The diagnosis is considered when a child with congenital rubella develops progressive spasticity, ataxia, mental deterioration, and seizures. Testing involves at least CSF examination and serology. Elevated CSF total protein and globulin and elevated rubella antibody titers in CSF and serum occur. CT may show ventricular enlargement due to cerebellar atrophy and white matter disease. Brain biopsy may be necessary to exclude other causes of encephalitis or encephalopathy. Rubella virus cannot usually be recovered by viral culture or immunohistologic testing.

Diagnosis of BMCF depends on a combination of history and symptoms, histopathology and detection in the blood or tissues of viral antibodies by ELISA or of viral DNA by PCR. The characteristic histologic lesions of MCF are lymphocytic arteritis with necrosis of the blood vessel wall and the presence of large T lymphocytes mixed with other cells. The similarity of MCF clinical signs to other enteric diseases, for example blue tongue, mucosal disease and foot and mouth make laboratory diagnosis of MCF important. The world organisation for animal health recognises histopathology as the definitive diagnostic test, but laboratories have adopted other approaches with recent developments in molecular virology. No vaccine has as yet been developed.

Although no specific treatment exists, the disease can be managed with anticonvulsants, physiotherapy, etc.

While the progression of dysfunction is variable, it is regarded as a serious complication and untreated can progress to a fatal outcome. Diagnosis is made by neurologists who carefully rule out alternative diagnoses. This routinely requires a careful neurological examination, brain scans (MRI or CT scan) and a lumbar puncture to evaluate the cerebrospinal fluid. No single test is available to confirm the diagnosis, but the constellation of history, laboratory findings and examination can reliably establish the diagnosis when performed by experienced clinicians. The amount of virus in the brain does not correlate well with the degree of dementia, suggesting that secondary mechanisms are also important in the manifestation of ADC.

Acute Cerebellar ataxia is a diagnosis of exclusion. Urgent CT scan is necessary to rule out cerebellar tumor or hemorrhage as cause of the ataxia; however in acute cerebellar ataxia, the CT will be normal. CSF studies are normal earlier in the course of disease. Later on CSF shows moderate elevation of proteins.

Supportive treatment is the only intervention for acute cerebellar ataxia of childhood. Symptoms may last as long as 2 or 3 months.

The CDC states that PCR testing from a single blood draw is not sufficiently sensitive for "B." "henselae" testing, and can result in high false negative rates due to a small sample volume and levels below the limit of molecular detection.

"Bartonella" spp. are fastidious, slow-growing bacteria that are difficult to grow using traditional solid agar plate culture methods due to complex nutritional requirements and potentially a low number of circulating bacteria. This conventional method of culturing "Bartonella" spp. from blood inoculates plated directly onto solid agar plates requires an extended incubation period of 21 days due to the slow growth rate.

Bovine malignant catarrhal fever (BMCF) is a fatal lymphoproliferative disease caused by a group of ruminant gamma herpes viruses including Alcelaphine gammaherpesvirus 1 (AlHV-1) and Ovine gammaherpesvirus 2 (OvHV-2) These viruses cause unapparent infection in their reservoir hosts (sheep with OvHV-2 and wildebeest with AlHV-1), but are usually fatal in cattle and other ungulates such as deer, antelope, and buffalo.

BMCF is an important disease where reservoir and susceptible animals mix. There is a particular problem with Bali cattle in Indonesia, bison in the US and in pastoralist herds in Eastern and Southern Africa.

Disease outbreaks in cattle are usually sporadic although infection of up to 40% of a herd has been reported. The reasons for this are unknown. Some species appear to be particularly susceptible, for example Pére Davids deer, Bali cattle and bison, with many deer dying within 48 hours of the appearance of the first symptoms and bison within three days. In contrast, post infection cattle will usually survive a week or more.

"Bartonella" growth rates improve when cultured in an enrichment inoculation step in a liquid insect-based medium such as "Bartonella" α-Proteobacteria Growth Medium (BAPGM) or Schneider’s Drosophila-based insect powder medium. Several studies have optimized the growing conditions of "Bartonella" spp. cultures in these liquid media, with no change in bacterial protein expressions or host interactions "in vitro". Insect-based liquid media supports the growth and co-culturing of at least seven "Bartonella" species, reduces bacterial culturing time and facilitates PCR detection and isolation of "Bartonella" spp. from animal and patient samples. Research shows that DNA may be detected following direct extraction from blood samples and become negative following enrichment culture, thus PCR is recommended after direct sample extraction and also following incubation in enrichment culture. Several studies have successfully optimized sensitivity and specificity by using PCR amplification (pre-enrichment PCR) and enrichment culturing of blood draw samples, followed by PCR (post-enrichment PCR) and DNA sequence identification.

The administration of immunotherapy, in association with chemotherapy or tumor removal, .

Immunosuppressive therapies, encompassing corticosteroids, azathioprine, methotrexate and more recently, rituximab, are the mainstay of therapy. Other treatments include PE, IVIG, and thymectomy. Patients reportedly exhibited a heterogenous response to immunomodulation.

Antiepileptics can be used for symptomatic relief of peripheral nerve hyperexcitability. Indeed, some patients have exhibited a spontaneous remission of symptoms.

AIDS Dementia Complex (ADC) is not a true opportunistic infection; it is one of the few conditions caused directly by HIV itself. However, the cause of ADC can be difficult to discern because the central nervous system can be damaged by a number of other causes related to HIV infection:

- opportunistic infections

- Primary cerebral lymphoma or metastasis of other AIDS-related cancers

- direct effects of HIV in the brain

- toxic effects of drug treatments

- malnutrition

Many researchers believe that HIV damages the vital brain cells, neurons, indirectly. According to one theory, HIV either infects or activates cells that protect the brain, known as macrophages and microglia. These cells then produce toxins that can set off a series of reactions that instruct neurons to kill themselves. The infected macrophages and microglia also appear to produce additional factors such as chemokines and cytokines that can affect neurons as well as other brain cells known as astrocytes. The affected astrocytes, which normally nurture and protect neurons, also may now end up harming neurons. HIV protein gp120 inhibits the stem cells in the brain from producing new nerve cells. In the neuronal cells, the HIV gp120 induces mitochondrial-death proteins like caspases, which may influence the upregulation of the death receptor Fas leading to apoptosis. Researchers hope that new drugs under investigation will interfere with the detrimental cycle and prevent neuron death.

A Canadian paper published in 2015 used a mouse model of chronic hepatitis B infection and showed that interfering with certain proteins can facilitate clearance of the virus which may have implications for human disease.

In March 2015, a group in China published an article regarding the development of a vaccine for hepatitis E. As of March 2016, the United States government was in the process of recruiting participants for the phase IV trial of the drug Hecolin.

At present this can only be made definitively by liver biopsy or post mortem examination. Given the isolation of a causative virus it should soon be possible to diagnose this by serology, polymerase chain reaction or viral culture. On necropsy, the liver will be small, flaccid, and "dish-rag" in appearance. It has a mottled and bile stained surface. On microscopy there is marked centrilobular to midzonal hepatocellular necrosis and a mild to moderate mononuclear infiltrate. Mild to moderate bile duct proliferation may also be present. On radiology, the liver may be shrunken and difficult to visualize on ultrasound. Ascites may be present.

This depends on the degree of hepatocellular necrosis that has occurred. Decreases in the SDH and prothrombin time along with improvement in appetite are the best positive predictive indicators of recovery. GGT may remain elevated for weeks even if the horse is recovering. Horses that survive for greater than one week and that continue to eat usually recover. Cases with rapid progression of clinical signs, uncontrollable encephalopathy, haemorrhage or haemolysis have a poor prognosis. Horses that display clinical signs have a mortality rate of 50–90%.

Due to the importance of disease caused by "S. pneumoniae" several vaccines have been developed to protect against invasive infection. The World Health Organization recommend routine childhood pneumococcal vaccination; it is incorporated into the childhood immunization schedule in a number of countries including the United Kingdom, United States, and South Africa.

Depending on the nature of infection an appropriate sample is collected for laboratory identification. Pneumococci are typically gram-positive cocci seen in pairs or chains. When cultured on blood agar plates with added optochin antibiotic disk they show alpha-hemolytic colonies and a clear zone of inhibition around the disk indicating sensitivity to the antibiotic. Pneumococci are also bile soluble. Just like other streptococci they are catalase-negative. A Quellung test can identify specific capsular polysaccharides.

Pneumococcal antigen (cell wall C polysaccharide) may be detected in various body fluids. Older detection kits, based on latex agglutination, added little value above Gram staining and were occasionally false-positive. Better results are achieved with rapid immunochromatography, which has a sensitivity (identifies the cause) of 70–80% and >90% specificity (when positive identifies the actual cause) in pneumococcal infections. The test was initially validated on urine samples but has been applied successfully to other body fluids. Chest X-rays can also be conducted to confirm inflammation though are not specific to the causative agent.

Because OMS is so rare and occurs at an average age of 19 months (6 to 36 months), a diagnosis can be slow. Some cases have been diagnosed as having been caused by a virus. After a diagnosis of OMS is made, an associated neuroblastoma is discovered in half of cases, with median delay of 3 months.

The interictal EEG pattern is usually normal.

In October 2007 an astute medical interpreter noticed similar neurological symptoms being reported by Spanish-speaking patients seeking treatment from different physicians at the Austin Medical Center, in Austin, Minnesota. Not only did these patients share similar neurological symptoms, they also worked at the same pork processing plant. Dr. Daniel LaChance, a physician at both the Austin Medical Center and the Mayo Clinic in nearby Rochester, Minnesota, was notified. He launched a request to area physicians to refer other patients with similar symptoms to him. The Minnesota Department of Health (MDH) was notified and began an investigation into the "outbreak." The MDH identified workers from two other pork processing plants in Indiana and Nebraska who also had parallel neurological complaints. Several agencies including the Occupational Safety and Health Administration (OSHA) and the Center for Disease Control and Prevention (CDC) were brought in to assist. Simultaneously investigations were conducted to rule out contagious disease, to locate the source or carrier, and to identify what exactly was causing these workers to develop these symptoms.

Removal from exposure was the first line of treatment. Due to progressive sensory loss and weakness, immunotherapy was often required. These treatments included intravenous methylprednisolone, oral prednisone, azathioprine, and/or immunoglobulin. All 24 patients improved, including 7 who received no treatment and 17 who required immunotherapy.

It is expected that there will be no new cases of progressive inflammatory neuropathy since the process of aerosolizing the pig brains has been discontinued at all pork processing facilities.

There continues to be a very practical problem with diagnosis of prion diseases, including BSE and CJD. They have an incubation period of months to decades during which there are no symptoms, even though the pathway of converting the normal brain PrP protein into the toxic, disease-related PrP form has started. At present, there is virtually no way to detect PrP reliably except by examining the brain using neuropathological and immunohistochemical methods after death. Accumulation of the abnormally folded PrP form of the PrP protein is a characteristic of the disease, but it is present at very low levels in easily accessible body fluids like blood or urine. Researchers have tried to develop methods to measure PrP, but there are still no fully accepted methods for use in materials such as blood.

In 2010, a team from New York described detection of PrP even when initially present at only one part in a hundred billion (10) in brain tissue. The method combines amplification with a novel technology called Surround Optical Fiber Immunoassay (SOFIA) and some specific antibodies against PrP. After amplifying and then concentrating any PrP, the samples are labelled with a fluorescent dye using an antibody for specificity and then finally loaded into a micro-capillary tube. This tube is placed in a specially constructed apparatus so that it is totally surrounded by optical fibres to capture all light emitted once the dye is excited using a laser. The technique allowed detection of PrP after many fewer cycles of conversion than others have achieved, substantially reducing the possibility of artefacts, as well as speeding up the assay. The researchers also tested their method on blood samples from apparently healthy sheep that went on to develop scrapie. The animals’ brains were analysed once any symptoms became apparent. The researchers could therefore compare results from brain tissue and blood taken once the animals exhibited symptoms of the diseases, with blood obtained earlier in the animals’ lives, and from uninfected animals. The results showed very clearly that PrP could be detected in the blood of animals long before the symptoms appeared.

Recent research from the University of Toronto and Caprion Pharmaceuticals has discovered one possible avenue that might lead to quicker diagnosis, a vaccine or possibly even treatment for prion diseases. The abnormally folded proteins that cause the disease have been found to expose a side chain of amino acids that the properly folded protein does not expose. Antibodies specifically coded to this side-chain amino acid sequence have been found to stimulate an immune response to the abnormal prions and leave the normal proteins intact.

Another idea involves using custom peptide sequences. Since some research suggests prions aggregate by forming beta barrel structures, work done "in vitro" has shown that peptides made up of beta barrel-incompatible amino acids can help break up accumulations of prion.

A third idea concerns genetic therapy, whereby the gene for encoding protease-resistant protein is considered to be an error in several species, and therefore something to be inhibited.

The clinician should first rule out conditions with similar symptoms, such as subarachnoid hemorrhage, ischemic stroke, pituitary apoplexy, cerebral artery dissection, meningitis, and spontaneous cerebrospinal fluid leak. This may involve a CT scan, lumbar puncture, MRI, and other tests. Posterior reversible encephalopathy syndrome has a similar presentation, and is found in 10–38% of RCVS patients.

RCVS is diagnosed by detecting diffuse reversible cerebral vasoconstriction. Catheter angiography is ideal, but computed tomography angiography and magnetic resonance angiography can identify about 70% of cases. Multiple angiographies may be necessary. Because other diseases (such as atherosclerosis) have similar angiographic presentations, it can only be conclusively diagnosed if vasoconstriction resolves within 12 weeks.

Diagnosis includes dilated fundus examination to rule out posterior uveitis, which presents with white spots across the retina along with retinitis and vasculitis.

Laboratory testing is usually used to diagnose specific underlying diseases, including rheumatologic tests (e.g. antinuclear antibody, rheumatoid factor, angiotensin converting enzyme inhibitor <-- error) and serology for infectious diseases (Syphilis, Toxoplasmosis, Tuberculosis).

Major histocompatibility antigen testing may be performed to investigate genetic susceptibility to uveitis. The most common antigens include HLA-B27, HLA-A29 (in birdshot chorioretinopathy) and HLA-B51 (in Behçet disease).

Radiology X-ray may be used to show coexisting arthritis and chest X-ray may be helpful in sarcoidosis.

Blood tests, cerebrospinal fluid examination by lumbar puncture (also known as spinal tap), brain imaging studies, electroencephalography (EEG), and similar diagnostic studies may be used to differentiate the various causes of encephalopathy.

Diagnosis is frequently clinical. That is, no set of tests give the diagnosis, but the entire presentation of the illness with nonspecific test results informs the experienced clinician of the diagnosis.