin receptor transcripts, but not of dopamine receptor transcripts.

Development of a Multimodal Apparatus to Generate Biomechanically Reproducible Spinal Cord Injuries in Large Animals.

Rodents are widespread animal models in spinal cord injury (SCI) research. They have contributed to obtaining important information. However, some treatments only tested in rodents did not prove efficient in clinical trials. This is probably a result of significant differences in the physiology, anatomy, and complexity between humans and rodents. To bridge this gap in a better way, a few research groups use pig models for SCI. Here we report the development of an apparatus to perform biomechanically reproducible SCI in large animals, including pigs. We present the iterative process of engineering, starting with a weight-drop system to ultimately produce a spring-load impactor. This device allows a graded combination of a contusion and a compression injury. We further engineered a device to entrap the spinal cord and prevent it from escaping at the moment of the impact. In addition, it provides identical resistance around the cord, thereby, optimizing the inter-animal reproducibility. We also present other tools to straighten the vertebral column and to ease the surgery. Sensors mounted on the impactor provide information to assess the inter-animal reproducibility of the impacts. Further evaluation of the injury strength using neurophysiological recordings, MRI scans, and histology shows consistency between impacts. We conclude that this apparatus provides biomechanically reproducible spinal cord injuries in pigs.

Cellular reactions and compensatory tissue re-organization during spontaneous recovery after spinal cord injury in neonatal mice.

Following incomplete spinal cord injuries, neonatal mammals display a remarkable degree of behavioral recovery. Previously, we have demonstrated in neonatal mice a wholesale re-establishment and reorganization of synaptic connections from some descending axon tracts (Boulland et al.: PLoS One 8 (2013)). To assess the potential cellular mechanisms contributing to this recovery, we have here characterized a variety of cellular sequelae following thoracic compression injuries, focusing particularly on cell loss and proliferation, inflammation and reactive gliosis, and the dynamics of specific types of synaptic terminals. Early during the period of recovery, regressive events dominated. Tissue loss near the injury was severe, with about 80% loss of neurons and a similar loss of axons that later make up the white matter. There was no sign of neurogenesis, no substantial astroglial or microglial proliferation, no change in the ratio of M1 and M2 microglia and no appreciable generation of the terminal complement peptide C5a. One day after injury the number of synaptic terminals on lumbar motoneurons had dropped by a factor of 2, but normalized by 6 days. The ratio of VGLUT1/2+ to VGAT+ terminals remained similar in injured and uninjured spinal cords during this period. By 24 days after injury, when functional recovery is nearly complete, the density of 5-HT+ fibers below the injury site had increased by a factor of 2.5. Altogether this study shows that cellular reactions are diverse and dynamic. Pronounced recovery of both excitatory and inhibitory terminals and an increase in serotonergic innervation below the injury, coupled with a general lack of inflammation and reactive gliosis, are likely to contribute to the recovery. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 928-946, 2017.

Unilateral Holmes tremor, clearly responsive to cerebrospinal fluid release, in a patient with an ischemic midbrain lesion and associated chronic hydrocephalic ventricle enlargement. Case report.

The authors describe a 58-year-old man with sudden onset of a unilateral tremor caused by a midbrain lesion that affected the substantia nigra and the cerebellothalamic pathway. There were also clinical and neuroimaging signs of a communicating chronic hydrocephalus. The patient was severely handicapped by this tremor, which was a typical Holmes tremor with rest, posture, and intention components. Parkinson disease or multiple-system atrophy as causes for the tremor could be ruled out by DaTSCAN and 123I iodobenzamide and single-photon emission computerized tomography (SPECT), respectively. The tremor was completely supressed by temporary and permanent cerebrospinal fluid release after ventriculoperitoneal shunt placement, without any additional medication, for a period of 6 months. Afterward, the tremor returned, and the patient had to be treated by a stereotactic electrode implantation in the contralateral ventralis intermedius nucleus, which led to complete tremor suppression during the 1.5-year follow-up period. In this case report, the authors present the clinical description and the electrophysiological, SPECT, and magnetic resonance imaging data of a rare combination of symptoms and their surgical treatment.

A Neonatal Mouse Spinal Cord Compression Injury Model.

Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal cord. A major current area of research is focused on the mechanisms of adaptive plasticity that underlie spontaneous or induced functional recovery following SCI. Spontaneous functional recovery is reported to be greater early in life, raising interesting questions about how adaptive plasticity changes as the spinal cord develops. To facilitate investigation of this dynamic, we have developed a SCI model in the neonatal mouse. The model has relevance for pediatric SCI, which is too little studied. Because neural plasticity in the adult involves some of the same mechanisms as neural plasticity in early life(1), this model may potentially have some relevance also for adult SCI. Here we describe the entire procedure for generating a reproducible spinal cord compression (SCC) injury in the neonatal mouse as early as postnatal (P) day 1. SCC is achieved by performing a laminectomy at a given spinal level (here described at thoracic levels 9-11) and then using a modified Yasargil aneurysm mini-clip to rapidly compress and decompress the spinal cord. As previously described, the injured neonatal mice can be tested for behavioral deficits or sacrificed for ex vivo physiological analysis of synaptic connectivity using electrophysiological and high-throughput optical recording techniques(1). Earlier and ongoing studies using behavioral and physiological assessment have demonstrated a dramatic, acute impairment of hindlimb motility followed by a complete functional recovery within 2 weeks, and the first evidence of changes in functional circuitry at the level of identified descending synaptic connections(1).

Idiopathic ventral spinal cord herniation: an increasingly recognized cause of thoracic myelopathy.

Idiopathic spinal cord herniation (ISCH), where a segment of the spinal cord has herniated through a ventral defect in the dura, is a rarely encountered cause of thoracic myelopathy. The purpose of our study was to increase the clinical awareness of this condition by presenting our experience with seven consecutive cases treated in our department since 2005. All the patients developed pronounced spastic paraparesis or Brown-Séquard syndrome for several years (mean, 4.7 years) prior to diagnosis. MRI was consistent with a transdural spinal cord herniation in the mid-thoracic region in all the cases. The patients underwent surgical reduction of the herniated spinal cord and closure of the dural defect using an artificial dural patch. At follow-up, three patients experienced considerable clinical improvement, one had slight improvement, one had transient improvement, and two were unchanged. Two of the four patients with sphincter dysfunction regained sphincter control. MRI showed realignment of the spinal cord in all the patients. ISCH is probably a more common cause of thoracic myelopathy than previously recognized. The patients usually develop progressive myelopathy for several years before the correct diagnosis is made. Early diagnosis is important in order to treat the patients before the myelopathy has become advanced.

A neonatal mouse spinal cord injury model for assessing post-injury adaptive plasticity and human stem cell integration.

Despite limited regeneration capacity, partial injuries to the adult mammalian spinal cord can elicit variable degrees of functional recovery, mediated at least in part by reorganization of neuronal circuitry. Underlying mechanisms are believed to include synaptic plasticity and collateral sprouting of spared axons. Because plasticity is higher in young animals, we developed a spinal cord compression (SCC) injury model in the neonatal mouse to gain insight into the potential for reorganization during early life. The model provides a platform for high-throughput assessment of functional synaptic connectivity that is also suitable for testing the functional integration of human stem and progenitor cell-derived neurons being considered for clinical cell replacement strategies. SCC was generated at T9-T11 and functional recovery was assessed using an integrated approach including video kinematics, histology, tract tracing, electrophysiology, and high-throughput optical recording of descending inputs to identified spinal neurons. Dramatic degeneration of axons and synaptic contacts was evident within 24 hours of SCC, and loss of neurons in the injured segment was evident for at least a month thereafter. Initial hindlimb paralysis was paralleled by a loss of descending inputs to lumbar motoneurons. Within 4 days of SCC and progressively thereafter, hindlimb motility began to be restored and descending inputs reappeared, but with examples of atypical synaptic connections indicating a reorganization of circuitry. One to two weeks after SCC, hindlimb motility approached sham control levels, and weight-bearing locomotion was virtually indistinguishable in SCC and sham control mice. Genetically labeled human fetal neural progenitor cells injected into the injured spinal cord survived for at least a month, integrated into the host tissue and began to differentiate morphologically. This integrative neonatal mouse model provides opportunities to explore early adaptive plasticity mechanisms underlying functional recovery as well as the capacity for human stem cell-derived neurons to integrate functionally into spinal circuits.

Implantation of electrodes for deep brain stimulation of the subthalamic nucleus in advanced Parkinson's disease with the aid of intraoperative microrecording under general anesthesia.

OBJECTIVE: Deep brain stimulation (DBS) is widely accepted in the treatment of advanced Parkinson's disease (PD) and other movement disorders. The standard implantation procedure is performed under local anesthesia (LA). Certain groups of patients may not be eligible for surgery under LA because of clinical reasons, such as massive fear, reduced cooperativity, or coughing attacks. Microrecording (MER) has been shown to be helpful in DBS surgery. The purpose of this study was to evaluate the feasibility of MER for DBS surgery under general anesthesia (GA) and to compare the data of intraoperative MER as well as the clinical data with that of the current literature of patients undergoing operation under LA. CLINICAL PRESENTATION: The data of nine patients with advanced PD (mean Hoehn and Yahr status, 4.2) who were operated with subthalamic nucleus (STN) DBS under GA, owing to certain clinical circumstances ruling out DBS under LA, were retrospectively analyzed. All operations were performed under analgosedation with propofol or remifentanil and intraoperative MER. For MER, remifentanil was ceased completely and propofol was lowered as far as possible. INTERVENTION: The STN could be identified intraoperatively in all patients with MER. The typical bursting pattern was identified, whereas a widening of the baseline noise could not be as adequately detected as in patients under LA. The daily off phases of the patients were reduced from 50 to 17%, whereas the Unified Parkinson's Disease Rating Scale III score was reduced from 43 (preoperative, medication off) to 19 (stimulation on, medication off) and 12 (stimulation on, medication on). Two patients showed a transient neuropsychological deterioration after surgery, but both also had preexisting episodes of disorientation. One implantable pulse generator infection was noticed. No further significant clinical complications were observed. CONCLUSION: STN surgery for advanced PD with MER guidance is possible with good clinical results under GA. Intraoperative MER of the STN region can be performed under GA with a special anesthesiological protocol. In this setting, the typical STN bursting pattern can be identified, whereas the typical widening of the background noise baseline while entering the STN region is obviously absent. This technique may enlarge the group of patients eligible for STN surgery. Although the clinical improvements and parameter settings in this study were within the range of the current literature, further randomized controlled studies are necessary to compare the results of STN DBS under GA and LA, respectively.