We would like all of you to give your comments and participate actively in our discussion forum. Dr Rafay Zafar has kindly consented to become the coordinator for the discussion forum. Please reply with your comments to rafayzafar@hotmail.com; sharifsalman73@gmail.com.
Departments of Neurology and Radiology, Massachusetts General Hospital, and Neuroscience Program, Harvard Medical School, 149 13th Street, Charlestown, MA02129, USA.
Glioblastoma tumour cells release microvesicles (exosomes) containing mRNA, miRNA and angiogenic proteins. These microvesicles are taken up by normal host cells, such as brain microvascular endothelial cells. By incorporating an mRNA for a reporter protein into these microvesicles, we demonstrate that messages delivered by microvesicles are translated by recipient cells. These microvesicles are also enriched in angiogenic proteins and stimulate tubule formation by endothelial cells. Tumour-derived microvesicles therefore serve as a means of delivering genetic information and proteins to recipient cells in the tumour environment. Glioblastoma microvesicles also stimulated proliferation of a human glioma cell line, indicating a self-promoting aspect. Messenger RNA mutant/variants and miRNAs characteristic of gliomas could be detected in serum microvesicles of glioblastoma patients. The tumour-specific EGFRvIII was detected in serum microvesicles from 7 out of 25 glioblastoma patients. Thus, tumour-derived microvesicles may provide diagnostic information and aid in therapeutic decisions for cancer patients through a blood test.
NATURAL HISTORY OF BRAIN ARTERIOVENOUS MALFORMATIONS: A LONG-TERM FOLLOW-UP STUDY OF RISK OF HEMORRHAGE IN 238 PATIENTS Hernesniemi, Juha, Dashti, Reza, Juvela, Seppo, Vaart, Kristjan, Niemela, Mika, Laakso, Aki
Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland (Hernesniemi) (Dashti) ((Juvela)) (Vaart) (Niemela) (Laakso)
Posted on: 21st Nov, 2008. Author:
Source: Neurosurgery. 63(5):823-831, November 2008.
OBJECTIVE: Long-term follow-up studies in patients with brain arteriovenous malformations (AVM) have yielded contradictory results regarding both risk factors for rupture and annual rupture rate. We performed a long-term follow-up study in an unselected, consecutive patient population with AVMs admitted to the Department of Neurosurgery at Helsinki University Central Hospital between 1942 and 2005.
METHODS: Patients with untreated AVMs were followed from admission until death, occurrence of AVM rupture, initiation of treatment, or until the end of 2005. Patients with at least 1 month of follow-up were included in further analysis. Annual and cumulative incidence rates of AVM rupture as well as several potential risk factors for rupture were analyzed using Kaplan-Meier life table analyses and Cox proportional hazards regression models.
RESULTS: We identified 238 patients with a mean follow-up period of 13.5 years (range, 1 month-53.1 years). The average annual risk of hemorrhage from AVMs was 2.4%. The risk was highest during the first 5 years after diagnosis, decreasing thereafter. Risk factors predicting subsequent AVM hemorrhage in univariate analysis were young age, previous rupture, deep and infratentorial locations, and exclusively deep venous drainage. Previous rupture, large AVM size, and infratentorial and deep locations were independent risk factors according to multivariate models.
CONCLUSION: According to this long-term follow-up study, AVMs with previous rupture and large size, as well as with infratentorial and deep locations have the highest risk of subsequent hemorrhage. This risk is highest during the first few years after diagnosis but remains significant for decades.
Stem cells may act as "Trojan horse" to deliver gene therapy to injured central nervous system
Posted on: 18th Oct, 2008. Author:
Houston -- Amyotrophic lateral sclerosis (ALS) researchers at - The Methodist Hospital in Houston have shown that transplanted bone marrow stem cells can attach themselves to injured areas in the brain or spinal cord, possibly providing a way to deliver future gene therapy.
According to Dr. Stanley H. Appel's study published in the Oct. 14, 2008, issue of Neurology®, the medical journal of the American Academy of Neurology, these "Trojan horse" cells may improve the ability to deliver gene therapy to the brain and spinal cord.
The original intent of this study focused on whether transplanted bone marrow stem cells in six patients with sporadic ALS would suppress neuroinflammation and improve the patients' clinical outcomes, said Appel, co-founder and co-director of the Methodist Neurological Institute at The Methodist Hospital. While the results showed no benefit in fighting the disease, Appel's research team found that transplanting bone marrow stem cells that are closely matched to the patients' own bone marrow allowed for a significant percentage of those cells to travel to and reside in the brain or spinal cord. However, it is clear from the study that unless the bone marrow stem cells are engineered to secrete neuroprotective factors, such transplants are not likely to be beneficial in human ALS.
Neurotechnology: The Cutting Edge Of Epilepsy Treatment
Posted on: 30th Sep, 2008. Author:
Despite improved pharmacological options, about 20% of patients with primary generalized epilepsy and 35% of partial epilepsies remain medically refractory. Difficult to control seizures affect the patient's ability to live a normal life and have enormous psychosocial, behavioral, and cognitive effects. Refractory epilepsy also decreases life expectancy. Patients with uncontrolled seizures are at greater risk for sudden unexplained death (SUDEP), which accounts for about 50% of deaths in refractory epilepsy. Surgery is one alternative option, neurostimulation another.
Several electronic methods of neurostimulation are gaining adherents and others are still under clinical investigation, according to a recent press conference held by the American Medical Association which defined new and emerging methods of neuromodulation.
1) Vagus nerve stimulation (VNS) is . VNS Therapy™ was first approved in 1997 as adjunctive therapy for partial onset seizures refractory to AEDs in patients over 12 years of age. This indication is based on outcomes of five controlled, clinical trials which showed median reductions in seizures of 31.% to 41% at 1 to 3 years, and a favorable side effect profile.
2) Deep brain stimulation (DBS) is FDA-approved for movement disorders such as Parkinson's disease, but it is still under investigation in refractory epilepsy. Studies have successfully targeted deep brain sites such as the hippocampus, mammillary bodies, and cingulate gyrus for DBS seizure inhibition, according to and Hans Luders of Cleveland Clinic Foundation. A frequent target appears to be the thalamus, but it is still not clear which brain region exhibits the most effective seizure control when stimulated. Andres Lozano of the University of Toronto reported on five patients with generalized or complex partial seizures who received anterior thalamic stimulation and had a 93% seizure reduction. Mexico's Francisco Velasco and colleagues implanted bilateral electrodes in both centromedial thalamic nuclei in patients with generalized seizures, using intermittent, alternating, bilateral stimulation. Best results were obtained in Lennox-Gastaut patients. Velasco also administered continuous stimulation of the epileptic focus in another group of 10 patients scheduled for temporal lobectomy, with a resultant significant decrease in clinical seizures and interictal spikes. At the 2002 American Epilepsy Society meeting, Vonck et al reported on the use of central, localized, chronic stimulation of medial temporal lobe structures in uncontrolled epilepsy, with a 50% to 90% seizure reduction and no significant side effects during 3 to 6 months
3) Transcranial magnetic stimulation (TMS) is currently used to treat conditions ranging from depression to cerebral ischemia, and is now being studied for refractory epilepsies. The National Institutes of Health is still recruiting medically refractory patients between 5 and 65 years of age whose seizures originate from a neocortical focus near the surface of the brain. TMS produces a brief, high-current pulse in a circular magnetic coil to produce a magnetic field with lines of flux passing perpendicularly to the coil. The magnetic field is then conducted through the skull and converted to an electrical current when it reaches the brain. Some studies looked at single pulses, others at repetitive pulses. At the 2002 AES meeting, Tergau et al from Germany, gave an interim analysis of an ongoing placebo-controlled multicenter trial which suggested that low-frequency TMS using 0.3 Hz over a 4 week period achieved significant seizure reduction compared with 1.0Hz and placebo stimulation. According to Mark Hallett of the National Institute of Neurological Disorders and Stroke, TMS has limited use because it affects only the superficial cortex, but Hallett remains hopeful that coils can be developed that will stimulate at greater depth.
4) Arguably the most interesting and technically challenging emerging technology is the closed-loop system developed by NeuroPace, Inc. (NP) (Sunnyvale, CA). The device is inserted in the skull, and electrodes are implanted directly at the site of seizure onset to deliver impulses that terminate seizures before they develop. Obviously locating the site of the seizure requires accurate and sensitive imaging methodology. Once identified, ictal patterns are programmed into the device and the computer recognizes the pattern and delivers an electrical stimulation to stop progression. Michael Smith, director of the Epilepsy Center at Rush-Presbyterian St. Luke's Medical Center in Chicago, is an investigator in an ongoing FDA clinical study of NP Model 300 which is still recruiting patients. He uses several imaging and computer assisted physiology methods such as high resolution MRI, subtracted interictal/ictal SPECT co-registered to MRI (SISCOM), and magnetoencephalography (MEG) to locate the seizure focus. Early studies by Esteller et al at the University of Pennsylvania used NP in mesial or neocortical partial seizures and reported a sensitivity of 92%.
VNS Therapy™ - Cyberonics, Inc.
Since 1997, VNS Therapy™ has been approved for use as an adjunctive therapy in reducing the frequency of seizures in adults and adolescents over 12 years of age with partial onset seizures that are refractory to antiepileptic medications. This indication is based on outcomes from 5 controlled, clinical trials. Efficacy, measured as median seizure reduction, was observed in these clinical trials and other study populations. VNS Therapy resulted in median reductions in seizures of 31.3%, 40.7%, and 40.4% at 1, 2, and 3 years, respectively. Moreover, VNS Therapy offers a unique and favorable side effect profile that avoids cerebral toxicity.
Model 200² - Magstim Company US LLC
Based upon the original Magstim design the new Magstim 200² monophasic transcranial stimulator draws upon the years of knowledge and expertise gathered in both the clinical and research environments. Resulting in an innovative design that will help further establish the new Magstim range as the system of preferred choice.
Ergonomic modular approach to design to complement any operating environment and facilitate simple upgradeability to future Magstim systems.
Total compatibility and flexibility through additional intelligent hardware, the Magstim 200² is fully compatible with all existing Magstim coils (remote control operation requires new coils).
New Microprocessor controlled system hardware for added system safety whilst also enabling remote software upgrades and PC interfacing capabilities via standard internal serial port.
Activa® Therapy System - Medtronic Inc.
Activa Parkinson's Control Therapy uses electrical stimulation to safely and effectively treat some of the most disabling motor symptoms of Parkinson's disease. Activa Parkinson's Control Therapy is a safe and effective adjunctive treatment option for many Parkinson's patients. Activa Therapy controls rigidity, bradykinesia/akinesia and/or tremor while reducing the duration of dyskinesia related to antiparkinsonian medication.
EGENERATION OF CHOLINERGIC RAT BASAL FOREBRAIN NEURONS AFTER EXPERIMENTAL SUBARACHNOID HEMORRHAGE Mario Löhr, M.D.
Department of General Neurosurgery,
University of Cologne, Cologne,
Germany.
Posted on: 22nd Sep, 2008. Author:Dr. Shahzad Shamim
AKUH, Karachi.
OBJECTIVE: The reasons for neuropsychological deficits after subarachnoid hemorrhage (SAH) are fairly unknown. Cholinergic basal forebrain (BFB) neurons are essential for attention, memory, and emotion. We investigated possible changes in the cholinergic BFB and its hippocampal and neocortical terminals after experimental SAH.
METHODS: SAH was induced in 19 male Wistar rats by stereotactic injection of 150 microL of autologous blood into the prechiasmatic cistern. Five control animals received 150 microL of saline. Continuous monitoring of brain tissue oxygen tension, intracranial pressure, and cerebral perfusion pressure was performed. After 4 and 14 days, the BFB was analyzed for cholinergic and gamma-aminobutyric acid-ergic cell counts. The number of cholinergic terminals in the hippocampus and neocortex was calculated by optical densitometry.
RESULTS: SAH resulted in a 20 to 30% decrease in cholinergic BFB neurons in the medial septum and diagonal band at 4 and 14 days. A similar decline in the density of hippocampal and neocortical cholinergic terminals was demonstrated. Animals treated with saline did not exhibit significant cholinergic cell loss, and gamma-aminobutyric acid-ergic neurons appeared unaffected by the SAH. Courses of intracranial pressure and cerebral perfusion pressure did not differ between animals injected with blood and saline, but brain tissue oxygen tension decreased considerably and continued to stay below baseline in SAH, although it returned to normal values after saline injection.
CONCLUSION: The present study provides evidence for a decrease of cholinergic BFB neurons after SAH. The direct effect of blood in the basal cisterns seemed to result in an enduring tissue hypoxia as a significant mechanism for cholinergic degeneration.
Hypothermia Therapy after Traumatic Brain Injury in Children James S. Hutchison, for the Hypothermia Pediatric Head Injury Trial Investigators and the Canadian Critical Care Trials Group
Posted on: 19th Sep, 2008. Author:James S. Hutchison
ABSTRACT
Background: Hypothermia therapy improves survival and the neurologic outcome in animal models of traumatic brain injury. However, the effect of hypothermia therapy on the neurologic outcome and mortality among children who have severe traumatic brain injury is unknown.
Methods: In a multicenter, international trial, we randomly assigned children with severe traumatic brain injury to either hypothermia therapy (32.5°C for 24 hours) initiated within 8 hours after injury or to normothermia (37.0°C). The primary outcome was the proportion of children who had an unfavorable outcome (i.e., severe disability, persistent vegetative state, or death), as assessed on the basis of the Pediatric Cerebral Performance Category score at 6 months.
Results: A total of 225 children were randomly assigned to the hypothermia group or the normothermia group; the mean temperatures achieved in the two groups were 33.1±1.2°C and 36.9±0.5°C, respectively. At 6 months, 31% of the patients in the hypothermia group, as compared with 22% of the patients in the normothermia group, had an unfavorable outcome (relative risk, 1.41; 95% confidence interval [CI], 0.89 to 2.22; P=0.14). There were 23 deaths (21%) in the hypothermia group and 14 deaths (12%) in the normothermia group (relative risk, 1.40; 95% CI, 0.90 to 2.27; P=0.06). There was more hypotension (P=0.047) and more vasoactive agents were administered (P<0.001) in the hypothermia group during the rewarming period than in the normothermia group. Lengths of stay in the intensive care unit and in the hospital and other adverse events were similar in the two groups.
Conclusions: In children with severe traumatic brain injury, hypothermia therapy that is initiated within 8 hours after injury and continued for 24 hours does not improve the neurologic outcome and may increase mortality.
Better Backs by Better Beds?
Bergholdt, Spine. 33(7):703-708, April 1, 2008.
Study Design. A "randomized"/stratified, single-blinded, parallel-group study.
This is an elegant study from Tom Bendix in Denmark. They evaluated 3 structurally different mattresses relative influence on patients with chronic low back pain (CLBP). You know the patient that asks 'should I buy an orthopaedic mattress? This helps you answer them.
In several advertisements, it is proclaimed that certain mattresses have a positive effect on LBP, and especially a hard mattress is commonly believed to have a positive effect. One hundred sixty CLBP patients were randomized to 1 of 3 groups, having a mattress/bed mounted in their sleeping room for 1 month. The beds were: (1) waterbed (Akva), (2) body-conforming foam mattress (Tempur), and (3) a hard mattress (Innovation Futon).
There was a high 'drop-out' rate despite astonishing efforts by the research group to provide the double beds where requested. The analyses were performed on 141 patients. During the 1-month trial period another 27 patients stopped ahead of time, which were accounted for by "worse case" as well as "no-change" analyses. Both the waterbed and the foam mattress seemed superior to the hard mattress, especially when using the probably most relevant "worst case"
They conclude that the Waterbed and foam mattress' did influence back symptoms, function and sleep more positively as apposed to the hard mattress, but the differences were small.
The discussion is really interesting regarding possible reasons for this. The soft beds maybe cause more movement and so less stiffness. Staying active again.
Posted on: 29th Aug, 2008. Author:John W. German
Thomas R. Inman, PTA, CPT
Physical Therapist
Boca Raton, FL
The use of backpacks has risen dramatically over the past ten years. Some studies have shown backpack usage to be greater than 90% among school-aged children ages 8-17. As a result, many complaints of back, shoulder, and neck pain have increased secondary to the use of these devices.
Wearing a backpack properly allows the back and stomach muscles to support the backpack's weight. When the bag is overloaded, lifted incorrectly, or carried over one shoulder, the soft tissues in the back become strained. Daily repetition of these types of actions promotes incorrect posture by damaging the spinal column and creating muscular imbalance.
Wrong! This backpack is overloaded and too heavy.
The solutions to reducing spinal stress caused by book bags are as follows:
#1 - Backpacks should be loaded to a maximum of 10-15% of the total body weight of the person.
#2 - Use both shoulder straps that are padded and adjusted to carry the pack no lower than 2-3 inches above the waist.
#3 - Educate correct lifting techniques of bending at the knees and lifting with the legs while donning and doffing the backpack.
#4 - Students should clean out the bag once a week and make frequent trips between classes to replace needed materials.
#5 - Participate in a regular exercise program to maintain strong and flexible back and trunk musculature.
Parents: Educate your children about the importance of postural awareness and proper lifting techniques. Prevention of an incorrectly carried backpack will lead to your child's healthy spine today and in the future.
Perioperative results following lumbar discectomy: comparison of minimally invasive discectomy and standard microdiscectomy John W. German, M.D.,Division of Neurosurgery, Albany Medical College, New York;
jwgerman@hotmail.com
Posted on: 09th Aug, 2008. Author:John W. German
M.D., Division of Neurosurgery,
Albany Medical College,
New York.
Abstract
Object
Minimally invasive lumbar discectomy is a refinement of the standard open microsurgical discectomy technique. Proponents of the minimally invasive technique suggest that it improves patient outcome, shortens hospital stay, and decreases hospital costs. Despite these claims there is little support in the literature to justify the adoption of minimally invasive discectomy over standard open microsurgical discectomy. In the present study, the authors address some of these issues by comparing the short-term outcomes in patients who underwent first time, single-level lumbar discectomy at L3–4, L4–5, or L5–S1 using either a minimally invasive percutaneous, muscle splitting approach or a standard, open, muscle-stripping microsurgical approach.
Methods
A retrospective chart review of 172 patients who had undergone a first-time, single-level lumbar discectomy at either L3–4, L4–5, or L5–S1 was performed. Perioperative results were assessed by comparing the following parameters between patients who had undergone minimally invasive discectomy and those who received standard open microsurgical discectomy: length of stay, operative time, estimated blood loss, rate of cerebrospinal fluid leak, post-anesthesia care unit narcotic use, need for a physical therapy consultation, and need for admission to the hospital.
Results
Forty-nine patients underwent minimally invasive discectomy, and 123 patients underwent open microsurgical discectomy. At baseline the groups did differ significantly with respect to age, but did not differ with respect to height, weight, sex, body mass index, level of radiculopathy, side of radiculopathy, insurance status, or type of preoperative analgesic use. No statistically significant differences were identified in operative time, rate of cerebrospinal fluid leak, or need for a physical therapy consultation. Statistically significant differences were identified in length of stay, estimated blood loss, postanesthesia care unit narcotic use, and need for admission to the hospital.
Conclusions
In this retrospective study, patients who underwent minimally invasive discectomy were found to have similiar perioperative results as those who underwent open microsurgical discectomy. The differences, although statistically significant, are of modest clinical significance.
Intramedullary Spinal Cord Tumors and Pseudotumors.
How to Deal With? Jacques Brotchi
Posted on: 26th July, 2008. Author: Jacques Brotchi
President WFNS
Department of Neurosurgery
Erasme Hospital, Université libre de Bruxelles
808, Route de Lennik, B-1070 Brussels, Belgium
Abstract:
Surgery is the best treatment to offer patients with an intramedullary spinal cord tumor.
In experienced hands, radical surgery can be performed with acceptable surgical risks in most ependymomas, hemangioblastomas, and cavernomas and in 40% of astrocytomas. However, some inflammatory lesions may mimic an intramedullary tumor. That is the reason why, one should pay attention to spinal cord morphology on MRI to avoid unnecessary surgery on pseudotumors that may benefit from a medical treatment.
Introduction
With MRI diagnosis, more and more intraspinal cord lesions are found with, sometimes, difficulties to assess the differential diagnosis between tumoral and non-tumoral lesions. Therefore, the practical decision on the best therapeutic attitude to recommend is not always easy. Clinical examination remains an important data that should not be forgotten by people who are faced with intramedullary lesions. Of course, there are well-known radiological aspects suggesting vascular or demyelinating myelitis. We shall not emphasize them. We would only remind a case we had several weeks ago. Our opinion was requested for a 77y-old man who had an intramedullary lesion at TH8 level that was thought to be responsible of a left pyramidal syndrome at lower limbs. History started two years before by a progressive left drop-foot. The patient complained of increasing difficulties for walking. MRI showed a small intramedullary signal on T2W images located at TH8 level on right side. There was no gadolinium enhancement of that eccentric lesion. Therefore, the diagnosis of ependymoma was excluded. But astrocytoma and inflammatory disease were kept in the differential diagnosis. However, in the absence of sensory or sphincter deficits with a lesion located on the opposite site to the clinical signs, an MRI investigation of the brain was requested allowing the discovery of a huge rolandic parasagittal meningioma on right side. That tumor was the cause of the clinical complains. So, the patient got surgery for the brain meningioma and not at TH8 spinal cord level. Of course, the question of the nature of the spinal cord lesion remains open and the patient has been proposed to get a clinical and radiological follow-up. That case illustrates the difficulty to make a correct diagnosis in non-specific MRI lesions and the danger of pitfall.
Many papers have been published on the surgical treatment of intramedullary spinal cord tumors. We have selected some. Surgery is the gold standard treatment. Radiation therapy should not be applied anymore, except in malignant tumors as a palliative treatment.
Few papers have emphasized non-neoplastic intramedullary spinal cord lesions mimicking tumors. That pathology is not well known. We have also selected several papers on that topic.
[1] Radical excision of intramedullary spinal cord tumors: surgical morbidity and long-term follow-up evaluation in 164 children and young adults.
J Neurosurg (Spine 2)(2000) 93: 183-193.
Information.
The authors give their wide experience on 164 patients 21 years of age and younger in whom an intramedullary spinal cord tumor (IMSCT) was resected. They succeeded in performing what they call a gross-total resection (>95%) in 76.8% and a subtotal resection (80-95%) in 20.1%. All the patients had gliomas, the majority of low-grade (79.3%), most of astrocytic nature due to the pediatric population. There were no deaths related to surgery. When comparing the preoperative and 3-month postoperative functional grades, they observed: 60.4% stable, 15.8% improvement and 23.8% deterioration. Surgery was the only anti-tumor treatment used for the majority (73.5%) of patients, even if the tumor recurred, as long it was low grade. In patients with low-grade intramedullary lesions, long-term results of radical surgery without routine postoperative radiation treatment compare favourably with the results of modest surgery followed by radiation treatment. The major determinant of long-term patient survival was histological composition of the tumor. The 5-year progression-free survival rate was 78% for patients with low-grade gliomas and 30% for those with high-grade gliomas. Patients in whom an IMSCT was only partially resected (<80%) fared significantly worse.
Analysis:
There are many important facts in that paper dealing essentially with intraspinal cord glioma in pediatric population. The first and perhaps the most important is that in experienced surgeons hands, radical surgery for IMSCTs can be performed with acceptable surgical risks. As said before by others, the authors confirm that IMSCTs should be recognized as potentially excisable lesions, both at presentation and if they recur. They give arguments discrediting adjunctive radiation therapy. It is important since one may still find in the literature papers recommending radiation therapy after complete or partial removal of intraspinal cord low-grade ependymomas or astrocytomas. That concept is no more acceptable and I fully agree with the authors. Another good message is on the timing of surgery. Functional postoperative results are closely related to preoperative situation and the presence or absence of preoperative deficits. When no plane of dissection is found, it is safer to do a subtotal removal. It is interesting to see that in their experience, subtotal tumor removal may be sufficient for long-term progression free survival.
[2] Intramedullary ependymomas: clinical presentation, surgical treatment strategies and prognosis.
J Neuro-Oncol (2000) 47: 211-218.
Information.
This is a general overview by an experienced team on intramedullary ependymomas, which comprise the majority of intramedullary glial neoplasms in the adult. There is no typical clinical presentation but dysesthesias are the earliest symptoms to present in upwards of 70% of patients. These tumors are benign slow-growing lesions, which are optimally treated with gross total surgical resection without adjuvant therapy. This objective can be attained safely in a majority of patients. Post-operative functional outcome is related to pre-operative functional status. Early diagnosis, prior to symptomatic progression, is critical to the successful treatment of these tumors. Adjuvant therapy is indicated for the rare malignant or disseminated tumors or following sub-total resection.
Analysis:
Surgical technique is very well detailed in that paper. In adult population, standard laminectomy is performed. Laminoplasty, which is mandatory in children, is not required in the adult population. The authors rightly insist on the importance of strict hemostasis prior to dural opening to prevent ongoing blood contamination. Surgery of intramedullary tumors needs a very clean operative field. They open the arachnoid separately, as we do. They recommend posterior midline opening extending over the entire rostrocaudal extent of the tumor. That helps finding the polar cysts, very frequent in ependymomas. Most of the times, ependymomas are sharply demarcated from the surrounding spinal cord. In huge tumors, debulking is recommended with ultrasonic aspirator or laser. Once significant tumoral internal decompression has been performed, dissection of the lateral and ventral margins may be accomplished, taking care hurting anterior spinal artery that gives the feeding arteries, which should be identified, cauterised and divided. If no plane is apparent between tumor and surrounding spinal cord, biopsy is obtained to confirm the histological diagnosis of an infiltrative tumor. That is the classical way to remove an intraspinal cord ependymoma. The authors don't perform a closure of the myelotomy. We do it, so as the closure of the arachnoid whenever possible. The authors also emphasize the importance of preservation rather than expected restoration of neurologic function in surgery for intramedullary tumors.
[3] Spinal cord astrocytomas: presentation, management and outcome.
J Neuro-Oncol (2000) 47: 219-224.
Information.
This is a general overview by an experienced team on intramedullary astrocytomas, which is slightly less frequent than ependymomas in adult series. There is no typical clinical presentation. But local or radicular pain is the earliest and most frequent presenting complaint. Astrocytomas have less well-defined margins on MRI and are more likely to be eccentrically located within the spinal cord unlike ependymomas, which are always central in location. Ideal candidates for surgery are patients who are still ambulatory. The infiltrating nature of some spinal cord astrocytomas may make total removal impossible without unacceptable neurological deficits. In such instances, subtotal resection may still be worthwhile to reduce tumor mass in preparation for adjunctive therapy. Intraoperative somatosensory and motor evoked potentials are used. They provide information to guide the surgeon in the resection but their intraoperative utility is limited by many factors. So, their use is still a matter of debate. Technique of surgery is similar to what is described for ependymomas in the above paper. The outcome is worse than that of ependymomas, except for pilocytic astrocytomas, more frequent in paediatric population, and which can be totally removed. High-grade astrocytomas have a bad prognosis with an average survival of 6 months in adults and 13 months in children.
Analysis.
We agree that MRI cannot be used confidently to distinguish between astrocytomas and ependymomas. MRI cannot predict the presence or the absence of a plane of separation between tumor and spinal cord. That is a sufficient reason to recommend surgery, especially in patients with few neurological deficits. Finding a plane at surgery will make the tumor removable. Otherwise, it is safer to limit to biopsy and to decompressive surgery. Malignant astrocytomas have a grim prognosis, as do intracranial anaplastic gliomas, even with adjunctive therapy.
[4] Non-neoplastic intramedullary pathology. Diagnostic dilemma: to Bx or not to Bx?
J Neuro-Oncol (2000) 47: 283-292.
Information.
That is a very good synthesis on a difficult diagnosis to which the consulting neurosurgeon, pressured to operate on a rapidly deteriorating patient, may be faced with the uncomfortable decision of whether to operate on potentially nonsurgical pathology or recommend medical management. Multiple sclerosis can mimic an active neoplasm leading to mistaken biopsies. Granulomatous disease in the spinal cord has been reported for sarcoidosis, tuberculosis, brucellosis and histoplasmosis. These lesions often have systemic manifestations but sometimes, they may be the first manifestation of the illness. A biopsy may be the only way to get a diagnosis, which is important since in sarcoidosis, corticosteroids therapy dramatically improves the patient, cleaning the MRI. Isolated pseudotumors have also been described. Infections may also happen, especially in HIV patients where they are not infrequent. Intramedullary cysticercoids and toxoplasmosis have been occasionally mistaken for intramedullary tumors. Vascular lesions have also been described: amyloidosis, isolated intramedullary vascular lesions of ischemic origin, arterial infarcts. Finally, other lesions like subacute necrotizing myelopathy or radiation myelopathy may also be encountered.
Analysis.
When something about the MRI (spinal cord not significantly enlarged, minimal enhancement) or clinical course raises suspicion of a non-neoplastic lesion (symptoms have progressed rapidly), we recommend a cautious attitude. If the illness is slowly progressing, one may suggest performing a new MRI 3 months later. When there is a suspicion of multiple sclerosis, a brain MRI can bring the correct diagnosis, avoiding an unnecessary biopsy. CSF diagnosis may be of great help. In suspected granulomatous diseases, systemic manifestations should be searched since the diagnosis may be assessed on those systemic manifestations or serum analyses. Primary sarcoidosis may happen. Several such a cases have been reported. In the absence of diagnosis, a cautious biopsy of the intraspinal cord lesion is to be done but not resection as deterioration following nodule removal has been reported. Cautious MRI analysis may reveal a ring enhancement, which is not often seen with intramedullary tumors. The later demonstrate homogeneous or heterogeneous patchy enhancement, exceptionally a ring enhancement that is more suggestive of cord infarction, radiation myelopathy or subacute necrotizing myelopathy. In certain circumstances, non-neoplastic lesions will require open biopsy or surgical treatment as a part of the optimal management: bacterial, fungal, tuberculous or parasitic lesions may benefit of surgery in addition to medical treatment.
This is a case report of a 40-year-old female presenting with a two months history of progressive weakness of the right leg and numbness of the left leg with urinary and fecal incontinence. Four months before, she had been diagnosed with systemic brucellosis with a period of radiculomeningoencephalitis successfully treated with medical treatment. MRI revealed a 10 x 30 mm intramedullary heterogeneous mass at T5 level with considerable enhancement and surrounding edema. Due to the past medical history, a Brucella granuloma was suspected and CSF analysis performed with finding of lymphocytic pleocytosis and elevated levels of albumin, immunoglobulins and antibody titers for Brucella. The medications were modified to rifampicin 1200mg daily, doxycycline 400mg, TMP/SMZ (trimethoprim/sulfamethazole) 480/2400 mg daily, and methylprednisolone 100 mg in decremental doses for (for 6 weeks). No surgery was done. After 2 months, the patient was almost symptom-free and her medication doses were decreased. Follow-up MRI at 5 months showed a dramatically decrease of the mass lesion. The treatment was discontinued after 2 years.
Analysis.
Brucella infections continue to cause serious problems in developing countries.
That paper is a good warning to neurosurgeons to consider a non-neoplastic lesion before recommending surgical resection when some data are not typical for a tumor. Here, the medical history was short (2 months), the MRI suspicious (eccentric heterogeneous mass) although the authors had the knowledge of a systemic brucellosis 4 months before. Infectious disease may mimic neoplastic mass on MRI. When a medical history keeps the attention, there is few risk of misdiagnosis but when the past history is unknown, it is not easy to take the good decision: medical treatment as an initial treatment rather than surgery.
[6] Intraspinal sarcoidosis: diagnosis and management.
Surg Neurol (1997) 48: 514-521.
Information.
The authors report 3 patients with intraspinal sarcoidosis and absent systemic manifestations of the disease. Two of the three patients had a preoperative diagnosis of a cervicomedullary spinal cord tumor The third one had a cauda equina location. Since MRI with gadolinium did not suggest an inflammatory process, all three patients underwent laminectomy and biopsy. Pathologic examination demonstrated sarcoidosis in all three patients. It is recommended not to attempt complete resection if this granulomatous process is suspected. Treatment is prolonged corticosteroids.
Analysis.
One should be aware that there are no distinct MRI signal characteristics for intraspinal cord sarcoidosis. It may mimic an infiltrative glioma. That is one of the reasons why in intramedullary lesions, no adjunctive treatment (especially radiation therapy) should be performed without histologic analysis, even in poorly delineated lesions. In my department, we have experienced two cases of primary intraspinal cord sarcoidosis and we did what the authors have recommended: limited laminectomy, biopsy rather than attempt to resect, and intraoperative frozen sections that in both cases pointed to an inflammatory process. Treatment is corticosteroids, sometimes over several months.
Among a series of 212 patients undergoing surgery for intramedullary spinal cord tumors, the authors have reviewed a group of 9 patients with atypical, nonneoplastic intramedullary lesions that all underwent surgery. All patients were preoperatively evaluated with MRI. The extent of enhancement with gadolinium varied from homogeneous enhancement to no enhancement. This illustrates well the difficulty to assess the diagnosis of nonneoplastic intramedullary spinal cord lesions. All lesions showed marked T2 changes. There was a lack of significant spinal cord expansion associated with the lesions in all cases. The histology of the surgical specimens showed demyelinating lesions in four patients, sarcoidosis in two patients, amyloid angiopathy in two patients, and a mass of nonneoplastic inflammatory cells of unknown origin in one patient. Although it was difficult to antecedently distinguish these lesions from neoplastic spinal cord tumors by case history and physical examination, the most consistent clue was absent or minimal spinal cord expansion on the preoperative MRI.
Analysis.
The surgical management of intramedullary spinal cord tumors is based on oncological principles. The goal is complete resection or significant cytoreduction of the tumor. But in nonneoplastic diseases, theses oncological principles do not apply. We need a biopsy only to offer the patient the best medical treatment. Among the preoperative signs that could warn us, the only reliable one is MRI feature. Like the authors, we have observed that spinal cord expansion is always present on MRI of patients with spinal cord tumors. On the other hand, MRI images of patients with nonneoplastic lesions showed no lesional spinal cord expansion, except for mild expansion associated with edema. That is the most important message from that paper.
Synthesis
More and more papers are published on intramedullary spinal cord tumors and lesions mimicking that pathology. In experienced neurosurgeons hands, radical surgery for these tumors can be performed with acceptable surgical risks. It is also clear that the surgical outcome is directly related to the patient's preoperative conditions. The greater are preoperative neurological deficits, the greater are surgical risks and postoperative sequelae.
However, one should avoid operating unnecessary lesions that may be better medically treated. Pseudotumors, inflammatory lesions, sarcoidosis and others may mimic on MRI intramedullary tumors. But if one pay attention to spinal cord morphology, it is also clear that in the absence of spinal cord widening, the first diagnosis to think for is not a tumor but a nonneoplastic lesion.
Papers reviewed
1. Constantini S, Miller DC, Allen JC, Rorke LB, Freed D, Epstein FJ (2000) Radical excision of intramedullary spinal cord tumors: surgical morbidity and long-term follow-up evaluation in 164 children and young adults. J Neurosurg (Spine 2) 93: 183-193.
2. Schwartz TH, McCormick PC (2000) Intramedullary ependymomas: clinical presentation, surgical treatment strategies and prognosis. J Neuro-Oncol 47: 211- 218.
3. Houten JK, Cooper PR (2000) Spinal cord astrocytomas: presentation, management and outcome. J Neuro-Oncol 47: 219-224.
4. Schwartz TH, McCormick PC (2000) Non-neoplastic intramedullary pathology. Diagnostic dilemma: To Bx or not To Bx? J Neuro-Oncol 47: 283-292.
5. Bingöl A, Yücemen N, Meço O (1999) Medically treated intraspinal "Brucella" granuloma. Surg Neurol 52: 570-576.
6. Jallo GI, Zagzag D, Lee M, Deletis V, Morota N, Epstein FJ (1997) Intraspinal sarcoidosis: diagnosis and management. Surg Neurol 48: 514-521.
7. Lee M, Epstein FJ, Rezai AR, Zagzag D (1998) Nonneoplastic intramedullary spinal cord lesions mimicking tumors. Neurosurgery 43: 788-795.
Comments:
I read this post from Prof. Jacques Brotchi with quite interest. He described very interesting operative and neuroradiological naunces about this operative challenge. This is reminiscent of one case we operated and piblished not long ago.We operated an Intramedullary ependymoma in a young girl with NF-2 and we were able to remove it completely as we were lucky enough to find a interface between tumor and spinal cord. Some author has reccommended use of lasers as an essential adjunct to operate thes tumors but in our set up we don't have this luxury and we were able handle this with simple microsurgical instruments. We reported our case emphasing that basic microsurgical skills provide enough armament to tackle this surgical challenge in practical clinical neurosurgery even if one is not equipped with highly advanced technology which goes true for many Neurosurgical set up in developing countries. (BJNS 2004)
Arshad Ali, MBBS, FCPS, FINR (Switzerland),
Jinnah Postgraduate Medical Center,
Posted on: 30th July, 2008 Author: Arshad Ali
MBBS, FCPS, FINR
Switzerland
Jinnah Postgraduate Medical Center
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