Bacterial Meningitis

Overview of Canine and Feline Bacterial Meningitis

Cause: Bacterial meningitis is caused by a variety of pyogenic bacteria that enter the subdural space. Organisms are usually microfloral species or from environmental contamination of penetrating objects.

Affected Hosts: Dogs and cats of all ages are affected.

Geographic Distribution: Worldwide

Mode of Transmission: Bacteria can spread to the meninges from (1) sites of infection in the nasal sinuses, retrobulbar tissues, or middle or inner ear when host immune defenses are compromised; (2) sites of traumatic focal penetration; (3) sites of infection in adjacent venous sinuses or bony structures; or (4) via hematogenous arterial dissemination.

Major Clinical Signs: Fever, reluctance to move, stiff gait, and muscle spasms are the most common clinical signs. Paraspinal hyperesthesia and progressive neurologic dysfunction are progressive features.

Differential Diagnoses: Meningeal inflammation caused by nonbacterial microorganisms and immune-mediated causes should be considered. Myeloid or lymphoid neoplasias that affect the meninges may cause similar diffuse signs of inflammation.

Human Health Significance: None. The organisms that cause bacterial meningitis are indigenous microflora or environmental contaminants. Precautions should always be taken in collecting or handling cerebrospinal fluid potentially laden with microorganisms during diagnostic medical procedures.

Etiology and Epidemiology

Bacterial meningitis involves inflammation of the subdural covering of the brain and spinal cord, including the arachnoid membrane, subarachnoid space, pia mater, and cerebrospinal fluid (CSF), in response to a bacterial infection. The subarachnoid space projects into the nervous tissue alongside penetrating blood vessels. Bacterial infections can spread into the meningeal spaces from natural orifices such as the nasal sinuses, retrobulbar tissues,1–3 and middle or inner ear.⁴ Bacteria that proliferate in middle or inner ear infections can enter the cranial vault and produce cranial meningitis or subdural abscess formation (empyema) and, frequently, central vestibular dysfunction.^5–8 Bacteria can also enter the meningeal spaces through traumatic focal penetration (foreign bodies or bite wounds),^9,10 spread from sites of infection in adjacent venous sinuses or bony structures, or spread via hematogenous arterial dissemination.^11,12 Vascular spread can result in lodgment of bacteria in the endothelial cells of capillaries or the choroid plexus, which results in bacterial invasion of the parenchyma of the central nervous system (CNS) or colonization of the CSF, respectively. In the CSF, bacteria have adequate nutrients and a paucity of phagocytes and immunoglobulin, and they can proliferate, which produces a progressive inflammatory process that can readily spread along CSF pathways.

Bacteria that cause meningitis in dogs or cats are varied and can include aerobic, microaerophilic, and anaerobic species. Staphylococci, streptococci, Pasteurella spp., Actinomyces spp., Nocardia spp., and a variety of anaerobic bacteria have been isolated.5,13–15

Clinical Features

Signs and Their Pathogenesis

On entry into the CSF, bacteria can replicate to a moderate degree before they trigger a host protective response, because the immune response in this area is slow. The immune response of the host, rather than virulence of the pathogen, is usually responsible for most of the subsequent pathologic events. Toll-like receptors (TLRs), which are present on astrocytes, neurons, microglia, and oligodendrocytes, initiate innate recognition of the microorganisms. TLR signals initiate the release of a wide variety of proinflammatory mediators including reactive intermediates, cytokines, and chemokines within the CNS tissues and CSF spaces.¹⁶ Within the nervous tissue, inflammatory processes lead to increased expression of TNF-α; thus, higher CSF concentrations of TNF-α have been used to distinguish bacterial from aseptic meningitis in humans.^17,18 Immunologic damage to bacteria leads to the release of breakdown products into the CSF and local CNS tissue. This further stimulates release of cytokines and prostaglandins, which are chemotactic for leukocytes and contribute to meningeal and ependymal inflammation. Subsequent inflammation leads to vascular injury and vascular thrombosis; tissue inflammation, edema, and necrosis; and increased CNS pressure within the confines of the dura mater and bony spaces. Inflammatory processes may also lead to adhesions and obstruction to CSF flow, resulting in obstructive internal or external hydrocephalus.¹⁹

Hyperesthesia from nerve root irritation is an important clinical sign of meningitis from any cause. Any stretching of extremities or palpation of muscles, especially of the paraspinal region, can lead to hyperesthesia and muscle spasm. The gait of animals with meningitis is often choppy and stiff. With progression, the inflammatory process may penetrate the spinal cord and brain parenchyma, which results in additional neurologic deficits. Manifestations of intracranial deficits include seizures, behavioral abnormalities, and progressive decline in mental status until coma occurs.

Physical Examination Findings

Elevated rectal temperature may be found on examination because of fever, as well as excessive muscular exertional activity. Animals walk with a short stiff stride. Often the back of affected dogs is arched and the neck is outstretched with the head pointing in a downward direction. Paraspinal and extremity hyperesthesia is present with limb and spinal manipulation (Figure 90-1). When inflammation is confined to the meninges, postural reactions that involve motor responses are often stilted. As the inflammation progresses into the CNS parenchyma, deficits in sensory and motor responses are observed. Delayed placing reactions, paresis, and ataxia can be observed if cerebrospinal pathways are affected. Cranial nerve deficits are often observed on neurologic examination. Further signs of cerebral dysfunction include signs such as altered mentation (depression, aggression) or seizures. Myotatic and flexor reflexes may be difficult to elicit because of increased muscle tone from the animal’s extreme tenderness and unwillingness to relax. Loss of reflex function occurs if spinal nerves become damaged in the inflammatory process.

Diagnosis

Inflammation or compression of muscle, bone, and joints can be initially confused with that of nerve root or peripheral nerve inflammation. The differential diagnosis for bacterial meningitis includes other infectious causes of meningeal irritation including that caused by viral, rickettsial, fungal, protozoal, and algal organisms (Table 90-1).²⁰ Feline infectious peritonitis is probably the most common cause of meningomyelitis in cats.^21,22 When parenchymal neurologic dysfunction is apparent, such as evidenced by delayed placing reactions, then protozoal meningoencephalomyelitis should also be considered. Frequently, more localized hyperesthesia associated with upper or lower motor neuron deficits can be observed with epidural empyema, discospondylitis, or paraspinal osteomyelitis. Steroid-responsive meningitis-arteritis in dogs can mimic all the signs of bacterial meningitis.²³ Diseases associated with myositis (such as American canine hepatozoonosis and leptospirosis) can also produce clinical signs that resemble those of meningitis.

TABLE 90-1

Examples of Infectious Agents That Can Cause Meningitis in Dogs and Cats ^∗

	Dogs	Cats
Viruses	Canine distemper virus Arboviruses Suid herpesvirus 1 (pseudorabies)	Feline infectious peritonitis virus Borna disease virus Suid herpesvirus 1 (pseudorabies)
Bacteria	Staphylococcus spp. Streptococcus spp. Pasteurella multocida Enterobacteriaceae (including Salmonella spp.) Actinomyces spp. Nocardia spp. Mycoplasma spp. Anaerobes Brucella canis Bartonella spp.? Borrelia burgdorferi? Leptospira spp.? Anaplasma phagocytophilum? Rickettsia rickettsii Neorickettsia helminthoeca Ehrlichia canis	Streptococcus spp. Pasteurella multocida Nocardia spp. Mycoplasma spp. Anaerobes
Fungi	Blastomyces dermatitidis^† Coccidioides spp. Cryptococcus spp.^† Aspergillus spp.^† Candida spp. Histoplasma spp. Phaeohyphomycoses Hyalohyphomycoses (e.g., Paecilomyces spp.)	Cryptococcus spp.^†
Protozoa	Toxoplasma gondii Neospora caninum Leishmania spp. Balamuthia mandrillaris Acanthamoeba spp.	Toxoplasma gondii
Algae	Prototheca spp.

^∗Many of the listed agents also cause encephalitis or encephalomyelitis in association with meningitis.

^†Via dissemination or cribriform plate destruction as a result of extension of nasal cavity disease.

Laboratory Abnormalities

Although there are no hematologic or biochemical abnormalities that are specific for bacterial meningitis, the CBC may reveal leukocytosis, often with a left shift, especially if the process that leads to the meningitis resulted from hematogenous spread; however, an absence of neutrophilic leukocytosis is common in dogs or cats with meningitis.¹⁵ Serum chemistry abnormalities are variable and nonspecific and can include increased ALT and ALP activities, hyperglycemia, and variable changes in serum electrolytes.

Definitive diagnosis of bacterial meningitis requires evaluation of the CSF. Precautions should be taken not to remove too much fluid if CSF pressures could be increased. If imaging capabilities are available, they should be performed and evaluated before CSF removal, since they may reveal evidence of increased intracranial pressure. However, findings on medical imaging should not be used to eliminate CNS inflammatory disease, because CSF findings have the highest sensitivity for its detection.²⁴ Abnormalities found on CSF analysis in animals with bacterial meningitis usually consist of marked neutrophilic pleocytosis (Figure 90-2), and CSF protein concentration is increased. CSF protein concentration (often >100 mg/dL) and leukocyte numbers (usually >100 cells/µL) tend to be greatest in suppurative meningitis (especially of infectious origin) as compared to other CNS diseases; however, the electrophoretic patterns of the proteins are not specific for a diagnosis.²⁵ Neutrophils generally predominate; however, especially in chronicity or with concurrent antimicrobial use, monocytes, lymphocytes, or eosinophils may be observed. In human bacterial meningitis, glucose levels in the CSF are reduced because of inflammatory cell utilization, and lactic acid levels may be increased. Further studies are needed to determine if these can be used in dogs and cats to differentiate bacterial from other causes of meningeal inflammation. Finding organisms in the CSF on cytologic examination is exceedingly rare, and isolation of organisms in culture is also uncommon despite their visible presence on histopathologic examination.