Mark D. Krieger

Recurrence Patterns and Anaplastic Change in a Long-Term Study of Pilocytic Astrocytomas

Thirty-six cases of pilocytic astrocytomas treated at the Childrens Hospital of Los Angeles from 1984 through 1995 were reviewed. The mean age at initial presentation was 8 years (range 15 months to 14 years). These patients were followed for an average of 5.5 years. No patient was given chemotherapy or radiation therapy after the initial surgery for pilocytic astrocytoma. Twenty-three patients (64%) had a gross total resection with no residual tumor on immediate postoperative imaging studies. Three of these children had tumor recurrences 2-5 years after their initial surgery, requiring re-excision of their tumors. All 3 patients are subsequently tumor-free, with follow-up ranging from 4 to 10 years. In 4 patients with residual tumor involving the brainstem, there has been neither imaging evidence of tumor enlargement nor progression of clinical findings at 2.5, 4, 6 and 6 years, respectively. Nine of the 13 patients with residual tumor underwent re-excision, either for progression of symptoms or documented tumor growth on imaging studies. The second operation was undertaken an average of 1 year (range 1 month to 6 years) after the first. In 4 of these children (11% of our whole series), the recurrent tumor was classified as anaplastic astrocytoma. Three of these 4 children received radiation and/or chemotherapy, with only 1 patient showing disease progression in the follow-up period. Repeat blinded histopathological examination of these tumors confirmed both diagnoses. However, it was noted that 3 of the 4 pilocytic astrocytomas which subsequently showed anaplastic change initially displayed increased perivascular cellularity, while only 2 of the remaining 32 tumors exhibited this feature. These results encourage continued vigilance in the follow-up of pilocytic astrocytomas, and describe a histological feature which might indicate a more aggressive disease course.

Role of stereotactic biopsy in the diagnosis and management of brain tumors

Stereotactic biopsy has evolved as a powerful and safe tool to provide tissue diagnoses with minimal disruption of normal functioning brain. It plays a significant role in the management of malignant brain tumors, where the benefit of open surgery might not justify the concomitant risks. Stereotactic procedures are closed procedures, and thus direct feedback is not provided to the surgeon during manipulation of brain tissue. This difference from most other neurosurgical procedures necessitates rigor in the preoperative workup, the planning of the procedure, and the conduct of the procedure. The success of the procedure is measured by the ability of the team to make an accurate histopathological diagnosis of the lesion; in experienced hands, the rate of success should exceed 95%. Complications and mortality can be minimized with appropriate attention to detail.

Proton-decoupled 31P MRS in untreated pediatric brain tumors

Proton‐decoupled 31P and 1H MRS was used to quantify markers of membrane synthesis and breakdown in eight pediatric patients with untreated brain tumors and in six controls. Quantitation of these compounds in vivo in humans may provide important indicators for tumor growth and malignancy, tumor classification, and provide prognostic information. The ratios of phosphoethanolamine to glycerophosphoethanolamine (PE/GPE) and phosphocholine to glycerophosphocholine (PC/GPC) were significantly higher in primitive neuroectodermal tumors (PNET) (16.30 ± 5.73 and 2.97 ± 0.93) when compared with controls (3.42 ± 1.62, P < 0.0001 and 0.45 ± 0.13, P < 0.0001) and with other tumors (3.93 ± 3.42, P < 0.001 and 0.65 ± 0.30, P < 0.0001). Mean PC/PE was elevated in tumors relative to controls (0.48 ± 0.11 versus 0.24 ± 0.05, P < 0.001), but there was no difference between PNET and other tumors. Total choline concentration determined with quantitative 1H MRS was significantly elevated (4.78 ± 3.33 versus 1.73 ± 0.56 mmol/kg, P < 0.05), whereas creatine was reduced in tumors (4.89 ± 1.83 versus 8.28 ± 1.50 mmol/kg, P < 0.05). A quantitative comparison of total phosphorylated cholines (PC+GPC)/ATP measured with 31P MRS and total choline measured with 1H MRS showed that in tumors a large fraction of the choline signal (>54 ± 36%) was not accounted for by PC and GPC. The fraction of unaccounted choline was particularly large in PNET (>78 ± 7%). The pH of tumor tissue was higher than the pH of normal brain tissue (7.06 ± 0.03 versus. 6.98 ± 0.03, P < 0.001). Magn Reson Med 53:22–29, 2005.

Metabolism of diffuse intrinsic brainstem gliomas in children

Progress in the development of effective therapies for diffuse intrinsic brainstem gliomas (DIBSGs) is compromised by the unavailability of tissue samples and the lack of noninvasive markers that can characterize disease status. The purpose of this study was to compare the metabolic profile of DIBSGs with that of astrocytomas elsewhere in the CNS and to determine whether the measurement of metabolic features can improve the assessment of disease status. Forty in vivo MR spectroscopy (MRS) studies of 16 patients with DIBSG at baseline and after radiation therapy were retrospectively reviewed. Control data for baseline studies of DIBSGs were obtained from 14 untreated regular and anaplastic astrocytomas. All spectra were acquired with single-voxel, short echo-time (35 ms), point-resolved spectroscopy. Absolute metabolite concentrations (mmol/kg) and lipid intensities (arbitrary units) were determined. At baseline, creatine and total choline (tCho) were significantly lower in DIBSGs than in astrocytomas elsewhere in the CNS (4.3 +/- 1.1 vs. 7.5 +/- 1.9 mmol/kg, p < 0.001; 1.9 +/- 0.7 vs. 4.2 +/- 2.6, p < 0.001). Serial MRS in individual subjects revealed increasing levels of tCho (p < 0.05) and lipids (p < 0.05) and reduced ratios of N-acetylaspartate, creatine, and myoinositol relative to tCho (all p < 0.01). Metabolic progression defined by increased tCho concentration in serial MRS preceded clinical deterioration by 2.4 +/- 2.7 months (p < 0.04). Low tCho of DIBSG at baseline is consistent with low proliferative tumors. Subsequent metabolic changes that have been associated with malignant degeneration preceded clinical deterioration. MRS provides early surrogate markers for disease progression.

Invasive pituitary adenomas: significance of proliferation parameters.

Although most pituitary adenomas behave in a purely benign fashion, microscopic invasion of the subjacent dura is very common, and clinically overt infiltration of the surrounding dura and bone is apparent at intraoperative inspection in about one third of cases. The factors governing invasive behavior remain unknown but are believed to be separate from those regulating cell proliferation. Histological features alone do not distinguish between benign, invasive, and malignant tumors of adenohypophyseal origin. Multiple attempts have been made to identify prognostic markers of aggressive behavior among these tumors. They include cytogenetic analysis of putative tumor suppressor genes or proto-oncogenes as well as immunohistochemical detection of cell-cycle specific antigens. At present, however, these analyses can neither distinguish the indolent pituitary adenoma from one that will pursue an invasive course, nor reliably predict the prognosis in individual patients.

Choroid plexus tumors; management, outcome, and association with the Li–Fraumeni syndrome: The Children's Hospital Los Angeles (CHLA) experience, 1991–2010†

Choroid plexus tumors (CPT) are rare, and predominate in early childhood. An association with the Li–Fraumeni syndrome (LFS) has been reported, but the biological and clinical implications of this association remain poorly defined. We have investigated the clinical features and overall survival of all CPT patients treated at Childrens Hospital Los Angeles (CHLA) over a 20‐year period, with particular attention to the association of CPT with LFS.

Iatrogenic Intraspinal Epidermoid Tumor: Two Cases and a Review of the Literature

Study Design. Two cases of patients whom intraspinal epidermoid tumors presented and were successfully removed 6 years after neonatal lumbar puncture are reported. Objective. To describe the presentation of this type of spinal tumor and strategies for diagnosis and treatment. Summary of Background Data. Cells iatrogenically implanted into the spinal canal during lumbar puncture can slowly grow until symptomatic. Diagnosis can be difficult and is often delayed. MRI appears to offer some advantages in diagnosis provided that gadolinium is used. Treatment is by surgical excision. Methods. The first patient, a 6-year-old boy, presented with severe episodic hip pain of unknown etiology. MRI of the lumbar spine revealed a 1-cm epidermoid at L1–L2. The second child, a 6-year-old girl, presented with low back pain and dragging of the feet. MRI revealed a mass at L3. Results. In both cases, complete excision via lumbar laminectomy was performed. Both patients were asymptomatic at the 1-year follow-up with resolution of preoperative weakness. Conclusions. This study highlights an uncommon but not rare tumor that may present to the spine specialist in a variety of ways. The diagnosis is often delayed. The advent of MRI has improved the ease and accuracy of diagnosis. Complete excision is usually possible and is curative.

Complications of Halo Use in Children

Study Design. Retrospective review. Objective. To evaluate complications of halo use in children. Summary of Background Data. Halos have been used in children for correction of spinal deformity and immobilization of the spine. Complications of halo use in children have been reported, including pin-site complications and neurologic injury from halo traction. The purpose of this report is to report on complications of halo use in children. Methods. The medical records of 68 patients treated with a halo for correction of spinal deformity or immobilization from 1996 to 2005 were reviewed. Mean age of children was 10 (1–20) years. The halo device was used to apply traction for correction of spinal deformity in 31 patients, and immobilization alone with halo vest in 37 patients. Results. The overall rates of complications are significant at 53% (36/68). Pin-site complications included 13 infections successfully treated with oral antibiotics and 4 pins that needed to be removed. Two pins were replaced due to skull penetration, and 1 scar site was surgically revised. There were a total of 9 neurologic complications that occurred in 7 of 31 patients undergoing halo traction (31% incidence), including 3 cranial nerve injuries, 1 Horner syndrome, 4 extremity weaknesses, and 1 bradycardia. All traction-related neurologic problems resolved with removal or decrease of the magnitude of traction, with 4 cases improving immediately, 3 cases within 2 days, and the 2 other cases resolving in 1 and 5 months. Lastly, there were 7 vest-related complications including 5 pressure sores, 1 cracking of the vest, and 1 halo-vest readjustment. Conclusion. This is the largest reported series of halo use in children. The overall rate of complications is 53% (36/68), and 10% (7/68) of children required unanticipated surgery for treatment of these complications. The most common complication was pin-site infections, with 76% (13/17) of these resolving with oral antibiotics alone. Traction-related neurologic injuries that occurred were common, 31% (9/31) but all resolved with a decrease or removal of traction weight, with complete resolution occurring immediately in 4 of 9 events. We recommend serial neurologic examinations of children in halo traction, with immediate removal or decrease in weights at the first sign of injury.

Scoliosis and Chiari malformation Type I in children

OBJECT The identification of Chiari malformations Type I (CM-Is) has increased in recent years, commonly during MR imaging for evaluation of a possible cause of scoliosis. The treatment of this abnormality remains controversial, and the expected success of treatment is unclear. The goal of the present study is to evaluate the effects of a craniotomy for CM-I decompression on scoliosis in children and adolescents. METHODS The authors conducted a 10-year retrospective review of pediatric patients who were found to have a CM-I during evaluation for scoliosis. Seventy-nine patients were identified, ranging in age from 6 months to 18 years (median 12 years). There were 42 girls (54%) and 37 boys (46%). All were noted on MR imaging to have hydrosyringomyelia of the spinal cord. Forty-nine patients had curvatures less than 20° prior to treatment. The other 30 patients had curves ranging from 25° to 80° and underwent orthopedic follow-up and treatment. None of these patients were referred for specific neurological complaints, but 12 (16%) had neurological signs on physical examination. All were treated with a craniocervical decompression in a standard fashion. Follow-up ranged from 6 to 93 months with a median of 35 months. Magnetic resonance images obtained at 6 months postoperatively and serial standing anteroposterior spine radiographs were used to evaluate outcomes. RESULTS On the MR images obtained 6 months postoperatively, 70 patients (89%) had a significant reduction in the syrinx with an associated ascent of the cerebellar tonsils. Persistent large syringes were treated with reoperation in 6 patients, and shunts were inserted for hydrocephalus in 2 patients. None of the 49 patients with curves less than 20° had progression of their curvature postoperatively. Of the 30 patients with curves greater than 25°, 9 had no change in the scoliosis or had a reduction in curve magnitude after Chiari decompression. This group required no further therapy and was effectively treated by Chiari decompression alone. Twenty-one patients required further scoliosis treatment after Chiari decompression; 12 required orthotic treatment, 11 received spinal instrumentation and fusion surgery, and 2 received orthoses followed by fusion and instrumentation. The severity of the curvature beyond 20° did not predict the need for spinal surgery. CONCLUSIONS This large series reports on the efficacy of treatment for scoliosis associated with a CM-I and syrinx in children. A CM-I decompression alone was adequate treatment for mild scoliosis of less than 20°. Patients with scoliosis greater than 20° required bracing and/or spinal fusion surgery 70% of the time in addition to the CM-I decompression.

Surgical management of primary central nervous system germ cell tumors: proceedings from the Second International Symposium on Central Nervous System Germ Cell Tumors.

The successful treatment of children with a primary CNS germ cell tumor can be greatly influenced by the neurosurgeon involved in the diagnostic and therapeutic care of these children. Variability in surgical philosophies no doubt exists due to the relatively infrequent incidence of these tumors, a lack of consensus regarding diagnostic and therapeutic approaches, and the advent of recent surgical innovations. Many of these issues were discussed at the Second International Symposium on Central Nervous System Germ Cell Tumors through presented abstracts and invited presentations. The neurosurgical aspects of these proceedings are summarized here in an effort to present the agreed-upon and debated issues that may confront the pediatric neurosurgeon.