Mark K. Lyons

A Randomized, Controlled Trial of Methylprednisolone or Naloxone in the Treatment of Acute Spinal-Cord Injury

Abstract Studies in animals indicate that methylprednisolone and naloxone are both potentially beneficial in acute spinal-cord injury, but whether any treatment is clinically effective remains uncertain. We evaluated the efficacy and safety of methylprednisolone and naloxone in a multicenter randomized, double-blind, placebo-controlled trial in patients with acute spinal-cord injury, 95 percent of whom were treated within 14 hours of injury. Methylprednisolone was given to 162 patients as a bolus of 30 mg per kilogram of body weight, followed by infusion at 5.4 mg per kilogram per hour for 23 hours. Naloxone was given to 154 patients as a bolus of 5.4 mg per kilogram, followed by infusion at 4.0 mg per kilogram per hour for 23 hours. Placebos were given to 171 patients by bolus and infusion. Motor and sensory functions were assessed by systematic neurologic examination on admission and six weeks and six months after injury. After six months the patients who were treated with methylprednisolone within eigh...

Seizure Prophylaxis in Patients With Brain Tumors: A Meta-analysis

OBJECTIVE To assess whether antiepileptic drugs (AEDs) should be prescribed to patients with brain tumors who have no history of seizures. METHODS We performed a meta-analysis of randomized controlled trials (1966-2004) that evaluated the efficacy of AED prophylaxis vs no treatment or placebo to prevent seizures in patients with brain tumors who had no history of epilepsy. Summary odds ratios (ORs) were calculated using a random-effects model. Three subanalyses were performed to assess pooled ORs of seizures in patients with primary glial tumors, cerebral metastases, and meningiomas. RESULTS Of 474 articles found in the initial search, 17 were identified as primary studies. Five trials met inclusion criteria: patients with a neoplasm (primary glial tumors, cerebral metastases, and meningiomas) but no history of epilepsy who were randomized to either an AED or placebo. The 3 AEDs studied were phenobarbital, phenytoin, and valproic acid. Of the 5 trials, 4 showed no statistical benefit of seizure prophylaxis with an AED. Meta-analysis confirmed the lack of AED benefit at 1 week (OR, 0.91; 95% confidence interval [CI], 0.45-1.83) and at 6 months (OR, 1.01; 95% CI, 0.51-1.98) of follow-up. The AEDs had no effect on seizure prevention for specific tumor pathology, including primary glial tumors (OR, 3.46; 95% CI, 0.32-37.47), cerebral metastases (OR, 2.50; 95% CI, 0.25-24.72), and meningiomas (OR, 0.62; 95% CI, 0.10-3.85). CONCLUSIONS No evidence supports AED prophylaxis with phenobarbital, phenytoin, or valproic acid in patients with brain tumors and no history of seizures, regardless of neoplastic type. Subspecialists who treat patients with brain tumors need more education on this issue. Future randomized controlled trials should address whether any of the newer AEDs are useful for seizure prophylaxis.

The results of radiotherapy for ependymomas: the Mayo Clinic experience.

PURPOSE This analysis was performed to examine the outcome of patients with histologically confirmed ependymomas of the brain or spinal cord who received postoperative radiotherapy. METHODS AND MATERIALS Eighty patients with histologically confirmed ependymomas were evaluated retrospectively. All were treated with various combinations of surgery, radiotherapy (RT), and chemotherapy. Follow-up ranged from 5 to 30 years (median 10.4 years). RESULTS The 5- and 10-year survival rates for the entire study group were 79% and 73%, respectively. Patients with low-grade (1 and 2 of 4) tumors had a 5-year survival rate of 87% as compared to 27% for those with high-grade (3 and 4 of 4) tumors (p < 0.0001). Patients with tumors of the spine had a 5-year survival rate of 97% as compared to 68% for those with infratentorial tumors, and 62% for those with supratentorial tumors (p = 0.03). Patients with myxopapillary ependymomas of the spine had a 5-year survival rate of 100% as compared with 76% for patients with other histological subtypes of ependymoma (p = 0.02). Multivariate analysis revealed that the survival rate was independently associated with tumor grade (p = 0.0007) and histological subtype (p = 0.02). Twenty-eight patients (35%) experienced local failure and 10 patients (13%) developed leptomeningeal seeding. The 5-year leptomeningeal failure rate was 10% in patients with low-grade tumors as compared to 41% for patients with high grade tumors (p = 0.01). CONCLUSION Patients with low-grade tumors, especially those with myxopapillary subtypes, have high 5-year survival rates when treated with post-operative radiotherapy. High grade ependymomas are associated with a much poorer outcome. New forms of therapy are required to improve the outcome of patients with high-grade ependymomas.

Posterior Fossa Ependymomas: Report of 30 Cases and Review of the Literature

Thirty patients with histologically confirmed posterior fossa ependymomas operated on between January 1976 and December 1988 were reviewed. The median age was 44 years (range, 1-69 yr). There were 7 children (aged 5 yr or younger) and 23 adults (aged 16 yr or older). There were 18 female patients and 12 male patients. Headache, nausea and vomiting, and disequilibrium were the most frequent symptoms. The most common findings were ataxia and nystagmus. Gross total resection was performed in 8 patients (27%), subtotal resection in 21 patients (70%), and biopsy in only 1 patient (3%). Tumors were low grade in 73% and high grade in 27%. Twenty-seven patients underwent posterior fossa radiotherapy (median dose, 5400 cGy). Fourteen patients also underwent spinal irradiation (median dose, 3520 cGy). Age was the only significant prognostic factor identified (P less than 0.01). The 5-year survival rates were 76% for adults and 14% for children. All 14 patients who died had recurrent or residual tumor at the primary site. This review suggests that in patients with primary posterior fossa ependymomas the following is true: 1) the young patient (5 yr old or younger) has a poor prognosis; 2) there was a trend toward a better 5-year survival rate with a gross total resection; 3) if recurrence occurs, it will be at the primary intracranial site; and 4) symptomatic spinal seeding does not occur frequently.

Deep Brain Stimulation: Current and Future Clinical Applications

Deep brain stimulation (DBS) has developed during the past 20 years as a remarkable treatment option for several different disorders. Advances in technology and surgical techniques have essentially replaced ablative procedures for most of these conditions. Stimulation of the ventralis intermedius nucleus of the thalamus has clearly been shown to markedly improve tremor control in patients with essential tremor and tremor related to Parkinson disease. Symptoms of bradykinesia, tremor, gait disturbance, and rigidity can be significantly improved in patients with Parkinson disease. Because of these improvements, a decrease in medication can be instrumental in reducing the disabling features of dyskinesias in such patients. Primary dystonia has been shown to respond well to DBS of the globus pallidus internus. The success of these procedures has led to application of these techniques to multiple other debilitating conditions such as neuropsychiatric disorders, intractable pain, epilepsy, camptocormia, headache, restless legs syndrome, and Alzheimer disease. The literature analysis was performed using a MEDLINE search from 1980 through 2010 with the term deep brain stimulation, and several double-blind and larger case series were chosen for inclusion in this review. The exact mechanism of DBS is not fully understood. This review summarizes many of the current and potential future clinical applications of this technology.

Frequency of seizures in patients with newly diagnosed brain tumors: A retrospective review

Brain tumors may lead to symptomatic epilepsy. A retrospective analysis was undertaken to evaluate the frequency of seizure as the presenting symptom leading to brain tumor diagnosis in adults. One hundred and forty-seven consecutive patients with newly diagnosed brain tumors were analyzed regarding the frequency of seizures as the initial presenting symptoms and those subsequently developing seizures. One hundred twelve patients had primary central nervous system tumors (CNS) and 35 had metastatic lesions. Statistical evaluation was carried out using the Chi-square test with p values of <0.05 considered to be statistically significant. Astrocytomas and meningiomas were the most common primary CNS tumors in this study. Of these, oligodendrogliomas and grade 2 astrocytomas were significantly more likely to present with seizures (p<0.001). Seizures were a frequent presenting symptom, occurring in over 38% of those with primary brain neoplasms and 20% of those with cerebral metastases. Primary location of tumor also correlated amongst primary CNS tumors and was associated with a trend in seizure risk: parietal (80%); temporal (74%); frontal (62%); and occipital (0%) (p<0.5). The findings highlight the importance of obtaining appropriate evaluation for underlying malignancy in adults with new-onset seizures as well as provide more information to the patient for prognosis and counseling.

CORTICOTROPIN RELEASING FACTOR ANTAGONIST REDUCES ISCHEMIC HIPPOCAMPAL NEURONAL INJURY

This experiment tested the hypothesis that corticotropin-releasing factor (CRF) contributes to hippocampal ischemic injury. The antagonist to CRF (alpha-CRF) was administered intraventricularly 15 min prior to 10 min of transient forebrain ischemia in the Wistar rat. alpha-CRF demonstrated a neuroprotective effect in a dose-dependent manner most notable in CA1. There was also an increase in postischemic EEG recovery. It is postulated that CRF contributes to hippocampal ischemic injury through increased neuronal activity.

Cerebrospinal Fluid Physiology and the Management of Increased Intracranial Pressure

Increased intracranial pressure can result in irreversible injury to the central nervous system. Among the many functions of the cerebrospinal fluid, it provides protection against acute changes in venous and arterial blood pressure or impact pressure. Nevertheless, trauma, tumors, infections, neurosurgical procedures, and other factors can cause increased intracranial pressure. Both surgical and nonsurgical therapeutic modalities can be used in the management of increased intracranial pressure attributable to traumatic and nontraumatic causes. In patients with cerebral injury and increased intracranial pressure, monitoring of the intracranial pressure can provide an objective measure of the response to therapy and the pressure dynamics. Intraventricular, intraparenchymal, subarachnoid, and epidural sites can be used for monitoring, and the advantages and disadvantages of the various devices available are discussed. With the proper understanding of the physiologic features of the cerebrospinal fluid, the physician can apply the management principles reviewed herein to minimize damage from intracranial hypertension.

Responsiveness of short-lasting unilateral neuralgiform headache with conjunctival injection and tearing to hypothalamic deep brain stimulation

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) is a severe primary headache disorder that is often refractory to medical therapy. Although the pathogenesis of this and other trigeminal autonomic cephalalgias is not completely understood, ipsilateral activation of the posterior and inferior hypothalamus has been identified on functional imaging studies during attacks. The authors report on a case of SUNCT syndrome successfully treated with hypothalamic deep brain stimulation and discuss the current literature.

Basic fibroblast growth factor promotes in vivo cerebral angiogenesis in chronic forebrain ischemia.

This experiment was designed to determine if intraventricular administration of basic fibroblast growth factor (bFGF) could promote cerebral angiogenesis in a model of mild chronic forebrain ischemia. Wistar rats underwent bilateral carotid artery ligation. Animals received intraventricular injections of bFGF every 4 days for 28 days. Basic fibroblast growth factor caused a significant dose-dependent increase in capillary density compared to ischemic controls in all regions examined. These results support the hypothesis that chronic intraventricular administration of bFGF induces in vivo cerebral angiogenesis.