Color Atlas of Neurology

Normal PrPc synthesis

Infectious prion disease

Continuous sharp wave complexes (CJD)

Creutzfeldt-Jakob disease (CJD)

Spontaneous conversion of 6PrP zu PrPsc

Hereditary prion disease

Dementia,

ataxia,

myoclonus, visual disturbances, behavioral changes

Symptoms and Signs

The clinical manifestations of a brain tumor may range from a virtually asymptomatic state to a constellation of symptoms and signs that is specific for a particular type and location of lesion. The only way to rule out a brain tumor for certain is by neuroimaging (CT or MRI).

! Nonspecific Manifestations

Tumors whose manifestations are mainly nonspecific include astrocytoma, oligodendroglioma, cerebral metastasis, ependymoma, meningioma, neoplastic meningitis, and primary CNS lymphoma.

Behavioral changes. Patients may complain of easy fatigability or exhaustion, while their relatives or co-workers may notice lack of concentration, forgetfulness, loss of initiative, cognitive impairment, indifference, negligent task performance, indecisiveness, slovenliness, and general slowing of movement. Such manifestations are often mistaken for signs of depression or stress. Apathy, obtundation, and somnolence worsen as the disease progresses. There may also be increasing confusion, disorientation, and dementia.

Headache. More than half of patients with brain tumors suffer from headache, and many headache patients fear that they might have a brain tumor. If headache is the sole symptom, the neurological examination is normal, and the headache can be securely classified as belonging to one of the primary types (p. 182 ff), then a brain tumor is very unlikely. Neuroimaging is indicated in patients with longstanding headache who report a change in their symptoms. The clinical features of headache do not differentiate benign from malignant tumors.

Nausea, vertigo, and malaise are frequent, though often vague, complaints. The patient feels unsteady or simply “different.” Vomiting (sometimes on an empty stomach) is less common and not necessarily accompanied by nausea; there may be spontaneous, projectile vomiting.

may be present earlier in milder form. Hemiparesis, aphasia, apraxia, ataxia, cranial nerve palsies, or incontinence may occur depending on the type and location of the tumor.

Intracranial hypertension (elevated ICP) (p. 158) may arise without marked focal neurological dysfunction because of a medulloblastoma, ependymoma of the fourth ventricle, cerebellar hemangioblastoma, colloid cyst of the 3rd ventricle, craniopharyngioma, or glioblastoma (e. g. of the frontal lobe or corpus callosum). Cervical tumors very rarely cause intracranial hypertension. Papilledema, if present, is not necessarily due to a brain tumor, nor does its absence rule one out. Papilledema does not impair vision in its acute phase.

! Specific Manifestations

Some tumors produce symptoms and signs that are specific for their histological type, location, or both. These tumors include craniopharyngioma, olfactory groove meningioma, pituitary tumors, cerebellopontine angle tumors, pontine glioma, chondrosarcoma, chordoma, glomus tumors, skull base tumors, and tumors of the foramen magnum. In general, these specific manifestations are typically found when the tumor is relatively small and are gradually overshadowed by nonspecific manifestations (described above) as it grows.

Early papilledema

(irregular margins, disk elevation, reduced venous pulsation)

Peripapillary hemorrhage

Advanced papilledema

Incontinence, focal neurological signs

Hemorrhage

Blurring of disk

Fully developed margins papilledema

Nausea, vomiting

Vertigo, unsteady gait

Benign Brain Tumors

! Astrocytoma (WHO grades I and II)

Astrocytomas arise from blastomatous astrocytes. They are classified as benign (WHO grade I) or semibenign (WHO grade II) according to their histological features (p. 377).

Pilocytic astrocytoma (WHO grade I) is a slowly growing tumor that mainly occurs in children and young adults and usually arises in the cerebellum, optic nerve, optic chiasm, hypothalamus, or pons. It is not uncommonly found in the setting of neurofibromatosis I. There may be a relatively long history of headache, abnormal gait, visual impairment, diabetes insipidus, precocious puberty, or cranial nerve palsies before the tumor is discovered.

Low-grade astrocytoma (WHO grade II). Fibrillary astrocytoma is more common than the gemistocytic and protoplasmic types. These tumors most commonly arise in the frontal and temporal lobes and often undergo malignant transformation to grades III and IV over the course of several years. They may be calcified. They may produce epileptic seizures and behavioral changes.

Oligodendroglioma (WHO grade II) usually appears in the 4th or 5th decade of life. It tends to arise at or near the cortical surface of the frontal and temporal lobes and may extend locally to involve the leptomeninges. Oligodendrogliomas are often partially calcified. Tumors of mixed histology (oligodendrocytoma plus astrocytoma) are called oligoastrocytomas.

Pleomorphic xanthoastrocytoma (WHO grade II) is a rare tumor that mainly arises in the temporal lobes of children and young adults and is associated with epileptic seizures in most cases. It can progress to a grade III tumor.

! Meningioma (WHO grade I)

CNS but are most often found in supratentorial (falx, parasagittal region, sphenoid wing, cerebral convexities), infratentorial (tentorium, cerebellopontine angle, craniocervical junction), and spinal locations. Multiple or intraventricular meningioma is less common. Extracranial meningiomas rarely arise in the orbit, skin, or nasal sinuses. Familial meningioma is seen in hereditary disorders such as type II neurofibromatosis.

! Choroid Plexus Papilloma (WHO grade I)

This rare tumor most commonly arises in the (left) lateral ventricle in children and in the 4th ventricle in adults. Signs of intracranial hypertension, due to obstruction of CSF flow, are the most common clinical presentation and may arise acutely.

! Hemangioblastoma (WHO grade I)

These solid or cystic tumors usually arise in the cerebellum (from the vermis more often than the hemispheres) and produce vertigo, headache, truncal ataxia, and gait ataxia. Obstructive hydrocephalus may occur as an early manifestation. 10% of cases are in patients with von Hip- pel–Lindau disease (p. 294).

! Ependymoma (WHO grades I–II)

Ependymomas most commonly arise in children, adolescents, and young adults. They may arise in the ventricular system (usually in the fourth ventricle) or outside it; they may be cystic or calcified. Subependymoma of the fourth ventricle (WHO grade I) may appear in middle age or later. Spinal ependymomas may arise in any portion of the spinal cord.

Metastatic Disease

Metastases spread to the nervous system through the bloodstream (cerebral, spinal, and leptomeningeal metastases), lymphatic vessels (metastases to the PNS), and cerebrospinal fluid (so-called drop metastases in the spinal subarachnoid space). Aside from direct metastatic involvement, the nervous system can also be affected by local tumor infiltration (e. g., of the brachial plexus by a Pancoast tumor), by external compression (e. g., of the spinal cord by a vertebral tumor, or of a peripheral nerve by a tumor-infiltrated lymph node), or by perineural infiltration (e. g. melanoma or salivary gland carcinoma). Only a small fraction of proliferating tumor cells are capable of metastasizing; thus, the biological behavior and drug response of metastasizing cells may differ from that of the primary tumor. Angiogenesis is essential for tumor growth and metastasis. Local invasion of surrounding tissue by the primary tumor makes it possible for tumor cells to break off and metastasize by way of the lymphatic vessels, veins, and arteries. Metastatic cells often settle in a vascular bed just downstream from the site of the primary tumor, thus (depending on its location) in the lungs, liver, or vertebral bodies. The nervous system may become involved thereafter in a second phase of metastasis (cascade hypothesis), or else directly, in which case the metastasizing cells must have passed through the intervening capillary bed without settling in it. Metastases may also bypass the lungs through a patent foramen ovale (paradoxical embolism).

! Intracranial Metastases

are usually asymptomatic. Skull base metastases cause pain and cranial nerve deficits. Dural-based metastases may compress or infiltrate the adjacent brain tissue, or exude fluid containing malignant cells into the subdural space. Pituitary metastases (mainly of breast cancer) cause endocrine dysfunction and cranial nerve deficits.

! Spinal Metastases

The clinical manifestations of vertebral metastases, including vertebral or radicular pain, paraparesis/paraplegia, and gait ataxia, are mainly due to epidural mass effect. The bone marrow itself being insensitive to pain, pain arises only when the tumor compresses the periosteum, paravertebral soft tissue, nerve roots, or spinal cord. Spinal instability and pathological fractures cause additional pain. Pain in the spine may be the first sign of spinal metastasis. Subarachnoid and intramedullary metastases are rare (!5%).

!Leptomeningeal Metastases (Neoplastic Meningeosis, “Carcinomatous Meningitis”)

Seeding of the meninges may be diffuse or multifocal. Meningeal metastases may spread into the adjacent brain or spinal cord tissue, cranial nerves, or spinal nerves. Cerebral leptomeningeal involvement produces headache, gait ataxia, memory impairment, epileptic seizures, and cranial nerve deficits (e. g., facial nerve palsy, hearing loss, vertigo, diplopia, and loss of vision). Spinal involvement produces neck or back pain, radicular pain, paresthesia, paraparesis, and atony of the bowel and bladder.