167
17
Pediatric Brain Tumors
BRAINSTEMGLIOMA 167
Brainstem Glioma
Vignette
A 7-old-girl, for the preceding six weeks, seemed irritable, depressed, and less interested in her usual school activities and dance classes. The teacher no- ticed that she was unsteady, at times staggering and falling, and that her speech was garbled. She had a few episodes of unexplained vomiting. On exam- ination, gaze to the right was limited with incom- plete abduction of the right eye. She blinked poorly on the right side and had a mild right facial weak- ness. Gag was decreased and the uvula pulled slightly to the left. There was a left pronator drift and increased reflexes compared with the right.
Gait was wide-based, unsteady.
Summary A 7-year-old girl with personality changes as- sociated with focal neurological signs.
Localization
The involvement of multiple cranial nerves and a crossed motor paralysis (cranial nerves on one side and long tract signs on the opposite side) are indicative of a lesion in- trinsic to the brainstem. In this particular case, the lesion localizes to the right brainstem, with involvement of fifth, sixth, seventh, and tenth cranial nerve nuclei, long tract pyramidal system, and cerebellum or its peduncles.
Differential Diagnosis
The differential diagnosis includes tumors, infections, and vascular malformations. Considering tumors first, diffuse instrinsic brainstem gliomas typically present with cranial nerve involvement, ataxia, and long tract signs, and should rank high in the differential diagnosis of this child. The location of the tumor is responsible for the
clinical manifestations. Other posterior fossa tumors, in- cluding cerebellar astrocytoma, medulloblastoma, and ependymoma, are usually characterized by early signs of increased intracranial pressure that manifest with head- ache, vomiting, visual dysfunction, and altered con- sciousness. Vomiting is one of the most constant signs of increased intracranial pressure in children (Maria and Menkes). It represents a nonlocalizing sign and can also occur in isolation, particularly in the morning.
Contrary to adult patients with increased intracranial pressure, in whom headache represents a typical and steady sign, this is a less constant feature in children with brain tumors. Headache in children can be transitory, tend to manifest in the morning, and can be localized in the frontal or occipital areas. Occipital headache, neck stiff- ness, and head tilt may indicate a posterior fossa mass.
Altered vision can be due to papilledema or unilateral or bilateral paresis of the lateral rectus muscle. Altered con- sciousness can cause drowsiness, stupor, or coma.
The association of long tract signs with ataxia and cra- nial nerve dysfunction is usually suggestive of brainstem pathology, whereas scanning speech, dysmetria, and ataxia are more often indicative of a cerebellar process (Duchatelier and Wolf in Keating et al.).
Infectious processes, such as brainstem encephalitis, enter the differential diagnosis because they can cause ataxia and cranial nerve dysfunction. Other symptoms are usually present and help the diagnosis, including fever, altered level of consciousness, hallucinations, meningeal signs, headache, photophobia, seizures, and so on.
Chronic fungal or tubercular meningitides involving the base of the brain may cause multiple cranial neurop- athies and ataxia, but other important signs, such as head- ache, fever, mental status changes, signs of meningeal irritation, and seizures, may predominate.
Cerebral abscesses localized to the brainstem usually are characterized by a more acute symptomatology and can present with low-grade fever, altered mentation, headache, persistent vomiting, and focal neurological findings.
168 17. Pediatric Brain Tumors
Vascular malformations of the posterior fossa can oc- casionally simulate a neoplasm, manifesting with insidi- ous and progressive brainstem and cerebellar signs but are relatively rare in children.
Clinical Features
Tumors intrinsic to the brainstem represent 10 to 25 per- cent of all pediatric brain tumors, with diffuse intrinsic brainstem gliomas accounting for 60 to 80 percent of brainstem tumors (Blum and Goodrich Tait in Keating).
Packer separates brainstem gliomas based on the location into three groups that can be overlapping and include dif- fuse pontine gliomas, which carry the worst prognosis;
tectal lesions, which have a benign histology and manifest a slow clinical progression; and cervical medullary junc- tion tumors, which have a low grade of malignancy, man- ifest an indolent course and are amenable to surgical treat- ment with possibility of good recovery.
Diffuse intrinsic brainstem gliomas, which almost al- ways shows involvement of the pons and can extend ros- trally to the midbrain and caudally to the medulla, pref- erentially affect the first decade of life, particularly children between 6 and 10 years of age. Diffuse ponto- medullary brainstem gliomas classically present with the combination of cranial nerve palsies, ataxia, and long tract signs. The neurological manifestations are based on the localization of the mass.
Cranial neuropathies commonly include abducens and facial nerve paralysis that can be the initial symptom of a growing brainstem tumor and reflect the pontine loca- tion of the mass. The involvement of the ninth and tenth nerves is not usually an initial feature.
Signs of corticospinal tract dysfunction manifest with spastic weakness, hyperreflexia, and Babinski’s signs.
Ataxia, which is due to involvement of the cerebellum and its peduncles, represents another clinical sign of dif- fuse brainstem glioma and is responsible, together with the spastic paresis, for the gait disturbance.
Mental changes include memory dysfunction, apathy, and crying alternating with irritability, etc. (Strange and Wohlert). The reason for such personality changes is un- clear but could be attributed to the interruption of tha- lamic projections (Packer).
Signs of increased intracranial pressure are usually a late manifestation, but vomiting unaccompanied by head- ache can occur at the time of the initial presentation and is caused by direct infiltration of the medullary vomiting center.
Diffuse brainstem gliomas tend to have an insidious onset and carry a very poor prognosis with few children surviving after 18 months (according to Packer less than 10 percent are alive and free of progressive disease 18 months after the diagnosis). In contrast, focal brainstem tumors are circumscribed masses and manifest few neu-
rological signs and slow progression. Focal intrinsic tu- mors localized in the upper midbrain and lower medulla are demarcated from the surrounding tissue and often carry a favorable prognosis.
Diagnosis
MRI of the brain remains the study of choice for the di- agnosis of brainstem tumors. Characteristic feature of the neoplasm should be identified, such as location, degree of infiltration, enlargement and distortion of the brain- stem, and associated cystic, hemorrhagic, or necrotic components. Malignant gliomas tend to show hypoin- tensity on T1- and hyperintensity on T2-weighted images with varying degrees of contrast enhancement. Other fea- tures that can be demonstrated are distortion of the pons with exophytic growth, edema, mass effect, and presence of necrosis and hemorrhages. The fourth ventricle can be displaced posteriorly or assume a slit-like shape. With the advent of the neuroimaging studies, patients are usually diagnosed within two months.
Treatment
Brainstem gliomas are very difficult to treat due to their resistance to radiotherapy and poor response to chemo- therapy. Radiation therapy remains the only treatment that is beneficial, at least transiently, in order to arrest the disease progression. Tumors that carry a more favorable prognosis, such as those that arise in the cervicomedullary junction, can be treated surgically with total or partial resection followed by radiothearpy or chemotherapy.
References
Brett, E.M. Paediatric Neurology, ed. 2. New York: Churchill Livingstone, 1991.
Cogen, P.H. and Nolan C.P. Intracranial and intraspinal tumors of children. In: Berg, B.O. (Ed.). Principles of Child Neurol- ogy. New York: McGraw-Hill, 731–748, 1996.
Keating, R.F. et al. Tumors of the Pediatric Central Nervous System. New York: Thieme, 206–220, 2001.
Littman, P. et al. Pediatric Brain Stem Gliomas. Cancer 45:2787–2792, 1980.
Maria, B.L and Menkes, J.H. Tumors of the Nervous System.
In: Menkes, J.H. and Sarnat, H.B. (Eds.). Child Neurology, ed. 6. Philadelphia: Lippincott Williams & Wilkins, 787–858, 2000.
Maria, B.L. et al. Brainstem and other malignant gliomas: II.
Possible mechanisms of brain infiltration by tumor cells. J.
Child. Neurol. 8:292–305, 1993.
Munsat, T.L. Primary brain tumors in children and adolescents.
Continuum, Part A 1:48–52, 1994.
Packer, R.J. Brainstem gliomas in childhood. Neurobase MedLink; Arbor, 2000.
Strange, P. and Wohlert, L. Primary brainstem tumors. Acta Neurochirurg. 62:219–232, 1982.
