Analysis of CSF is an invaluable resource in the diagnosis of many primary encephalopathies, but findings are rarely specific, and results must be interpreted considering clinical and MRI findings. Analysis of CSF infrequently provides a definitive diagnosis unless infectious agents such as Cryptococcus spp. (Fig. 30.2) or neoplastic cells are identified. In one report, despite extensive evaluation, a definitive diagnosis could not be made after CSF analysis in 37% of cats.⁹

Treatment is directed at the underlying disease and pharmacologic management of the seizures (Table 30.1). Phenobarbital (PB) is the drug of choice for most feline seizure disorders because of its efficacy, relative safety, ease of administration, and bioavailability. A starting dose of 2.5 mg/kg, administered orally every 12 hours, is recommended, but serum PB concentrations vary greatly among individuals on the same dosage, which suggests there are differences in elimination kinetics.¹⁰ These differences emphasize the need for individual monitoring of cats receiving PB, and cats require more frequent monitoring of PB levels with dogs.¹¹ Elimination of PB may be accelerated in cats receiving glucocorticoids and in kittens, which suggests a probable need for higher dosing in these individuals.¹¹ In a retrospective study of 77 cats receiving PB for control of seizures, adverse effects were reported in 47%; sedation and ataxia were most common.¹² The likelihood of adverse effects increased with increasing drug dose. In most cases, the adverse effects occurred within the first month of treatment and were transient. Serious adverse effects are unusual in cats receiving therapeutic doses of PB but may include thrombocytopenia, neutropenia, facial pruritus, or swelling of the feet. Hepatotoxicity is rare.

Transdermal PB may be an alternative to oral administration to facilitate adherence. In a study of 19 healthy cats, blood levels of PB were studied after transdermal application of PB (9 mg/kg every 12 hours) in pluronic lecithin organogel and Lipoderm Activemax (a proprietary lipophilic cream) vehicles. The authors concluded that therapeutic concentrations of PB could be achieved in most cats with either vehicle with only minor side effects, although there was more individual variation in serum PB concentrations with Lipoderm Activemax.13 In a prospective crossover clinical trial in cats with seizures, transdermal PB in Lipoderm Activemax (median starting dose 18.8 mg/kg/day, divided, every 12 hours) was compared with oral PB (median starting dose 3.8 mg/kg/day, divided, every 12 hours).¹⁴ Therapeutic serum PB concentrations were achieved in some cats with transdermal drug but correlation between the transdermal dosage and serum levels was poor and more dosage adjustments were required with transdermal drug. Despite this, owners preferred transdermal administration and fewer doses were missed than with the oral drug. Close monitoring of seizure control and serum PB concentrations as well as appropriate owner education are necessary with transdermal administration.

The author suggests checking PB levels approximately 10 days after initiation of therapy or after a change in dose, as well as every 4 months along with a CBC, chemistry panel, and assessment of bile acids. The target therapeutic range is a steady-state PB concentration of 15–45 µg/mL. However, hepatotoxicity is more likely at levels >35 µg/mL. Blood samples for analysis can be drawn at any time during the day relative to the time of drug administration.

Potassium bromide (KBr) is commonly used in dogs as an adjunct to PB or as a sole agent in patients with hepatic disease. Although relatively effective for seizure control, KBr has fallen out of favor for cats because of the high incidence of drug-induced eosinophilic pneumonitis associated with its use.¹⁵ Similarly, diazepam, once considered the second line of therapy for controlling seizures in cats, is not recommended owing to the risk of fatal hepatic necrosis associated with oral administration.¹⁶ Zonisamide, a newer anticonvulsant medication, has been used by the author in cats refractory to PB with promising results. Toxicity is reportedly low, but approximately half of cats in one study developed adverse reactions such as anorexia, vomiting, diarrhea, somnolence, and ataxia.¹⁷ Oral zonisamide (2.5 mg/kg, every 12 hours) was studied in eight cats with familial spontaneous epilepsy.¹⁸ The authors concluded that zonisamide may be useful in cats with PB-resistant seizures or in cats that cannot tolerate PB when the blood levels of the drug are within the therapeutic range used for humans and dogs (10–40 µg/mL). Further investigation is needed regarding efficacy and pharmacokinetics of this drug, but anecdotally, a starting dose of 5 mg/kg, administered orally once daily, has proved effective in several cases.

When used as an adjunct to PB therapy in cats with idiopathic epilepsy, LEV is effective and safe.¹⁹ Adverse effects were not reported, and 7 of 10 cats treated experienced >50% reduction in seizure frequency. It is noteworthy that there appears to be no hepatic metabolism of this drug. The suggested starting dose is 20 mg/kg, administered orally every 8 hours. In a study using nine healthy cats, extended-release LEV (500 mg/cat) was administered orally once daily for 10 days.²⁰ Mean trough serum LEV concentrations were >5 µg/mL and adverse effects were minimal. The authors concluded that once daily administration of extended-release LEV may improve client adherence for long-term management of seizures. In another study, transdermal LEV in Lipoderm (60 mg/kg, 400 mg/mL concentration) was applied to the inner pinnae of six healthy cats every 8 hours for 6 days.²¹ Median serum concentrations of LEV were >5 µg/mL and adverse effects were minimal.

Pregabalin may be useful for seizure disorders and in the management of neuropathic pain. While there are no studies assessing the efficacy of this medication in cats, one study evaluated pharmacokinetics after one oral dose of 4 mg/kg. The elimination half-life supported the need for dosing every 12 hours.²² Most cats experienced sedation at this dose, so a lower dose was recommended. An oral dosage of 1–2 mg/kg every 12 hours seems to be an appropriate starting dose, but clients should be advised of the potential for sedation.

Imepitoin has been suggested as a potential treatment for epileptic cats but there is limited data regarding efficacy.²³ In a small study of 8 cats, treatment with oral imepitoin at 30 mg/kg every 12 hours resulted in a seizure-free interval of at least 8 weeks. Side effects were mild and self-limiting and included lethargy, hyporexia, and vomiting. However, due to the small sample size and the short follow-up period, more information is needed before the author can recommend this drug.

The prognosis for seizure disorders depends on the underlying cause and is discussed for individual diseases in detail in the following sections. It is important to note that the severity of seizures does not predict prognosis,¹¹ and cats without other neurologic abnormalities may have excellent outcomes with aggressive management.

Diagnosis of a storage disease can be challenging. An index of suspicion may be raised if an at-risk breed is involved or if there is a history of prior progeny of the same parents being similarly affected. Results of routine hematologic and biochemical testing is usually normal in these patients, although careful examination of blood smears may alert the clinician to the presence of storage vacuoles within leukocytes. Biopsy of lymphoid tissue, including the spleen, or liver may reveal evidence of vacuolation. In some subgroups, such as MPS, connective tissue abnormalities are common and radiography may reveal skeletal abnormalities, particularly of the spine. Muscle biopsies may reveal pathologic changes, particularly with glycogen storage diseases, and peripheral nerve biopsies are recommended in the diagnosis of globoid cell leukodystrophy. Urine metabolic screening is available to identify the presence of urinary excretory products; characteristic excretory profiles have been described for specific diseases. A definitive means of diagnosis is using lysosomal enzyme analysis, in which activity of select lysosomal enzymes in the affected cat are measured against an age-matched control. Affected animals typically have 0% to 5% of the normal activity of the enzyme in question, whereas carrier animals have approximately 50% of normal activity. Molecular genetic testing is increasingly available and is another means of diagnosing this group of disorders. For example, DNA testing is available for MPS VI, GM2 gangliosidosis in Burmese and related breeds, GM1 and GM2 gangliosidosis in Korats, and glycogen storage disease type IV in Norwegian Forest cats. In addition, whole genome sequencing of affected patients is possible in human disease and has been performed for a cat with novel Niemann–Pick type C1.25 More information on testing for storage diseases is found in Chapter 52: Genetics of Feline Diseases and Traits.

Hydrocephalus is one of the more commonly recognized congenital central nervous system (CNS) disorders in young cats, with clinical signs becoming apparent in kittens as young as 2 to 3 months of age.26 Hydrocephalus is also associated with selection for extreme brachycephaly in breeds such as Persians.²⁷ It is characterized by an increase in volume of CSF caused by compensatory or obstructive mechanisms leading to varying degrees of dilation of the ventricular system. Enlargement of the cranium, small stature, an open fontanelle, calvarial distortion, divergent strabismus, abnormal behavior, ataxia, seizures, visual deficits, head pressing, and stupor may all be sequelae to hydrocephalus, depending on the severity of the pathologic changes in the brain. Advanced imaging is necessary to confirm the diagnosis and rule out other causes of intracranial disease. Typical findings on MRI include varying degrees of ventricular dilation, reduction of periventricular white matter, expansion of the cranial cavity, and loss of cortical bone (Fig. 30.4).

Treatment of congenital hydrocephalus may include medical management to reduce CSF volume and production with diuretics and glucocorticoids. Furosemide (0.5 to 4.4 mg/kg, oral, intravenous [IV], intramuscular [IM], every 12 to 24 hours), may be used to decrease CSF production through inhibition of the sodium–potassium cotransport system. Oral acetazolamide (10 mg/kg, every 8 hours) decreases CSF production through inhibition of carbonic anhydrase. Prednisone may also be administered to reduce production of CSF. However, medical management usually provides only temporary relief of clinical signs. Surgical intervention requires placement of a ventriculoperitoneal or ventriculoatrial shunt, with prognosis dependent on the severity of the underlying disease. A review of ventriculoperitoneal shunts in 13 cats with hydrocephalus found complications were most likely during the first 6 months after shunt placement and included coiling of the shunt in subcutaneous (SC) tissue, kinking, and obstruction.28

Cerebellar hypoplasia is a well-recognized syndrome in cats resulting from in utero or perinatal exposure to feline panleukopenia virus. The virus has a predilection for rapidly dividing cells and targets the external germinal layer of the cerebellum. The result is hypoplasia of the granule layer and disorganization of the Purkinje cells (Fig. 30.5), leading to varying degrees of impairment. Clinical signs become evident as soon as the kitten can walk and include a base-wide stance, coarse whole-body tremors, intention tremors, cerebellar quality ataxia, and hypermetria. Neurologic deficits are symmetric and nonprogressive in nature. Depending on severity of disease, a cat may have good quality of life provided adequate measures are taken to prevent injury from falling and the cat is kept indoors. This disorder is best prevented by vaccinating queens before pregnancy. Although similar clinical signs are seen in cats with cerebellar abiotrophy, the two disorders can be readily distinguished. Signs of abiotrophy usually do not become apparent until several months to years of age and are progressive in nature.^29–31

Other congenital anomalies are less well-recognized and occur sporadically from genetic, toxic, or infectious causes:

Meningiomas are the most common primary brain tumor in cats and are mesenchymal in origin, arising from the arachnoid layer of the meninges. Most cases involve older patients with males slightly overrepresented.39 The topography is similar to that of dogs, with most being supratentorial and frequently involving the third ventricle. In cats, there is a tendency for these tumors to be multiple; in one report, 19% of cats had more than one meningioma.⁴⁰ In another report, three cats had two meningiomas, and another cat had four meningiomas.⁴¹ The presence of multiple lesions may result in multifocal signs, confounding the clinical picture and differential diagnosis. However, despite multiple lesions, 75% of cats in one study presented with signs suggestive of a focal lesion.⁴¹

Microscopically, most feline meningiomas are meningotheliomatous or psammomatous (heavily calcified), and many have cholesterol deposits. Clinical signs depend on the location and rate of growth of the tumor but are usually insidious in onset because of the slow growth rate.⁴² In a retrospective study of 42 cases, the median duration of clinical signs before presentation was 1.25 months.⁴³ Signs included mentation changes (100%), visual deficits (93%), paresis (83%), and seizures (19%). If cerebral herniation has occurred, clinical signs may also include ataxia, impaired consciousness, head pressing, torticollis, and personality changes.⁴⁴

Definitive diagnosis of meningioma ultimately requires histopathologic analysis, but advanced imaging (computed tomography [CT], MRI) can be highly suggestive based on the characteristic imaging features and anatomic location. Computed tomography is not as useful for detection of intracranial masses as MRI because of its poor soft tissue detail and lack of ability to identify lesions in the caudal fossa. However, in a study of canine brain tumors, CT correctly predicted histologic type in 86% of cases.⁴⁵ Meningiomas appear isodense to hyperdense, homogenous, and brightly enhanced on CT, and calcification is easily recognized (Fig. 30.6).

Magnetic resonance imaging is considered the superior modality for detecting these tumors. In one study of 33 cats, meningioma was correctly diagnosed on the basis of MRI features alone in 96% of cases.46 Imaging features are variable but include an extra-axial location, distinct margins, mild peritumoral edema, mass effect, dural tail, and broad base (Fig. 30.7). In the study of 33 cats with meningioma, enlargement of the lateral ventricle was present in 64%, and herniation under the tentorium or cerebellum was evident in 63% of cases.⁴⁶ Hyperostosis, frequently seen in the calvarium overlying feline meningiomas, is readily detected by MRI and is reported to occur in approximately 73% of cases.⁴⁶ Results of CSF analysis in cats with meningioma have not been reported, but in dogs they are nonspecific and unlikely to be of diagnostic benefit.

The mainstay of treatment for feline meningioma is surgical removal. Surgery is often successful owing to the superficial location over the cerebral convexities and frontal lobes, the lack of invasion of underlying parenchyma (unlike dogs), and the well-circumscribed nature of these generally benign tumors. Postoperative mortality rates have been reported to be as high as 19%,43 but in the author’s experience and that of other experienced clinicians,⁴² the mortality rate is typically lower. The most common postoperative complication after meningioma excision is anemia, which occurs in as many as one-third of cats.⁴³ Overall, median survival time (MST) in a study of 42 cats was 26 months, with a 1-year survival rate of 66% and a 2-year survival rate of 50%.⁴³ In the same report, 30% of cats developed a recurrence of neurologic signs, with a median time of 30.75 months. In another report of 34 cats with surgically treated meningioma, MST was 685 days, with 20% of cats experiencing a recurrence of clinical signs (median, 285 days).³⁷ Cats with concurrent cerebral herniation may also have good outcomes. Median survival time after surgery for 7 cats with concurrent cerebral herniation was 612 days (range, 55–1453 days).⁴⁴

Data regarding treatment of feline meningioma with radiation or chemotherapy are lacking, probably because of the high success rate and long survival times after surgery. In a study of 22 cats with intracranial tumors treated with radiation therapy, 50% (11 cats) had meningioma.⁴⁷ The mean total dose of radiation was 41 Gy. In all but one cat, neurologic signs improved after therapy. The overall MST was 515 days; data was not reported for individual tumor types.

Definitive diagnosis requires advanced imaging of the brain (CT or MRI) and usually reveals a mass lesion in the sella with dorsal expansion into the overlying diencephalon (Fig. 30.8). The majority of macroadenomas are contrast enhancing and may have areas of necrosis, hemorrhage, or calcification.

Medical management of these tumors is largely unrewarding, and more definitive treatment requires surgical intervention or radiation. In seven cats treated with transsphenoidal hypophysectomy, surgery was well-tolerated in most cases, with clinical signs resolving in five cats and two cats surviving 28 and 46 months after surgery.48 However, surgeons competent in this procedure are lacking, and complications, including chronic oronasal fistula, can have a significant impact on quality of life. Treatment with radiation therapy may ameliorate or resolve clinical signs and has been associated with prolonged survival times in numerous studies.^49,50 Median survival time in a report of eight cats treated with radiation was 17.4 months (range, 8.4 to 63.1 months).⁴⁹ More information on diagnosis and treatment of acromegaly is found in Chapter 27: Endocrinology.

Lymphoma of the brain can be primary or secondary or may be an aspect of multicentric disease. It is seen uncommonly, accounting for only 14.4% of cases in a series of 160 cats with intracranial tumors.37 In a retrospective of 18 cats with CNS lymphoma, 14 had intracranial involvement and 10 presented with a chief complaint of seizures.⁵¹ Most important, the prevalence of involvement of bone marrow and other organs was extremely high, suggesting that perhaps the most reliable means of diagnosing lymphoma in the CNS is through confirming its presence in other body systems.

There are no pathognomonic findings on MRI of cats with intracranial lymphoma, and in some cases, imaging features are similar to those of meningioma.⁴⁶ However, MRI features may aid in presumptive diagnosis when combined with histopathology or cytology.⁵² Analysis of CSF may be highly useful as malignant cells were seen in the CSF of 5 of 11 cats in one report⁵¹ and 6 of 17 in another.⁵³

Although lymphoma is considered sensitive to chemotherapy, prognosis in cats with intracranial disease is guarded, as the MST is approximately 21 days in patients treated with prednisone alone.³⁷ Chemotherapy has not proved to substantially prolong survival times, but when combined with radiation, the MST in one study was 125 days (range, 40 to 210 days).⁵²

The incidence of other types of intracranial tumors in cats is not known, and they are rarely seen in clinical practice. Of 160 cats with intracranial tumors, astrocytoma, oligodendroglioma, olfactory neuroblastoma, and ependymoma accounted for only 7.6% of cases.37 Because of the rarity of these tumors, there is a paucity of information regarding treatment and prognosis.

Gliomas appear to carry a grave prognosis.^37,54 A case series evaluated the pathologic and diagnostic features of 13 cases diagnosed over a 16-year period.⁵⁴ The average age was 8 years and male neutered domestic shorthair cats were overrepresented. Clinical signs had an acute onset and were progressive. Euthanasia was elected in all but one cat. At necropsy, most tumors were in the telencephalon (8/13). Gross changes included well or poorly demarcated, gray to brown, soft, gelatinous masses that were often associated with secondary changes. The 2007 World Health Organization Classification of Tumors of the Central Nervous System was used. Final diagnoses (based on histopathology and immunohistochemistry) were oligodendroglioma (6/13), anaplastic astrocytoma (2/13), and one case each of oligoastrocytoma, anaplastic ependymoma, gliomatosis cerebri, glioblastoma, and anaplastic oligodendroglioma.

A case report of a cat with astrocytoma treated with surgery and radiation had a survival time of only 179 days.³⁷ Another case report described long-term remission with radiation and chemotherapy (nimustine) for a 10-year-old spayed female Abyssinian cat with anaplastic oligodendroglioma.⁵⁵ The cat died 4 years later from tumor lysis syndrome following treatment of a high-grade lymphoma. Ependymomas may have a favorable prognosis and seem to respond well to surgical intervention, with survival times as long as 2 years reported.^37,56

Feline infectious peritonitis (FIP) is the most common and clinically significant inflammatory disorder of the CNS, accounting for 48% of cases of infectious neurologic disease.57 The causative agent, a highly pathogenic variant of feline enteric coronavirus, produces immune-mediated disease through infection of macrophages, with severity of signs determined by host susceptibility, the host-specific immune response, and virus strain.⁵⁸ The majority of cases are younger than 2 years of age and come from multicat households, with male and pedigreed cats being overrepresented.^58,59

Neurologic signs can be seen with both the effusive (“wet”) and the noneffusive (“dry”) form of this disease, but the noneffusive form appears more common in the CNS. Signs referable to cerebellomedullary involvement are most common, but seizures may also be evident and have been reported in up to 25% of cats with histopathologically confirmed FIP.^60,61 Ataxia, spastic paresis, head tilt, nystagmus, hyperesthesia, proprioceptive deficits, blindness, and behavioral changes have all been reported. Nonneurologic signs frequently accompany the CNS signs and include uveitis, chorioretinitis, respiratory infections, mesenteric lymphadenopathy, dehydration, weight loss, lethargy, fever, and pica. In a study of 26 cats with FIP involving the CNS, 20 cats had lesions in multiple organs.⁶⁰ Importantly, rabies was initially suspected in 11 of the cases.

Antemortem diagnosis of FIP can be extremely challenging and requires a high index of suspicion, especially in patients with no obvious systemic involvement. Complete blood count findings are nonspecific, but serum protein concentration is often elevated, specifically the alpha-2, beta, and gamma–globulins. Analysis of CSF in cats with FIP is characterized by increased cellularity (which may be predominantly neutrophilic or mononuclear), as well as protein levels as high as 2 g/L.⁶² The presence of anti-coronavirus antibodies in serum or CSF proves only that the cat has been exposed to a coronavirus and is not a means of definitively diagnosing FIP. In a prospective study of 67 cats, detection of anti-coronavirus antibodies in CSF had a sensitivity of 60% and a specificity of 90%.⁶³

When intracranial FIP is suspected, MRI is useful to help confirm the diagnosis and rule out other causes of neurologic signs (Fig. 30.9). Typical findings include ventricular dilation, ependymitis, choroid plexitis, meningitis (most evident on the ventrocaudal surfaces of the brain), cervical syringomyelia, ventriculomegaly, foramen magnum herniation, and periventricular inflammation.^62,64 However, there are no pathognomonic imaging findings, and results must be considered in light of clinical and clinicopathologic findings. While PCR can be performed on CSF, other fluids (e.g., abdominal effusion), and tissues, sensitivity is relatively low, and a negative test does not necessarily rule out FIP.⁵⁸

Postmortem examination of the brain often reveals gross lesions, including meningeal opacity around the medulla and choroid plexus of the fourth ventricle and coating of the choroid plexuses with a white tenacious exudate. In a description of 15 cases at postmortem, hydrocephalus was identified in 10 cases, cerebellar herniation through the foramen magnum in six cases, cerebral swelling with flattening of gyri in two cases, and accumulation of fibrin within ventricles (two cases) or leptomeninges (one case).60 Ependymal cells may be coated by fibrin and may lead to hydrocephalus rostral to the obstruction. Histologically, there is a severe pyogranulomatous leptomeningitis, choroiditis, ependymitis, and encephalomyelitis, with lesions predominantly surface-oriented. Immunohistochemistry on tissue was found to be sensitive and reliable for confirming the diagnosis in one study.⁶⁰

Development of new antiviral nucleoside analog drugs offers some promise for treatment of FIP. One report of four cats with neurologic FIP treated with GS-441524 (5–10 mg/kg, SC, once daily) for at least 12 weeks demonstrated clinical efficacy for long-term resolution. The authors noted that neurologic FIP cases may require higher doses of the antiviral than nonneurologic cases.⁶⁵ More information on the diagnosis and treatment of FIP is found in Chapter 39: Viral Diseases.

Clinical findings include fever, pneumonia, icterus, abdominal discomfort, dyspnea, pericardial effusion, ascites, pancreatitis, and mesenteric lymphadenopathy. Lesions in the CNS are uncommon, accounting for only 7 of 100 cats with histologically confirmed toxoplasmosis in one report.66 Clinical signs of CNS involvement are often multifocal and include seizures, blindness, ataxia, abnormal behavior, depression, anisocoria, head tilt, and nystagmus.

Antemortem diagnosis can be challenging. Serum antibody tests (IgG, IgM) are not useful, but a negative test can help rule out toxoplasmosis. Results of CSF antibody testing must be interpreted cautiously because T. gondii–specific IgG has been found in the CSF of normal cats. T. gondii can be detected in CSF with PCR testing, and results were found to be positive in seven of seven cats with immunohistochemical or serologic evidence of toxoplasmosis.⁶⁷ In rare cases, organisms may be seen directly in CSF (Fig. 30.10) or other biologic material, such as bronchoalveolar lavage fluid.

Fungal infections are occasionally identified in the CNS of cats, with Cryptococcus neoformans being the most often reported. Because cats with cryptococcosis frequently are infected through inhalation of unencapsulated organisms, it is not unusual for the cat to have concurrent upper respiratory signs as well as swelling of the nose. Clinical signs usually reflect a multifocal process, but forebrain signs may predominate because of the route of entry. When present, pain may be localized to the thoracolumbar spine or pelvic limbs.68 Ocular involvement often accompanies lesions in the CNS, with organisms being found between the choroid and the retina. There is no significant age or sex predilection, and both indoor and outdoor cats can become infected.

Definitive diagnosis can be obtained by testing serum with the latex agglutination test for capsular antigen, a test that is both highly sensitive and specific. The latex agglutination test may also be performed on CSF and may be preferable in cats without obvious systemic involvement. Sensitive and specific point-of-care cryptococcus antigen assays for serum are also available.⁶⁹ The organism may be directly visualized in CSF, nasal exudates, skin lesions, urine, and lymph node aspirates. Analysis of CSF in cats with toxoplasmosis may show neutrophilic, eosinophilic, mononuclear, or mixed pleocytosis with elevated protein even if the organism is not seen.

Findings on MRI are variable and may include solitary granuloma, multifocal masses, meningeal inflammation, and enhancement of the ependyma and choroid plexuses.⁶⁸ Histopathologic findings include the presence of numerous, tightly packed organisms filling the subarachnoid space and expanding the sulci with a mild nonsuppurative inflammatory response in the meninges and parenchyma (Fig. 30.11).

The treatment of choice is currently fluconazole (25 to 50 mg orally every 12 hours) because of its ability to cross the blood–brain barrier, its relative safety margin, and its reported efficacy. However, prognosis is considered extremely guarded in cats with CNS involvement and relapses are common. More information on cryptococcosis is found in Chapter 37: Fungal Diseases.

Other fungal infections, such as Blastomyces dermatitidis, Histoplasma capsulatum, and Cladophialophora spp., are sporadically reported in endemic areas and are typically associated with a grave prognosis.^70,71

Borna disease virus (BDV) is the cause of a severe nonsuppurative encephalomyelitis reported in cats in many parts of the world, particularly Europe and Australia. It is most often seen in rural cats that hunt birds and rodents and is characterized by pelvic limb ataxia followed by mentation changes, visual deficits, photophobia, circling, and seizures.72 Clinical signs last from 1 to 4 weeks and usually result in progressive impairment and death, although in some cases recovery is possible. Cats that have recovered may have permanent ataxia, behavioral changes, and polyphagia.

Definitive diagnosis can be difficult, and other causes of multifocal CNS disturbances, such as FIP, must be ruled out. Testing for BDV-specific antibodies has low sensitivity as many affected cats test negative.⁷³ Detection of viral RNA in blood and other body fluids by PCR can be helpful for antemortem diagnosis.⁷³ The disease can be definitively diagnosed only through postmortem examination. Findings include inflammatory changes, mostly in gray matter, perivascular cuffing, and neuronophagia; BDV antigen can be detected in the CNS parenchyma. Prognosis is grave, and there is no known treatment.

Feline spongiform encephalopathy is a neurodegenerative disease caused by a prion (infectious protein) that is also responsible for bovine spongiform encephalopathy (BSE). It is believed to be transmitted in BSE-contaminated food and can cause disease in domestic cats as well as several species of wild cats. The disease is found in countries where BSE occurs; most cases have been in the United Kingdom. Clinical signs include behavior changes, gait abnormalities, ataxia, hyperesthesia, head tilt, tremors, and many others. Once clinical signs appear, the disease is fatal within weeks and there is no treatment. The disease is diagnosed postmortem by detecting prions in the CNS with histology and immunohistochemistry.

Many other infectious encephalitides in cats have been reported uncommonly, including rabies, FIV, rickettsial disease, and pseudorabies.

Cerebrovascular accidents (CVAs) are recognized in veterinary medicine with increasing frequency because of the greater availability of MRI. There are two broad categories of CVAs: ischemic stroke, in which a vessel is occluded by thrombus or vasospasm, and hemorrhagic stroke, which arises from rupture of blood vessels into CNS parenchyma or subarachnoid space.79 The incidence of CVA in cats is unknown as the majority of reports in the veterinary literature are based on canine studies. Risk factors include hyperfibrinogenemia, polycythemia, coagulopathies, neoplasia (e.g., intravascular lymphoma), hypertension, multiple myeloma, cardiac disease, infectious diseases (e.g., FIP), renal disease, vasculitis, and others.^79–81 Postanesthetic cerebellar ischemia has been reported in Persian cats after anesthesia with ketamine.⁸²

Clinical signs reflect the location and extent of the affected area and are usually acute in onset and asymmetric, with minimal progression after the first 24 hours. The cerebellum is the most common site for vascular accidents to occur,⁸³ but the cerebral hemispheres and thalamus are also frequently affected. A minimum database in any cat with suspected brain infarction should include a CBC, chemistry panel, FeLV and FIV testing, urinalysis, thyroid panel if applicable, coagulation profile if applicable, multiple blood pressure measurements, electrocardiogram, and possibly thoracic radiographs and abdominal ultrasound. If cardiomyopathy is suspected, echocardiography should also be performed. Definitive diagnosis requires advanced imaging of the brain; MRI is considered the superior modality for detecting intracranial infarction (Fig. 30.12). Findings vary depending on the amount of time that has elapsed between the onset of the stroke and performance of imaging. Typical abnormalities noted on MRI include a focal, sharply demarcated lesion that is hyperintense on T2 and FLAIR images, hypointense on T1, with a discrete cutoff between normal and abnormal tissue. Mass effect or midline shifting is usually not seen, and there is minimal, if any, contrast enhancement.

A unique vascular disorder of the CNS, ischemic encephalopathy is well-described in cats and is thought to be related to Cuterebra spp. larvae myasis.84 Affected cats typically have access to the outdoors and present in summer and early fall with unilateral prosencephalic signs, including progressive seizures, behavior changes (often aggression), blindness, and depression. In some cases, neurologic signs are preceded by signs of upper respiratory tract disease, including sneezing. Abnormal rectal temperature, either hyperthermia or hypothermia, has been noted.

No findings on routine hematology and CSF analysis are specific for this disorder. Parasitic track lesions as well as cerebrocortical degeneration caused by toxin release from the parasite may be seen on MRI (Fig. 30.13). Grossly, marked atrophy of the affected cerebral hemisphere can be apparent (Fig. 30.14). Vasospasm secondary to release of toxin produced by the parasite results in infarction in the region perfused by the middle cerebral artery or its branches. Histologic findings include parasitic track lesions, superficial laminar cerebrocortical necrosis, cerebral infarction, subependymal rarefaction, and subpial astrogliosis.⁸⁵ Larvae are most commonly found in the olfactory bulbs and peduncles, optic nerves, and cribriform plate, suggesting entry from the nasal cavity.