History

There are no specifics factors in the patient’s history that are pathognomonic for low-grade glioma. The history, however, should alert the clinician to the presence of a neurologic disorder and the need for an imaging study. Characteristically, low-grade gliomas present with headache, focal deficit and/or, most notably seizures. The latter can be present in up to 80% of patients.^[6]Other common symptoms are secondary to mass effect of the lesion on the surrounding brain parenchyma (ie, hemiparesis, sensory deficits, alterations in speech or visual field defects).

A small percentage of low-grade astrocytomas present in the spinal cord of both children and adults. The history of this tumors is characterized by a slow onset of back pain and neurologic deficits. The pain is usually localized over the region of the tumor, which is most common in the cervicothoracic area. Neurologic symptoms include paresthesias in the arms or legs; weakness, objective numbness, and bowel or bladder symptoms may also be seen.

Patients suffering from low-grade gliomas typically exhibit three clinical stages.^{[45, 44, 46]}The first is a pre-symptomatic stage in which the tumor slowly infiltrates the brain, yet the patient remains largely asymptomatic. This period is usually long, but exceptions do exist. The second is a symptomatic stage that classically starts with a first-time seizure or subtle story of recurrent episodes suggestive of mild evolving epileptic activity secondary to the tumor. Subtle changes in cognitive ability and personality also emerge. The time period for this symptomatic stage is usually between 5 and 10 years. The third state is malignant transformation. Patients deteriorate in their neurological functions in a gradual but progressive fashion, eventually leading to death. This transformation tends to occur as a result of a multifactorial process, including tumor-specific molecular biology and genetics, as well as tumor burden.

This understanding has led to a treatment paradigm that advocates aggressive early treatment and moves away from the watchful waiting approach that was common in the past.

Physical

A comprehensive neurological exam must be performed on any patient who is suspected of harboring an intracranial lesion. In most centers specialized in neurooncology, it is common to use the Karnofsky Performance Score (KPS) in order to assess the functional status of the patient before, during, and after treatment. Cranial nerve deficits are not pathognomonic of low-grade gliomas, but the presence of multiple cranial neuropathies is common with brainstem lesions. The motor and sensory exam may disclose hemiparesis, as well as hemisensory deficits, increased deep tendon reflexes, and signs of corticospinal tract involvement (ie, Babinski reflex). In patients with posterior fossa lesions (which are more common in children), signs of cerebellar involvement like ataxia, intention tremor, and dysdiadochokinesia are common.

Preoperative neuropsychological assessment may be indicated in patients with a lesion close to or in an eloquent region. Eloquent regions are areas of the brain that control speech, motor and sensory functions, visual perception, and higher cortical functions.

Causes

The etiology of low-grade gliomas is poorly understood. There are numerous studies published throughout the literature that have attempted to link specific environmental factors with the subsequent development of brain tumors. Although many potential associations have derived from these studies, the only clear predisposing factor is prior exposure to ionizing radiation. Other factors like socioeconomic status, occupational exposure, and the ingestion of certain types of food (those containing a high concentration of N- nitroso compounds) have not shown conclusively that they could be linked to an increase in the development of gliomas.^[7]

Definitive genetic associations have been made between conditions like neurofibromatosis (NF-1 and NF-2), tuberous sclerosis, Li-Fraumeni syndrome, and Turcot syndrome with the development of gliomas.

Differential Diagnoses

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Media Gallery

A 28-year-old male taxi driver presented to the emergency department after having a seizure. Noncontrast head CT scan was obtained showing the typical appearance of a low-grade astrocytoma. The lesion in the mesial left frontal lobe was hypodense on CT scan.
Preoperative MRI of the brain of a 28-year-old male taxi driver who presented to the emergency department after having a seizure. On T1-weighted sequences, the tumor does not enhance and shows decreased signal intensity compared to normal brain. These findings are consistent with low-grade astrocytoma.
For tumors, MRI has the advantage of showing the lesion in multiple planes. This image, a T1-weighted sagittal image of the brain of a 28-year-old male taxi driver who presented to the emergency department after having a seizure, shows the tumor along the mesial aspect of the frontal lobe. Note that mass effect is minimal, typical of a low-grade lesion.
T2-weighted sequences of an MRI of the brain of a 28-year-old male taxi driver who presented to the emergency department after having a seizure show increased signal intensity compared with normal brain. The radiologic appearance is typical of low-grade astrocytoma.
A 9-year-old boy presented with headaches and gradual onset of right hemiparesis. MRI of the brain was obtained. The T2-weighted sequence in this MRI shows a tumor in the left thalamus, which is a typical location for a juvenile pilocytic astrocytoma. Note the relatively well-circumscribed nature of the lesion.
Coronal T1-weighted gadolinium-enhanced MRI of the brain shows the tumor of a 9-year-old boy who presented with headaches and gradual onset of a right hemiparesis. Note the heterogeneous enhancement of the tumor.
Sagittal T1-weighted MRI of the brain shows juvenile pilocytic astrocytoma of a 9-year-old boy who presented with headaches and gradual onset of right hemiparesis. Stereotactic surgery has made resection of these low-grade tumors in this deep location feasible.
A 3-year-old boy presented with speech regression. MRI of the brain revealed a tumor in the left mesial temporal lobe. This T1-weighted gadolinium-enhanced image shows an enhancing tumor involving the hippocampus, uncus, and amygdala. The surgical pathologic studies revealed a low-grade mixed tumor of astrocytes and atypical neurons, a ganglioglioma.

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Author

George I Jallo, MD Professor of Neurosurgery, Pediatrics, and Oncology, Director, Clinical Pediatric Neurosurgery, Department of Neurosurgery, Johns Hopkins University School of Medicine

George I Jallo, MD is a member of the following medical societies: American Association of Neurological Surgeons, American Medical Association, American Society of Pediatric Neurosurgeons

Disclosure: Nothing to disclose.

Coauthor(s)

David A Chesler, MD, PhD Clinical Assistant Professor of Neurological Surgery and Pediatrics, Stony Brook University Hospital; Co-Director of Pediatric Neurosurgery, New York Spine and Brain Surgery, UFPC

David A Chesler, MD, PhD is a member of the following medical societies: American Association of Neurological Surgeons, American Medical Association, Congress of Neurological Surgeons, International Society of Pediatric Neurosurgery, Medical Society of the State of New York, Suffolk Pediatric Society

Disclosure: Nothing to disclose.

Meleine M Martinez-Sosa, MD Resident Physician, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine

Disclosure: Nothing to disclose.

Nir Shimony, MD Director of Pediatric Neurosurgery, Director of Epilepsy Surgery, Geisinger Health System

Nir Shimony, MD is a member of the following medical societies: American Association of Neurological Surgeons, American Epilepsy Society, Congress of Neurological Surgeons, Society for Neuro-Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Jorge C Kattah, MD Head, Associate Program Director, Professor, Department of Neurology, University of Illinois College of Medicine at Peoria

Jorge C Kattah, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, New York Academy of Sciences

Disclosure: Nothing to disclose.

Chief Editor

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS † Professor Emeritus of Neurology and Psychiatry, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Neuroscience Director, Department of Neurology, Crouse Irving Memorial Hospital

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS is a member of the following medical societies: American Academy of Neurology, American Academy of Pain Medicine, American College of Forensic Examiners Institute, American College of International Physicians, American College of Physicians, American Heart Association, American Stroke Association, National Association of Managed Care Physicians, Royal College of Physicians, Royal College of Physicians and Surgeons of Canada, Royal College of Surgeons of England, Royal Society of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Rodrigo O Kuljis, MD Esther Lichtenstein Professor of Psychiatry and Neurology, Director, Division of Cognitive and Behavioral Neurology, Department of Neurology, University of Miami School of Medicine

Rodrigo O Kuljis, MD is a member of the following medical societies: American Academy of Neurology, Society for Neuroscience

Disclosure: Nothing to disclose.

Eveline Teresa Hidalgo , MD Surgeon, Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center

Eveline Teresa Hidalgo , MD is a member of the following medical societies: Swiss Society of Neurosurgery, Swiss Young Neurosurgeons Society

Disclosure: Nothing to disclose.

Rafael Uribe-Cardenas, MD Resident Physician in Neurosurgery, Department of Neuroscience, Hospital Universitario San Ignacio, Pontificia Universidad Javeriana, Colombia

Rafael Uribe-Cardenas, MD is a member of the following medical societies: Colombian Association of Neurosurgery

Disclosure: Nothing to disclose.

Acknowledgements

Ethan A Benardete, MD, PhD Staff Physician, Department of Neurosurgery, New York University Medical Center

Disclosure: Nothing to disclose.