Advanced Diagnostic Techniques in Feline Brain Disease

Clinical signs of brain dysfunction include changes in behavior or mental status, visual and postural reaction deficits, and partial, or generalized seizures. On the basis of signalment, history, and the results of a physical and neurologic examination, it may be possible to localize a lesion to the brain and occasionally to determine an approximate location. A similar neurologic syndrome will result from any one of a number of different diseases occurring at a given location. Many degenerative, metabolic, infectious, inflammatory, toxic, and vascular diseases may result in clinical signs similar to a brain tumor.

Diagnosis of brain disorders

1. Signalment

2. History

3. Physical examination

4. Neurological examination

It should be kept in mind that the neurological examination allows localization of the lesion only. Further diagnostic tests necessary to make the diagnosis include:

1. Minimum data base: CBC, biochemical profile, urinalysis, thoracic radiographs, abdominalultrasound

2. Imaging: CT and or MR; MR is preferred for visualization of soft tissues

3. CT-guided brain biopsy—cytology and histopathology

4. Cerebrospinal fluid (CSF) analysis

5. Serology of serum and CSF

6. Polymerase chain reaction (PCR) test (distemper, FIP, neospora, etc)

7. Necropsy

Differential diagnosis for cerebral dysfunction

The brain is affected by the same degenerative, anomalous, metabolic, nutritional, neoplastic, infectious, inflammatory, idiopathic, traumatic, toxic, and vascular diseases as the rest of the body.

Diagnostic techniques

A minimum data base for an animal with a suspected brain lesion should include a complete blood count, serum chemistry analyses, urinalysis, thoracic radiographs, and abdominal ultrasound. These tests are especially important when a metastatic brain tumor is suspected or when clinical signs of metabolic or endocrine disturbances are present.

Skull radiographs

Radiographs of the skull appear normal in most cats with a brain tumor, however, sometimes hyperostosis or osteolysis of the overlying calvarium may be induced by a meningioma. A modified occipital projection may help in therecognition of hyperostosis. Hyperostosis may be as a result of direct bone invasion of tumor cells, or occur as a purely reactive change without detectable tumor cells in bone. Enlarged vascular channels may be suggestive of a tumor of the dura matter or calvaria and has been reported in association with meningiomas in cats. Occasionally calcification may be evident within a tumor. Survey radiographic abnormalities provide only indirect evidence of the presence of disease and deep seated lesions may not induce any radiographic changes. More advanced imaging is necessary to provide precise information regarding exact location and extent of disease.

Cerobrospinal fluid analysis

Analysis of CSF serves to help rule out inflammatory diseases and may support a tentative diagnosis of an intracranial tumor. The typical result of CSF analysis most often seen in cats with a brain tumor is an increase in protein in the presence of a normal cell count. This is a variable finding, however, and it is possible to have normal results for these tests. Tumor cells rarely are seen in CSF.

Care must always be taken in the collection of CSF, as increased intracranial pressure (ICP) may be present in association with a brain tumor and the removal of CSF may lead to brain herniation. Administration of mannitol and hyperventilation may help to decrease ICP prior to CSF collection.

Advanced imaging

Computed tomography (CT) and magnetic resonance imaging (MRI) provide the information required for accurate recognition of the presence and location of an intracranial mass lesion. The information obtained helps to provide a meansto plan further diagnostic and therapeutic interventions Characteristic CT features of a meningioma include a hyperdense or isodense space-occupying lesion, usually visible on non-contrast CT images, that may contain areas of mineralization. Following contrast administration dense homogeneous enhancement usually occurs. Tumor margins often are smooth, but may be lobulated and peritumoral edema often is evident. Hyperostosis, osteolysis, and apparenttumoral mineralization may be detected. A non-specific sign of a meningioma is evidence of accommodation of the brain to the presence of a long-standing, slow growing, space-occupying lesion. The falx cerebri may become bowed, and the brain may exhibit less shift than would be anticipated for the size of the tumor. Certain other extradural or dural-based lesions of cats may mimic the CT appearance of meningioma.

CT and MRI should be viewed as complementary diagnostic imaging modalities, each with its own advantages and disadvantages. CT is better in the detection of osseous changes, such as skull fractures or sclerotic changes in the tympanic bullae. MRI provides better soft tissue detail than CT and allows visualization of subtle changes accompanying non-enhancing or diffuse brainlesions not easily seen using CT. A percentage of intracranial mass lesions may not be visible by means of CT. The high resolution and soft tissue contrast achieved with MRI is especially useful in the identification of these brain tumors.

Images obtained using MRI are superior to those of CT in certain brain regions (eg, the brainstem), and the diagnostic specificity of MRI may eventually render the biopsy of tumors prior to treatment unnecessary. MRI also allows the secondary effects of a tumor to be assessed and is generally superior to CT in the detection of many of the features associated with brain tumors (eg, edema, cyst formation, changes in vascularity, hemorrhage, and necrosis). Other subtle effects such as displacement of the ventricular system and gyral folds and displacement of the external capsule or herniation of the temporal lobe, also may be visible using MRI. Unlike CT scanning, beam hardening artifact caused by thick compact bone does not occur with MRI.

It must be remembered that non-neoplastic space-occupying lesions may mimic the CT or MR appearance of a neoplasm and that occasionally a metastasis may resemble a primary brain tumor on CT or MR. At the present time, biopsy and/or surgical excision is the sole method available for the diagnosis of brain tumor type in cats.

CT-guided brain biopsy

Although cat meningiomas have characteristic CT and MRI features, occasionally non-neoplastic space-occupying lesions or a metastasis may mimic the CT or MRI appearance of a meningioma. Biopsy of an intracranial lesion may be an important step prior to initiation of any type of therapy. Modification of a CT-guided stereotactic brain biopsy system (Pelorus Mark III; Ohio Medical Instruments) for use in cats and dogs provides a relatively rapid and extremely accurate means of tumor biopsy, with a low rate of complications. Cytological evaluation of brain tumor biopsy samples can be done within minutes of biopsy collection by means of crush preparations.

Intraoperative diagnosis using the smear technique

Rapid cytological evaluation of a brain lesion from a biopsy sample can provide crucial information on operative management, medical management, chemotherapy, or radiation therapy. In people intraoperative cytological evaluation of smear preparations of brain tumors, supported by frozen and paraffin-embedded tissue, has become a routine procedure, and cytologicalprofiles of smears of various types of human brain tumors have been well described. Smear preparations are generally wet fixed in 95% alcohol and stained with hematoxylin and eosin although toluidine blue, geimsa, or Papanicolaou's stain may also be used.

In a recent study, tissue samples wereobtained from lesions either by CT-guided stereotactic brain biopsy (44 samples) or intraoperatively during craniotomy (49 samples) and the results from the smear technique compared with those from sections of paraffin-embedded tissue. The overall diagnostic accuracy from samples obtained by both craniotomy andstereobiopsy was about 80%. This compares favorably with the 69–94% accuracy reported in some large series of human cases. The main advantages of this method of intraoperativediagnosis are speed, ease of preparation, technical simplicity, need for minimal equipment, high degree of cytological resolution compared to frozen preparations, low cost, and small sample size required. A limitation of this system is that it is difficult to prepare adequate smear preparations in certain tough and coherent tumors (eg, schwannomas, fibrillary astrocytomas, and some meningiomas). Smear preparations provide excellent cytologic detail, however, these differ from the conventional histologic appearance of HE-stained paraffin-embedded tissue. Experience is required in the correct interpretation of smear preparations.