CNS Pathology

·         BRAIN HERNIATIONS are classified according to the area of the brain that is herniated.

1.       Subfalcine herniations are caused by herniation of the medial aspect of the cerebral hemisphere (cingulate gyrus) under the falx, which may compress the anterior cerebral artery. Leg weakness and bladder abnormalities are features.

2.       Transtentorial herniation, which occurs when the medial part of the temporal lobe (uncus) herniates over the free edge of the tentorium, may result in compression of the oculomotor nerve, which results in pupillary dilation and ophthalmoplegia (the affected eye points “down and out”). Tentorial herniation may also compress the cerebral peduncles, within which are the pyramidal tracts. Ipsilateral compression produces contralateral motor paralysis (hemiparesis), while compression of the contralateral cerebral peduncle against Kernohan’s notch causes ipsilateral hemiparesis. Further caudal displacement of the entire brainstem may cause tearing of the penetrating arteries of the midbrain (Duret hemorrhages). This caudal displacement may also stretch the trochlear nerve (cranial nerve VI), causing paralysis of the lateral rectus muscle (the abnormal eye turns inward).

Ipsilateral third nerve findings (pupillary dilation, ptosis, loss of medial gaze) and contralateral hemiparesis and decerebrate posturing.

3.       Masses in the cerebellum may cause tonsillar herniation, in which the cerebellar tonsils are herniated into the foramen magnum. This may compress the medulla and respiratory centers, causing death. Tonsillar herniation may also occur if a lumbar puncture (LP) is performed in a patient with increased intracranial pressure. Therefore, before performing an LP, check the patient for the presence of papilledema. Abnormalities of tone, bradycardia, hypertension, and progressive respiratory distress (Cushing's triad).

·         Astrocytomas, the most common primary brain tumors in adults, range from low-grade to very high-grade (glioblastoma multiforme). These grades of astrocytomas include

grade I (the least aggressive and histologically difficult to differentiate from reactive astrocytosis),

 grade II (some pleomorphism microscopically),

grade III (anaplastic astrocytoma, characterized histologically by increased pleomorphism and prominent mitoses), and

grade IV (glioblastoma multiforme). Glioblastoma multiforme is a highly malignant tumor characterized histologically by endothelial proliferation and serpentine areas of necrosis surrounded by peripheral palisading of tumor cells. It frequently crosses the midline (“butterfly tumor”).

In contrast, schwannomas generally appear as extremely cellular spindle cell neoplasms, sometimes with metaplastic elements of bone, cartilage, and skeletal muscle.

Medulloblastomas occur exclusively in the cerebellum and microscopically are highly cellular with uniform nuclei, scant cytoplasm, and, in about one-third of cases, rosette formation centered by neurofibrillary material.

Oligodendrogliomas, which are marked by foci of calcification in 70% of cases, commonly show a pattern of uniform cellularity and are composed of round cells with small dark nuclei, clear cytoplasm, and a clearly defined cell membrane.

Ependymomas are distinguished by ependymal rosettes, which are ductlike structures with a central lumen around which columnar tumor cells are arranged in a concentric fashion.

·         Dorsal midbrain syndrome (Parinaud’s syndrome) affects the superior colliculus and pretectal areas (producing paralysis of upward and downward gaze) and obstructs the cerebral aqueduct (producing a noncommunicating hydrocephalus). Parinaud’s syndrome is frequently the result of a tumor of the pineal.

·         The microscopic changes produced by global hypoxia are grouped into three categories. The earliest histologic changes, occurring in the first 24 h, include the formation of red neurons (acute neuronal injury), characterized by eosinophilia of the cytoplasm of the neurons, followed in time by pyknosis and karyorrhexis. The Purkinje cells of the cerebellum and the pyramidal neurons of Sommer’s sector in the hippocampus are particularly sensitive to ischemic damage and are most likely to demonstrate these early changes. The last two microscopic categories of global hypoxic change are subacute changes, which occur at 24 h to 2 weeks, and repair, which occurs after 2 weeks. Subacute changes include tissue necrosis, vascular proliferation, and reactive gliosis, while repair is characterized by the removal of the necrotic tissue.

·         The “alien hand” syndrome is an unusual neurologic disorder in which one of the patient’s hands seems to have a life of its own; that is, the patient does not recognize their hand as being a part of his own body and they can’t control movement of the hand or arm. There are many different causes of the “alien hand,” such as damage to the anterior part of the corpus callosum. However, the combination of “alien hand” along with extrapyramidal rigidity, sensory cortical dysfunction, and tau-positive inclusions in astrocytes, oligodendroglia, and neurons, is most suggestive of corticobasal degeneration. The cortical dysfunction seen in this syndrome includes disorders of language and apraxia, which is the inability to carry out learned movements.

·         Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system that results from infection of oligodendrocytes by the JC polyomavirus. Signs and symptoms of PML are varied but include dementia and ataxia along with abnormal vision and speech. The pathognomonic feature of PML is the oligodendrocytes in areas of demyelination, which have a “ground-glass” appearance of their nuclei due to infection with the viral particles. PML occurs as a terminal complication in immunosuppressed individuals, especially individuals with AIDS.

·         Patients with CJD initially have subtle changes in memory and behavior, which are followed by a rapidly progressive dementia and death within several months. Microscopically, there is characteristic spongiform change in the gray matter (“cluster of grapes” vacuolation) without inflammation.

·         Primitive neuroectodermal tumors (PNETs) are a type of malignant embryonal tumor that can be found at sites within or outside of the central nervous system. An example of a PNET located outside of the CNS is Ewing’s sarcoma of bone. PNETs of the CNS can be divided into supratentorial tumors (sPNET) and infratentorial tumors (iPNET). The latter are also called medulloblastomas, these tumors being the most common tumor located in the posterior fossa of a child. They usually arise in the midline of the cerebellum (the vermis) but in adults, where the incidence is much less than in children, they are more apt to arise in the cerebellar hemispheres in a lateral position. Medulloblastomas grow by local invasive growth and may block cerebrospinal fluid circulation (CSF block) via compression of the fourth ventricle. Recently, aggressive treatment with the combined modalities of excision, radiotherapy, and chemotherapy has improved survival rates.

Dysembryoplastic neuroepithelial tumor (DNT) and primary brain germ cell tumor (PBGCT) are also tumors that are more common in children. DNT is a low-grade tumor that is most commonly located in the superficial portions of the temporal lobe, while PBGCTs are located most often in the pineal and suprasellar region.

·         Histologically, oligodendrogliomas consist of sheets of cells with clear halos (“fried-egg” appearance) and various amounts of calcification (which can be seen on x-ray)