A case for further investigating the use of controlled lumbar cerebrospinal fluid drainage for the control of intracranial pressure.

OBJECTIVE: Increased intracranial pressure (ICP) that is refractory to medical measures and ventriculostomy placement after severe traumatic brain injury or aneurysmal rupture is associated with high mortality. In some recent reports, authors have described the use of lumbar cerebrospinal fluid drainage in these patients. We report the results of a prospective study involving the use of lumbar drainage in 15 patients with elevated ICP that was refractory to medical management and ventriculostomy placement. METHODS: A prospective study was designed to enroll patients at Loma Linda University Medical Center. Ten patients with traumatic brain injury and five patients with ruptured aneurysms were enrolled. Medical management included maintaining serum Na >150 mEq/L, mild hyperventilation, deep sedation, and maintenance of normothermia. A lumbar drain was placed when ICP was >20 mm Hg for an average of 3 hours despite the optimization of the aforementioned parameters. RESULTS: After lumbar drain placement, ICP was reduced from a mean of 28.2 ± 6.5 mm Hg to 10.1 ± 7.1 mm Hg (P <0.001). Requirements for hyperosmolar therapy, sedatives, and paralytics were also significantly decreased (P < 0.05) after lumbar drain placement. One patient had unilateral papillary changes four hours after lumbar drain placement. The pupil returned to its normal state after decompressive craniectomy. There was no incidence of CSF infection. Three of the 15 patients died during the study period. CONCLUSIONS: This study shows the beneficial role of lumbar cerebrospinal fluid drainage as an effective and safe treatment modality for elevated ICP.

Preoperative mucosal tolerance to brain antigens and a neuroprotective immune response following surgical brain injury.

OBJECT: Intracranial surgery causes cortical injury from incisions, hemorrhage, retraction, and electrocautery. The term "surgical brain injury" (SBI) has been developed to categorize this injury inherent to the procedure. Neuroinflammation plays a significant role in SBI. Traditional antiinflammatory therapies are often limited by their immunosuppressive side effects and poor CNS penetration. This study uses mucosal tolerance to develop an immune system that is tolerant to brain myelin basic protein (MBP) so that inflammation can be suppressed in a timely and site-specific manner following surgical disruption of the blood-brain barrier. METHODS: A standard SBI model using CD57 mice was used. Nasopharyngeal mucosa was exposed to vehicle, ovalbumin, or MBP to develop mucosal tolerance to these antigens. Immunological tolerance to MBP was confirmed in vivo through hypersensitivity testing. Neurological scores, cerebral edema, and interleukin (IL)-1ß and transforming growth factor (TGF)-ß1 cytokine levels were measured 48 hours postoperatively. RESULTS: Hypersensitivity testing confirmed the development of immune tolerance to MBP. Myelin basic protein-tolerant mice demonstrated reduced neurological injury, less cerebral edema, decreased levels of IL-1ß, and increased levels of TGFß1 following SBI. CONCLUSIONS: Developing preoperative immunological tolerance to brain antigens through mucosal tolerance provides neuroprotection, reduces brain edema, and modulates neuroinflammation following SBI.

Role of controlled lumbar CSF drainage for ICP control in aneurysmal SAH.

BACKGROUND: a prospective study of lumbar CSF drainage in the setting of raised intra-cranial pressure refractory to medical management and ventriculostomy placement is presented. There has been increasing data that this may be a effective and safe intervention for reduction of ICP. METHOD: an IRB approved prospective study was conducted. Six patients with increased intracranial pressure secondary to aneurysm rupture were initially managed with sedation, ventriculostomy placement, mild hyperventilation (pCO(2) = 30-35), and hyperosmolar therapy (Na = 150-155). A lumbar drain was placed if ICP continued to be above 20 mmHg despite optimization of medical therapy. FINDINGS: after lumbar drain placement, ICP was reduced from 30.2 mmHg ± 6.7 to 9.7 mmHg ± 7.4, an average decrease of 20.5 mm H(2)O (P < 0.001). There was no significant change in CPP. Requirements for hypertonic saline and/or mannitol boluses and sedation to control ICP were decreased. There was no incidence of CSF infection or cerebral herniation. CONCLUSIONS: we have shown that controlled lumbar drainage is a safe, efficacious and minimally invasive method for treatment of elevated ICP which refractory to medical management. Ventriculostomies are always placed before utilizing lumbar drains to minimize the risk of cerebral herniation. We would advocate making controlled lumbar drainage a standard part of ICP control protocols.

Intrathecal endoscopy to enhance the diagnosis of tethered cord syndrome.

OBJECT: Tethered cord syndrome (TCS) is being diagnosed in an increasing number of adults and late teens. Before referral to neurosurgeons, however, the majority of patients in this group suffers back and leg pain for a long period without a definitive diagnosis. The diagnostic difficulty derives from 2 factors: the signs and symptoms are subtle and easily overlooked, and the combination of an elongated cord and a thickened filum is lacking in 65% of patients. When a patient presents with signs and symptoms typical for TCS but demonstrates no elongated cord or thickened filum on MR imaging, one must search for a more reliable finding to establish a diagnosis of TCS. Based on the authors' earlier surgical experiences, posterior displacement of the terminal filum is consistently found at surgery in all patients with TCS. In previous publications they interpreted this finding as the lower cord and filum traveling along the concave side of the lumbosacral spinal canal to minimize cord tension. In the present prospective study, the authors attempt to confirm posterior displacement of the filum terminale by using intrathecal endoscopy prior to wide exposure of the spinal cord and filum. Further, the stretch test was applied to the terminal filum to evaluate its elasticity. METHODS: Sixty-eight patients with signs and symptoms as well as MR imaging studies indicative of TCS underwent endoscopic examination of the filum and cauda equina. After lumbar or sacral laminectomy, a flexible endoscope was inserted through a small dural and arachnoid incision into the subarachnoid space. The filum and cauda equina fibers were identified. Once the dura mater and arachnoid were opened widely, a stretch test was done to confirm filum inelasticity. In 3 patients, percutaneous endoscopy was also performed before open surgery to determine its applicability as compared with the open method. RESULTS: On inserting the endoscope into the intrathecal space, the filum was immediately identified medioposterior to the cauda equina fibers in all 68 patients. The stretch test revealed a lack of filum elasticity in all patients. Preoperative percutaneous endoscopy was equally effective in identifying the position of the filum. CONCLUSIONS: Currently, endoscopic identification of the posteriorly displaced filum, which was confirmed at open surgery, is the essential diagnostic study for TCS or the tethered spinal cord. Furthermore, the stretch test of the filum proves its inelasticity, and filum sectioning leads to ascension and relaxation of the caudal spinal cord. These results can be linked to the impaired oxidative metabolism of the lumbosacral cord under excessive tension and to the metabolic and neurological improvements seen after filum sectioning.

Interlaminar spacer: a review of its mechanism, application, and efficacy.

BACKGROUND: The management of neurogenic intermittent claudication encompasses myriad modalities, with the use of Interlaminar spacer being among the newer ones. METHODS AND RESULTS: A review of work-to-date on Interlaminar spacer is presented, which was first introduced in November 2005. A multitude of both clinical and radiographic studies among both orthopedists and neurosurgeons embracing its ease of insertion, decreased operative duration and morbidity, and often same-day hospital discharge while obtaining therapeutic benefits seemingly comparable to more traditional decompressive techniques is discussed. It acts via modification of the normal relationships between both soft and hard tissues, and some initial studies have reported patient satisfaction exceeding 70%. CONCLUSIONS: This review will allow the clinician to better understand Interlaminar spacer's indications in the context of current literature and, moreover, help one determine when its insertion is most likely to produce symptom relief. Although never directly compared against traditional decompression, there is evidence based on standard outcome reporting instruments that it can offer therapeutic efficacy at least comparable to its proven operative predecessors. More recent work examining its long-term patient outcomes has begun to reveal its shortcomings as well as the urgency of further studying its efficacy. Clinicians should consider its insertion with cautious enthusiasm, especially considering some of its recently published poor patient outcomes and the newer interspinous devices on the horizon.

Bypass coaptation for cervical root avulsion: indications for optimal outcome.

OBJECTIVE: Previously, we reported bypass coaptation of the C3 and C4 anterior rami to the upper trunk of the brachial plexus for restoration of the muscles denervated as a result of C5 and C6 nerve root avulsion. This procedure is thought to be superior to the transfer of individual peripheral nerve fibers to the brachial plexus branches. Therefore, the benefits of the bypass coaptation procedures in the treatment of various root avulsions are presented. METHODS: Twenty-six patients were selected as suitable candidates for bypass coaptation procedures. They were divided into 3 groups: 1) Erb-Duchenne palsy due to C5 and C6 root avulsion, 2) Klumpke palsy due to C8 and T1 root avulsion, and 3) the flail arm (or flail upper limb) due to C5 through T1 root avulsion. The surgical techniques are described in detail. RESULTS: The coaptation procedures for the first group resulted in excellent recovery of all the denervated muscles. The patients in the second group showed reinnervation of the finger muscles and finger sensory distributions in infants within the first year after surgery. The flail arm group regained satisfactory proximal muscle function but only mild distal muscle function. One exception was a child who showed significant recovery in proximal and distal motor and sensory function. CONCLUSION: We recommend the bypass coaptation as a useful procedure for the following categories: Erb-Duchenne palsy due to C5 and C6 root avulsion in all ages, Klumpke palsy due to the C8 and T1 avulsion, and the flail arm due to C5 through T1 avulsion in young children. However, bypass procedures for the flail limb in adults require additional innovative methods to facilitate the growth rate of regenerating nerves.

Controlled lumbar drainage in medically refractory increased intracranial pressure. A safe and effective treatment.

BACKGROUND: A prospective study of lumbar CSF drainage in the setting of raised intra-cranial pressure refractory to medical management and ventriculostomy placement is presented. There have been no controlled trials of its use reported in the literature, to the best of our knowledge. METHOD: An IRB approved prospective study was conducted. 8 patients with increased intracranial pressure secondary to traumatic brain injury or aneurysm rupture were initially managed with sedation, ventriculostomy placement, mild hyperventilation (pCO2 = 30-35), and hyperosmolar therapy (Na = 150-155). A lumbar drain was placed if ICP continued to be above 20 mmHg despite optimization of medical therapy. FINDINGS: After lumbar drain placement, ICP was reduced from a mean of 27 +/- 7.8 to 9 +/- 6.3, an average decrease of 18 mm H2O (p < 0.05). Requirements for hypertonic saline and/or mannitol boluses and sedation to control ICP were also decreased. There were no complications noted. CONCLUSIONS: We have shown that controlled lumbar drainage is a safe, efficacious and minimally invasive method for treatment of elevated ICP refractory to medical management. Ventriculostomies are always placed before utilizing lumbar drains to minimize the risk of cerebral herniation. We would advocate making controlled lumbar drainage a standard part of ICP control protocols.

Pathophysiology of tethered cord syndrome and similar complex disorders.

Tethered cord syndrome (TCS) is a stretch-induced functional disorder of the spinal cord due to the fact that its caudal portion is anchored by an inelastic structure. The functional lesion of TCS is generally situated in the lumbosacral cord, and many authors have shown that the syndrome is reversible via surgery to untether the cord. To clarify the expressions relevant to TCS, such as "cord tethering" and "tethered cord," the authors have formulated three categories. These categories include cases that show the anatomical appearance of spinal cord stretching. Among them, Category 1 is isolated to represent the "true TCS." The authors focus their discussion of the pathophysiology of TCS on Category 1 to explain the impaired oxidative metabolism and electrophysiological derangements within the tethered spinal cord, which is the primary intrinsic cause of the dysfunction. Furthermore, they extend the discussion to the extrinsic (outside the spinal cord) factors and other complex conditions that mimic TCS.

Traumatic subarachnoid hemorrhage: our current understanding and its evolution over the past half century.

Traumatic brain injury (TBI) is a common cause of morbidity and mortality in the US, especially among the young. Primary injury in TBI is preventable, whereas secondary injury is treatable. As a result, considerable research efforts have been focused on elucidating the pathophysiology of secondary injury and determining various prognosticators in the hopes of improving final outcome by minimizing secondary injury. One such variable, traumatic subarachnoid hemorrhage (tSAH), has been the focus of many discussions over the past half century as numerous clinical studies have shown tSAH to be associated with adverse outcome. Whether the relationship of tSAH with poorer outcome in TBI is merely an epiphenomenon or a result of direct cause and effect is unclear. Some investigators believe that tSAH is merely a marker of severer TBI, while others argue that it directly causes deleterious effects such as vasospasm and ischemia. At the present time, no proven treatment regimen aimed specifically at decreasing the detrimental effects of tSAH exists, although calcium channel blockers traditionally thought to target vasospasm have shown some promises. Given that tSAH may primarily be an early indicator of associated and evolving brain injury, vigilant diagnostic surveillance including serial head CT and prevention of secondary brain damage owing to hypotension, hypoxia and intracranial hypertension may be more cost-effective than attempting to treat potential adverse sequelae associated with tSAH.

Mechanisms of hyperbaric oxygen-induced neuroprotection in a rat model of subarachnoid hemorrhage.

Acute cerebral ischemia occurs after subarachnoid hemorrhage (SAH) because of increased intracranial pressure (ICP) and decreased cerebral perfusion pressure (CPP). The effect of hyperbaric oxygen (HBO) on physiological and clinical outcomes after SAH, as well as the expressions of hypoxia-inducible factor-1alpha (HIF-1alpha) and its target genes, such as BNIP3 and VEGF was evaluated. Eighty-five male SD rats (300 to 350 g) were randomly assigned to sham, SAH, and SAH+HBO groups. Subarachnoid hemorrhage was induced by endovascular perforation. Cortical cerebral blood flow (CBF), ICP, brain water content, brain swelling, neurologic function, and mortality were assessed. HBO (100% O2, 2.8 ATA for 2 h) was initiated at 1 h after SAH. Rats were sacrificed at 24 h to harvest tissues for Western blot or for histology. Apoptotic morphology accompanied by strong immunostaining of HIF-1alpha, VEGF, and BNIP3 were observed in the hippocampus and the cortex after SAH. Increased expressions of HIF-1alpha, VEGF, and BNIP3 were quantified by Western blot. HBO reduced the expressions of HIF-1alpha, VEGF, and BNIP3, diminished neuronal damage and improved CBF and neurologic function. HBO reduced early brain injury after SAH, probably by inhibition of HIF-1alpha and its target genes, which led to the decrease of apoptosis and preservation of the blood-brain barrier function.

Role of p53 and apoptosis in cerebral vasospasm after experimental subarachnoid hemorrhage.

Our previous studies indicate that apoptosis in endothelial cells of major cerebral arteries contributes to cerebral vasospasm after subarachnoid hemorrhage (SAH). This study examined the pathologic roles of tumor suppressor p-53 in cerebral vasospasm using an established dog double-hemorrhage model. Twenty mongrel dogs were divided into four groups: (1) control, (2) SAH, (3) SAH+DMSO (vehicle), and (4) SAH+pifithrin-alpha (PFT) (p53 inhibitor). The p53 inhibitor (200 nmol/L) was injected into the cisterna magna daily from Day 0 through Day 3. Angiogram was performed on Day 0 and Day 7. Western blot, cell proliferation assay, histology, and TUNEL staining were conducted on the basilar arteries collected on Day 7 after SAH. The arterial diameter on Day 7 was 42%+/-4%, 40%+/-5%, and 59%+/-4% for SAH, SAH+DMSO, and SAH+PFT, respectively. In addition, positive staining of TUNEL and increased protein expression of p53, Bax, and PCNA in the basilar artery were observed on Day 7. PFT suppressed apoptosis in endothelial cells and proliferation in smooth muscle cells, and attenuated angiographic vasospasm. In conclusion, p53 may be a key factor in endothelial apoptosis and smooth muscle proliferation after SAH. Inhibition of p53 may potentially reduce or even prevent cerebral vasospasm.

Multiple effects of hyperbaric oxygen on the expression of HIF-1 alpha and apoptotic genes in a global ischemia-hypotension rat model.

Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor specifically activated by hypoxia. Activation of proapoptotic caspase-9 and caspase-3 pathways, by binding with tumor suppressor p53, HIF-1alpha could lead to harmful actions such as apoptosis. We examined whether increasing oxygen levels by hyperbaric oxygen (HBO) offers neuroprotection, at least partially by suppression of HIF-1alpha and apoptotic genes. Male SD rats (n = 78) were randomly divided into 13 groups: 1 sham group, 6 groups of global ischemia-hypotension (GI), and 6 groups of HBO treatment after global ischemia-hypotension (GI + HBO). HBO (3 ATA for 2 h) was applied at 1 h after global ischemia-hypotension. Rats were sacrificed at 6, 12, 24, 48, and 96 h and 7 days. Global ischemia-hypotension (10 min ischemia, 30-35 mm Hg) produced a marked increase of HIF-1alpha expressions in the hippocampus and cortex at 6 h and peaked at 48-96 h. The expressions of p53, caspase-9, and caspase-3 were all increased in a similar time course. These molecular changes were accompanied by massive cell loss in the hippocampal regions and to a lesser degree in the cortex, with features of apoptosis. HBO treatment reduced expressions of HIF-1alpha, p53, caspase-9, and caspase-3 and decreased cell death. The protein levels of proapoptotic caspase-8 and antiapoptotic bcl-2 were increased after global ischemia-hypotension and HBO potentiated the expression of caspase-8 and decreased expression of bcl-2. These results indicate that HBO has multiple actions on apoptotic genes even though the overall effect of HBO was decreased HIF-1alpha expression and reduced apoptosis after global ischemia-hypotension.

Concept of arteriovenous malformation compartments and surgical management.

Cerebral AVMs are known to be a source of intracranial hemorrhages and epileptic seizures. Their natural history indicates approximately 15% mortality and 35% morbidity over a 15-year period. This significant mortality and morbidity mandates a need for satisfactory treatment of this entity, ideally by elimination of AVMs. Microsurgical resection, endovascular embolization and radiosurgery (irradiation) are the three effective modes of treatment currently available. However, no objective criteria have been established for which mode(s) of treatment should be selected for individual patients with AVMs. Considering the complexity of AVMs and variable conditions of individual patients, neurosurgeons, intravascular interventionalists and radiosurgeons must make their own decisions on how to treat each patient based on their experience. In practice, treatment of small AVMs in non-functional areas is favored equally by each of these specialists, while they tend to avoid treatment of large AVMs, particularly those in functional areas of the brain. The authors report the surgical intervention of large AVMs, including those located in functional areas of the hemisphere by special techniques. One can demonstrate AVM compartments by using angiography and with the aid of color Doppler ultrasonography, each compartment can be outlined and dissected individually until all the compartments are isolated without causing any damage to the surrounding brain and the entire AVM is rendered shrunken and then removed. The concept of compartmental treatment of AVMs may be applied in the future to radiosurgery and intravascular embolization of large AVMs.