Idiopathic vestibular disease:

1) Acute to peracute in onset; often peaking in less than 24 hours. In cats occurs most frequently in late spring, summer, and early fall, but may occur any time of year.

2) No age predilections in cats; but in dogs middle or older age.

3) Common, accounting for 39% of all canine vestibular cases, probably a higher percentage in cats.

4) Clinical signs include: loss of balance, severe (often incapacitating) disorientation, ataxia, nystagmus, and head tilt. Nausea may be seen initially and many patients (about 25% in my experience) vomit during the first 24 hours. Signs stabilize rapidly, nystagmus disappears over several days. The ataxia gradually resolves over 3-6 weeks.

5) Diagnostic testing is generally normal, with the possible exception of the brain stem evoked response; so the diagnosis is one of exclusion.

SPONTANEOUS FACIAL PARALYSIS:

1) Unilateral or bilateral paralysis of cranial nerve seven (CN 7).

2) Signs: acute onset of facial paralysis (unilateral or bilateral), including loss of eye blink, drooping of lip, and sagging of the ear. Owners often complain of excessive salivation, because of the diminished lip tone. If the lacrimal gland is denervated, the eye on the affected side will be dry as will the nostril on the same side.

3) Clinically may be associated with endocrine dysfunction (hypothyroidism and Cushing's disease primarily) and toxins such as lead poisoning.

4) Most cases appear idiopathic.

BRAIN ABSCESSES: Brain abscesses are focal accumulations of pus in the CNS with clinical signs of a steadily progressive mass lesion. More common in ruminants than other species.

1) Signs begin subacutely, are usually focal in nature and referable to the part(s) of the nervous system involved. There is often a prior history of inner ear, respiratory or oral infection (especially in cattle). Brain abscesses usually progress steadily unless they are being treated.

2) CSF Analysis shows an increased number of WBC, usually PMN'S. You may see phagocytized organisms in the WBC. CSF cultures may be positive and gram stains may reveal the organism in the CSF. CSF protein is usually elevated, with local globulin production. If the abscess is extradural, CSF may be normal. Image enhancing techniques (Computerized Tomography/MRI) localize an abscess.

3) Brainstem abscesses usually arise by direct extension. Hematogenous abscesses are frequently multiple and occur in any part of the brain. Most brainstem abscesses are cerebellopontine in location and arise from otogenic infections. They are usually unilateral

4) Therapy: Antimicrobials are the basis of therapy. The drug should be chosen based on its ability to penetrate the BBB and its availability in both parenteral and oral forms. Use your gram stain to choose the most appropriate drug.

NEOPLASTIC DISORDERS

1) Most common in middle-aged and older animals. Neuroepithelioma’s are frequently seen in juvenile animals, especially the thoracic spinal cord. Signs often transiently steroid responsive but otherwise constantly progressive. Seizures are among the most commonly reported first sign in patients with cerebral neoplasms. Brain stem neoplasms = vestibular signs; which are usually acute in onset. Cerebellopontine angle, you may see paradoxical vestibular syndrome. In spinal neoplasms, the tumor may be quite advanced before clinical signs are seen.

2) CSF Tap: Most patients with CNS tumors will have abnormal CSF, provided CSF is collected downstream from the lesion. May see inflammatory CSF response with Meningiomas and choroid plexus tumors. Elevated CSF protein is generally seen with intramedullary tumors. On electrophoresis, the protein elevations should be primary albumin.

3) Plain skull films usually normal unless bony tumors or meningiomas. Computerized Axial Tomography (CT Scan) and Magnetic Resonance Imaging (MRI) the diagnostic tool of choice.

POLIOENCEPHALOMALACIA (PEM): Most commonly caused by Thiamin Deficiency. Thiamin is an essential, water soluble, B vitamin (B 1) that is a cofactor in the decarboxylation of pyruvate and alpha-ketoglutarate, reactions essential for aerobic metabolism. Thiamin deficiency blocks CNS aerobic metabolism, resulting in glycolysis, CNS lactic acidosis, and neuronal dysfunction. Thiamin cannot be manufactured by mammals, so must be provided in the diet in monogastrics or produced by rumen bacteria in ruminants. Certain fish (e.g.tuna and salmon) contain the enzyme thiaminase. Cats fed these fish may develop thiamin deficiency. Certain diets (e.g. Concentrates used in feedlots) alter rumen microflora, leading to thiamin deficiency. PEM may also be caused by lead poisoning, water deprivation/salt intoxication, and, in ruminants, a high sulfur/low fiber/high carbohydrate diet.

Clinical signs are usually acute in onset and rapidly progressive.

The diagnosis if based primarily on the history.

If treated early and appropriately patients recover completely.

HYPOGLYCEMIA: Glucose deprivation causes neuronal energy depletion, CSF lactic acidosis and severe neurotransmitter alterations. Blood glucose of less than 50 is considered to be abnormal.

Reported causes of hypoglycemia include: laboratory error, improper handling of the blood sample, functional hypoglycemia, idiopathic neonatal hypoglycemia, severe exercise, starvation, severe parasitism (in neonatal animals), glucagon deficiency, epinephrine deficiency, adrenocorticosteroid deficiency, glycogen storage diseases, iatrogenic (insulin overdose), insulin secreting pancreatic tumors, non pancreatic tumors (hepatoma, hepatocellular adenocarcinoma, hepatic hemangiosarcoma, hepatic leiomyosarcoma, splenic hemangiosarcoma, plasma cell dyscrasia, metastatic mammary carcinoma, lymphosarcoma, primary pulmonary carcinoma, salivary adenocarcinoma, and metastatic oral melanoma), and septicemia.

Because two common causes of reported hypoglycemia are misrepresentations of the patient's true state, e.g. laboratory error or improper sample handling, always re-verify your laboratory results, preferably with a new blood sample.

The most commonly seen signs include altered consciousness, shifting focal deficits, collapse and/or seizures, blindness, weakness, and ataxia. Polydipsia and polyuria may occur. The signs are related to rapidity of glucose drop, duration of hypoglycemia, and level of hypoglycemia.

HEPATOENCEPHALOPATHY (HE) may result from: shunting of portal blood, structural liver disease, or urea cycle enzyme deficiency. Explanations for the cause of clinical signs include hyperammonemia, altered BBB permeability, and circulation of abnormal (or false) neuro-transmitters. There is also an accumulation of endogenous benzodiazepine like substances.

Avoid anticonvulsants, especially benzodiazepine derivatives. Patients with HE are at increased risk for drug intoxication. Avoid drugs, especially tranquilizers and or anticonvulsants. If anticonvulsants are needed, carefully monitor serum levels. Administering benzodiazapine-blocking agents may reverse the coma in these patients.

METRONIDAZOLE INTOXICATION: Metronidazole, a nitronidazole antibiotic used to treat anaerobic bacterial and certain protozoal infections, may also produce CNS intoxication as a result of overdosage. The drug crosses the BBB readily, so may accumulate in CNS (which is why it is a good drug for CNS anaerobic infections). The mechanism of CNS intoxication is not understood, but appears dose related.

Both cats and dogs develop CNS metronidazole intoxication. Clinical signs included ataxia, weakness, disorientation, diminished postural reactions, seizures and apparent blindness. Metronidazole had been administered for periods ranging from 5 days to 10 months prior to the onset of signs. The signs are acute in onset. The diagnosis rests primarily on a history of metronidazole being administered in excessive and or chronic doses. Treatment consists of stopping the metronidazole and providing supportive therapy. The patient should begin to improve within 48 hours and a complete recovery is expected.

LEAD POISONING impairs neuronal respiration. Intoxication causes primarily a cerebral disturbance with seizures and behavioral changes; although megaesophagus has been seen. Gastrointestinal signs such as diarrhea are common.

Lead poisoning may be seen at any age, but is more common in younger animals. There appears to be a higher incidence in intact males.

Half of affected cases have nucleated RBCs and 25% have basophilic stippling. The definitive test is to measure blood lead levels. Levels above 40 ug/ml are abnormal in patients with clinical signs.

Therapy consists of administering chelating agents (e.g. Calcium disodium edetate). If lead objects are in the gastrointestinal system they should be removed.

HYDROCEPHALUS is a pathologic accumulation of fluid within the ventricular system of the brain. It may be a primary or a secondary condition, and does not always result in clinical signs.

CEREBELLAR HYPOPLASIA results from failure of cerebellar development in-utero. The condition may be seen in dogs, horses and cattle, but is most common in cats. It may be heritable, result from in-utero viral or toxic injury, or be idiopathic. Inherited cerebellar hypoplasia has been reported in the Airedale, Irish Setter, and Chow Chow dog. In cerebellar hypoplasia, clinical signs are present at birth. Cerebellar Hypoplasia is a diagnosis of exclusion. Viral - Bluetongue, Akabane virus, BVD, Feline Panleucopenia

HYPOMYELINOGENESIS - DYSMYELINOGENESIS: a group of diffuse disorders preferentially affecting fiber tracts of the general proprioceptive system, most commonly seen in Dogs. Oligodendroglial cells may be present in reduced numbers, or normal appearing cells may fail to produce myelin. Since myelin in the peripheral nerves is under separate genetic control, it will be unaffected. Hypomyelination may result from prenatal viral infection occur following infection of oligodendroglial cells. Myelin reduction is often most extensive in the spinal cord, but also occurs in the cerebellum and brainstem. Inherited hypomyelination is seen in Chow Chow dogs. Other affected breeds include samoyeds, lurchers, Weimeraners, Dalmatians, Australian silkie terriers and schnauzers.

At birth or when the animals first walk you will see tremors (myoclonus) of limbs and head. Neurologic signs include a base wide stance and rocking horse gait. Ataxia is pronounced, but there is no weakness. The tremors are enhanced with excitement and movement. Some animals in affected litters appear more ataxic than others. This disease usually affects multiple animals in a given litter. The signs are not usually progressive. Many patients improve over several weeks to months.

Known causes of hypomyelinogenesis/dysmyelinogenesis include inheritance and in-utero infections.

LYSOSOMAL STORAGE DISEASES(LSD): These occur as the result of inherited genetic mutations resulting in dysfunctional enzyme (lysosomal) activity that prevents normal degradation of products of cellular metabolism. Lysosomes are single membrane bound cytoplasmic particles containing hydrolytic enzymes which are present in all cells responsible for degradation of protein, polysaccharides and nucleic acids. They require an acid pH environment for proper functioning. Without normal lysosomal function, metabolic substrates accumulate within cells. Thus, distended cells are the basic cellular pathology. The mechanism of cell injury is poorly understood, but it is proposed that the accumulated metabolic by-products physically interfere with normal cellular function. Intracellular storage material may or may not be demonstrable histopathologically depending upon the its solubility in solutions used during histopathologic preparation. Ultrastructurally the material is contained within membrane bound structures. Pathologically, the gangliosidoses and ceroid-lipofuscinoses are characterized by swollen, vacuolated neurons, while the leukodystrophies are characterized by dysmyelination and degeneration of the white matter.

Typically, these disorders have autosomal-recessive inheritance, affect young animals, and progressively worsen; resulting in death or euthanasia within a year of onset of signs.

CEREBELLAR ABIOTROPHIES are a group of slowly progressive, generally inherited, degenerative diseases of the cerebellum reported in many species and breeds including: dogs (Kerry blue terriers, Gordon setters, Labrador retrievers, golden retrievers, cocker spaniels, cairn terriers, great Danes, Airedales, Finnish harriers, Bern running dogs); and cats.

In most animals signs begin after birth, usually at 2 months of age or older. Normally the disease is confined to the cerebellum, so affected animals show only cerebellar signs. Clinical signs are normally slowly progressive, eventually incapacitating the animal.

INFLAMMATORY DISORDERS usually produce subacute, multifocal symptoms. Although they may occur in any age animal, they are most common in the young. The clinical signs normally progress unless appropriately treated. The disease progression is usually random.

LISTERIOSIS (Circling Disease): A bacterial meningoencephalitis caused by Listeria monocytogenes. Listeria is a gram-positive organism, which normally resides in soil and silage. The disease is usually seen in ruminants; but may occur in cats and dogs. The route of entry appears to be the oral cavity. Abrasions of the mucous membranes allow penetration by the organism. The bacteria travels via a cranial nerve to the brainstem. The signs center around the nerve traveled, usually cranial nerves 5,7,9, and 10.

Young adults are most likely to be affected. The signs start acutely, then progress. The signs are brainstem and include: asymmetric cranial nerve deficits, limb weakness, depression, and vestibular dysfunction. Torticollis, circling, head tilts, ataxia, and weakness are other common signs.

CSF Analysis remains diagnostic test of choice. WBC count increased, with a predominately monocellular pleocytosis. Neutrophils comprise a small percentage of the cell population. Elevated protein CSF cultures are generally unrewarding and the organism is rarely seen on gram stain.

• Listeria monocytogenes - gram positive, hardy, long-lived in environment, found in soil, plants, silage, feces.

• Subclinical infections may be common based on serology

• 7 serotypes and 14 subtypes recognized

• common cause of illness in sheep, cattle, goats, and llamas.

• 3 distinct disease patterns

• septicemia, young ruminants, pigs, rabbits, guinea pigs, birds

• metritis, placentitis, abortion: sheep & cattle

• meningoencephalitis: sheep, goats, cattle and sporadically in other species.

• Episodic in flock

• CNS disease, primarily brainstem

• CSF - mononuclear cells

• Intraaxonal transport of bacteria

RABIES ENCEPHALITIS: a CNS infection caused by a rhabdovirus. Can affect any warm-blooded animal, including man. Once CNS infected, invariably fatal. Transmission through bite wounds; however, aerosol transmission and absorption through mucous membranes is reported. Virus shed up to 13 days before the onset of clinical signs. Drying, lipid solvents and low pH destroy the virus. There appear to be antigenic differences between the rabies viruses found in dogs, bats, foxes, and some other reservoirs.

• Endemic - all continents except Australia

• Most important zoonotic infection in world

• Disease of "Exceptions"

• No typical presentation - diversity of presentations most typical

• Clinical signs usually fatal in 7-10 days (typically 3-4)

• Transmission via saliva

• Most common -traumatic inoculation from carnivore bite

• Aerosol reported in bat caves and laboratory

• Herbivores - usually "dead end" hosts

• All bat types may carry and be asymptomatic

• Incubation

• Short as 1 week

• Long as 1 year +

• Average 1-3 months

• Incubation affected by: viral strain, viral quantity, host age, host immune status, location of viral entry

• Recovery rare - but reported

• Diagnosis

• Negri body inclusions (absent in 15-30% of cases)

• Killing animal before complete clinical course decreases negri bodies

• Pseudo negri bodies found in normal animals

• Immunofluorescence of Brain

• Neonatal mouse innoculation

AUJESKY'S DISEASE (Pseudorabies)herpes virus disease, reservoir is pigs, may occur in dogs and cats. Outbreaks are usually sporadic. Unusual for a herpesvirus because of lack of host specificity. Dogs and cats usually acquire the infection by ingesting infected tissue. Following exposure, the virus spreads centripetally along nerves until it reaches a ganglion; it then enters the spinal cord or brain and spreads throughout the CNS. The viral infection of the ganglion and spinal cord segment initiate the localized or generalized pruritus so characteristic of this disease.

• Endemic in pigs, sporadic in other species

• Herpes suis

• Pigs: embryonic deaths, abortions, neonatal mortality. Adults often asymptomatic carriers: CNS signs do not include pruritis in pigs: respiratory illness and diffuse CNS signs

• Other domestic animals: peracute, fulminant: acute death, pruritis most common in ruminants, dogs, cats - rare in horses: if not acute death, generalize - rapidly progressive CNS disease

INFECTIOUS CANINE DISTEMPER VIRUS ENCEPHALITIS (CDVE) is caused by a paramyxovirus of the morbillivirus group. The virus is antigenically similar to human measles and bovine rinderpest viruses. In CNS, the virus invades glia to produce destruction of white matter. CDVE remains the most common cause of encephalitis in the dog, followed by GME. Although CDVE may occur in any age dog, it is most common in dogs less than one year of age. In puppies systemic illness is frequent, in addition to encephalitis. CDVE involves meninges as well as neuraxis with lesions involving both grey and white matter. The clinical disease differs based on the patient’s age, virus biotype, and unknown host factors. CDV may also cause encephalitis in sea lions, tigers and lions. The neurologic form of CDV may occur in well vaccinated animals, without systemic signs.

Infection is principally through aerosol inoculation. Virus replicates in tonsils and bronchial lymph nodes, then infects lymphocytes which spread the virus. If antibodies fail to develop, clinical disease will occur. Normally, antibodies develop about 9 days following infection. CNS infection appears to occur 14-18 days post infection. If there is an appropriate immune response, the CNS may be spared. Without an immune response, infected lymphocytes enter the CNS either by crossing the BBB or by entering CSF and then crossing the CSF-Brain barrier. Once in the CNS, virus exits lymphocytes and enters glia of white matter. In the glia, the virus replicates and by some unknown mechanism produces demyelination. Some dogs survive the initial infection and then develop partial immunity. These dogs are at risk for later CNS injury from immunopathologic damage to white matter and secondary inflammation.

• Infects dogs and their relatives - includes Mustelidae (ferret, mink, skunk, weasel, otter), Procyanodae (raccoons), marine mammals (typically a related paramyxovirus), large cats.

• Several strains, but one serotype, therefore vaccination with one strain protects against all strains.

• Attenuation of virus is "relative" rather than absolute, therefore vaccination can produce disease. Especially fatal in non-canine species.

• Infection - usually respiratory, may be transplacental, 1 week incubation, virus carried into CNS by infected WBC & platelets

• Systemic phase not always seen.

• CNS infection seen in most cases, lack of clinical signs due to clearing of virus

• CNS signs diverse

• Grey Matter Disease - young dogs (less than 1 year), seizures, cerebral

• White Matter Disease- brainstem, cerebellar disease, any age

• Old Dog encephalitis - grey/white - subcortical cerebral nuclei

Post vaccinal - 1-2 weeks post vaccine; rapidly fatal; most typically due to inadequate attenuation or to patient immunosuppresion

FELINE INFECTIOUS PERITONITIS (FIP): FIP is a corona virus disorder of cats which causes polyserositis with peritoneal and pleural effusions. The virus also produces a nonsuppurative meningoencephalitis in about 63% of cases, with resultant clinical signs in about 29% of cases. This is the most common cause of encephalitis in cats. Signs are multifocal. CSF if profoundly abnormal, but due to excessive viscosity from CSF protein levels, you may not be able to collect fluid.

• Most common encephalitis of cats

• Fatal Arthus-type immune response to infection with a mutant feline enteric corona virus

• Young cats, typically less than 2

• Profound CSF changes

PROTOZOAL ENCEPHALITIS several metazoan, coccidian protozoa are now known to have the capacity to invade and colonize the CNS, e.g. Toxoplasma gondii and Neosporum caninum. Toxoplasmosis and Neosporum caninum may both infect cows, cats, dogs and possibly other species, Sarcocystis neuronii is primarily seen in the horse.

Infection with these coccidian protozoa may occasionally produce neurologic signs, but most cases are subclinical or have systemic illness. In patients with clinically neurologic signs, there are two different illnesses based on age. In adults, there is typically a multifocal histiocytic inflammation and CNS malacia. In animals under six months of age a generalized inflammatory muscle disease (polymyositis) and widespread nerve root inflammation (polyradiculoneuritis) are more likely to result. Protozoal illness is often seen in conjunction with concurrent immunosuppressive illness,e.g., cancer or immunosuppressive therapy.

Serologic confirmation is the definitive antemortem diagnostic tool.

MYCOTIC ENCEPHALITIS may occur in any animal. Fungal organisms which have been reported in the CNS include: Cryptococcus neoformans (the most frequent), Coccidioidomyces immitis, Histoplasma capsulatum, Blastomyces dermatididis, Aspergillus spp., and Mucor spp. Prototheca, an achlorophyllous alga, and Phaeohyphomycosis may also cause a disseminated CNS infection. All fungal organisms can cause encephalitis and chorioretinitis. Other signs vary with the organism. Cryptococcosis is the most frequent mycotic encephalitis and most patients with cryptococcosis will have neurologic signs.

Fungal encephalitis is most common in adults.

Organisms may be seen on cytologic examination, e.g. CSF, especially with Cryptococcal infections. There will be increased numbers of WBCs and increased CSF protein, including elevated globulins. The protein elevations may be so great as to cause the CSF to become gelatinous. Serologic assays are available to test both for antigen of organism and patient antibody against organism.

MENINGITIS: infection/inflammation of the meninges. Includes bacterial, viral, miscellaneous protozoal and Immune-mediated meningitis. A sterile suppurative vasculitis/meningitis has been reported in young dogs, along with a sterile eosinophilic meningitis.

Primary complaint is normally hyperesthesia, neck pain, depression, and fever. A previous history of systemic illness, bite wounds near spine, infections of sinuses and inner ears or other contiguous infections may be uncovered.

CSF should show normal to increased pressure, normal to increased cell number (the cell type will reflect the cause of meningitis), and increased protein. Depending on the etiology, you may find organisms. In the sterile suppurative meningitis of young dogs, the predominant cell type will be mature, healthy appearing neutrophils without organisms. In bacterial meningitis, the neutrophils are often toxic and organisms will be seen.

GRANULOMATOUS MENINGOENCEPHALITIS (GME, INFLAMMATORY RETICULOSIS) probably the second most common inflammatory disease of the canine nervous system. Tends to occur more in female, toy breed dogs. Mostly a disease of young, middle age (1-8 yrs), but may occur at any age. The onset is usually rapid, although indolent cases have been reported. Without treatment, the disease progresses to death within several months, although long term survivals are documented.

Diagnosis confirmed at necropsy or by brain biopsy. On CSF analysis, expect an elevated WBC with a mixture of cell types - predominantly mononuclear cells. Cell number range is great, with high cell numbers common. About 10-20% PMN's, 10-20% monocytes and macrophages and 60-80% lymphocytes and plasma cells. Eosinophils are rare in GME CSF. Large anaplastic looking mononuclear cells may be seen. Protein will be elevated (40-1000 mg/dl), with significant elevation of IgG on electrophoresis. CSF pressure is normal. CSF normalizes rapidly with steroid therapy.

• Inflammatory reticulosis

• Mature, adult dogs primarily; more likely female

• Variable clinical course

• Unique pattern of inflammatory cells accumulated around blood vessels.

Pug Dog Encephalitis

• Younger dogs (9 mo - 19 mo)

• Generalized CNS diseaseß∑

RICKETTSIAL DISEASES including Rocky Mountain Spotted Fever and Ehrlichiosis can produce meningoencephalitis. Signs are result of vasculitis induced meningoencephalitis. Most common neurologic signs are vestibular. Many patients will have thrombocytopenia, leucocytosis and other hematologic evidence of vasculitis. CSF may reveal a mild, nonsuppurative response. The definitive test is serologic evaluation.

Treatment with tetracycline appears effective at resolving both systemic and neurologic signs of rickettsial infection.

IDIOPATHIC TREMOR SYNDROME (White Dog Shaker Syndrome): These patients probably have a more diffuse CNS disorder. The signs are usually acute in onset and for unknown reasons the condition is seen primarily in young to middle aged dogs with white hair coats; especially the Maltese, Westhighland White Terrier; Bichon Frise, and poodle. This condition is highly steroid responsive.