MRI of the spine can help narrow the differential diagnosis, allow for surgical planning and identify potential sites of multifocal disease. The entire spine should be imaged with pre- and post-gadolinium contrast to maximize yield. Brain imaging may also be warranted if the lesions are suspicious for drop metastases or if the patient presents with signs or symptoms of increased intracranial pressure such as headache, emesis, hypertension with bradycardia, or cranial nerve palsies.

Steroid treatment is employed to relieve any vasogenic edema that may be contributing to cord compression. In the case of ALL and lymphoma, corticosteroids also have a direct antitumor effect that may benefit the patient in the short term, but ultimately make diagnosis of the underlying malignancy much more challenging. If a hematopoietic malignancy is likely, steroids should be given only when urgent diagnostic procedures have been scheduled (e.g., bone marrow aspiration and biopsy, lymph node excisional biopsy).

Outside of this scenario, the benefits of steroids are thought to outweigh their risks and are routinely used when cord compression is diagnosed, although clinical trials in children are lacking. In adults there is no evidence supporting high-dose dexamethasone; an initial dose of 1–2 mg/kg (max 10 mg) followed by 0.25–0.5 mg/kg (max 4 mg) every 6 h can be considered while awaiting further therapy (Kaal and Vecht 2004; Loblaw et al. 2005; George et al. 2008).

Surgery in spinal cord compression can be utilized for tumor debulking with spinal cord stabilization or for diagnostic biopsy in the highly chemotherapy- or radiotherapy-sensitive tumor. Prospective studies in adult patients with cord compression have favored early laminectomy and debulking over radiation therapy alone although more recent retrospective studies have called this into question (Patchell et al. 2005; Rades et al. 2010). Laminectomy in the young child can lead to spinal deformities requiring future surgical intervention and therefore pediatric retrospective studies argue against an early surgical approach (Parikh and Crawford 2003). Recovery from surgery can also lead to delays in instituting definitive chemoradiotherapy.

An early case series from St. Jude Children’s Research Hospital suggested that initial debulking is warranted for sarcomas, whereas biopsy with chemotherapy or radiotherapy should be considered for patients with neuroblastoma, germ cell tumors and lymphomas (Klein et al. 1991). Patients presenting with rapid evolution of symptoms or complete loss of motor function were treated with urgent surgical decompression regardless of tumor histology. Smaller case series have supported the use of initial chemotherapy in neuroblastoma, Ewing sarcoma and germ cell tumors (Hayes et al. 1984). A study of 76 children with neuroblastoma from Italy found no difference in the success rates of chemotherapy, radiotherapy or surgical debulking in improvement of neurological signs, but noted that patients receiving radiotherapy or surgical debulking all went on to receive additional therapy for cord compression, whereas chemotherapy patients did not (De Bernardi et al. 2001). A follow-up study from this same group also noted a higher incidence of spinal deformities in the group receiving surgical intervention with a trend towards worse neurologic outcomes. As with the St. Jude data, patients with rapidly progressive symptoms or severe presentations were all treated with emergent surgery, making that group much higher risk than those treated with chemotherapy or radiotherapy (Angelini et al. 2011). A more contemporary study of 122 patients did not find any difference in spinal outcomes in patients treated with chemotherapy or surgery which the authors attribute to improvement in surgical technique (Simon et al. 2012).

In summary, each case of cord compression warrants individual consideration before a decision to proceed with debulking or biopsy can be made. Rapid progression of symptoms and total plegia are indications for emergent surgical management. Spinal column instability, which warrants surgical intervention, will also often necessitate surgical debulking. If the malignancy is known to be chemotherapy sensitive (i.e., hematopoietic malignancies, neuroblastoma, Ewing sarcoma, germ cell tumors), biopsy either at the site of cord compression or at another more easily accessible site can be considered prior to institution of chemotherapy. The timely availability of these options may also influence the treatment decision.

The advantages of external beam radiation therapy include rapid onset of action and minimal invasiveness making radiation therapy an attractive option for patients who are too unstable to be considered surgical candidates, or in the palliative setting. Tumors that are radiosensitive such as hematologic malignancies (i.e., chloromas) and lymphoma may benefit from urgent radiotherapy while leaving additional diagnostic disease sites intact. Extensive metastatic disease may similarly be more amenable to radiation therapy than a surgical approach; when surgery is the primary therapeutic modality, adjunctive radiation may have a role in local control.

A case series from Children’s Hospital of Philadelphia demonstrated the benefit of urgent radiation therapy in combination with chemotherapy in a pediatric population with a variety of tumor types: of 33 patients presenting with cord compression, 55 % demonstrated improvement following chemoradiotherapy and 30 % had stabilization of their neurologic symptoms (Bertsch et al. 1998).

Dose-dependent long-term complications arising from radiation therapy can include future growth complications such as scoliosis as well as risk of secondary malignancy, particularly meningioma (Hoffman and Yock 2009). Stereotactic radiosurgery can deliver a single treatment dose up to 13 Gy to localized tumors without exceeding spinal cord tolerance; additionally, the spinal cord can tolerate high total doses, with a risk of myelopathy of <1 % at 54 Gy in adult patients (Kirkpatrick et al. 2010).

Primary CNS tumors can directly lead to seizures. Oligodendrogliomas and gangliogliomas are common causes of brain tumor-induced seizure, though other low-grade gliomas and dysembryoblastic neuroepithelial tumors (DNETs) can be associated with seizures as well (Ogiwara et al. 2010). Such low-grade lesions may be surgically resected to provide relief from symptomatic seizures. Extracranial tumors can invade the CNS either by direct invasion, as with parameningeal rhabdomyosarcoma, or by hematogenous metastasis, as in Ewing sarcoma (the most common cause of pediatric CNS parenchymal metastasis), extracranial germ cell tumors, and leukemias.

Intracranial hemorrhage is another consideration in the seizing patient. Intratumoral hemorrhage has been variably reported in adults receiving the monoclonal antibody bevacizumab for primary CNS tumors (Seet et al. 2011; Khasraw et al. 2012). Certain primary childhood CNS tumors have a high proclivity for spontaneous intratumoral hemorrhage due to their intrinsic high vascularity; notorious examples are primary CNS choriocarcinoma, choroid plexus carcinoma and malignant gliomas. Derangement of the hemostatic system as seen in acute promyelocytic leukemia or after asparaginase therapy can also lead to intracranial hemorrhage in a patient without CNS disease.

Patients who have undergone resection of CNS tumors may develop postoperative seizures. No clear consensus exists regarding the use of prophylactic antiepileptic therapy in the postoperative setting. The American Academy of Neurology recommends tapering antiepileptic drugs (AEDs) within the first postoperative week, though it does not make a recommendation regarding AED initiation due to a lack of evidence even in the adult setting (Glantz et al. 2000). A retrospective study of 223 patients from Children’s Hospital of Philadelphia found that age younger than 2 years, supratentorial location of tumor and postoperative hyponatremia were the only independent predictors of postoperative seizure (Hardesty et al. 2011). Of the 229 operations reviewed, 7.4 % of patients seized and only 4.4 % received routine postoperative AEDs (Hardesty et al. 2011). Due to insufficient evidence, the use of prophylactic AEDs should be determined under consultation with the patient’s neurosurgeon and intensive care team. Given the low incidence of unprovoked postoperative seizure, workup of new seizures following tumor resection is warranted to exclude alternative etiologies.

The metabolic causes of AMS or seizure in pediatric oncology are similar to other pediatric patients: hyponatremia, hypoglycemia, and, less frequently, hypocalcemia secondary to hyperphosphatemia in severe tumor lysis syndrome (discussed in Chap.​ 3).

Patients receiving immunosuppressive chemotherapy have an increased risk for CNS infection which may present with AMS or seizure. Lumbar puncture is a helpful diagnostic tool in this setting, but should be deferred until the patient has been stabilized and CT imaging performed. Institution of broad antimicrobial coverage should not be delayed to obtain cerebrospinal fluid (CSF); cell counts can be informative in non-cytopenic patients even after sterilization of CSF and polymerase chain reaction (PCR)-based assays for viruses can remain positive after antiviral therapy has been instituted.

Infectious studies should include cultures of blood and CSF. Enterovirus, herpes simplex virus (HSV) and human herpesvirus-6 (HHV6) can be detected by CSF PCR. Culture or direct fluorescence antibody (DFA) testing of oropharyngeal lesions should also be considered. Treatment with high-dose acyclovir should be initiated urgently if viral meningoencephalitis is suspected.

A study of 40 cases of bacterial and fungal meningitis in pediatric oncology patients found that recent neurosurgery or a CNS device was present in the majority of cases (Sommers and Hawkins 1999). Among patients without neurosurgical intervention, those with hematologic malignancies and prolonged neutropenia were at the highest risk for infection.

Methotrexate, ifosfamide, and cytarabine (Ara-C) are commonly used pediatric chemotherapeutic agents that can provoke seizures and encephalopathy. Transverse myelitis is a peculiar complication described following the combined intravenous and intrathecal administration of cytarabine. Vincristine is most commonly known for its associated peripheral neuropathies, but medical errors in administration have highlighted its extreme neurotoxicity when introduced into the CNS or given at erroneously high doses systemically. Thiotepa, carmustine (BCNU) and busulfan are myeloablative agents used at high doses in stem cell transplant with neurologic dose-limiting toxicities (Papadopoulos et al. 1998). Other less commonly used agents such as nelarabine (a prometabolite of Ara-G) have similarly been implicated in patients developing new encephalopathy or seizures.

Posterior reversible encephalopathy syndrome (PRES, also called RPLS, reversible posterior leukoencephalopathy syndrome) was first described as a syndrome of encephalopathy accompanied by transient subcortical white matter changes on T2-weighted MRI (Hinchey et al. 1996). The clinical manifestations of PRES include headaches, seizures, AMS and cortical blindness. Hypertension is a clear antecedent and most significant risk factor in the development of PRES. Hypertension may be secondary to medications, such as corticosteroids, or concurrent medical conditions such as renal failure from tumor lysis syndrome (Greenwood et al. 2003). Retrospective studies also suggest a higher incidence of PRES during induction chemotherapy, independent of tumor lysis syndrome or hyperleukocytosis (Norman et al. 2007).

Since its initial description, PRES has been recognized to not be limited to the posterior circulation of the brain nor to white matter exclusively nor be fully reversible in all cases (Lucchini et al. 2008). While the initial report postulated a role for immunosuppression in the pathogenesis of PRES, it has been subsequently described in non-immunocompromised patients such as in pregnancy-induced hypertension. Specific immunosuppressive medications, such as tacrolimus and cyclosporine, continue to be implicated in case reports in part due to their effect on blood pressure.

PRES has been noted in pediatric malignancies including ALL, AML, non-Hodgkin lymphoma, and solid tumors including neuroblastoma, osteosarcoma, and Ewing sarcoma. Hypertension was a clearly identified preceding event in the majority of cases. Seizures were the most common clinical manifestation, with AMS, headache and some form of visual disturbance occurring in 30–40 % of cases (de Laat et al. 2011). While the majority of patients had a reversible course, 12 % had persistent neurologic symptoms.